Studies of the Mechanism of Postgastrectomy
Steatorrhea
C. WILMER WIRTS, M.D., F.A.C.P., and
Philadelphia,
T
FRANZ GOLDSTEIN, M.D.
Pennsylvania
of weight loss or failure
to gain weight after resectional surgery
for peptic ulcer disease has been shown to
vary from approximately 40 to 70 per cent
in most series (1-4). Ellison (5) found that,
among 290 postgastrectomy patients he
followed personally, 2 of every 3 were
below their ideal weights and one of 3
was more than 10 per cent below the
ideal minimal weight. Seven of 100 patients who had undergone an 85 per cent
Hoffmeister resection were so debilitated
after their operation that they were unable
to return to their normal occupation.
Fat excretion studies (2, 5-8) have revealed that approximately one-third to
one-half of patients who undergo a subtotal resection of the Billroth II type
develop steatorrhea. In addition to weight
loss and steatorrhea, patients with the
more advanced states of malnutrition following gastric surgery may suffer from
anemia, hypoproteinemia, edema, hypoprothrombinemia, and electrolyte deficiencies. It is significant that steatorrhea
is minimal or absent in the stools of patients whose gastroduodenal continuity is
maintained after operations of the Billroth I type. Shingelton and his colleagues
(2) found an average excretion of 4.5 per
cent of radioactive iodine-labeled triolein
in the stools of patients after Billroth I
operations, compared to an average excretion of 0.6 per cent in control patients
without operations. Conversely, after Billroth II operations or after gastrojejunostomy with vagotomy, the labeled triolein
excretion amounted to 14 per cent and 17
per cent, respectively, of the test doses administered.
A controversy still exists as to the extent
to which steatorrhea contributes to the
development of weight loss in postgastrectomy patients. Although it had been shown
that patients with the most severe weight
loss ingest the smallest number of calories,
the negative caloric balance cannot be
completely corrected by simply increasing
the intake of food. In Shingelton's series
(2), 11 of the abnormal fat tests occurred
in 13 patients whose weights were below
normal, and in only one of these patients
was there an estimated daily average
caloric intake of fewer than 2,000 calories.
Several investigators have suggested that
fecal losses of fat and calories may contribute to the poor nutritional status of
postgastrectomy patients, although inadequate food intake was considered the major
cause of weight loss (4, 6, 8).
The mechanisms whereby steatorrhea
develops in postgastrectomy patients are
not fully established. A variety of theories
HE INCIDENCE
Received May 16, 1962; accepted for publication
September 19, 1962.
From the Department of Medicine, Division of
Gastroenterology, The Jefferson Medical College
Hospital, Philadelphia, Pennsylvania.
Presented at the Forty-third Annual Session of
The American College of Physicians, Philadelphia,
Pennsylvania, April 9-13, 1962.
Supported by grant A2804 of the Institute of
Arthritis and Metabolic Diseases of the National
Institutes of Health, United States Public Health
Service.
Requests for reprints should be addressed to C.
Wilmer Wirts, M.D., Department of Medicine, The
Jefferson Medical College of Philadelphia, 1025
Walnut Street, Philadelphia 7, Pennsylvania.
25
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26
Annals of
Internal Medicine
C. W . WIRTS AND F . GOLDSTEIN
have been proposed, including the suggestions t h a t there is i m p a i r e d pancreatic
function (2, 9-12), t h a t there is i n a d e q u a t e
m i x i n g of food with digestive enzymes due
to r a p i d gastric emptying (9, 13, 14), a n d
that stasis in the afferent loop of the gastrojejunostomy may i m p a i r absorption ( 1 5 18). A n interesting speculation in conjunction w i t h the last theory suggests t h a t bacteria from the afferent loop may cause deconjugation of bile salts a n d t h a t unconjugated bile acids produce toxic degeneration
of small intestinal mucosa with impairm e n t of intracellular esterification of fats
(19). W e have previously submitted evidence
that stasis a n d excessive bacterial growth
occur in the afferent loops of the gastrojejunostomies of patients with postgastrectomy steatorrhea, a n d we have suggested
that these bacteria play a role in causing
defective absorption of fat (20, 21). T h e
present r e p o r t deals with the further
investigation of this problem.
M A T E R I A L S AND M E T H O D S
Our initial studies have been extended,
using the methods described previously (20, 21).
Thirty postgastrectomy patients with Billroth II
anastomoses form the basis of the major
analysis contained in this report. Fat absorption
was estimated by means of measurements of
3-day fecal fat excretion, measurements of
fecal excretion of a dose of radioactive iodinelabeled triolein, or both. The upper limits of
normal were accepted as 5 g of fat excretion/24 hr and 5% triolein excretion. Sixteen
of the patients included in this group were
part of the series reported previously (21).
When subsequent fat and triolein excretion
measurements revealed higher values than the
original ones, the highest values were used.
Material from the afferent loop was obtained
by direct intubation of the loop with a sterile
Rehfuss tube in 8 patients. In the remaining
22 patients, the material was obtained through
a tube placed at the site of the afferent loop
stoma under fluoroscopic vision using the
technique previously described (21). The material was subjected to quantitative bacterial
culture on 4 differential growth media, and
antibiotic sensitivities of the major bacteria
were determined by the disc method. The
bacterial floras of 22 normal control patients without operations and without achlorhydria were also studied for comparison.
