Intestinal Injuries Resulting from Irradiation Treatment of Uterine Carcinoma

INTESTINAL INJURIES RESULTING FROM IRRADIATION TREATMENT OF UTERINE CARCINOMA* ALBERT H. ALDRIDGE, B.S., l\tD., F.A.C.S., KEw YoRK, N. Y. (F-rom the Clinic of the Woman's Hospital)

M

OST of our knowledge and experience in the use of irradiation therapy for the treatment of uterine carcinoma has been acquired in the past twenty-five years. Within this time, reports from various excellent clinics throughout the world have appeared, describing a variety of techniques for radium and roentgen ra~' therap~' and presenting statistical summaries of the results that have been ohtained. Although there is still some difference of opinion as to optimum amounts of irradiation to he used and the safest and most effective methods for its application, in general it ma:v he stated that irradiation therapy for uterinr carcinoma has become fairly wdl standardized. Recognizing the value of this form of therapy and the risks involved in its use, gynecologists strive to meet two ohjectives, namel~·:

1. To deliver an amount of irradiation -..vhi<'ll can now lw determined with reasonable accuracy as sufficient to destroy the malignant process provided it is radiosensitive and is eonfined to the uterus and its parametrial supporting structures. 2. To protect adjacent anatomic structures, and especial]~, the urinary and intestinal tracts, against exeessivt' st"eondary irradiation effeds whi(•h may be dt'structiYe to their substance and fundion.

In reporting the results of tlwrapy, it has he<>n em;tomary to record facts regarding the effect of irradiation on the progTe:>s of the disease and the smvival rates of patients treatC'tl. Until rec(•nt ~'ears relatively little has heen written rega1·ding the 11ndesirable nnd oc-casionally dangerous secondary effects of irradiation on the :>nrrounding healthy tissues. The few 1·eports in medical literature regarding· snell eomplications have given detailed clinical and pathologic descriptions of :-;orne of the serious intestinal injuries that have hcen ohsrrved. They have also included difwnssions as to the pmhahle causeR of Hnch injuries, but as a rule have provided little information as to the fr-equenc-y of their oceurrcnce. However, in 1937, Corscadcn, Kasabach and Lenz 1 reported an incidence of 8.7 per cent of intestinal injuries which occurred as a result *Read at the Sixty-Seventh Annual Meeting of the American Skytop Lodge, Pa., June IS to 17, 194~.

8

.,., •loJ

Gyne~ological

Society.

834

AMERICAX ,JOFRXAL OF OI3BTE1'RICS AND GYNECOLOGY

of irradiation treatment of 442 patients for uterine rarcinoma. The cases reported h1 this series included only the more serious injuries with symptoms requiring active treatment or surgical intcrwntion. Reporting from England in 1938, Todd 2 stated that the ineidenee of irradiation intestinal complications following treatment of uterine carcinoma was approximately () per <·ent in all dinies. His statement was haserl upon his knowledge of the results of tTeatment at the Christie Hospital and Holt Radhnn Institute h1 1\'lanchcstcr, the 1\Iarie Cur](' Hospital in London and the Radiumhemmct in Rtockholm. His statistics probahl~ included only the mon' severe types of injuries. In 19'41, Chydenius, 0 of Helsingfors, reported an ineidcncP of 10.2 per cent of intt>sl ina I strictures that followed irradiation therapy fol' uterine earrinoma in a series of 321 rases trea(!;'d from 1937 to 1940. The purpose of this report is to record om experience in th(' diagnosis and treatment of intestinal irradiation injnries at the \Vom11n 's Hospital from 1937 to 1941, inclusive. This n:(·eni fiv(:-year JWriod \Yas selected because we believ(• that r1nring this time, data ·wel'e reernating wHh diarrhe
ALDRIDGE:

IXTESTINAL IN.JURIF.B FROM IRRADIATIO~ TREATMENT

835

As a check on the extent of a malignant growth, irradiation therapy is preceded, in our clinic, by routine examinations of the lower bowel and urinary tract. In Table I, it will be noted that: 1. 16.9 per cent, or approximately one out of every six patients treated for uterine carcinoma, developed some degree of proved injury to the intestine. 2. Only one intestinal injury occurred following treatment of 47 patients for carcinoma of the corpus uteri. 3. Of 142 patients treated for carcinoma of the cervix uteri, 31 developed postirradiation intestinal injuries includi~g 23 intestinal strictures. In other words, an intestinal injury developed in one out of every 4 to 5 cases treated for carcinoma of the cervix, and one out of approximately every 6 patients treated had a postirradiation intestinal stricture. TABLE I. TYPE AND INCIDENCE OF INTESTINAL IRRADIATION INJURIES THAT OCCURRED DURING TREATMENT OF 189 CASES OF UTERINE CARCINOMA AT THE WOMA:-r 'S HOSPITAL FROM 1937 TO 1941, INCLUSIVE INTESTINAL LESION RESULTING FROM INJURY DIAGNOSIS IN CASES TREATED Carcmoma of corpus f'areinoma of cervix

NO. OF CASES

I

142

I

189 100

Total cases treated {~ent treated

Per

of cases

PROCTOSIGMOIDITIS

47

I

ULCER WITHOUT STRICTURE

0

5 6

I

:1.17

I

TOTAL

3 3

23* 2:3

1 31 32

1.58

12.16

16.!1

1

I

STRICTURE (I

I

•Includes one carcinoma of cervix following supravaginal hysterectomy.

The incidence, 16.9 per cent, of intestinal inadiation injuries which occurred in patients treated in our cancer clinic appears to be relatively high. This is true because in this series, every case of proved injury has been reported regardless of the fact that some were extremely mild, giving rise to only transient symptoms. In previously published reports, statistical data have included only the severe types of injuries requiring active treatment or surgical intervention for relief of symptoms. Had it not been our policy to investigate all cases with postirradiation intestinal symptoms, some of the injuries reported in this series would undoubtedly have been missed. TABI~E

Il.

