A new endoscopic procedure provides insight into an old disease: Acute acalculous cholecystitis

1718

SELECTED

SUMMARIES

factor p (Adv Cancer tumor-derived

GASTROENTEROLOGY

Res 1993;60:247-267).

immune

suppressors

or well-characterized

molecularly.

technical

of working

limitations

in cultured

cell supernatants

multiplicity

of factors

Despite derived important

genetically

controlled

to the precision

cell

Today

During

In contrast phenomenon.

irradiation,

Res

Immunol

normal

circumstances

1972;26:239-257,

in

(Anat Embryo1

Within

the dying calcium

renewal

cell loss

and overall archi-

a form of cellular

suicide in response and not a passive

cell, the process leading

is associated

to digestion

associated with spillage of potentially as nucleic

body remains phagocytes. the light

acid

into

with

nonlysosomal

of nuclear

membrane-bound

microscopy

small groups tracted cytoplasm Cancer

milieu.

Rather,

and is recognized apoptosis

chro-

chromatin

with

and are typically

J

and disposed

of by

recognized

at

or in

healthy

tissue.

They show con-

a small

amount

of eosinophilic

surrounded

1972;26:239-257,

contents

cells occur individually

by normal

by a halo of lucency

R Co11 Physicians

of apoptosis

is an endogenous

positive

and negative

2 proto-oncogene apoptosis.

program

regulatory

product

this is thought tions

is poorly understood.

Lond

influences

in

an

(Br J

blockade

of esophageal

the prospect

to

The bcl-

regulator

final pathway

(Cell

molecule

of and in

that func-

1993;75:229-240,

Cell

Within

the immune (Adv

1992; 10:267-293, occurs

during

and lymphoid

natural

apoptosis

mechanism, killer

Annu Rev Immunol

1992; 10:267-293).

thymic

of

maturation B cells after

cytotoxic

lymphoT cells,

1991; 146:393-400,

In this context,

carcinoma.

of strategies

In addition,

for the

to the treat-

the future

identification

immunosuppressive

factors

for several immunologically reduced

occurring,

toxicity

offers

mediated

they may have

over currently

available

M.D.

FERGUS SHANAHAN,

A NEW ENDOSCOPIC PROCEDURE PROVIDES INSIGHT INTO AN OLD DISEASE: ACUTE ACALCULOUS CHOLECYSTITIS Department

of Internal

tals and Clinics,

645 -65

Iowa City,

it is particu-

for Digestive

University

Diseases,

of Iowa, Hospi-

Iowa). Drainage

cholecystostomy.

of the gallbladder

cholecystitis

by transpapillary

Gastrointest

Endosc

1993; 39:

1 (September/October).

Therapeutic

endoscopists

array of equipment large number describes

continue

to cannulate,

of pancreatic

to the

to design

drain,

and biliary

the use of a new biliary

approach

cholecystitis.

disorders.

catheter

This

fix a report

for the treatment

As is often

management

an increasing

and, in general,

the case, a novel

of a disease

offers

additional

into its pathophysiology. aspects of the study relate to the use of a newly

catheter.

retrograde

Most

biliaty

catheters

cholangiopancreatography

the tip of the catheter lumen.

The

Selector

Catheter;

signed

Center

Medicine.

with acute acalculous

endoscopic

biliary

to orient

common

centered catheter

the cystic

Terumo

in this

tip toward

duct.

the wall of

is radiopaque, of contrast

in the cystic

(Terumo

Corp.,

Tokyo,

can be passed into the cystic duct and gallbladder. ter can then be passed over the guidewire, ened cystic

duct,

gallbladder

catheter

sample

and into

of gallbladder

abnormal

viscosity,

inflammation

white

or infection,

der can be evacuated this study,

bile.

through

the gallbladder

is in place,

to

duct,

a

Japan)

A 5F cathethe straight-

lumen.

