`
`U vA
`
`SURGERY
`Gynecology
`er Obstetrics
`
`BIOMEDICAL LIBRARY
`
`JAN 1 4 1985
`
`LOS ANGELES
`
`Eeeigentum v Cosmo
`
`UNIVERSITY OF GALSFURNIA
`
`January 1985
`
`VOLUME 160 - NUMBER 1
`
`"ey
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`Cosmo Ex. 2017-p.1 °° %&
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`IPR2018-00080
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`DIFFERENCES IN PATHOGENESIS, INCIDENCE AND
`OUTCOME OF PERFORATION IN INFLAMMATORY
`
`BOWEL DISEASE
`
`A. J. Greenstein, M.D., F.R.C.S.(EDIN.)(ENG.), F.A.C.S., and
`A. H. Aufses, Jr., M.p., r.a.c.s., New York,
`New York
`
`PERFORATION is an uncommonbutlethal com-
`plication of inflammatory intestinal disease. It
`occurs more frequently in ulcerative colitis than
`in Crohn’s disease irrespective of whether the
`latter originates in the small or large intestine.
`Despite early reports to the contrary (1), perfor-
`ation in ulcerative colitis is usually preceeded by
`colonic dilation (2—6).
`In Crohn’s disease,
`perforation without dilation of the small or large
`intestine is more common (7), The incidence and
`outcome of perforation. with and without toxic
`megacolon in the two forms of inflammatory in-
`testinal disease are compared herein.
`MATERIAL AND METHODS
`
`The records of 1,623 patients with inflamma-
`tory intestinal disease admitted to The Mount
`Sinai Hospital between 1960 and 1980 were re-
`viewed retrospectively:
`there were 613 patients
`with ulcerative colitis
`(UC) and 1,010 with
`Crohn’s disease (CD). Of the patients with CD,
`457 had ileocolitis (IC), 166 had Crohn’s colitis
`(CC) and 387 regional enteritis (RE). Severity-
`five patients hadcolonic dilation, 61 with UC and
`14 with CD, and 29 patients with UC and20 pa-
`tients with CD hadeithera free or sealed off per-
`foration.
`
`DEFINITIONS
`
`The diagnosis of granulomatous disease was
`based upon criteria published previously (8-10).
`The clinicopathologic diagnosis of ulcerative co-
`litis was made on the basis of mucosal colitis ex-
`tending proximally from the rectum in the ab-
`sence of transmural disease, fissures, fistulas or
`skip areas. Free perforation was defined as spon-
`taneous rupture of the small or large intestine
`
`From the Department of Surgery, Mount Sinai School of
`Medicine of the City University of New York and The Mount Sinai
`Hospital, New York.
`Reprint requests: Dr. Adrian J. Greenstein, Mount Sinai Medi-
`ee One Gustave L, Levy Place, New York, New York
`29.
`
`with spillage of intestinal contents into the gene-
`ral peritoneal cavity and resulting peritonitis. A
`sealed perforation was occasionally recognized
`preoperatively as a tender palpable mass and es-
`tablished at laparotomy as an area of localized
`perforation sealed by adherent mass of omentum
`or peritoneum. Toxic dilation was based upon
`criteria similar to that described in one study (4)
`and included one or more of these findings: ab-
`dominaldistension, signs of peritonitis, tempera-
`ture of more than 101 degrees F., tachycardia of
`more than 120 per minute and a leukocyte count
`of more than 11,000 white blood cells per mil-
`limeter cubed. The diagnosis of colonic dilation
`wasaccepted if the colon measured 6.0 centime-
`ters or more in diameter on a roentgenogram or
`6.5 centimeters in diameter on barium enema.
`Mortality was defined as a death occurring dur-
`ing the same hospital admission. Analysis of the
`ulcerative colitis and Crohn’s disease data (Table
`I) was calculated using the programmed2 XK chi
`square contingency table of a 9815A Hewlett-
`Packard calculator.
`
`RESULTS
`
`Perforation in ulcerative colitis. Twenty-nine
`of 613 patients with ulcerative colitis (4.7 per
`cent) sustained a perforation (Fig. 1).'wenty-
`two of these occurred among 61 patients with
`toxic dilation (T'CD) (36 per cent). Seven occur-
`red among the remaining 552 patients without
`toxic dilation (1.3 per cent).