SUMMARY OF DIAGNOSES AND DIS1'RIBUTION OF THE CELL TYPE (EWING) NO. OF

I

38 CASES AS TO

CELL TYPE (EWING)

~,----D-IA_G-;N-'o_s_Is_ _ _ _ _cA_S_E_s_ _ _l_~~~--2-1_E_I __ 3 _1 __ 4_ Adenocarcinoma : 8

=--g-~_;~_.U_x---;-,..--Squamous cell ·carcinoma :

1

I

I

I

I

I

I

I

___ 4 _ _ _ _ _ _ _ _ _ _1_ _ _ _

---;;~;;-:-,-::,;_x____ ---;;~-;;-~-- --;- --~-

;~

I--~-I

_ __

I--~-I--!-I--~-

Within the five-year period (•on•red hy this l'<·pott (i patients i11 addition to the 32 listed in Tahk I <·am<· ttn
~'ig. 1.-Mrs. S . (Hospital N o. 740 84 ) . aged 3:; year ~. wa~ trea ted for adenocarcinoma of cervix with 4,200 mg. hr. of radium delivered in twenty-four hours. Intestinal symptoms began immediately a fter radium th e rapy. No roentgen therapy was used. Intestin a l stricture was diagnosed at three weeks aft e r r a months a fter irradiation therapy. Comment: Intestina l strictm·e wa,; J•roba bl~· 11t11~ t o hy]lerem ia, e rle ma, a nd intestina l spasm at s ite of injury.

Table II is a snnunalT u[ the Jiagnoses maJe in the :3H cases. It will be noted that the series included on h · mw ease of adenocarcinoma. of the corpus uteri. Of tlw 37 patients ~''ith tmnot·s ot the eervix uteri, 4 cases were diagnosed as adenorm-einonuts and :1:3 as squamous cell carcinomas. Tabl e II also Rhows the distrihntion o f th<' 38 r•ases of uterine carcinoma in aceordan(·<' with tlw l•:win ~r ehtssifi(·ation as to eell type. Our own ohservat iom; arr in ag.l'<'<'lllt·llt with prr,viotlsl:v published reports 1 • 2 ' • that in test ina I com plir·at ions l'l'sttlt ing from irradiation injuries
Any one or a eombination of these 1y pt>s of tissue reaction may develop in the same patient.

Acute proctosigmoiditis is f lw mildest form of intestinal injury ohserved as a rc~mlt of the seeondary dfeets of inadiation therapy for uterine carcinoma. Charaetcristir intestinal symptoms appearing during the course of trcatuwnt or soon after its completion give the first warning of the presenre of such an injur;\'. The symptoms include abdominal pain, diarrhea, rertal tenesmus,
A..

B. Fig. 2.-Mrs. E. (Hospital No. 75463), aged 09 ye;us, was treated for adenocarcinoma o f ce rvix with 4 . ~00 mg. hr. of radium d e li w .re d in twenty-four h ours a n d 8,000 r. of roentgen therapy in thirty-six days. Onset of symptoms and diagnosis of intestinal stricture, A, occurred a t fiv e months aft er irradia tion. P a tie nt was free of symptoms and roentgen examination. FJ . m8<1 e thirty-nine days a f t e r Fig. 2, A showed much less constriction of the bowel at the site of injury. Sigmoidoscopic examination s how ed a n increase in th t> s ize of thr, bowel lum t> n . Comment: Rapid improvement would suggest that hypero;mia, edema, antl spa.~m of tlw bow<'l wPre important fact or s in ca u sati on of the ~tr i <"tur e se<>n in A..

Examination will reveal a typical localized inflammatory process involving the anterior wall of the rectum and distal end of the sigmoid

838

AMER1CAN ,JOURNAL OF OBSTF.'rRtCS AXD GYNRCOLOGY

A.

B.

Fig. 3.-Mrs. J. (Hospital N o . 6&8 12) , ag·ect :, 1 years, w as treated fo r squamous cell carcinoma of cervix with 4, 800 rng . hr. of r adi um d eliver ed in forty-e ight houn; a nd 8,8 00 r. of roentgen th erapy in twenty -nine days. Intestina l symp t oms b egan a t f ou r and one-half months after t ermination of irradi a tion. Diag nos is of intestinal s tricture, A, was made one month la t e r. Treatm ent was pallia tive . At two years a nd seven months after the diagnos is of intestina l s tric ture w as m a d e, the pa tient is free of intestinal symptoms . and roentgen study, B , s hows the bowel to be practically normal in appeara nce. Comment : This is a good demon s tra ti on of Nature's s u ccess in healing such injuries.

ALDRIDGE:

INTESTINAL 1:::-
839

A.

B.

a.

Fig. 4.-Mrs. M. (Hospital N o. 60323), aged 56 years, was treated for adenocarcinoma of cervix with 4,800 mg. hr. of radium in thirty-six hours, a nd 8,800 r. of roentgen therapy in thirty-two day s. Intestinal s y mptoms began two months after t ermina tion of irradia tion ther a py. Diagnosi s of intestin a l stric ture, A , was made as soon as symptoms a ppeared. At four months a fte r irradiation , symptoms were Jess troublesome although a roentgenogram, B, still s howed definite cons triction of the bowel a t the site of the injury. Another roentgenogr am, 0, m a de four years a f t er irradiation shows les s constriction of the bowel. At this time the patient was symptom free, and h a s continued in good health up to now, over six years from time of irradiation thera py. Comment: This shows the success of pallia tive therapy and that bowel function may be normal although evidence of stricture persists.

