David

B. Bach,

Bertha

M. Garcia,

MD

J.

#{149} David

MD

Hurlbut,

J.

#{149} William

MD

Wall,

Human Orthotopic Transplantation: The

authors

describe

tive

anatomy

and

logic who

examinations underwent

the

#{149} Walter

MD

M. Romano,

#{149} Cameron

Small Radlologic

peared

patients small

in-

NATIVE PORTAL

This

in the

re-

after transplantation. hanced examinations were useful to exclude

VEIN

NATIVE AORTA

long-

VC AORTIC CONDUIT

‘

Bowel peristalsis apas early as 31 days

normal

I

AORTIC CONDUIT

Contrast-enof the intestine surgical com-

plications such as anastomotic or strictures, but were insensitive biopsy-proved cytomegalovirus teritis or rejection.

leaks for ena.

Index

terms:

74.26,

74.459

Intestines, Intestines,

74.459

#{149}Liver,

creas,

transplantation,

Radiology

abnormalities, transplantation,

#{149}

transplantation,

1991;

74.25,

761.459

b. 1.

(a) Diagram of isolated small bowel transplantation. Hatched areas represent the native organs. An aortic conduit containing the SMA is attached to the native aorta below the renal arteries. The end of the donor portal vein is attached to the side of the native portal vein. The proximal end of the donor bowel is attached to the native jejunum. The distal end is brought out as an ileostomy. (b) Diagram of combined small bowel and orthotopic liver transplantation. Hatched areas represent the native organs. The aortic conduit contains both the SMA and celiac artery origins. The venous drainage of the small bowel proceeds in normal fashion via the donor portal vein to the transplanted liver. The end of the native portal vein is attached to the side of the donor portal vein. Both the suprahepatic and infrahepatic portions of the inferior vena cava (IVC) are attached to the corresponding native part. Figure

Pan-

#{149}

770.459 180:37-41

S

bowel transplantation lagged behind the notable of heart,

lung,

transplantation

liver,

because

munosuppression

and

azathioprine, antilymphocyte lin, and corticosteroids) failed vent From

the

Departments

of Diagnostic

Radiol-

ogy (D.B.B., W.M.R.), Pathology (D.J.H., B.M.G.), Surgery (W.J.W., D.R.G.), and Medicine (C.N.G.), University Hospital, University of Western Ontario, 339 Windermere Rd, London, Ont, Canada N6A 5A5; and the Department of Surgery, Health Sciences Centre, University of Calgary, Alberta, Canada (F.R.S.). Received November 28, 1990; revision requested January 17,

1991;

revision

received

March 14. Address c RSNA, 1991

March

reprint

12; accepted

requests

to D.B.B.

rejection

in large

kidney

standard

(treatment

animals

imwith

globuto pre-

resulted

small

transplantation tology,

gut

absorption,

and

(2,3).

This

findings

underwent tion at this

article

reports

of

All

patients

the

radio-

in five patients small bowel institution.

PATIENTS

AND were

who

transplanta-

METHODS

female,

ranging

in age

from 8 to 46 years (Table). The first three patients had short-gut syndrome; two of

in consistently

intestine allograft with normal graft

for whom total parenteral nu(TPN) was no longer possible

logic

and

humans. However, experimental work in the pig model (1) with use high-dose intravenously administered cyclosporine successful

drome trition

has suc-

MALL

cesses

I

MD

MD

contrast and was

edema.

2 weeks

R. Grant,

the radio-

of five orthotopic

to submucosal

R. Sutherland,

#{149} David

postopera-

review

on the first postoperative material-enhanced images solved within term survivors.

MD

Intestine Assessment’

testine or combined orthotopic liver and small intestine transplantation. Mucosal thickening of the transplanted intestine was demonstrated

due

#{149} Francis

MD

N. Ghent,

his-

those

patients

moses.

The

had fourth

duodeno-colic patient

had

anastorecurrent

growth

and development. This success provided a rationale to begin an experimental clinical program in 1988 to treat patients with short gut syn-

Abbreviations:

CMV

=

SMA = superior mesenteric parenteral nutrition.

cytomegalovirus,

artery,

TPN

=

total

37

.

/.

\.

a.

b.

Figure

2. Patient

1.

obtained on day 14 shows air in the wall of several loops of bowel. The patient is supine. (b) Pathologic bowel after removal (day 15). Variable histologic findings range from entirely normal intestinal mucosa (lower left) to lymphatic lacteals (center) adjacent to focal areas of mucosal necrosis (top right). Edema fluid is present in the submustain; original magnification, x 115). (c) Oblique radiograph of small bowel (day 9). Water-soluble contrast material was

specimen of transplanted mucosa showing dilated cosa (hematoxylin-eosin infused

age

via

was

the jejunostomy

tube.