Small bowel biopsy was performed using the
Rubin tube, in 7 patients with severe steatorrhea, which followed operations of the Billroth II type for peptic ulcer.
T o investigate the possible effect of bacteria
upon deconjugation of bile salts, bacteria were
incubated with pure conjugated bile acid in
the laboratory of Dr. John J. Schneider at The
Jefferson Medical College. Glycocholic, taurocholic, and desoxyglycocholic acids were incubated (2 to 3 hours, pH 7.3, gas phase O s ) with
mixed cultures. Paper chromatography was performed on the acid fractions, using systems
suitable for the detection of the free acids.
Reference free and conjugated acids, using
parallel chromatography, served as standards.
In an effort to evaluate the relationship
between postgastrectomy steatorrhea and pancreatic function, the fasting amylase and lipase
activities of duodenal juice were measured in
normal individuals, in patients with proven
pancreatic disease, and in afferent loop secretions of postgastrectomy patients. Amylase
activities were determined by a modification of
the Somogyi method developed in the Fels
Institute of Temple University (22). Lipase
activities were measured by the method of
Cherry and Crandall (23). Experiments were
carried out in vitro, incubating pancreatic juice
of normal patients at a temperature of 37 C,
with and without added bacteria, and measuring amylase and lipase activities after varying
periods of incubation. Penicillin and tetracycline were added to the tubes containing
pancreatic juice without added bacteria to offset the effect of bacteria present at the time of
aspiration. The normal patients represent subjects who had normal pancreatic function on
secretin testing, had not undergone gastric
surgery, and were free of steatorrhea.
RESULTS
T h e 15 patients represented in T a b l e 1
who h a d gastric resections of the Billroth
I I type did n o t have steatorrhea as determ i n e d by the tests indicated, a n d their
symptoms, if any, consisted primarily of
vomiting, d u m p i n g , anemia, or belching.
Cultures of the afferent loop aspirates
showed that the p r e d o m i n a n t organism in
the majority of patients was an alpha hemolytic streptococcus. I n this g r o u p of pa-
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Volume 58, No. 1
January 1963
27
M E C H A N I S M O F POSTGASTRECTOMY STEATORRHEA
TABLE 1. Postgastrectomy Patients without Steatorrhea
Patient
J131
Fat
Excretion
H.C.
g/24 hr
Not done
C.S.
P.B.
J.B.
A.S.
J.S.
Not
Not
Not
Not
Not
2
1.5
R.S.
G.F.
D.F.
0.6
2.1
2.3
D.P.
A.B.
0.0.
1.9
4.5
3
D.I.
4.3
Alpha-hem. strep.
Weight stable, no
symptoms
Vomits bile
Vomits bile
Recurrent bleeding
Anemia, iron deficiency
Weight stable, no
symptoms
Anemia
Initial weight loss,
stable
Mild anemia
Recurrent bleeding
Abdominal pains,
pancreatitis
% of dose
0.5
lflOO/ml
390
5
0
4.8
0.65
2.96
321
4,300
3.3
170
347
3
Contaminated
with urine
0.35
3.2
4.2
111
56
Coliforms
Alpha-hem. strep.
680
740
1,340
Alpha-hem. strep.
Alpha-hem. strep.
Mixed (strep.,
staph., and
coliforms)
Alpha-hem. strep.
E. coli and strep.
Alpha-hem. strep.
3.3
2.8
Contaminated
with urine
3.0
Median of colony counts.:
Mean of colony counts:
Remarks
Bacterial
Colony
Count *
done
done
done
done
done
D.P.
D.M.
Predominant
Organisms
Triolein
Excretion
1,980
6,800
10.7
387
Alpha-hem.
Coliforms
Alpha-hem.
Alpha-hem.
Alpha-hem.
strep.
strep.
strep.
strep.
E. coli
Dumping
Diarrhea, dumping
Anemia
Iron deficiency anemia
387,000 colonies/ml.
1,182,000 colonies/ml.
* Obtained by direct intubation of the afferent loop, or at stoma of gastroenterostomy.
tients, the mean of the bacterial counts was
1.182 million colonies per ml and the
median was 387,000 colonies per ml. In
the 15 postgastrectomy patients with steatorrhea represented in Table 2, weight loss,
diarrhea, or both were present in each,
and a colonic type of predominantly Gramnegative flora tended to be present in the
afferent loop fluid. Mean bacterial count
was 99.4 million colonies per ml and
median, 25.6 million colonies per ml. The
median of the colony counts in the control
group was 10,000 colonies per ml, with a
range from zero to 380,000 colonies per ml.
Eight of the 15 patients with steatorrhea
were treated with antibiotics selected on
the basis of determined bacterial sensitivities. Temporary and, at times, striking improvement, consisting of weight gains and
return to normal stool frequency and
normal fat absorption, was obtained in 5
patients. These results correlated well with
reductions in the flora of the afferent loop.