`Thirteen of 29 patients with UC died; nine of
`22 with TCD andfour of seven without TCD.
`Among the patients with TCD, 13 sustained a
`free perforation with five deaths and nine a sealed
`perforation with four deaths, Thus, the mortality
`was similar for patients with and without toxic
`colonic dilation and wasalso similarirrespective
`of whether the perforation was free or sealed at
`the time of operation. All patients with free per-
`foration except one were operated upon within
`
`63
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`rr
`387
`457
`Heocoliis
`ae
`Enteritis
`ia
`4
`
`Toxic Dilalation
`4
`
`Non TO
`609
`
`P.
`3
`
`Non P.
`"
`
`Deaihs Deaths
`2(67%)
`(0%)
`
`P
`wt
`
`Deaths
`0(0%)}
`
`re
`4(SB)
`
`Deaths
`0(0%)
`
`Morlabty 2°18 P (11%)+
`
`- January 1985 + Volume 160
`consistent with disseminated intravascular coag~-
`ulation (DIC). By contrast, DIC developed in
`only two of nine patients with a perforated UC
`and toxic colonic dilation who later died. Per-
`foration in patients with toxic megacolon was
`likely to be multiple and occured predominantly
`(52 per cent) in the transverse colon including the
`hepatic and splenic flexures; 20 per cent occurred
`in the sigmoidcolon.
`-erforation in Crohn’s disease. A free perfora-
`tion developed in twenty of 1,010 patients with
`Crohn’s disease (2 per cent) (‘Table I] and Fig. 1).
`Fourteen occurred among 623 patients with co-
`Jonic involvement (CDC), four developed in 387
`patients with regional enteritis (RE) and two pa-
`tients had perforations through areas of recurrent
`disease (one in the ileum proximal to an ileostomy
`andone in the sigmoid colon). Toxic dilation oc-
`curred in 14 of 623 patients with CDC and co-
`lonic involvement(2.24 per cent); five occurred in
`ileocolitis (1.1 per cent) and nine in granuloma-
`tous colitis (5.4 per cent). Perforation occurred in
`three of 14 patients with CDC and toxicdilation.
`One perforation was free and two were sealed.
`The two patients with sealed perforations and
`toxic colonic dilation died. ‘The one patient with
`the free perforation survived.
`Among the 609 patients with CDC, sponta-
`neous [ree perforation with peritonitis occurred
`in an additional 11 patients (nine in the colon
`alone, one in the ileum alone and one synchro-
`nously in the ileum and colon) without mortality.
`Seven were single perforations; one had foursi-
`multaneous synchronous perforations of ascen-
`
`
`
`64 Surgery, Gynecology & Obstetrics
`TOTAL NO. OF CASES
`1
`
`—SS}
`
`Crohn’s Disease*
`1080
`
`Ulcerative Colitis
`
`Ulcerative Collis
`613
`
`Toxic Dilatation
`
`Non-TD.
`582
`
`Perlorated
`22
`
`None.
`39
`
`Pp
`7
`
`Deaths
`9(41%)
`
`Deaths
`(2.6%)
`
`Deaths
`4(57%)
`
`Morlality 13/29 P (45%)?
`
`Fic. 1. Comparison of the incidences of perforation and
`mortality in 613 patients with ulcerative colitis and 1,010
`patients with Crohn's disease. *, Two additional deaths in
`perforation in recurrent disease in ileocolitis, one in the
`small intestine and onein the colon. f, ‘Ten colonic (one with
`two ileal perforations), one smal] intestine. $, In perforated
`instances (excluding recurrent disease *).
`
`one to nine hours of the presumed perforation,
`whereas the patients with a sealed perforation
`had severe symptomsfor an average of two days
`before operation.
`In UC without colonic dilation, massive bleed-
`ing developed in four patients with perforation
`who later died. Three had a decreased platelet
`count and increased partial thromboplastin time
`
`TABLE I—-A COMPARISON OF INCIDENCES OF TOXIC MEGACOLON, PERFORATION AND MORTALITY IN
`ULCERATIVE COLITIS AND CROHN’S DISEASE
`UC.