Thickened

Type

Patient

Cluster

Note.-SB

=

Graft

functioning,

tPatient

small

1 died

ulceration

liver

=

as of October 18 months

which

eight

LSB

bowel,

and stenosis

jejunum,

previous

Indications

an oral with

for

to complications

formaThe fifth

or enlarging

tumor artery

on figure

including

access because and deteriorating desmoid

underwent of the

a cluster

stomach,

pancreas, and graft in patient

of reliver

are the date

the im-

2/28/8

2 wk

23 mo*

Outcome

9/22/89

9 wk

Rejection, Normal Death

11/14/89 7/27/90

11 mo*

Normal

11 wk*

Normal

graft diet

removed’

diet diet and TPN

boweL

later from variceal bleeding to TPN-induced cirrhosis.

died

10 weeks

via the transplanted

In all tine)

and

receive

transplantations,

donor

portal

Before

the

in three all of their gut. SMA

(the

level

of the

renal

arteries.

vein, providing

The

venous

bowel

the native side of the

mains

transplantation, portal donor

in continuity

suprahepatic and the donor inferior to the corresponding

the

end

of

vein is attached to the portal vein, which re-

with

the liver.

infrahepatic vena cava native

transplantation,

(barium

enema

on the venous

patient’s thrombosis

the was

The

portions of are attached parts. In all

study)

manner,

surgical were

cal are

(up-

depending

history. Sites documented

portal when

of and

venous system liver transplanta-

was being considered. After the transplantation, were

tests

the extent and bowel. These

in an antegrade series) or retrograde

patency of the demonstrated

aminations

end of the with the nais created.

radiologic

to assess remaining

tests were performed per gastrointestinal

tion

drainage of the isolated small bowel allograft, is attached to the side of the native portal vein. In the combined liver and small

18

of whom

transplantations, the proximal bowel is placed in continuity live gut, and a distal ileostomy were performed position of the

supply to the transplanted intesis maintained as an aortic conduit is attached to the side of native aorta

an isolated (Fig la). The

liver,

with procedure,

remain

nutrition arterial

secPatient

transplantation.

intestines

the

transplanta-

the

two

below

because of rejection This patient died

after

patients,

tumor.

small bowel. The isolated I was removed 2 weeks

after transplantation and patchy necrosis. #{149} Radiology

duodenum,

Survival

3, who suffered cerebral hypoxia neurologic damage during the

were

of TPN,

next three patients underwent combined small bowel and orthotopic liver transplantation procedures (Fig ib). The fifth

38

Numbers

Graft

of

11/14/88

Transplanted

on

transplantation

small

months ondary

diet

dependent

The first patient underwent small bowel transplantation

tion

bowel.

boweL

of the transplanted

operations-in-

were

inadequate venous current thromboses

small

of the proximal

prevented

All patients

and

removal

patient had an enlarging desmoid encircling the superior mesenteric

patient

small

1990.

after

cluding a total gastrectomy lion of an esophagojejunostomy.

function,

Date

LSB

5/27

related

in the proximal

Transplantation

SB LSB LSB

3/46 4/36

TPN.

are apparent

of

Transplant

(y)

1/ 2141

(SMA).

folds

Data

NoiAge

despite

mucosal

obtained.

Patient

*

c.

(a) Radiograph

radiologic

tailored

ex-

to specific

clini-

problems. common

Many of these examinations in liver transplant recipients (4), and are not discussed here. These indude cholangiograms to assess the biliarybiliary or biliary-enteric leak or stenosis), computed

(CT) pelvis

examinations (in

search

anastomoses tomographic

of the abdomen of abscess),

(for

and

ultrasound

July

1991

C.

Figure

3. Patient

bowel

obtained

a barium

meal.

4.

before There

(a) Radiograph

of small

transplantation, are

areas

after

of dilatation

and stenosis in the proximal small bowel, with a normal appearance of the distal small bowel. Numbers on figure are the date the image was obtained. (b) Radiograph obtamed during a barium examination (day 8). Thickened mucosal folds are present in the transplanted gut, including the jejuno-jejunostomy.

Numbers

on figure

are

the

date

the image was obtained. (c) Radiograph obtamed during a barium examination (day 14) shows

normal

mucosal

markings.

on figure are the date the image

Numbers

was ob-

tamed.

examinations (to

assess

the

of the liver,

and

hepatic

portal

and

angiograms

planted

vascula-

cause

ture).