One patient was moribund when treatment was started and died shortly thereafter; autopsy revealed severe pyelonephritis and extensive muscle atrophy. In 2
other patients who failed to improve, no
significant effect of the administration of
antibiotics on the bacterial colony counts
in the afferent loop was noticed. The cause
of this lack of response was thought to be
changing bacterial flora with the emergence
of bacterial resistance to the antibiotics
administered. Improvement, when it occurred, was temporary, lasting from one
week to 6 months. Repeated courses of
antibiotics brought about renewed improvement in degrees comparable to that
after the initial course in some patients,
but less striking in others.
Most of the patients with steatorrhea
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28
Annals of
Internal Medicine
C. W . WIRTS AND F . GOLDSTEIN
TABLE 2. Postgastrectomy Patients with Steatorrhea
Patient
Fat
Excretion
J131
Triolein
Excretion
Bacterial
Colony
Count *
Remarks
Predominant
Organisms
W.M.L.
M.C.
B.J.
g/24 hr
Not done
Not done
49.6
% of dose
20
8
16.8
1,000/ml
760,000
46,000
250,000
R.P.
M.L.
J.G.
J.B.
Not done
10
25.3
7.7
9.8
1.8
6.6
Not done
78,000
16,600
41,600
2,760
Proteus
Aerobacter
Aerobacter
Alpha-hem. strep.
H.R.
7.2
7.3
4,820
E. coli and strep.
F.R.
14.6
7.9
179,000
F.M.
E.M.
12.4
10.9
8.2
62.2
25,600
6,010
M.W.
T.R.
T.L.
CD.
5.2
10.2
8.8
9.4
Not done
34.8
Not done
Not done
1,245
27,070
4,300
48,460
Severe weight loss
Weight loss, diarrhea
Weight loss, diarrhea,
anemia
Weight loss
Weight loss
Mild weight loss
Initial weight loss,
then stable
Anemia, mild weight
loss
Weight loss and
diarrhea, dumping
Weight loss, diarrhea
Wasting, anemia, diarrhea; died
Weight loss
Weight loss, diarrhea
Weight loss, diarrhea
Weight loss, diarrhea,
dumping
Proteus
Proteus
Paracolon
Alpha-hem. strep.
Coliforms
Aerobacter,
E. coli, and strep.
Alpha-hem. strep.
Aerobacter
Alpha-hem. strep.
Aerobacter
Median of colony counts:: 25,600,000 colonies/ml.
Mean of colony counts:
99,400,000 colonies/ml.
* Obtained by direct intubation of the afferent loop, or at stoma of gastroenterostomy.
and weight loss have been studied for
months to years after gastrectomy, and
the question has been raised how soon
after operation steatorrhea and bacterial
proliferation in the afferent loop might
occur. We have now studied 6 patients
(Table 3) as early as 2 weeks following
surgery and found that both steatorrhea
and an abnormal bacterial flora of the
afferent loop may appear at such an early
date. Although we have studied only 2 patients following a Billroth I procedure
TABLE 3. Early Postgastrectomy Patients
Patient
Fat
Excretion
J131
Triolein
Excretion
Bacterial
Colony
Count *
R.P.
J.F.
W.T.
S.P.
E.L.
(month later)
g/24 hr
7.8
Not done
1.45
14.7
Not done
20.1
% of dose
3.9
Not done
2.5
16.4
Not done
8.7
1,000/ml
4,500
3,310
3,690
686
26,300
5,500
F.P.
3.7
0.5
4.2
Predominant
Organisms
Strep.
Strep.
Strep, and E. coli
Strep, and E. coli
E. coli and Aerobacter
Mixed
Remarks
Time
wk
2
2
2
2
2
8
Strep.
2
No complications
No complications
No complications
No complications
Diarrhea
Weight loss, partially
improved after therapy with antibiotics
No complications
* Obtained by direct intubation of the afferent loop, or at stoma of gastroenterostomy.
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Volume 58, No. 1
January 1963
MECHANISM OF POSTGASTRECTOMY
STEATORRHEA
29
TABLE 4. Patients with Billroth I Operations
Patient
Fat
Excretion
J131
Bacterial
Colony
Count *
Triolein
Excretion
CD.
g/24 hr
2.4
% of dose
7.1
(Contaminated
with urine)
M.M.
3.7
3.7
Predominant
Organisms
Remarks
Streptococci
Vagotomy; had acid
Streptococci
Gained 30 pounds
since operation
one year earlier
for carcinoid of
stomach
colonies/ml
900,000
3,640
* Obtained by direct intubation of the duodenum.
(Table 4), it is of interest that the duodenal
cultures revealed relatively little growth,
and steatorrhea was absent; the increased
fecal excretion of radioactive triolein
noted in patient C D . was attributed to
contamination with urine.
The jejunal mucosal biopsies performed
in 7 patients with severe steatorrhea
showed minimal or no change from
normal. In 3 instances, mild inflammatory
cell infiltrations were present, but there was
no evidence of clubbing, shortening, or
flattening of the villi.
In the 4 incubations of bacteria with
pure conjugated bile acid, no free bile
acid was detected. It was concluded that,
under the conditions of the experiment,
the bacteria employed were unable to effect
hydrolysis of the conjugated acids.