`
`C.D.
`
`Percent® C.D.C. Percentt
`
`X*
`
`~Pvalue
`
`Per cent
`
`mi
`
`| tt
`
`Toxic megacolon
`61/613
`WG worsus QD aie seen cag nce nese hese Rees
`UC versus CDC... ee eee eee 61/613
`UG Were GS wick tages sie METRO CISL Soe we
`61/613
`UG vergus 1G. cc epaccda ctanssectawersmesasaeee
`61/613
`Perforation
`rll POT ESET ETE TET ELCTIT TET TEE PITT rere
`Golo... asymysemes HSE eee ieee Ree TEE RES *.
`DTM nso serer xvii n sia HONG es mee
`0 as ow aie ew ge won ee see
`Tei PME sive secs ina en a6 2h O8e OE SER Ey ewe
`Mortality
`13/613
`Perforation of colon 2.0... 0.0. cece ee en eee
`4/7
`Free perforation, no TM «oie esc c ieee vee neces
`4/7
`Free pecloration§,; no TM. oi sx. sicvameswos mass
`9/22
`Perforation in TM .... 2.0.00. cee eee eee eee
`All primary perforation ...... 656.6200 see eee 13/29,
`All perforations. Se picis ce uel wielWiel's wow SAKw t
`¢ Wee
`13/29
`t
`UC, Ulcerative colitis, 613 patients.
`*CD, Crohn's disease, 1010
`patients.
`7oDe, Crohn's colitis (CC)and ileocolitis (IC), 623 patients.
`‘TM, Toxic megacolon, 75 patients—61 UC and 14 CDC.
`Free perforation without toxic megacolon in 20 patients.
`“Includes two mortalities in recurrent Crohn's disease.
`*Failed to reach statistical significance.
`
`29/613
`29/613
`22/613
`22/61
`
`10
`10
`10
`10
`
`4.7
`4.7
`3.6
`36
`
`2
`57
`Se
`41
`45
`45
`
`14/1010
`
`1.4
`
`20/4010
`
`2.0
`
`0/15
`
`2/18
`4/20
`
`0
`
`11
`20
`
`14/623
`9/166
`5/457
`
`13/623
`3/623
`3/14
`
`3/623
`0/10
`
`2/3
`
`nie
`5.4
`1.1
`
`pI
`0.5
`21
`
`0.5
`0
`
`67
`
`0.001
`63.49
`0.001
`30.1
`3.28 NSt
`35.49
`0.001
`
`9.9
`6.2
`14.4
`2.83
`
`6.3
`7.47
`10.47
`0.71
`5.81
`3.22
`
`0.005
`0.02
`0.005
`NS
`
`0.02
`0.01
`0.005
`NS
`0.02
`NS?
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`
`
`PERCENTAGEINCIDENCE
`
`ULCERATIVE
`COLITIS
`
`CROHN'S
`(ILEO)COLITIS
`
`Oo O
`
`Toxic
`megacolon.
`Total cases
`
`61
`613
`(10 %)
`
`14
`623
`(2.2 %)
`
`Fic. 2. A significant greater incidence of toxic megacolon
`in ulcerative colitis than in Crohn’s disease involving the
`colon is shown (Crohn’s disease and ileocolitis).
`
`ding, transverse, descending and sigmoid colon,
`and one had metachronous perforations each in
`the descending colon.
`Four of 383 patients with regional enteritis
`(1.04 per cent) sustained a spontaneousfree per-
`foration, Two occurredin the jejunumin jejuno-
`ileitis and two in the ileumin regional ileitis. All
`four patients had evidence of dilation with stric-
`ture distal to the site of perforation. Three had a
`segmental small
`intestine or ileocolic resection
`and one resection with ileostomy and distal mu-
`cous fistula. The latter underwent subsequent
`successful reanastomosis. The four patients sur-
`vived, as did the patient with synchronousileal
`and colonic perforations. Thus, the 15 patients
`with spontaneous free perforation with perito-
`nitis without toxic colonic dilation in CD all sur-
`vived; this compares favorably with two deaths
`among three patients with toxic dilation in
`Crohn’s disease and nine deaths among 22 pa-
`tients with toxic colonic dilation in UC.