Once

the

it can be used to aspirate

If examination blood cells, the entire

a

of the bile shows

or bacteria, contents

and the gallbladder

the investigators

o’clock

NC) is de-

along

injection

of the catheter

Guidewire

(10

the lateral wall of the

tip, which

After

with

of the bile duct

study

the catheter

the catheter

the placement

are oriented

Winston-Salem,

By moving

bile duct,

can flip into

used

the catheter

used in endoscopic

(ERCP)

in the middle

Wilson-Cook,

bile duct.

curved-tip

is one of the mechanisms,

(J Immunol

cell death

for the elimina-

be a useful adjunct

of tumor-derived

drugs.

apoptosis

The process is involved

cells, K cells, and cytotoxic

deliver a lethal hit to their targets

might

immunosuppressive

confirm

of T cells and in the

by which

by

squamous

programmed

a mechanism

Because such factors are naturally

Immunol

where development

antibody-producing

In addition,

the primary

centers,

Rev

Extensive

T-cell clones during

of high-affinity

stimulation. including

Annu

cells is initiated.

of autoreactive

and the selection and possibly

occurs under several circum-

the development germinal

B cells and plasma

in the deletion

apoptosis

1991;50:55-85,

Blood Rev 1993;7:63-73).

in the thymus

bone marrow memory

system,

Immunol

esophageal

induce

providing

of novel therapies

the common

1993;75:241-251). stances

by human

The development

including

designed

for a common

pathway

report

T cells and evasion of the host’s immuno-

several advantages,

likely that

is subject

negative

repressor

thereby

by the tumor.

and purification

insights

by bcl-2,

evidence

produced

of this mechanism

1992;26:

cell are inhibited

to be a death

antioxidant

that

of gene products.

is the best-studied

to be strong

Bcl-2 appears

It appears

for cell death

Most types of apoptotic

mammals.

cytes,

surveillance

The technical

Regulation

antigen

lymphocytes,

of acute acalculous

25-35). there

a factor

has been shown to directly

in patients

the apoptotic

can be easily

level. Apoptotic

surrounded

basophilic

harmful intracellular

the local

Morphologically,

In summary,

Jo/din FC, Neil GA (Clifton

stimuli.

levels, which activates

endonuclease,

of tissue,

between

is gene-directed

on lymphocytes

in the present

et al.

carcinoma

ment

No. 6

contributes

tissue proportion

apoptosis

factor as described

Nature

apoptosis

noxious

that the same process can be inflicted

cell-derived

O’Mahony

disorders.

In further contrast to necrosis, programmed cell death is not

matin. such

NIH

Rev Immunol

and other

of cytosolic

cation-dependent

(J

of the balance

maintains

to necrosis,

(apo-

trees) is a form of

there is continual

also represents

drugs,

cells. Apoptosis

Annu

under

for the maintenance

Apoptosis

of ac-

in organs such as the gastrointestinal

bone, and skin, in which

to cytotoxic

its mechanism

and limb formation

Apoptosis

and renewal and thereby

by a tumor

tion of antitumor-reactive

tumor-

have made an

death

embryogenesis,

of organogenesis

is responsible

apparent

1986;7:115-119,

tissues (Br J Cancer

1990; 181:195-213).

an elevation

lymphoid

It occurs

1980;284:555-556).

tecture.

elucidating

programmed

1991;121:29-65).

tract,

study

off” as leaves from

Immunol

and diseased

of factor

and

for the esophageal

FASEB J 1991;5:2127-2128,

1992;10:267-293, healthy

identity

of the present within

“dropping

1991;3:75-78,

low concentrations

larly intriguing

within

by convincingly

Greek:

studied

involved.

tion, which involves apoptosis TOE-sis,

Rev

with

and the heterogeneity

the investigators

advance

most of the

This may be in part because of the

the lack of a molecular

factor,

However,

have not been rigorously

Vol. 106,

lumen

chose to irrigate

suggesting

of the gallbladirrigated.

In

the gallbladder

June 1994

with

SELECTED

lo-mL

aliquots

of 1% N-acetylcysteine

solve mucus and sludge. tion,

1 lo-

bladder

During

180 mL of the solution

of thickened

state. The catheter cholecystostomy

in saline to dis-

an average 30-minute

in a collapsed

and allowed

was later easily removed The aforementioned

without

to drain

by gravity.

the need for fluoroscopy.

technique

of transpapillary

(TEC) was used to treat seven patients

acute acalculous

cholecystitis.

Acute

acalculous

of acute cholecystitis,

verse diameter thickening,

>5

cm), gallbladder

ultrasonic

the gallbladder

distended

Murphy’s

wall. Patients

were acutely

underlying

diseases within

these two patients,

drainage.