In Table 5 are listed the ranges and
means of the concentrations of the fasting
amylase and lipase activities of the duodenal juice in normal individuals, in
patients with proven pancreatic disease,
and in afferent loop secretions of postgastrectomy patients. These data are preliminary, and the number of patients from
whom they were derived is too small for
definitive conclusions. However, the data
suggest that the concentrations of fasting
lipase of patients with postgastrectomy
steatorrhea are depressed to levels comparable to those observed in patients with
pancreatic disease. T h e amylase concentrations did not appear to be proportionately
depressed. These data do not establish
whether the lowered lipase concentrations
in fasting afferent loop secretions are
TABLE 5. Fasting Duodenal or Afferent Loop Enzyme Concentrations
Lipase
Amylase
Range
Mean
Range
Mean
Normal controls [ 1 2 ]
units/100 ml
444 to 3,990
1,849
units/ml
6.2 to 21.7
14.5
Patients with pancreatic
disease [ 7 ]
132 to 2,248
1,033
2.6 to 15
10.5
Postgastrectomy patients
without steatorrhea [ 3 ]
2,240 to 4,580
3,636
15
to 18.2
Postgastrectomy patients
with steatorrhea [ 6 ]
1,005 to 3,018
1,985
0
to 13.2
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16.3
9.83
C. W . WIRTS AND F . GOLDSTEIN
30
caused by impaired pancreatic function or
by inhibition or destruction of lipase after
its n o r m a l secretion by the pancreas.
Failure of lipase to be activated by bile is
an unlikely cause of the low lipase values,
since bile was a b u n d a n t in all samples.
Preliminary data suggest t h a t incubation
u p to 24 hours of pancreatic juice of
n o r m a l subjects with a n d without added
bacteria, simulating in vivo stasis, does not
interfere significantly with amylase activities. Lipase activities tended to diminish
after several hours of incubation, b u t from
the available data it could n o t be determ i n e d whether the addition of bacteria
further decreased the lipase activity.
CASE
REPORTS
The following case reports have been selected
to illustrate some of the problems and questions encountered in the management of postgastrectomy patients and to show the variable
response to administration of antibiotics.
CASE
1
A Negro male (B.J.) underwent a subtotal
gastric resection with gastrojejunostomy for a
benign gastric ulcer in October 1956. Early in
1959 he developed diarrhea, a 20-lb weight loss,
weakness, dyspnea, and leg edema. When admitted to the hospital April 9, 1959, he appeared to be severely malnourished, dehydrated,
and anemic. His vital signs were normal.
Weight, despite the edema, was 128 pounds,
compared with a preoperative weight of 162
pounds. The tongue was red and smooth, there
were moist pulmonary rales, the heart size was
normal, the liver was palpable 3 cm below the
right costal margin, and there was 3 -f- pitting
edema of the legs bilaterally. The patient continued to have as many as 12 foul-smelling,
bulky bowel movements daily, which produced microscopic evidence of fat. The hemoglobin was 9.2 g/100 ml; leukocytes, 14,700
cells/mm 3 ; and reticulocytes, 4.7%. The fasting
blood sugar was 69 mg/100 ml, and the blood
urea nitrogen, 10 mg/100 ml. Serum sodium
value was 122 mEq/liter, potassium 3.3 mEq,
chloride 97 mEq, carbon dioxide combining
power 19 mmole, and calcium 3.5 mEq/liter.
Liver function tests were normal. Gastric analysis revealed no free acid after histamine
stimulation. A Schilling test on May 20 re-
Annals of
Internal Medicine
vealed 3.7% urinary excretion of the labeled
vitamin B12 that had been administered. Fecal
triolein excretion was 16.8% of the dose
administered.
On April 20, the patient suddenly developed
hypotension, tetany, and stupor and required
vigorous treatment with intravenous fluids,
electrolytes, calcium, and adrenal steroids. The
diarrhea temporarily improved, but recurred
upon withdrawal of steroids.
Two cultures of the afferent loop revealed
250 million and 80 million colonies of paracolon bacilli/ml, respectively, which were sensitive to tetracycline. Another culture, after
treatment with 1 g tetracycline daily for 5
days, revealed 213,000 colonies/ml, predominantly streptococci. Concomitantly, 6 pounds
were gained, the number of stools was reduced
to one a day, and stainable fat disappeared.
A repeat Schilling test showed 9% urinary
excretion of labeled vitamin B12.
For 6 months after discharge, the patient
received additional courses of tetracycline whenever diarrhea occurred. In November 1959, his
weight had risen to 135 pounds from a low
of 116. Excretion of fecal triolein was now less
than 1%, and the Schilling test showed excretion of urinary cyanocobalamine to be 11%.
Subsequently, steatorrhea and malnutrition
followed episodes of alcoholism, and improvement occurred after administration of tetracycline. In June 1961, an attempt was made
to convert the anastomosis to a Billroth I
operation, but this proved to be technically
impossible; therefore, a jejunojejunostomy was
performed. Biopsy of the jejunal mucosa
showed an increase in chronic inflammatory
cells but villi of normal length. The patient
has continued to have bouts of diarrhea and
steatorrhea with continued evidence of stasis
and excessive bacterial growth in the upper
jejunum, but temporary improvement still
occurs after repeated courses of antibiotics.