The examinations small

bowel

that are specific

transplantation

deal

aging the transplanted nations are performed nasogastric

tube,

specified

indications

enhanced

to

with

im-

These examiby means of the gut.

mouth,

or ileostomy.

for contrast

examinations

were

The

material-

to exclude

anastomotic leaks (six examinations) or obstruction or stenosis (four examinations) and to demonstrate mucosal changes suggestive

of rejection

(CMV)

enteritis.

or cytomegalovirus

RESULTS

Abdominal radiographs were obtamed frequently, primarily to follow the pattern of bowel gas or to assess the position of tubes. In one patient (patient 1), air was detected in the bowel wall 14 days after the transplantation (Fig 2a), and the transVolume

180

#{149} Number

1

intestine of necrosis.

was

removed

be-

Pathologic

examination of this specimen revealed patchy areas of mucosal ulceration interspersed among segments of intestinal mucosa that appeared normal (Fig 2b). In another patient (patient 2), intraperitoneal air was demonstrated at radiography 9 days after transplantation following an upper gastrointestinal endoscopic procedure. Twenty contrast-enhanced examinations of the transplanted intestine were performed, 10 with diatrizoate meglumine or sodium (Hypaque-M, 30% or Oral Hypaque; Winthrop, Aurora, Canada) and 10 with barium. The most common indication for the examination was to exclude a leak at the anastomosis, which was a clinical concern in four of the five patients. In the one definite episode of perfora-

tion, in which free intraperitoneal air was demonstrated (patient 2), the site of perforation was not found, and this leak healed without intervention. Three examinations were performed to assess mucosal markings because of a concern about rejection. Several contrast-enhanced examinations helped assess bowel motility. In four patients, the mucosal folds of the transplanted small bowel were prominent at the first postoperative radiologic examinations (performed 9, 7, 8, and 7 days after transplantation, respectively) (Figs 2c, 3b), presumably due to submucosal edema; in one patient (patient 3), the small bowel mucosa had a normal appearance 5 days after the procedure (Fig 4a). Pathologic examination of superficial biopsy specimens of the small bowel obtained at this time in another patient showed dilated lacteals, consistent with lymphatic blockage (Fig 5a). One patient (patient 2) also had a transient obstruction at the native intestine-donor intestine anastomosis, presumably due to postoperative edema. This resolved by day 13. In patients 4 and 5, the mucosal pattern returned to normal by the second postoperative examinations on days 14 (Fig 3c) and 45, respectively. When patient 2 was readmitted to the hospital with a widespread CMV infection (day 452), a barium examination showed normal mucosal folds (Fig Sc). Random biopsy samples obtamed through the ileostomy 3 days later showed severe CMV enteritis (Fig Sd). In patient 3, barium examination showed thick mucosal folds (Fig 4b) and ascites at the time of biopsyproved CMV enteritis (day 61) (Fig 4c).

The

patient

died

12 days

later.

Video recordings were made of the small bowel fluoroscopic examinations in the two long-term survivors (patients 2 and 4). In patient 4, the earliest video-recorded examination, on day 14, showed free reflux from the jejunal pouch to the esophagus. Small bowel peristalsis was present but sluggish. Subsequent examinations

on

days

110

and

212

showed

good peristaltic activity. In patient 2, the earliest examination with video was on day 31. There was apparently normal peristaltic activity with clear migratory motor complexes progressing regularly across the small bowel.

DISCUSSION

Small bowel transplantation is on the verge of becoming an accepted clinical option for treatment of seRadiology

#{149} 39

b.

a.

Figure

c.

4. Patient 3. (a) Radiograph obtained during barium examination (day 5). gastrostomy tube is present. Numbers on figure are the date the image was obtained. (day 61). Mucosal fold thickening is now present. Numbers on figure are the date nal biopsy (day 64). Scattered epithelial cells contain intranuclear inclusions (arrows) saffron stain; original magnification, x 450). Inset shows high-power view of CMV tion, X 1,125). These stained positive for CMV with an indirect immunoperoxidase

The

mucosa of the transplanted intestine appears normal. A (b) Radiograph at the time of small bowel enteroclysis the image was obtained. (c) Pathologic specimen from intesticonsistent with CMV infection (hematoxylin-phloxineinclusions from separate area of biopsy (original magnificatechnique.

a.

d.

b.

Figure

5. Patient

lected

patients

c.

2. (a) Pathologic specimen from intestinal biopsy (day 16). There is marked dilatation of lymphatic lacteals within the lamina propria (hematoxylin-phloxine-saifron stain; original magnification, x450). (b) Radiograph obtained during a double-contrast barium examination performed via the ileostomy (day 84) shows normal mucosal markings. Numbers on figure are the date the image was obtained. (c) Radiograph obtained during a barium examination at time of CMV enteritis (day 452). Numbers on figure are the date the image was obtained. (d) Pathologic specimen from intestinal biopsy (day 455) shows mucosal ulceration with submucosal inflammation and necrosis (hematoxylmnphloxine-saffron stain; original magnification, x700). Staining for CMV by using an indirect immunoperoxidase technique (inset) showed fluclear positivity consistent with CMV enteritis (original magnification, x2,800).