Follow-up

response

ultrasonography

Aside from

Leukocytosis

improved

and serum bilirubin

levels improved

promptly

The investigators

within

gall-

48 hours

value in patients

percutaneous

a new ap-

cholecystitis

with

drainage

and may be

coagulopathy

or ascites

of the gallbladder

may be

contraindicated. Comment. gallbladder that

Although there is controversy

with

surgical argues

be drained

acute

either

with

against

that of a gravely

sepsis, coagulopathy, bypass patients

for cholecystectomy

mental

or surgical

introduced

with

suggests

that

tostomies

surgical

from Japan

patients

without

13%, including urgent

for the diagnosis

subject

criteria

to uncertainty.

three

patients

ous cholecystotomy

branch

wall can be a difficult

particularly

those with coagulopathy,

The problems atitis).

inadvertent

1442), prompt of the procedure

from the gallbladder because

limitations. problem systemic

relief

in 14 of 14 was

wall. One of continued

Thus, percutane-

Bleeding

in a gravely diseases,

from

the

ill patient, or metastatic

any episodes

time (by either

unit).

Obviously

results

With

is only about 80% anatomy

bile ducts

of

is common

We are not told whether of the pancreatic

duct produced

results

serve to remind

the pathophysiology

and its treatment.

of bacteria

Nevertheless,

reassuring;

and common

to

first-generation

and anomalous

of this study

concerning

bile brought

and sepsis

1):381-383),

from 26

TEC is not a procedure

endoscopist.

and injection

process of the gallbladder

bile.

ranged

of pancreatitis.

lous cholecystitis overgrowth

equippancre-

of fluoroscopy

1993;88:2102-2106).

uncertainties

bladder

the need for endoscopic the procedure

the cystic

cannulation

The encouraging many

bile are also of the bile duct

minutes

1989; 21(Suppl

(Am J Gastroenterol

was achieved

to have acute acalculous

of the gallbladder.

by an inexperienced

between

in these

level of I016

of gallbladder

the success rate of cystic duct cannulation

(Endoscopy

bile duct

to perform

3.8-16

a C arm or a Auocoscopy

by

provided

as well as the risks of ERCP (specifically,

with

review cholecys-

as evacuation

was that

as shown

phosphatase

bile duct bile, and evacuation

The time requited

to 92 minutes

which depends

observation

presumed

and

is no “gold

a papillotomy

alkaline

bile

and is therefore

from the common

with TEC are obvious:

ment and personnel

there

bile duct

and

in the viscosity

in the common

is just as important

interesting

ERCP,

in some patients

changes

Radio1

percutaneous

of the cystic artery.

gallbladder

Perhaps

of inflammation

cholecystitis,

in the common

of “sludge”

literature

The morbidity

is not without

IUlmL).

cholecystitis,

markers

than infec-

the aspirated

by the investigators

(one with a serum

is safer (Gastrointest

had to be performed

from an eroded

clearance

that the pathorather

bile salts. Indeed,

the

role in

and small number

is ischemic

for other

A second

during

the junction

of cholecystitis

two cases of bleeding

prompt

bile cultures

of acalculous

had debris

it is

bile sample had a large num-

168). Unfortunately,

used

be-

However,

with the hypothesis

or for abnormal

First,

presumably

did not play a major

cholecystitis

were not analyzed

catheters, Al-

infection

1992; 111:163-

of the

assessment

of this study.

for bacteria,

only one aspirated

genesis of acute acalculous

platelet

complications

to these patients.

ber of white blood cells. The negative

on the clinical

with

bled as a result of

findings

were positive

of white blood cells are consistent

necrosis

at any time,

In the series of

complications.

interesting

a bacterial

chole-

(Br J Surg 1993;80:1440-

cholecystectomy

bleeding

by radiologists.

a recent

approach

any mortality.

reported

is ultrasonography-

136). In a series of ultrasonography-guided

of the signs and symptoms

rate

of potential

were administered

cholecystitis;

standard”

can be removed

a larger series is needed for realistic

none of the bile cultures

tissue

little or no

there were three patients

There were two additional

be performed

trials comparing

approaches,

the radiological

1990; 15: 133-

was recently

performed

there are no controlled

in postcardiac

the mortality

1993;59:74-77). to surgery

though

by

catheter

associated

is apparently

In fact, there were no described

that

and leakage

avoids the problems There

and none of these patients

of the risk and spectrum

present

is usually

complicated

Indeed,

alternative

percutaneous

cystostomy

status.