Comment: The symptoms in this patient reflect the severe malabsorption of both fat and
vitamin B12 that may follow gastric surgery for
ulcer. The general state of malnutrition and
edema indicates that other nutrients probably
were also poorly absorbed. The afferent loop
v/as long, tortuous, and contained one of the
highest concentrations of bacteria we have encountered so far. The patient's response to the
administration of tetracycline initially was excellent, but frequent relapses led to a drainage
operation. Incomplete response to this operation necessitated additional treatment with antibiotics. In this patient, as well as in several
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Volume 58, No. 1
January 1963
MECHANISM O F POSTGASTRECTOMY
others with postgastrectomy steatorrhea, uncontrolled alcoholism appeared to contribute
significantly to further deterioration of the
nutritional status.
CASE 2
A 51-year-old housewife (F.R.) had a subtotal gastrectomy for gastric ulcer in 1953.
Weight loss of 70 pounds, large loose bowel
movements, and sweating and weakness after
meals developed progressively from 1959 until
September 1960, the time of her admission.
The patient appeared to be poorly nourished
and chronically ill. The hemoglobin was 10.4
g/100 ml, and there was achlorhydria after histamine injection. Excretion of fat in the stools
was 14.6 g/24 hr, and culture of the afferent
loop grew out 160 million colonies/ml of
streptococci sensitive to tetracycline. After
treatment with 1 g tetracycline daily for 5 days,
the stool fat was 8.2 g, and culture of the
afferent loop fell to 2 million colonies of
streptococci and Escherichia coli/ml. The patient now had only one to 2 bowel movements/
day, and the stools became formed. She gained
3£ pounds in 5 days and 7 more pounds later.
Comment: This case illustrates several characteristic features of many patients with postgastrectomy steatorrhea. The steatorrhea and
weight loss became manifest several years after
the operation and were associated with symptoms interpreted as representing dumping. In
response to treatment with antibiotics, the diarrhea and dumping symptoms abated and the
patient gained weight, but she had a relapse
about 6 weeks later.
CASE
3
On July 28, 1961, a 56-year-old housewife
(E.L.) underwent a subtotal gastrectomy for
intractable gastric ulcer. On August 7 she developed severe diarrhea; the stools were foamy,
and on microscopic examination were seen to
contain numerous fat globules. A culture of
abundantly available fluid from the afferent
loop (pH 7.5) grew out 26 million colonies/ml
of approximately equal numbers of Aerobacter
aerogenes and E. coli, which had varying sensitivities. Following readmission of the patient
a month later, excretion of fecal fat was 20 g/24
hr, and culture from the afferent loop grew out
5.5 million colonies of mixed bacteria/ml.
Tetracycline, 1 g daily for 5 days, was given;
however, steatorrhea continued, with 17.5 g of
fat/day being excreted. Another culture of the
afferent loop fluid revealed 3 million colonies/
STEATORRHEA
3i
ml, which was not considered to be a significant decrease. The patient's diarrhea subsided
gradually, and her weight stabilized.
Comment: This patient's illness illustrates
the occurrence of diarrhea and malabsorption
during the early postoperative period, with apparent stasis of secretions in the gastric pouch
and probably in the afferent loop. Treatment
with antibiotics was only partially effective, in
that it halted the severe diarrhea but did not
significantly reduce the malabsorption. The patient adjusted gradually and experienced a return to normal gastrointestinal function within
3 months of her operation. The incomplete
response to antibiotics was thought to be due
to the presence of a mixed bacterial flora
partly resistant to the antibiotic used.
CASE
4
A 65-year-old housewife (A.B.) underwent a
hemigastrectomy and vagotomy with a gastrojejunostomy for a penetrated duodenal ulcer
in September 1958. She was readmitted on
January 15, 1961, because of diarrhea and
weight loss of 48 pounds. She had symptoms
of dumping, consisting of feelings of weakness,
dizziness, and near fainting shortly after meals,
and had frequent mushy bowel movements
both day and night. Examination showed the
about 80/min with digitalis. The liver was
patient to be emaciated with a weight of 72
pounds. There was cardiomegaly and atrial
fibrillation; ventricular rate was slowed to
moderately enlarged, and the spleen was palpable. Severe rheumatoid arthritis was present.
Hemoglobin was 12 g/100 ml and the fasting
blood sugar, 73 mg/100 ml. X-ray studies revealed cardiomegaly, severe rheumatoid arthritis of the hips, and the remaining half
of the stomach with a well-functioning gastrojejunostomy.
A 3-day stool collection showed an average
24-hour excretion of 4.5 g of fat and 2.8%
excretion of labeled triolein. Culture of material aspirated from the region of the afferent
loop stoma (pH of 7) grew out 6.8 million
colonies/ml of approximately equal proportions of E. coli and streptococci, both sensitive
to tetracycline.
Within 48 hours after the administration of
1 g tetracycline daily, the diarrhea and the
dumping symptoms disappeared. However,
there was no increase in weight until anabolic
steroid therapy prompted a gain of 4 pounds
before the patient was discharged on February
7, 1961.