for whom feasible.

plex 40

with

intestinal

continued For

surgical #{149} Radiology

the

success

procedure,

TPN

failure

is no longer of this

intensive

com-

support is required ciplines, including The transplanted patients had thick

from various disradiology. intestine of most mucosal folds at

the earliest contrast-enhanced examinations. The radiologic demonstration of thick mucosal markings is nonspecific. However, in the context of intesJuly

1991

tinal

transplantation,

must

be given

ation. Interruption phatic drainage sults in mucosal mucosal biopsy grafts

showed

certain particular

causes

consider-

of the normal lymwith the surgery relymphedema, and specimens of the lymphatic

obstruction

in the early posttransplantation period (Fig Sa). In the one patient (patient 1) in whom the full thickness of the intestine was examined histologically (after rejection and removal), it was

apparent

thick

folds

ages 2b),

that

the

major

cause

on contrast-enhanced

was the although

of

im-

submucosal edema (Fig dilated lacteals were

present in the lamina propria. In the rat model, regeneration of the lymphatic vessels occurs within 6 weeks of transplantation, but the lymph yessels of the transplanted gut have a decreased diameter and calculated lymphatic flow rate compared with the normal gut (5). The thickened mucosal

markings

seen

at the

earliest

examinations resolved within 2 weeks in both long-term survivors, suggesting that lymphatic obstruction was not a major cause of the fold thickening apparent on contrast-enhanced images. However, the reestablishment of lymphatic drainage may have helped resolve the prolonged ascites seen

in these

cosal

markings

causes,

such

patients.

may

Thickened

result

as complications

from

mu-

other at the

vascular anastomoses (with venous engorgement or ischemia), postoperative inflammation and edema, rejection, and infection. To some extent,

Volume

180

#{149} Number

1

the cause of thickened mucosa can be differentiated on the basis of the time of occurrence in the clinical course. The number of patients who underwent transplantation was too small to discuss

the

sensitivity

of the

contrast-

enhanced examinations for detecting viral enteritis and rejection, but discordance between the radiologic and pathologic findings was not uncommon. Pathologic findings, which are subtle at the microscopic level, may not be reflected by gross morphologic changes. This is true of early rejection when there are blunted villi and lymphocytic infiltration at microscopic examination, but no gross morphologic changes. In one case of biopsyproved CMV enteritis, the radiologic appearance of the intestinal mucosa was normal, despite obvious mucosal destruction in the pathologic specimen (Fig Sc, Sd). Limitations of the radiologic examinations may be related to the patchy nature of rejection and CMV enteritis and the fact that the intestine is actively renewing cells. Notwithstanding these limitations, these procedures helped the clinicians to detect or exclude technical complications such as strictures, anastomotic leaks, or perforations. We demonstrated periods of apparently normal intestinal peristalsis in response to ingested barium, with clear and steady progression of penstaltic waves as early as 14 days after the surgery. In the absence of invasive techniques to monitor the small bowel (eg, serosal electrodes), we have no information on the pattern of contractile activity over longer peri-

ods-either in the fasting state or in response to specific meals. Experimental work in dogs with intestinal autografts (6) suggests that peristaltic activity does not become entirely normal for at least 3 months after transplantation, although the migratory motor complexes are present within 2 weeks in the dog jejunoileum. This finding suggests that peristalsis depends on local innervation and slimuli rather than on intact neurologic pathways to the spinal cord. U Acknowledgments: The authors gratefully acknowledge the secretarial assistance of Marilyn Johnson and the editorial advice of Cate Abbott.

References 1.

2.

3.

4.

5.

6.

Grant D, DuffJ, Zhong R, et al. Successful intestinal transplantation in pigs treated with cyclosporine. Transplantation 1988; 45:279-284. Grant D, Sommerauer J, Mimeault R, et al. Treatment with continuous high-dose intravenous cyclosporine following clinical intestinal transplantation. Transplantation 1989; 48:151-152. Grant D, Wall W, Mimeault R, et al. Successful small bowel/liver transplantation. Lancet 1990; 335:181-184. Cardella JF, Castaneda-Zuniga WR, Hunter D, Young A, Amplatz K. Angiographic and interventional radiologic considerations in liver transplantation. AJR 1986; 146:143-153. Clark E, Ferguson MK, Moynihan HL, Schraut WH. Mesenteric lymphatic function after total small-intestinal transplantation in rats. Curr Surg 1989; 46:115-117. Sarr MG, DuenesJA, Tanaka M. A model of jejunoileal in vivo neural isolation of the entire jejunoileum: transplantation and the effects on intestinal motility. J Surg Res 1989; 47:266-272.

Radiology

#{149} 41