cholecystitis,

cholecystostomy

guided

a

sense usually

setting

failure

cholecystostomy

to be as high as 32% (Am Surg A recently

common

The clinical

with multisystem

and altered

pawith

drainage

review,

Obviously,

three patients

or cholecystostomy

However,

with acute acalculous

the

Traditionally,

have been treated

cholecystectomy

this approach.

ill patient

how to drain

there is little discussion

promptly.

cholecystitis

J Surg 1990; 14:567-571). strongly

about

cholecystitis,

and drained

acalculous

approach,

(World

under

sphincterotomy.

causing

bile is

the gallblad-

bleeding,

or after several days of therapy.

<50,000/mmi,

also possible

wall

the gallbladder

of a seal between

entirely.

and the biliary

immediately

cholangiogtaphy

in acute acalculous

it should

tients

drainage

samples

that TEC provides

of acalculous

endoscopic

tious (Surgery

and alkaline phosphatase

in five patients.

concluded

proach to the treatment

to

of pain) after bile or continued

formation

a secure seal until

and abdominal

site.

Transpapillary

procedure.

the gallbladder

course of infection,

with percutaneous

cause antibiotics

did not show any signs

in four patients,

in whom

their

who were considered

(resolution

such as leaks, perforation,

wall necrosis.

of particular

from

14 days to provide that

to muco-

in the gallbladder,

wall occurs slowly, if at all. All of these difficulties

the cholecystostomy

seven patients

is placed

is no evidence

If ascites is present,

der and abdominal

counts

Most of the

died

6 days of the procedure.

five patients,

clinical

of complications, bladder

wall

if there was evi-

wall or perforation.

infected.

either

there seemed to be an overall clinical benefit

to TEC in the other have a prompt

gallbladder

ill, and two patients

even if there

risk of bleeding,

(trans-

sign, and fluid halo around

were excluded

dence of air in the gallbladder patients

sludge,

with

6 criteria:

gallbladder

develops,

around

cholecystitis

was defined by the presence of 4 out of the following

in place for lo-

of the tract between

1719

that may predispose

once a catheter

can result in a complicated

endoscopic

cholecystostomy

symptoms

It

with chemotherapy

Moreover,

maturation

was left in place for several days as a nasocatheter

treated

it must remain

was used to clear the gall-

bile and leave it empty

malignancy sal bleeding.

irriga-

SUMMARIES

Is this an infectious

in the gallbladder wall? Perhaps

on by fasting, in accumulation the long-term

all five survivors

us of the

of acute acalcuprocess with

bile or a focal ischemic prolonged

total parental of toxic follow-up

had complete

stasis of the gallnutrition,

substances of these recovery

narcotics, within

patients

the was

of gallbladder

1720

SELECTED

function

SUMMARIES

as assessed

GASTROENTEROLOGY

by emptying

after

cholecystokinin-octapeptide

a bowel

stimulation. No firm conclusion

can be made from this type of initial

tion of a new device. Clearly, a randomized ous cholecystostomy is necessary

with

to determine

whether

percutaneous

investiga-

trial to compare

transpapillary

endoscopic

the anticipated

percutane-

the TEC catheter treatment.

cholecystostomy

patients

lower complication

rate of TEC will offset the ease and simplicity guided

loop on the pre-TEC

The right within

amylase

upper

related

but one patient.

S. FRIEDMAN.

M.D.

This 36-year-old

to find cases in which this technique

cial to these very ill patients. for this therapy

To date, we have enrolled

and have been able to drain

in 19 patients.