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C. W . WIRTS AND F . GOLDSTEIN
32
Comment: This patient had severe weight
loss, diarrhea, and dumping, but no steatorrhea.
The afferent loop flora was slightly abnormal.
There was a striking cessation of the disabling
diarrhea and dumping symptoms following
therapy with antibiotics, but weight gain did
not ensue until after the administration of
anabolic steroids.
CASE 5
In 1953 a 48-year-old white male (D.I.)
underwent a subtotal gastrectomy for duodenal
ulcer. He was admitted on April 2, 1961, because of the gradual development of microcytic anemia, weakness, and numbness in the
arms without tingling. The patient had dumping symptoms consisting of weakness, sweating,
and flushing shortly after meals. Bowel habits
and weight had remained normal.
Physical examination revealed pallor, slight
cardiomegaly, and hepatomegaly. The spleen
was barely palpable. No neurological abnormalities were detected.
Hemoglobin was 6.7 g/100 ml, hematocrit
reading 28%; erythrocytes were 4.39 million/
mm 3 , and the leukocyte count was normal. The
serum iron concentration was 16 /Ag/100 ml,
despite the intake of oral iron before admission.
The total iron binding capacity was 466 /xg/100
ml. Blood chemical studies were normal.
Roentgen examination of the upper gastrointestinal tract revealed no abnormalities of the
remaining gastric pouch or gastrojejunostomy.
The free acid was 8 mEq/liter after histamine.
The stool fat was 4.33 g/24 hr. A culture of
afferent loop fluid grew out 380,000 colonies
of E. coli/ml. Since oral administration of iron
was ineffective, the patient was given 100 mg
of an iron-dextran complex (Imferon) I. M.
daily for 9 days, which produced a serum iron
level of 250 jug/100 ml and a rise in the hemoglobin concentration to 13.2 g by August 1961.
Comment: This case illustrates the frequently
observed dissociation of malabsorption of fat
and iron. The patient had severe iron deficiency
anemia and probable impairment of iron absorption in the absence of an abnormal afferent
loop flora or steatorrhea. He responded to
parenteral injections of iron.
DISCUSSION
T h e results presented here provide further evidence for the relationship suggested
previously between postgastrectomy malabsorption a n d the presence of afferent
Annals of
Internal Medicine
l i m b stasis a n d excessive bacterial flora.
A l t h o u g h stasis cannot be assessed q u a n t i tatively, its presence was assumed in m a n y
patients from the length a n d caliber of the
afferent loop, as seen on radiographic examination, a n d from the q u a n t i t y a n d character of the fluid aspirated from the afferent
loop, including its bacterial content. Patients who developed steatorrhea following
gastric resection tended to have longer afferent loops, frequently of an antiperistaltic
or left-to-right type, t h a n postgastrectomy
patients whose fat absorption was n o r m a l .
T h e subject was discussed more fully in a
previous communication (21). Gastric acid
secretion in patients with postgastrectomy
steatorrhea invariably was absent or minimal, a n d the p H of the afferent loop fluid
was always above 6. Anacidity was encountered in some postgastrectomy patients
whose fat absorption was u n i m p a i r e d , b u t
n o patients with steatorrhea h a d n o r m a l or
excessive acid secretion. W e have encountered n o patients w h o h a d b o t h steatorrhea
a n d recurrent peptic ulceration. T h e differences in quantitative bacterial growth,
seen by comparing the m e d i a n counts of
groups with a n d w i t h o u t postgastrectomy
steatorrhea, were statistically significant at
the 0.001 level. However, a m o n g the patients with steatorrhea, the severity of the
steatorrhea did n o t correlate closely with
the degree of bacterial proliferation in the
afferent loop. T h e r e were also qualitative
differences between the groups, as has been
previously noted, in t h a t the patients w i t h
steatorrhea often h a r b o r e d a colonic type
of flora, with Gram-negative organisms predominating. Conversely, in the non-steatorrhea group, alpha-hemolytic streptococci
were the sole or p r e d o m i n a n t organisms in
12 of 15 patients.
A causal relationship between the afferent
loop flora a n d steatorrhea is further suggested by the effects of antibiotic treatment.
T h e majority of patients with postgastrectomy steatorrhea, treated with appropriately selected antibiotics, showed p r o m p t ,
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January 1963
MECHANISM OF POSTGASTRECTOMY STEATORRHEA
though temporary, improvement in stool
frequency, fat absorption, and state of nutrition. Weight gain correlated well with
improved fat absorption and decreases in
bacterial growth in the afferent loop.
Therapeutic failures invariably accompanied failure to reduce the flora of the
afferent loop significantly, because of either
the presence of resistant bacilli or a rapid
change in the flora to a resistant type. The
limited duration of the improvement after
treatment with antibiotics suggests use of
surgical attempts to establish gastroduodenal continuity either at the time of the
original operation or later when corrective
surgery is needed. In several patients with
mild steatorrhea, repeated courses of antibiotic administration brought about sufficient improvement and weight gain to
permit the patients to return to relatively
normal activity without recourse to additional surgery. In our experience, repeated
bacteriological cultures with sensitivity determinations have been proven to be extremely important in charting the course
of antibiotic treatment of patients with
postgastrectomy steatorrhea—a procedure
comparable to quantitative urine cultures
in patients with chronic pyelonephritis (patient W. L., reference 21).