R40

AMERICA.'\ .TO{lR:\'AL OF 0Tl~1'ETRH'~ .\;-.,;[) UY:'\ECOLOUY

at about the ]p,·p] of the r·~>rYix. Tlw llllH'ott~ memhrmw m·pr 11w :JI'l'a is soft to palpation. intemwly h,\']WI'Pllli<• in appNll'am·e or Pdem:Jtous with ronsiderahlp mu<·ons sPrr<'iion on•r its snri'
''Then

injnr~-

to tht> ho\\-e1 is

l11oiT st'\Tf·p

1hail ihal \vhi(•h eauses an

acute pmctitis, nlePnl1 ion of t h<' intP~t iJH' nsnnll,\' urcnrs. Although nlceratiYP lesions haw l)('r•n ohs<'ITPd in both t hl' l'cetum mHl sig·moi1l. the nsnal lo('atioll fm thl'il' ;in. 'I'nmma of <'xamination or eYacuation of howd <'OJJtPnts l'Padil~· imlnePs l1l!'eding. Tlw t•xtent of nlcprativ0 le~ions prohahly dqH·11ds not onl:· ll pon t lw S1•verit,v of the original injuries hut also II)HHl s<·<·on1lary ini'Pd ion of the injured areas. In a small perePntagp of th<•s<· <·ases. pprforation of the bowel ocenrs into tlw pNitonea i <·avit y, eausing· JWl'iton it is; intu the vag·ina, produeing rectovag-inal fistulas; OJ' into the jWJ'ir·<•dal tissnc•s, g·iving· 1·ise to ischiorectal abscesses requiring; im·ision mH1 drainag·r. Ulcerative lesions mak!' their appPnl'illl('l' at any timt• from soon after termination of irradiation tlwrapy to within spn•ral wet>ks or months later. They tend tn ht:nl slo\\~1~, \Yitli ~<'Jnlratiun ol' slon~.d1s fl'onl their bases and inward gTowih of tlw smTonnding ht>a]th~· intestinal mucosa. \Vhen healing is <'ompl<'t<' t hP mtwosH is pHI<· nnd atrophic· in appearanee with sonw evidenee of 1Piang-iec·tasis. Palpation of the ]('sion is lilu~ly to revt•a l some fixation as a 1\'stdt of 1he format ion of fihrous tiss1w beneath thr injured al'<'sions appear to he eonfinp<] essentiall,,· 1oth\' mtwosa illl!l w;tll ol' the intestine itself and have been refpn·pd to as · · in1 rinsi1· ll'sions. ''" The!'!' a!'!' a t'ew otlwr eases in whi(·h tlH· prinwr.'· injur.'
pelvic st1·uctures be1o\v the uteroee1·viea1 junction and extending up-

ward and backward to the st>cond or third sacral vertebra. This type of tissue reaction to irradiation referred to as an "extrinsic lesion' ' 2 produces a pelvic condition whif•h is difficult to differPntiate from the so-

A..

B. 'Fig. 5.-Mrs. M. (Hospital No. 74794), aged 52 years, was treated for squamous cell carcinoma of cervix with 4,200 mg. hr. of radium delivered in twenty-four hours, and 8,000 r. of roentgen therapy in fifty-one days. Intestinal symptoms began immediately following· irradiation and the diagnosis of intestinal stricture, A, was made at three months from termination of irradiation. PelYic examination showed a "frozen pelvis" from the so-called "extrinsic"' type of injury. This is probably responsible for the distorted appearance of the lower bowel. A roentgenogram, B. made seven months later shows considerable improvement in the stricture<.! bowel. At one year and nine months from the time the diagnosis was made the patient s.till has intestinal symptoms but is much improved. Comment: This is a good example of disturbance in bowel function from an "extrinsic'' irradiation injury which has been treated by palliative means.

842

AMERICAN JOURNAL OF OBSTE'l'RICS AND GYNECOLOGY

called ''frozen pelvis ' ' caused by massive invasion of all pelvic struetures by malignancy. It. may be associated with an nlcerative lr..sion of the bowel. As healing of this type of injury progresses, the lower bowel is likely to be distorted by contraction o[ the fibrous tissue and by external pressure causing intestinal obstruction. Roentgen studies of the bowel are essential for diagnosis and proper management of many intestinal irradiation injuries. Some injuries resulting in strictures of the bowel occur at levels which do not permit satisfactory examinations through a sigmoidoseope. In others nmTowing of the bowel lumen at the site of an injury prevents passage Ill' a

Fig. 6.-Mrs . T . (Hospital Ko. 7()965). aged 63 Yt'ars. wa5: tr<>n le cl ft>r sq ua u• o u ~ cell carcinoma of ee r·vix with 6.00 0 m g . hr. of rnclium <1elivered in forty-eight h ours, a nd roentgen therapy 8,400 r. in thirty-eight d ays. Onst~t of symptoms and diagnos is of intestinal strict ure, occurred at two months afte r te rmination of ina diation thera py. Pelvic examination a t operath•n, one week aft,~ r d iagnosiH was m a d e . showed th e sigmoid markedly thickened for a dis t a n ce of 10 cnr. u.ncl adherent t o the uterus. A loop of ile um was fixed by a dhesions t o the p eritoneum o f tlw c ul-de-sac a nd was thi ckened for a distance of 1 2 em. Its lume n was s lightly constricted. Nonviable cancer cells were found in tissue removed from the s urface of the ile um at its point o f attac hment in the cul-de-sac. The surgica l procedure adopted w as Mikuli cz colostomy. Thil' pa tient died three months after opera tion from generalized carcinomatos is. Com ment : This case shows the risk of bowel injury to adherent loops of intestine. Diagnosis o f bowel stricture cau sed by irra dia tion was confirmed by operative findings. Ope r a tion was necessa r y one week a ft e r patient cam e un
sigmoidoscope to a point at which the lesion can be satisfactorily visualized. By roentgen studies the existence and location of intestinal strictures can be determined and the success of palliative therapy <·an be checked. The decision as to whether palliative therapy should be eoutinued or surgical intervention is necessary is usually based on physical symptoms and the results of sneh studies. Figs. 1 to 8 show typical roentgen findings in some of the cases included in this series. All of the 38 cases in the series that developed intestinal irTadiation injuries had treatment with radium, and 27 of the 38 cases had additional roentgen therapy. In 19 of the eases, r adium treatment was given

ALDRIDGE:

INTESTINAL IN,JURIES FROM IRRADIATION TREATMENT

843

"11

A.