Therefore, hepatic

duct

we feel that the success rate will continue

coagulation

We rarely

service continue

disorders,

perform

>4

with platelet

seconds

frequently

above control. contain

rates contain Culture

sphincterotomies

results

Enterococcus

also had refractory

advanced ascites,

thy, and a pancreatic ascites. The gallbladder red blood cells with

had evidence aspirate ganism

active

leukocytosis,

a reddish-black

for acalculous

showed

17 cm by 7.5

cholecystitis The gram

was positive

with a fluid-filled

within

in a sea of

fluid with crenated cells and the gramencephalopathy

culture-positive

complicated

patient

and was 2

by a cardiac arrest, who

and whose gallbladder stain

a field of polymorphonuclear

but the culture

communicated

blood

he

encephalopa-

measured

died of progressive

infarction,

cultures.

cirrhosis;

coagulopathy,

white

of

and ascites of a 65causing

of more than 6 mm floating

the numerous

peptostreptococci.

in the majority

had positive

alcoholism

4 days later. The second

weeks postmyocardial rate grew

(11%)

from the gallbladder

contained

cocci. This patient

liver failure

aspi-

developed

renal failure,

postdrainage

collapsed

nography.

This patient

ficulty

indications

arises

is that

in passing

too much

aspi-

of this cream-colored leukocytes,

and no or-

24 hours. This gallbladder

cavity that was thought

to represent

pre-TEC

for follow-up.

positivity,

can be lifesaving

the valves of the cystic

caused this syndrome, especially

in patients

with ascites.

positive

culture.

regional

ischemia

endoscopists. within duct.

reports

that

if performed

for

The greatest

dif-

the cystic The greatest

duct,

not in

fear we have though

the

or tear.

are the major player in this disease. then we would expect more culture

with neutropenia

and the liver disease

Only one of these patients

We believe

ultraso-

consumption.

force will be used in the advancing

patients

was 8 cm clot in the

Her mother

valves and that the cystic duct could perforate If bacteria

distur-

had a clot develop

The presumed

to excessive alcohol by experienced

the insertion

adult respira-

herself out of the alcohol rehabilitation

We believe that this procedure

accessing

hepatitis,

the clot on the last predischarge

signed

and has not returned

the correct

in all

was 2 cm by 3 cm, and the gallbladder

around

has returned

duct

into the gallbladder.

and a severe coagulation

wall thickness.

of the gallbladder

No cases

and post-TEC

the pancreatic bleeding

day. The gallbladder

a 5-mm

remained

the patient

in both of these

pre-TEC

time over two time control)

We do not believe that bacteria

mass. This gallbladder

cm and had a wall thickness

positive

in these patients

the gallbladder

to be negative

2 of 19 patients

was cultured

man with

whereas

time

black bile.

have continued

Only

use in those

or a prothrombin

The bile duct aspirates crystals,

bile

for this tech-

any cautery

of 50,000/mm3

cholesterol

viscous

the patients. year-old

counts

to be those

or signs of common

nique (6 of 21 cases; 28%) and have avoided patients

and does not insert

antibiotic

were infrequent.

woman with acute alcoholic

by 4.5 cm with fundus

pain resolved

cannulating

One patient

syndrome,

on the third

center

to the endoscopic

ascites,

pathology.

directly

duct.

The cases referred with massive

21 patients

the gallbladder

to be high if the cystic duct can be straightened into the right

is benefi-

to

We did obtain

levels. We avoided

M.D.

bance (prothrombin We continue

on

to the procedures

were noted.

R. BRUGGE,

tory distress

but was evident

abscess cavity that responded

and 2 weeks of parenteral

quadrant

No. 6

hours of the procedure.

of pancreatitis

cholecystostomy.

LAWRENCE

decompression

Complications

of ultrasonography-

WILLIAM

Reply.

ultrasonography

the TEC study to be a communicating

Vol. 106,

it is the degree

or the gallbladder

(1 of 8; 13%) had a

of wall distention

contents

that

with

are the cause of

this problem. We would guided

welcome

drainage

a comparison

of the gallbladder,

of TEC with but at present,

ultrasonographythe only patients

that are offered to our service are those who have relative contraindications to percutaneous pathology

in addition

drainage

that TEC will ever replace gallbladder

because

The advantage offers certain of their myriad

or some evidence

to gallbladder

disease.

ultrasonography-guided

the latter

of medical

patients

bile duct

drainage

is easier and less expensive

of TEC is that it creates very high-risk

of common

We feel it is unlikely of the

than TEC.

no new holes and therefore

some hope of a therapy

to one

problems, FREDERICK

C. JOHLIN,

M.D.