The favorable effects of administration
of antibiotics in several patients with dumping symptoms or with diarrhea without
steatorrhea (case 4) were unexpected and
unexplained. It is conceivable that an inflammatory reaction due to bacterial infection of the upper small intestine and
of the afferent loop may play a role in
causing these symptoms. Further work is
required to gain additional insight into
these aspects of postgastrectomy complications. In general, patients in our series with
relatively normal fat absorption had fewer
symptoms and little weight loss (Table 1).
Significant weight loss was present in all
but one of our patients with postgastrectomy steatorrhea, and most had diarrhea
(Table 2). These data suggest that steator-
33
rhea is perhaps more important in the production of postgastrectomy malnutrition
and weight loss than has previously been
thought. Anemia occurred with about equal
frequency in patients with and without
steatorrhea. The anemia was macrocytic in
2 patients, both of whom had associated
steatorrhea. A similar case was reported by
Adams (16), who also observed beneficial
results from antibiotic treatment. Badenoch,
Evans, Richards, and Witts (24) had previously drawn attention to a possible relationship between afferent loop stasis and
macrocytic anemia due to vitamin B 12 deficiency. Macrocytic anemia and vitamin
B 12 deficiency are not common in postgastrectomy patients (25) and may be
caused by other factors, especially loss of
intrinsic factor production in the residual
gastric pouch undergoing intestinal metaplasia. Iron deficiency anemia, even when
produced by failure of iron absorption as
in case 5, does not appear to be related to
malabsorption of other nutrients or abnormal bacterial growth.
The concept that postgastrectomy steatorrhea represents an example of the blind
loop syndrome is not entirely new, and a
comprehensive review of the subject was
presented recently by Starzl, Butz, and
Hartman (26). The work on this subject
in England by Butler, Capper, and Naish
(18) and Naish and Capper (17) has also
been important. Direct proof of bacterial
growth in the afferent loop and upper
small intestine of patients with postgastrectomy steatorrhea was not provided by
these earlier studies. It should be stated
that the blind loop theory of the cause of
postgastrectomy steatorrhea does not exclude some of the other mechanisms suggested, such as depression of pancreatic
function or inadequate mixing of pancreatic enzymes with food. Indeed, the
authors do not wish to suggest that the
factors of stasis and bacterial flora are
solely responsible for causing postgastrectomy steatorrhea.
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34
Annals of
Internal Medicine
C. W . WIRTS AND F . GOLDSTEIN
Our observations confirm those of Butler
(10) that pancreatic lipase activity of afferent loop juice is depressed in patients
with postgastrectomy steatorrhea. However,
our data do not permit us to state
whether lowered enzyme activity was due
to decreased pancreatic function or to inactivation of secreted lipase as the result
of prolonged storage and exposure to bacteria in a poorly draining afferent loop.
A comparable reduction in trypsin activities from samplings of intestinal fluid has
been found by Lundh (9) in postgastrectomy patients, especially those with a Billroth II anastomosis.
The findings of Tyor and Ruffin (14) of
increased absorption of triolein in patients
with postgastrectomy steatorrhea after preliminary pre-feeding of fat could also be
compatible with the concept of afferent
loop stasis. It is conceivable that the pre-fed
lipid stimulated pancreatic secretion and
gall bladder emptying, and that the secreted and excreted juices draining into the
afferent loop (duodenum) force out its stagnant contents and make available freshly
secreted pancreatic enzymes and bile for
the digestion of the test meal which follows.
The precise mechanism by which bacteria impair intestinal absorption in postgastrectomy steatorrhea or other blind loop
syndromes remains unknown. Drexler (27)
has demonstrated that a metabolite of E.
coli, indole, is capable of binding B 12 and
thus making it unavailable for utilization
by bacteria and presumably for absorption
by the intestinal mucosa. Similar toxic
metabolites may be active in inhibiting fat
absorption, but they remain unidentified.
Dawson and Isselbacher (19) suggest that
bacteria in areas of stasis may hydrolyze
conjugated bile acids, and they showed that
unconjugated bile acids are toxic to the
intestinal mucosa of the rat and inhibit
intracellular phosphorylation reactions necessary for absorptive processes. The preliminary experiments done by Dr.
Schneider of The Jefferson Medical College
in conjunction with our work have failed
to supply supportive evidence that bacteria
cause deconjugation of pure conjugated
bile acids. Also, neither patients with postgastrectomy steatorrhea generally, nor any
of the 7 patients with steatorrhea in our
series on whom biopsies were done showed
significant toxic changes of the jejunal
mucosa.