`Management ofpatients with perforation. Nine
`of 11 patients with colitis or ileocolitis in Crohn’s
`disease had resection with a proximal diverting
`ileostomy in eight and a colostomy in one. The
`
`TABLE I1—PERFORATION IN CROHN’S DISEASE ALL
`CROHN’S DISEASE 20 OF 1,010
`—COLITIS AND [ILEOCOLITIS—.
`——REGIONAL ENTERITIS_—
`N=16 of 623
`N=4of387
`
`Site
`Ileum
`Jejunum
`
`No.
`2
`2
`
`No.
`Site
`1
`Ileum
`10
`Colon*
`3
`Colon with TM (2+)
`2
`Recurrent disease (2})
`“Onc with two concomitantileal perforations.
`+Mortalities: 2 of three in toxic megacolon-sealed perforations.
`$Both with recurrent disease-free perforations (one ileum and one colon).
`TM, Toxic megacolon.
`
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`
`ULCERATIVE
`COLITIS
`
`CROHN'S
`COLITIS ;
`
`ILEO-
`COLITIS
`
`-
`4 10
`Oo
`= 8
`
`uw 6<i
`
`i7t
`
`da
`
`2
`
`P<0.00I |
`
`O .
`ieee SI
`
`Totalcases
`
`613
`
`2
`
`166
`
`5
`
`457
`
`(1.1%)
`
`(10%)
`
`(5.4%)
`
`Fic. 3. Toxic megacolonis significantly more commonin
`ulcerative colitis than in ilcocolitis and Crohn’s colitis than
`in ilcocolitis. Although the incidence is approximately twice
`as high in ulcerative colitis than in Crohn’s colitis, a sig-
`nificant difference could not be demonstrated.
`
`other two hadsuture and proximal colectomy and
`exteriorization with proximal colostomy, respec-
`tively.
`A comparison of the incidence of toxic megaco-
`lon in UC and CD.In this series, the incidence of
`toxic megacolon wassignificantly greater in UC
`than in CD (Fig. 2), GDC or IC (Fig. 3). In ad-
`dition,
`the incidence of
`toxic megacolon was
`significantly greater for Crohn’s colitis when
`compared with patients with ileocolitis (nine of
`166 versus five of 457, DF=1; X?=10.38; p<
`0.001)
`(Fig. 3). However, when patients with
`disease confined to the colon were compared, al-
`thoughcolonic dilation in UC was almost twice as
`common as in CC (UC 10 versus CC 5.4 per
`cent) a significant difference in 1'CD could not be
`demonstrated (Fig. 3) (Table I).
`A comparison of perforations of large or small
`intestine. In UC, the incidence of perforation was
`
`Greenstein and Aufses: PATHOGENESIS, INCIDENCE AND OUTCOME OF PERFORATION
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`66 Surgery, Gynecology & Obstetrics « January 1985 - Volume 160
`
`WITH
`TOXIC MEGACOLON
`Ulcerative colitis
`‘
`S
`:
`
`7
`bas
`Crohns (ileo)colitis
`
`oO
`
`TOTAL
`
`COLON
`PERFORATIONS
`
`a4
`
`w 5
`oO
`ia
`S
`="
`E
`i 2
`cr
`a |
`
`O.
`OSiee5teens
`
`Fic. 4. A signficantly greater incidenceof total colonic perforation and perforation with toxic
`megacolon in ulcerative colitis compared with Crohn’s disease involving the colon is shown (colitis
`and ileocolitis) when considered as a proportion of thetotal series.
`in ulcerative colitis and
`Fic. 5, Perforation in toxic megacolon is not significantly different
`Crohn’s colitis involving the colon when it
`is considered as a proportion ofall patients with
`megacolon.