B. Fig. 7.-Mrs. vV. (Hospital No. 74210), aged 40 years, was treated for squamous cell carcinoma of cervix with 4,200 mg. hr. of radium delivered in twenty-four hours, and 7,600 r. of roentgen therapy in thirty-six days. Intestinal symptoms began immediately following irradiation and intestinal stricture. A, was diagnosed at six months after termination of irradiation. Palliative treatment failed and a diagnosis of complete intestinal obstruction, B, was made five months la ter. At operation no evidence of malignancy was found in the abdomen or pelvis. The wall of the rectosigmoid was markedly thickened for a distance of 10 em. extending down to the ftoor of the cul-de-sac. The wall of the bowel was ulcerated and necrotic, and an impending perforation was sealed off by an adherent loop of ileum. The operative procedurEl adopted was permanent colostomy a nd abdominoperineal resection, removing the rectum and the damaged portion of the sigmoid. This patient is alive and well at seven m onths after operation. Comment: Timely operative interference is a lifesaving measure for some patients who develop postirradiation intestinal Injuries.

in one applieat.ion and i11 tlw n~mainiug- l!J easrs lwo applications Wf'l'l ! used. Roentgen therap~- prr(·ence of suhset~uenl slrietm·e. In (i of the 0 ca:,ws. a diagnosis of proetosigmoiditis was made, and in :3 eases uleeration of tlw howcd ahm oer·urred at t IH'

site of the injury. In one ease thr ulcer perforated th e rretovaginul septum, causing a reetovaginal :fistula whieh lwalt•d spuntaueonsl,\" a ftet' two months. It will he noted in Table Y that: 1. < )nset of int!'stina 1 symptoms was h ·om immediate],, - followingradium therapy in 5 eases to one ~-\'Ul' in on<> of tlw ulcer c·asC's . ~- Diag·nosis uf an intestinal le.o,;ion was mad\' in i'l'om one wet>k ro fom:teen months aftPr irrauiation tlwrn P.''·

3. Healing of the intestinal injnriPs was spon1mH'Olls in all uf tilt• 9 eases i1ielnding i.lw onP with ref·iovagiwtl fistula and the two tlwt died . At time ol' denth these two p<~ti <• nts had 110 intestinal symptoms.

Fig. 8.-~Irs . L . (Hospital 1\o. 55 947). agt>tl 43 J"(;a r>', was tr·ea ted for· squ a m n u ~ cell carcinoma of cel"\"ix with 6,000 mg. hr. o f ra dium in forty- e ight hours. :\ o roentgen thera py was used. Intes tina l sympto m s began at three months a fter irradiation th e nw~ ·. but a diagnosi s of intes tin a l ~ tricture w a~ not m a de until five and one-half years afte r sh e wa;; treated . Thi s pati<>nt was opc r·ated upon eight m onths after the cl iagn o ~is of intestinal st1·icture w Hs mar·us. The operative procedure was r es ec tion of th e damage
ute l"in ~!

carcinonHt mu st always b 0. k(•pt in n1ind.

In the series of ;38 \'11S (·.-.; of irradiation injuries, :Z!) had intestinal strictures as proved lry l'!)('Iltg-en stndics of t lw injured ho\\'f'l. In lK of the 29 rases with strif'tnres, s,vmpt.ollls have het•n 1·elievcd or contl·olled by palliatiw means. The results of treatment of these cases are summarized in Table VI.

.\LDRlD(H;:

R45

IN'rJ;;STI:\" AL IK.JFRIES FR0:\1 IRR.\DIATIOK 'l'RF.AT::\lF.XT

III A.. SuMMARY oF RADIUM DosM.a; UsED IN 19 OASES Wnu INTES'I'I:-iAJ, L:>rJrRIES FOLLOWI.!'i'G 0XE APPLICATIO:s' OF R\ll!UM FO!t C.utC'INO~L\ 01:' THE UTERU8

'l'ABL~~

Carcino-ma o_f Corp-us Ukri, 1 Case. Radium do,mge in the one ca~e was 2,400 mg. hr. given in one application to the uterine cavity in 24 hours. Carcinoma of Cen.•ix Ute1·i, 18 Casel'i. In the 18 cases one application of radium wal'i used as follows:

nmn; LOCATION OF APPI;[t'ATORS

2,000 IK 24 HR.

canal Cervix ( vagimtl surface) Parametrium (radium l:rwvi<'~

IN

2.400

24

IN JIR.

]()

l

HOI'ltS

:i,OOO IN :;n HR.

H011-1 XOO IN

24

rm.

CASES TRI':ATED

18

1

,,._1

l JS

~1.

ueeuu"'}

Range of total dosage in the 1S ea~es wa~ from :1,000 to 4,ii00 mg. h r·. in 17 r:aBes and 6,000 mg. hr. in one case. 17 of the 19 cases in this group had additional roent{len therapy mngin,q from 1,600 to 10,000 ·r. within 2li to 51 days.

TABLE

III B. SDMMAHY OJ<' RADIUllt DOSAGE USED IK 19 CASES WITH INTESTIKAT, l:-!Jl1RIES FOLLOWING TWO APPLICATIOKR OF R-ADil'M FO!t CARCINOMA OF THE CEKVJX UTt~IU ~'JR;';T

APPJ,ICATION

OF APPLICATORS

J,Ol~.\'l'ION

1,200 24

C<>rvix and eavitv Parametria (radium net>dli"S) fornil'es

JIR.

ll'i

24 llR.