SUMMARY
Thirty postgastrectomy patients were
studied, 15 without and 15 with steatorrhea,
as determined by measurements of excretion of fecal fat and radioactive iodinelabelled triolein. Material from the afferent
loop of the gastrojejunostomy was subjected to quantitative bacterial cultures. In
the patients with steatorrhea, colony counts
of the bacteria from the afferent loops were
consistently higher than those in patients
without steatorrhea; the differences between
the median values of the colony counts
of patients with and without steatorrhea
were statistically significant at the 0.001
level. The administration of appropriately
selected antibiotics was followed by gains
in weight and reductions in fat excretion
in 5 of 8 patients with steatorrhea treated
in this way. Improvement correlated well
with reductions in afferent loop bacterial
counts. The data demonstrate a highly significant association between postgastrectomy steatorrhea and the development of a
fecal type of resident bacterial flora in the
afferent loop of the gastrojejunostomy.
Other factors undoubtedly participate in
the production of steatorrhea in this group
of patients and may interact with factors
of stasis and bacterial flora.
Preliminary measurements of pancreatic
enzymes of fasting afferent loop fluid suggest a reduction in lipase activity in patients with postgastrectomy steatorrhea. It
was not established whether lowered lipase
activity was due to decreased pancreatic
function or to inactivation of secreted
lipase as the result of prolonged stasis and
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Volume 58, No. 1
January 1963
MECHANISM
exposure to bacteria in a poorly
afferent
O F POSTGASTRECTOMY
draining
loop.
Studies
of c o n j u g a t e d
bile
acids
incu-
b a t e d w i t h b a c t e r i a f a i l e d t o p r o v i d e evid e n c e of d e c o n j u g a t i o n , a n d j e j u n a l
sies f r o m
7 patients with
biop-
postgastrectomy
steatorrhea d i d n o t show more than minim a l histologic changes in t h e mucosa.
ACKNOWLEDGMENT
T h e a u t h o r s a r e grateful t o Doctors D a v i d
Ginsberg, H . J a y Cozzolino, a n d J a y A. Kern,
N a t i o n a l Institutes of H e a l t h Trainees-in-Gastroenterology, for their v a l u a b l e clinical assistance i n this work; to D r . H y m a n M e n d u k e ,
Associate Professor of Biostatistics, for performi n g t h e statistical analysis of t h e d a t a ; a n d to
Mrs. L e a h Josephs, B . A., M r s . B i n n i e R e m ,
a n d Miss Ellen J e n n e r for v a l u a b l e technical
assistance.
T e t r a c y c l i n e (Tetracyn) used i n this study
was supplied by t h e Pfizer Laboratories.
SUMMARIO
I N INTERLINGUA
Esseva studiate 30 p a t i e n t e s post gastrectomia.
L e g r u p p o includeva 15 q u i h a b e v a steatorrhea
e 15 q u i n o n lo h a b e v a secundo mesurationes
del grassia fecal e d e l excretion d e trioleina
m a r c a t e con iodo radioactive. M a t e r i a l a b le
afferente ansa del gastrojejunostomia esseva
subjicite a q u a n t i t a t i v e culturas bacterial. I n
le p a t i e n t e s con steatorrhea, le n u m e r a t i o n e s
d e colonias de bacterios a b le afferente ansas
esseva u n i f o r m e m e n t e p l u s alte q u e i n le p a tientes sin steatorrhea. L e differentias i n le
cifras m e d i a n d e l n u m e r a t i o n e s d e colonias
i n t e r le p a t i e n t e s con e sin steatorrhea esseva
statisticamente significative al nivello de 0,001.
L e a d m i n i s t r a t i o n d e a p p r o p r i a t e m e n t e seligite
antibioticos resultava—in 5 d e l 8 assi tractate
p a t i e n t e s con steatorrhea—in ganios d e peso e
declinos del excretion d e grassia. L e grados d e
m e l i o r a t i o n exhibiva u n b o n correlation con
le declino d e l n u m e r a t i o n e s bacterial a b le
afferente ansa. L e datos d e m o n s t r a u n altem e n t e significative association i n t e r steatorrhea
post gastrectomia e le d i s v e l o p p a m e n t o d e u n
typo fecal d e flora bacterial residente i n le ansa
afferente d e l gastrojejunostomia. Altere factores
participa i n d u b i t a b i l e m e n t e i n le p r o d u c t i o n d e
steatorrhea in iste g r u p p o d e p a t i e n t e s e interage possibilemente c o n factores d e stase e
d e flora bacterial.
Mesurationes p r e l i m i n a r i d e enzymas p a n -
STEATORRHEA
35
creatic i n fluido a b le ansa afferente in stato
j e j u n suggere le occurrentia d e u n declino i n
le activitate d e lipase i n p a t i e n t e s con steatorr h e a post gastrectomia. II n o n esseva determ i n a t e si le declino d e l activitate d e lipase
esseva causate p e r u n declino d e l function pancreatic o p e r le inactivation d e l secernite lipase
in consequentia d e l p r o l o n g a t e stase con exposition al action d e bacterios i n u n m a l
d r a i n a t e ansa afferente.
Studios d e conjugate acidos d e bile i n c u b a t e
con bacterios n o n provideva evidentia d e disconjugation, e biopsias j e j u n a l a b 7 p a t i e n t e s
con steatorrhea post gastrectomia n o n m o n strava plus q u e u n m i n i m e g r a d o d e alteration
histologic in le mucosa.
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