`28 times as frequent in patients with TCD than
`in those without; compared with ten times the
`frequencyin patients with CD and TCD (Table
`1). Within the context of the total series, colonic
`perforation in patients with disease confined to
`the colon and patients with perforation in toxic
`megacolon were bothsignificantly greater in pa-
`tients with UG (Fig. 4). The increase in perfora-
`tion in UG was dueto the higher incidence and
`proportion of toxic megacolon in UC and prob-
`ably also to the higher proportion of perforation
`in patients with UC and TCD(36 versus 21 per
`cent) (Fig. 5). However,if one examines only the
`75 patients with toxic megacolon with UC and
`CD,although the proportion of patients who had
`perforations was almost
`twice as great
`in the
`former, the difference wasnotstatistically signif-
`icant in this series (Fig. 5). The incidence of co-
`lonic perforation in the absenceof toxic megaco-,
`lon wassimilar in the twoseries (seven of 552 for
`UG, 1.2 per cent versus 11 of 607 with, DG,1.8
`per cent).
`Comparison of mortality. The over-all mor-
`tality for perforationsof the colonas a proportion
`of the total series was four times greater in UC
`
`PERFORATIONS
`
`ULCERATIVE
`0
`
`COLITIS
`
`(
`
`CROHN'S
`)C.
`
`ILEO)COLITIS
`
`=
`
`i
`Gj
`5
`es
`=
`.
`=
`‘
`O
`acLu
`
`(5
`
`0
`Perforations
`Total cases
`
`13
`29
`613 623
`(4.7 %) (2.1%)
`Fic. 4
`
`3
`22
`Perforations
`3 i aes
`22
`Toxicmegacolon
`61
`14
`S13. 623
`(3.6%) (0.5%)
`(36%)
`(21%)
`Fic. 5
`
`than in CDC (2 versus 0.5 per cent) andthe dif-
`ference wasstatistically significant (Table I). If
`one examines all 47 primary spontaneous per-
`forations, omitting the two deaths which occurred
`with recurrent disease, there is a significant dif-
`ference in mortality between UC and CD (Fig.
`6). With the addition of the two perforations in
`recurrent Crohn’s disease, the results of the chi
`squaretest fail to reach statistical significance.
`Mortality was significantly greater in patients
`with perforation in UC than in those with
`Crohn’s disease in both the over-all series and in
`the absence of toxic megacolon, but not in toxic
`megacolon if examined separately. A comparison
`of free perforation in the absenceof toxic dilation
`revealed a highly significant difference between
`the two groups (Fig. 7). More than one-half of
`the patients with UC died—four of seven pa-
`tients, 57 per cent. This incidence is comparable
`with the 41 per cent mortality for perforation in
`UC with toxic megacolon. All 15 patients with
`Crohn’s disease (includingall ten patients with
`free colonic perforation andfive with free small
`intestinal perforation) (Table IJ) survived (Fig.
`7.) Mortality was no different in toxic megacolon
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`
`
`ULCERATIVE
`COLITIS
`
`t
`
`CROHNS
`DISEASE
`
`WW 5 O
`O
`=
`O40
`O
`=
`= ou
`Oo
`
`-
`SS 20
`
`ac
`Lu
`a |O
`
`O
`Deaths
`.
`Perforations
`
`.
`
`2
`13
`18
`29
`(11%)
`(45%)
`Tic. 6. Mortality was significantly greater in primary per-
`forations ofthe intestine in ulcerative colitis than in Crohn’s
`disease when29 patients with ulcerative colitis are compared
`with 18 patients with Crohn’s disease.
`
`in the patients with UC compared with those
`with Crohn’s disease or in patients with UC with
`free perforation compared with those with sealed
`perforations. We have no explanation for
`the
`remarkable clifference in survival in free perfora-
`tion in the absence of toxic megacolon in UC and
`CD, but it may be due to differing immunologic
`states or pathogenetic mechanisms.
`
`DISCUSSION
`
`Perforation of the colon in UC wasrecognized
`in 1875 (11). The association of perforation with
`toxic megacolon was notedin 1955 (12) and since
`that time there have been many reports of this
`association.