18

l

16

Range of total dosage in the 19 t"ase~ wa< from 4.~nn to ii,OiiO milligram hour~. Total duration of radium Pxposure was 39 hours in one case and 4S hour~ in lil eases. 10 cases in this group had roentgen therapy ranging f-rom 6,000 to 10,000 r. within 22 to 50 days.

TABT,E

IV.

SUMMARY OF WOMAN'S HOSPITAl, ROENTGEN THRJtAPY TEClll';lQUE lfr->ED I;
em. Inten~ity:

(a) 25 r. per minute. .75 mm. <'Ollper. 2 mm. aluminum. (h) 10 r. pt'l' minute. .4 mm. tin. .25 mm. e.opper. 1.0 mm. aluminum. Number of fields: 4-6. Size of field": Maximum Hi x 12 em.; aye rage ltl x 10 r•nJ. Centering of fields: Over parametria with protertion of an area along the midline--2 t.o 3 em. in width. Daily dose: 150-200 r. to E'arh of two :fieltls. • 150 r. per field routinely since 19:\8. Total amount administered to pehis (measured in air): 8,000-10,000 r. Duration of cyde: 2?, to 42 day~ (present minimum 30 days). (a)

(b)

846

AMERICA~ .JOURNAL OF OBSTETRICS AXD HYNECOLOHY

From Table VI, it will be noted that in from three months to oyer six years of observation, 13 of the 18 patients had become symptom free, 2 were improved, 1 was unimprovrd. and :1 r1ird of generali?.ed carcinomatosis. It is frequently difficult to differentiatr between intestinal obstruc:tion caused by tissne reaction to inadiation injut·:v and ronditions resulting from malignarl<'y. The diagnosis of an irradiation intestinal slrirture in any patient under observation is hased upon impronmwnt in D'<>n<>l""l hMllth followin
.... ..._....., .... ...,.,_.._

..._..._.....,"".._..,..._ .....

~~.._-,J··~--L'

~-~-----·----,

-------

--

-------------

·-,,

-_j_·--

Table VII is a sumnwr.v of facts regarding irradiation therapy and diagnosis in 11 of the 29 eases of intestinal stricture whieh required surgieal intervention for relief of S;\'mptoms. In this table it will he noted that: 1. Diagnosis of stricture requiring operation was made in from two months to five years and five months aftrr termination of inndiation therapy. 2. Loeation of the stricture was in the rectum in one case, in the sigmoid in six cases, in the rectosigmoid in three cases and in the ileum in one easP. In one case of sigmoid injury the ileum wal' also involved. Table VIII is a summary of the smgiral 1t>chniques used and ontcome of the 11 cases of intPstinal strietnre that were operated upon for relief of symptoms. Surgical indications whirh arist' in the 1reat ment of these <•asel': inelude procedures to : 1. Relieve pain, bleechng and partial or (·oilipletf· intestinal ohRtl'lh'tion. 2. Remove necrotic bowel which may perforate resulting in death from peritonitis. 3. Promote healing of ulcerative lesions by diverting the feral stream. In some eases this can be accomplished h~~ c·olostomy whieh can be closed after the intestinal injnr,v has healed. Suceess in the treatment of irradiation intl~stinal injuries requi t·rs the skill and judgment of an experieneed surgeon. He must have the ability to select the surgical procedure best suited for treatment of injuries which vary considerably as to their extent and location. Surgieal treatment of such injuries is not infrequently eomplicated by the fact that they occur in patients who are either poor surgical risks or are in poor physical condition when operative interferenee becomes necessary . .Another factor which must be taken into eonsideration is the disturbance in circulation which occurs in tissues which have been subjected to intensive irradiation. With this in mind colostomy may be the primary procedure of choice to avoid eomplications arising from failure of wound healing following intestinal reseetion and anastomosis.

46

30 41 58

5

6 7 8 9

66

57

3 4

52

54

51

AGE

1 2 2

2

"

2

3 2 3 3

,)

3 2 3

-

2 1 2

-

LEAGUE OF NA· SCHMITZ TIONS

STAGE OF DISEASE

48

:w

8,000 8,400 10,000 R,OOO

24

18

(1,000 4,200 4,500 5,400

7,200

48

(i,OOO

None

7,800 3,200 8,000

24 20 24 24

TIME HR.

~,,

09

50 33 32

29

-

26 10 40

ROENTGEN R.A Y 'l'REAT· DOSE MENT R. DAYS

2,400 3,500 3,600 6,000

DOSE MG. HR.

RADIUM

IRRADIATION

Immediate Immediate 12 mo. (i mo. R. V. :fistula

Immediate

Immediate Immediate Immediate Immediate

ONSET OF SYMPTOMS

14 6

8

10

1

MO.

1

2

4

1 1 1

WK.

DIAGNOSIS

TIME FROM TERMINA'l'ION OF IRRADIATION TO:

8 2

~1-

4

-

-

YR.

7 4 10 5

-

-

7

MO. :---::-2 4 8

TIME FROM DIAGNOSIS TO PRESENT

Symptom free Symptom free Symptom free Dead. Cardiovascular disea8e after 4 years Dead. Carcinoma metas· tashl after 1 year Symptom free Symptom free Symptom free Reetovaginal fistula healed after 2 months

PRESENT C0NDI1'10N

SUMMARY OF DATA REGARDING 9 CASES WITH INTESTINAL INJURY WITHOUT EVIDENCE OF STRIC'l'URE

Dignosis: Case 1, carcinoma corpus uteri, all others carcinoma cervix uteri. In Case 2, roentgen therapy was discontinued on account of intestinal symptoms. In Cases l, 2, 8, 5, and 7, intPstinal symptoms began immerliately after radium.

Ulcer

]

Proctosigmoiditis

2

OASE

DIAGNOSIS

TABLE V.

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CASES OF [1\TESTI SAL STr:IC'l'l'RE REQUIRIS(; 0PE!UTI01\ FOil RELIE,. m•

IRRADIA'f[OK

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850

AMERICAN ,JOURNAL OF OBSTETRIC:S A:'\D GYNECOLOGY

TABLE

VIII. S<;MMAIW m' FINDINGs, Sl:RGICAJ. 'l'ECHNIQUES E).H'LOYEJJ OUTCOME OF 11 CASES OPERATED UPON FOR INTES1'IXAL STRICTURE>'

LOCATION" OF

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POSTOPERATIVE FOLLOW-L:P TIME li!l\"('E ITI !<'HOM Ol'EitATJO!\ DH:D OPERATION CAr:s~: or YR. MO. '1'0 DEATH

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In cases in which intestinal injuries have occurred as a result of irradiation treatments for uterine carcinoma, it is often impossible to determine whether they have been caused by radium or roentgen ray therapy. However, it is generally agreed that they are invariably due to overdosage of irradiation and that the primary injury is to the blood vessels which supply the injured howel.2 It is believed that damage to some of the smaller branches of the hemorrhoidal vessels results in their becoming thrombosed and occluded. This leads to infarction and mucosal ulceration in the portion of the bowel from which the blood supply has been withdrawn. There is reason to believe that muscular spasm of the bowel wall at the site of the injury may be another factor in decreasing its blood supply.

ALDRIDGE :

INTESTI:\fAL IX JURIES FROM IRRADIATION TREATMENT

851

From the study of specimens in our own laboratory, it appears that the blood supply to the injured bowel is gradually rather than suddenly withdrawn. The basis for this conclusion is that within the areas of tissue necrosis observed, foci of reparative (inflammatory) tissue reaction can be identified. It is assumed that the cellular elements for this defensive tissue reaction must have been supplied by blood vessels which had not lost their function. Figs. 9, 10, and 11 are drawings made from fresh surgical specimens. A reduction in the incidence of these serious intestinal complications of irradiation therapy for uterine carcinoma must depend upon a better understanding of their etiology, recognition of the fact that they may make their appearance at any time from immediately following irradiation therapy to within several years thereafter, and elimination of eonditions whieh are known to predispose to their occurrenee.

F ig. 9.-Showing the c ha r ac t eris tic external appearance of the bowel which has been injured bv irradia tion. The wall is thickened and h as the consistency of a thick-wa lled " mbber tube." In the midportion of thi s specime n , the re is a cons tricted, n ecro tic area, S. The d a rk color is due to e xtravasatio n of bl ood be nea th th e pe ritoneum.

Both elinical and experimental studies have contributed to our knowledge of factors which may be responsible for such injuries. The unusual susceptibility of the intestinal mucosa to damage from irradiation has been well established. 1 Overdosage of irradiation, which may be a frequent cause of such injuries, is undoubtedly the result of faulty technique or of conditions which are difficult to control. Cases have been reported in which intestinal injuries were due to accidental dislodgement of radium applicators from the cervieal canal or uterine eavity to the vagina. Other conditions which may result in excessive exposure of the intestine to radium include: a retroverted uterus, a uterus with a thin museular wall and peritoneal adhesions which fix one or more loops of the intestine to the external surface of the uterus, or to the cervical stump following supravaginal hysterectomy. Furthermore, Todd has called attention to the fact that ''the question of overdosage is a rela-

,\M:ERICA I'\ .JOUH!\AL OF Ollf;'I'E'l'HICS .\ :-\ 1> c:YC\El'OLOGY

Fig. 10.-Showing a long·itudina l section of thi s same SP<~ cime n of bowel. Tho: pe ritoneum a nd subperitoneal tissu es. F, are markedly edema tous. A typical mucosa l ulcer, U, can be seen. Induration of the wall extends far b eyond the limits of the ulcer. Nature's attempt t o heal the injury has resulted in a marked formation Clf fibrous tissue, a, which has n arrowed the lum en of th e bowel.

Fig. 11.-Longitudina l section of the same spec imen but in a different pla n e. This s hows the same c haract e r·rstic anatomic changes seen in Fig. 10. In addition it has been made at a point at whi ch the muco~
ALDRIDGE:

IXTESTINAL IX.JURIES FROM IRRADIATION TREATMEXT

853

tive one.'' In other words, tissue tolerance to irradiation may be reduced by poor general health and tissue changes resulting from degenerative diseases. In some cases overdosage is undoubtedly due to the combined effects of radium and roentgen ray irradiation. Danger from this source can be reduced if roentgen exposure is carefully foensed on the laterai pelvic structures and adjacent gland-bearing areas. ~1umerous suggestions haYe been made to prevent irradiation intestinal injuries. They inelude:

1. Procedures to prevent accidental dislodgement of radium applicators from the cervical canal and uterine cavity. 2. Distention of the vagina with gauze and insertion of a rectal tuhe during applie.ation of radium with the purpose of increasing the distance between the radium and walls of the rectum and sigmoid. 3. Caution in the use of irradiation for treatment of patients who have had pelvic infections or previous abdominal or pelvic operations. 4. Frequent changes in position of a patient during radium treatment with the hope of dislodging intestinal loops which may be in close proximity to the uterus. 5. Roentgen studies of the intestine before placing radium in the cervical canal or uterine cavity to determine whether loops of intestine are fixed to the uterus or eervical stun1p hy adhesions. Evidence produced by such studies is not always conclusive. 6. Preirradiation exploratory laparotomy to determine whether loops of intestine are adherent in positions that might subject them to too much irradiation. This seems a radical procedure and does not eliminate the possibility of intestinal adhesions re-forming immediately after the exploratory operation. 7. Reduction of intensity of irradiation by: a. lising· smaller amounts of radium and increasing duration of exposures. b. Decreasing the size of the fields of roentgen ray exposures and the amounts of roentgen therapy per treatment. CONCLUSIONS

1. Sufficient irradiation to effect a cure of uterine carcinoma cannot be applied without some damage to the intestinal tracts of a considerable percentage of patients treated. 2. The true incidence of such injuries cannot he determined without routine diagnostic studies of the intestinal tracts of all patients who develop significant postirradiation intestinal symptoms. 3. The development of intestinul symptoms and especially those of intestinal obstruction at any time from a few weeks to several years after irradiation for uterine carcinoma should always suggest the possibility of a post-irradiation intestinal injury. 4. Careful diagnostic studies will serve to differentiate intestinal irradiation injuries from reactivations or extensions of malignant growths and may be the means of saving lives.