`Althoughit has been suggested that Morgagni,
`in 1769, gave us the first description of Crohn’s
`disease with free perforation (13), others are
`skeptical of the actual nature of the original in-
`stance which Morgagni described. Janowitz be-
`lieves Crohn’s disease to be a disease of recent
`onset
`(14). The first perforated abscess
`in
`Crohn’s disease was described from this institu-
`tion in 1935 (15). Free perforation of the colonin
`
`Greenstein and Aufses: PATHOGENESIS, INCIDENCE AND OUTCOME OF PERFORATION
`
`67
`
`WITH
`WITHOUT
`lOO TOXIC MEGACOLON TOXIC MEGACOLON
`YY Ulcerative colitis
`Crohn's (ileo)colitis
`
`3
`
`
`
`wl
`oO
`ai 80
`QO
`3
`= 60
`Ww
`= 40
`
`zé
`
`a 20
`a
`
`O
`
`Deaths 92 4 0
`Noof perforations
`22.
`3
`7
`10
`(41%) (67%)
`(57%) (0%)
`Fic. 7. The mortality of 42 patients with colonic perfora-
`tionsis significantly greater in primary perforation of the in-
`testine without toxic megacolon in ulcerative colitis than in
`Crohn's disease involving the colon. In toxic megacolon, the
`mortality was equally high, although there were only three
`such patients in the group of patients with Crohn’s
`disease.
`
`
`
`iii
`
`i
`
`{
`|
`f
`i}
`
`fl
`
`|
`
`Ht
`AM}
`|
`
`
`
`|
`|
`te
`3 He
`ss
`Ss
`ie
`
`|
`
`
` ISOANGELES
`
`Crohn’s disease was described in 1965 (16). Since
`then an additional 15 instances have been repor-
`ted (17).
`In one study, 32 publications which reported
`upon 604 patients with toxic colonic dilation in
`UC were reviewed (18). One hundred and four-
`teen patients or 19 per cent had perforations with
`a mortality in surgically treated patients of 41.2
`per cent compared with 8.8 per cent associated
`with patients without perforations (18).
`In 1960, 16 instances of colonic dilation in UC
`were reported; in retrospect, two patients clearly
`had Crohn’s disease (19). ‘There have since been
`reports of toxic megacolon in Crohn’s disease
`(20-22), with an incidence of ‘TM as high as 20
`per cent (23). Colonic perforation in UC in the
`absence of toxic dilation is relatively rare (2-6).
`Perforation without dilation of the large or small
`intestine is more frequent in Crohn’s disease and
`TABLE IIL—PERFORATION WITH AND WITHOUT
`TOXIC MEGACOLON IN ULCERATINE COLITIS
`
`Authors
`Lumb and co-workers (12), 1955......
`Edwards and Truelove (1), 1964 ......
`Goligher and co-workers (27), 1970..,.
`Block andassociates (6), 1977.........
`Albrechtson and co-workers (5), 1981 ..
`Presént.séries; 1983 ac. tise: s suis om ayers
`
`—~Toxte megacolon_—
`Yes
`No
`Total
`
`1
`2
`38
`4
`61
`
`19
`6
`1
`0
`7
`
`20
`8
`39
`4
`68
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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` 68 Surgery, Gynecology & Obstetrics -
`
`
`January 1985 - Volume 160
`may occur in both the large and small intestines
`48 hours after admission to the hospital. Al-
`(7, 17, 24, 25).
`though nonoperative management remains the
`The relationship of perforation to TCD is ex-
`first therapeutic modality for toxic colonic dila-
`amined in Table III. In 1964 (1), 624 patients
`tion, the patient must be carefully monitored by
`with UC were reported upon. The incidence of
`both the gastroenterologist and surgedn. If mor-
`free perforation was 3.2 per cent and the inci-
`tality is to be avoided, then surgical treatment
`dence of toxic megacolon was 1.6 per cent. Nine-
`must be carried out early if there is no immediate
`teen of 20 patients had perforation develop with-
`response to primary therapy.