854

AMERICAN ,JOllRl':AL 01<' OB"''l'J<:'l'R!CS .\:'\D GYNECOLOnY

5. Success in the treatment of intestinal inadiation injuriPs will depend upon a kn
wi~h

~ultant

ltEI•'J<~RENCl<:S

1. Corscauen, J. A., Kasabach, H. H., anrl Lpnz, !>!.: Am . .1. RorntgPnoL & l{ad. Therapy 39: 871, 1938. 2. Todd, T~ F.: Surg. Gynee. & Obst. 67: tll7~6:.~1, .l~•:·tX. :t Chydenius, .J. .J.: N ordisk Medizin 11: 2595. HH 1. 4. White, W. C.: Ann. Sur g. 112: 7()(). 77'l, 1940. 899 PARK AVENUE

DISCUSI::iiON

DR. JOE V. MEIGS, BosTOs, MAntl Hospital and the Pondville Ho~pital we han• had :;:1 such patiPnt:;, or :>,.ti per e0nt out of a total llf 800 who werC' gin~n x-ray treat· mcnt plus radium. ln four other ca~P~ stridureH followed radium al01w. A great many othPr patients with ~ymptomH of bl<,(•ding, tenesmus, pain, ek., were ~<·Pn hut are not r<'purte'00 •~aRes had sup;orvoltage or 1,1100-1,200 kv. therapy. 01' t.hef'e ](10, S patiPnt:-; ""· velopetl obRtructing ksions. Twenty of 1.hf' 1otal of ::n followPd :JOO k\'. Uu:>rapy and 2 followed 400 kv. treatment. It is very probable that more cases will follow the million volt therapy until the proper rlo~age has hePn learned from a ltr rg;•• expcrien<>e. Of the 34 patients with obstruction and stricture at the Massachusetts GPneral Hospital and Pondville Hospital, 22 were operated upon. In the 12 patient~ not operated upon and diagnosed by x·ray and proctoscopy, ti had lesions in tlw rectum and 6 in the sigmoiU. The Rymptoms in all cases consisted of pain. rectal bleed· ing, nausea, vomiting, distention, and tenesmus. Of those operated upon, 11 had a colostomy done; 1 a colostomy with posterior excision of the rectum; 2 had ileo· transverse colostomies plus rcsedion of the ileum with ~igmoid colostomy; :l had ileotransversc colostomies plus resection of the ilt'um; ::! had ileostomies; 2 had resection of the ileum; in 1 a piece of adherent ileum was re!Pased; and in 1 an entero-enterostomy was done. There was only 1 postoperative death, but of the ~~ patients operated upon, 4 have since died. The average time to the onset of bowel symptoms from the time

ALbRil)GE:

lNTE8TtNAL 1::-;'.JURlES FROM iRRADIATIOK TREATMENT

855

of treatment wa.'! one month to twelve months in 17 cases, with an average of six months; in 13 cases, from one year to se\•en years, with an average of 3.4 years. In 4 cases the correct dates of onset were not known. One patient with symptoms of obstruction and bleeding, with strieture observed by x-ray six months after radiation treatment, was completely relieved of symptoms and an x-ray of her colon \vas normal without treatment at one year. In 2 patients temporary left-sided colostomies were closed successfully. The largest dose of x-ray therapy was 9,200 roentgen units with the 1,200 kv. maehine, and the :~mallest dose wa~ ],:;:lO roentgen units with the 200 kv. machine. 'rhe largest .lose of radium wn~ li,08!\ millieurie hours and the ~mallest was 2,001l millicurie hour~. To avoid injury to the bowel the rays mu~t be prevented from striking it. To aeeomplish this is h more diffirult in tl11me who may havr an atlherent loop of bowel. Perhaps radiation treatment of early eervieal canrer is not tlle best method ani! perhaps Rurgery Rhould bi> more widely nRrd for early rases. This would avoid the Thr latter eombination could be used for more danger~ of radium anas!'. About one-half of our !'ases of bowel injury were in an Nnly op<>rable group, awl operation in this group would haw been safer than radiation therapy. It is m~· feeling that the anSW\'r to the apparent inerea~e of bowel mJuries iR ra1lieal surgery for eaneer of the eervix in •~ertain eagc;<, the URe of high Trendelenburg position plus air injection in others, the u~e of the full hladder, and poRsibly the avoidanee of x-ray therapy in patientA who have been previomd, but the slanting position TI<'<'t'K~ary iK not possible with our preSPnt million volt therapy apparatus. Ten of our 34 patients had been operated upon and may have had adherent bowel, in whith <'ase this mnthod would not have worke<1. Air injection of tlw a.btlonwn has been suggester is full, thus displacing tlw ilt'um out of th<> pelvi~ and puHhing the sigmoisponsihle for its injury, an,] when a patient lie;; on lwr back, the terminal ileum i;; u:;mally the lowest 1oop of l'mall intestinf' anatm<>niH.

DR. THOMAS C. PEIGHTAJ_,, NRW YORK, N. Y.--Dr. Al
856

f,.,,.

deaths witltin a da,vs from [Writoniti,- i,- nuf•·worthy, as i~ tl.t• f:wt that in mo>
llr. Ahlridg<• 's :uw]y,;i~ plan•s tlw pt'r'<'<'nt:q.[<' of inte>'twly of pr;•sent-da.v therapy is •·arriPn•lt Ho~rit>ll<'t' of otht•rs here, lout it is of sonw interPst at tlw mona•nt iu that the radiation t<'<·lmiqn<' i~ >Q nearly likt· that usetl by ]Jr. Alri<'" may wPII lw <~ornpun•d as to rP~ulting iutestirml injuri<•s. From Hl::;i to 19-J.I IH' han• treat;;,] 100 <'as<'s of <'l'l'Yix 1·an·inoma. 1'h•·~·· pa ti<'nts han• n•<·e-ived i11 and about riH• l'l'rl'ix and lown utt>rin•• ··anal between :l,OOI> and ;J,OOO mg. hr. of radium elenwnt in •·:tp~ul••s with n.;; llllll, platiunltl filt.ration, of whi<·h :l,OOO to :l.:illil wg. hr. haw he;•n iu tht.> r·en·h·al <'anaL In tlw wajorit,v of instaw·P~ this radiation 1\'lts tH'<·omplisht•d iu oll<' appli<'ation hut in a small nnmlH'r (thos<' l'!'('E'iYing n total of -J.,fill.l to ;),0110 mg. hr.) l,i)OO to 1,800 mg. hr. of thl' total amouut 1\'l'l'P g-ivPn a~ a sl'eond app!ieation at lPa~t six wt•f'k~ lat••r.

High-voltag-<' thrral'~· Pit her foil om•lt'ntt•nt nHliation at a >H (avr•raging· in lliMt ··ases ahnut :::.:11 1·.) .-\ total x-ray do,;agt• of ti,il!lll to 7,500 r. Ita~ ht><'n Pmplo,vt•d, spl'l'H<1 on'l' fron1 hl't'nt,v-<'ig·ht to forty-two day;;. ('l'hiH j~ :?,!lll!l to :!,300 r. ],•;;" than llr. . \l'.) Jn tht>Hf' lOll l'!tS<~~ IYP han• had 1:: inslll!H'!'l< nf major inteKtina! dHumgP a;, l'Ol\i pared to Hr. Aldridge 'H l:?.lii p•·r •·••nt. 1\in<• of tltt'>'<' o•·•·m-r<'gTl'<:s of «t.rietun• of tlw re<"tosigmoid, ,;ollll' with ulr·eratil'e bl••••tling, lout 11on•• ha>' n·quire,l operati<>11. The time of app<'11l'',\'lli[!toms of th<'S<' injurh•;; ntrit•d from two months to one yrar. Thre<' •lPVI'loppd l'<'<•tovagimd fistula, om• of whi•·h healed spnnhm<•ously. the other two lwing in :uhant'l'rl r·a~PH.

Ln the Hmall bowPl, eonstr·iding lesion,; rw•·unr·d iH the -J. t•ai<·tion ami two of th<·sp nn• now alii'" and fr·N• of di~t•asl' in tht'ir fourth year·. One, a stump f•mw. who Jwd a loop of i!Ptlltl adhPl'P!lt jp tl11· •·r'l'\'lX, 'ix rnonrh~ aft<>r radiation, awl diPst•rtion hom intPstinal thrumhosif'. \Vt• haye r•ornjJl injuri<>t', TJIU, in our Pxperit>JH'P with II);! ··a,es Wt' han· notl'd a g·reat.••r in••i•len<'e and a gtPatPr ntriPty of iute~tinal injul'i<·' siw'P we han• stPpp<•a up th<' amount of high voltag<' therapy g-iv<·u. \\'•• heliew that gut damag<', PXePpt in tht.> ri1•x it i,; too t•arly to 'a.~· wlwtht>r an iu•·n·ase•l Ralval(e will !'otup<•n,.at<' for thifl im·rpa,ed inei
~~·rrf•n

our

r~ulintH lllOl'P

••tfe<'l"i\·ply

:.!. To l't'r· period

of time.

}'rom our expt•rienee we would urge the following: 1. Operative treatment of all small bowel le~ions as early as poHsihlP after !\iagnosis t•an he made. (In our eases x-ray h se<•m at first quit•· tight may funetion adequately with patienee and time. :1. Dr. Aldridge has pointed out how t•xtremely xploration, a:-< in the fpw instmwe~ in whi<'h Wf' have followed this plan we have bel'n rE'paid l>y finding a readily remedied benign pain-produeing leBion, or yery ~mall meta~tases on the lateml pelvic. walls which were not beyond tlw limit of satisfactory surgiral removal. If extensive growth i~ found, further therap,v <'.an b!' rnrriPd out with a ~ounXtent. DR. GEORGE GRAY WARD, NF:w YORK, N. Y.-1'hesf' in1Pstinal injuries are more eommon than it< generall,v realiZC'd that thi'S(' injuries WPre dut• to a thrombo~i>< of the ~muller hnmehe~< of tl1P hemorrhoid~.! \'esst>ls <'auHing obliteration of the blood >'uppl,v of tht> reetosigmoid, t hu,; produ{'ing infaretionH autl ulceratiou of the mu!•o,.;a an,.ulting in r·mtRtrietion of tht> bowel. Corseaden has rl'ported similar experiences and reeommends the amount of radium be reduced and prolongeu ~o as to giYe tin• same ultimate amount of irradiation. He suggests 70 mg. for one hundred hours. Our former aYemge dosagP varif'd from :1,600 to 4,~00 mg. hr. In later year>< it was increased by using, in addition, the rolpostat to the pt>rimetrium for 1,800 mg. more. There is a question whether in stepping up tlt(• dosage \Ve may have inereased the injurit>R whieh we are Pn••onntering. Cm·H<~aful follow-up of these east'~ as intestinal injurieR following irra•liation are usually ll late complieation.