`out evidenceof colonic dilation and 75 per cent of
`Colonic perforation remains a highly lethal
`these patients died (Table II). ‘Ten were diag-
`complication of inflammatory intestinal disease,
`particularly in the presence of toxic colonic dila-
`nosed at autopsy. ‘Thus,
`it
`is possible that these
`tion. Excellent survival is possible in Crohn’s dis-
`patients may well have had colonic dilation and
`perforation of a dilated intestine prior to their
`ease without TCD. The remarkable difference in
`death. However, three of nine patients with toxic
`survival in patients with free perforation and per-
`megacolon died. An autopsy was performed upon
`itonitis in CD compared with UC is difficult to
`two, and there was no evidence of perforation in
`understand. It may reflect differing immunologic
`any of the patients. In 1965, 465 patients with
`states. It may also indicate differing pathogenetic
`UC were studied (26) andassociated toxic dila-
`mechanisms. Perforation in CD is the endresult
`tion in five of 13 patients who had 20 separate
`of slowly progressive fissure formation culminat-
`perforations was found (26). However, it is be-
`ing in rupture, whereas in UC deep ulceration
`lieved that perforations without toxic dilation are
`and extensive tissue necrosis may occur rapidly
`uncommon (4) and the results of recent studies
`prior to rupture and result in systemic liberation
`support this impression (5, 6). In one study (6),
`of toxic tissue substances.
`only one instance of perforation withouttoxic di-
`lation (TCD) was found among 39 patients with
`UC who underwent emergency surgical
`treat-
`ment (Table II). In another study, no instances
`of perforation among 87 patients with UC and
`without TCD who were operated upon were
`found, andonly four of 45 instances of TCD were
`found, which wasattributed to a policy of early
`colectomy. We have similarly found that perfor-
`ation in UCis usually associated with TCD. In
`our series, TCD developed in 61 of 613 patients
`with UC, 10.0 per cent, but in only 14 of 623 pa-
`tients with CDC, 2.24 per cent (2). The correla-
`tion of perforation with ‘TCD in UC (2) is due
`mainly to the high incidence of toxic megacolon
`(10 per cent) in UC. In Crohn’s disease, 20 of
`1,010 patients had perforations, but only three
`occurred among 14 patients with TCD compared
`with 22 among 61 with toxic megacolon in UC.
`In inflammatoryintestinal disease, perforation
`may be difficult to recognize clinically (1), par-
`ticularly in patients taking high dosage steroids.
`‘Therefore, it has been suggested that early surgi-
`cal treatment should be carried out upon patients
`with a suspected perforation, signs of peritonitis
`or recognized toxic megacolon. In one study, a
`reduction in perforatien rates was found in UC
`treated by early operation—32.5 to 11.1 per cent
`(27). A perforation rate of only 3.0 per cent and
`mortality of 5.3 per cent was found (5) when
`surgical treatment was carried out within 24 to 48
`hoursof the onset of indications for operation and
`
`Wehave studied the patient records of 49 or
`1,623 patients in whom perforation occurred
`during the course of
`inflammatory intestinal
`disease. Perforation occurred most commonly
`with toxic megacolon in UC, but without toxic
`megacolon in Crohn’s disease of the colon.
`The incidence of perforation was significantly
`greater in UC than in Crohn’s disease involving
`the colon. ‘This was due primarily to the higher
`incidence of perforations with toxic megacolonin
`the former. Theincidence of toxic megacolon was
`significantly greater in ulcerative colitis than in
`Crohn’s disease involving the colon (CC and IC)
`and in UCthaninileocolitis. Although almost
`twice as frequent in UC than in Crohn’s colitis
`alone, a significant difference could not be dem-
`onstrated in this series for patients with UC
`compared with CC. In UG, the incidence of per-
`foration was 28 times as frequentif toxic colonic
`dilation occurred, compared with ten times the
`frequency of TCD in Crohn’s disease involving
`the colon. There wasa significantly higher inci-
`dence of perforation in patients with UC with
`toxic megacolon. The incidence of colonic per-
`foration in the absence of toxic megacolon was
`similar in the twoseries (7 of 552 for UC, 1.2 per
`cent, versus 11 of 607 for CDG, 1.8 per cent).
`Mortality was no different in toxic megacolon
`in patients with UC compared with those with
`Crohn’s disease or in patients with UC withfree
`
`SUMMARY
`
`ye
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`Greenstein and Aufses: PATHOGENESIS, INCIDENCE AND OUTCOME OF PERFORATION
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`69
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`ntum v Cosmo
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