Open Journal of Internal Medicine, 2012, 2, 19-26 OJIM
http://dx.doi.org/10.4236/ojim.2012.21005 Published Online March 2012 (http://www.SciRP.org/journal/ojim/)
Uncommon complications of biliary stones
S. Janssen1, I. van Mierlo1, L. P. L. Gilissen1, S. W. Nienhuijs2, J. Heemskerk3
1Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The Netherlands
2Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
3Department of Surgery, Laurentius Hospital, Roermond, The Netherlands
Email: sj.janssen@chello.nl
Received 7 July 2011; revised 16 November 2011; accepted 25 November 2011
ABSTRACT
Gallstone disease has a high incidence, and most com-
mon presentations are well known and recognized.
Particulalry in the elderly population though, un-
common presentations of gallstone disease are more
frequent, and can easily be missed or misinterpreted.
In this article we present 5 such patients with an
atypical presentation of gallstone disease. We will
then discuss atypical gallstone disease in more detail.
Keywords: Gallstone Disease; Gallstone Complications;
Elderly
1. INTRODUCTION
Gallstones are crystalline formations by accretion or
concretion of bile components. The occurrence has been
reported up to 25 percent [1]. This may, however, not be
a realistic representation of the prevalence, since most
gallstones are asymptomatic: only 10% - 30% of biliary
stones give symptoms [1], leading to aspecific abdominal
or dyspeptic complaints, cholecystitis, cholangitis and
pancreatitis. Patient history and clinical examination are
still pivotal in diagnosing symptomatic gallsto ne disease.
Usually the symptoms are readily recognized, after
which cholecystectomy is performed. However, not all
gallstone disease comes with a clear-cut presentation,
and not all abdominal complaints are attributable to the
presence of gallstones. Diagnostic tools such as ultra-
sound examination, computed tomography scan or mag-
netic resonance cholangio and pancreaticography may
not always reveal gallstone disease [2]. This rings espe-
cially true for the elderly patient, in which complicated
gallstone disease is more common, and disease presen-
tation or the disease itself may be atypical.
As gallstone disease may result in serious complica-
tions, it remains important to recognize even these
uncommon presentations. This case-series describes five
such patients with infrequent complications of biliary
stones, in order to improve awareness.
2. CASES
2.1. Patient A
A 76-year old woman visited the Emergency Ward of our
hospital with abdominal pain, constipation and vomiting
since one week. Her medical history revealed two previ-
ous admissions for postprandial pain in her upper abdo-
men, nause a, vomiting and diarrho ea. These ep isodes had
lasted for two weeks and dissolved spontaneously.
Physical examination now revealed a general ten-
derness of her abdomen, without distention of the ab-
domen or palpable masses. Laboratory analysis showed
leucocytosis and moderately elevated CRP (Ta bl e 1). A
plain abdominal X-ray revealed a big round cal-
cification in the right upper abdomen, which was moved
to the left upper ab domen on a second X-ray (Figure 1).
An abdominal CT scan was performed and showed a
dilated stomach, as well as a collaps ed gallblad der with a
Figure 1. The calcif icati on i s visibl e in the upp er left abdom en.
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S. Janssen et al. / Open Journal of Internal Medicine 2 (2012) 19-26
20
Table 1. Laboratory results on presentation.
Patient A Patient B Patient C Patient D Patient E
Hb mmol/L 7.7 7.8 8.9 8.9 6.5
Leukocytes /nL 12 17 11 6 27
CRP mg/L 68 49 100 64 22
Bilirubin µmol/L 16 51 14 21 7
ASAT U/L 36 190 26 21 20
ALAT U/L 45 120 33 12 12
AF U/L 61 197 120 43 128
γ-GT U/L 58 170 58 19 42
Amylase (serum) U/L 2200
Amylase (urine) U/L 4400
calcified mass. In the jejunum an obstructing calcified
mass was seen of 2.6 * 2.3 cm (Figure 2), with dis-
tension of the proximal jejunum. These findings estab-
lished the diagnosis of gallstone ileus. Retrospectively,
the stone was already detectable on a previous abdominal
X-ray nine months earlier. The patient was diagnosed
with an intermittent gallstone ileus. She underwent a
laparotomy with enterolithotomy (Figure 3) and re-
covered fully.
Her gallbladder was not resected due to the surround-
ing tissues being inflammated at the time of surgery. No
further symptoms were seen in a 2-year follow-up.
2.2. Patient B
An 88-year old woman presented with malaise. Her me-
dical history included a sliding hernia and diverticulosis.
Apart from frequent coughing, there were no other spe-
cific complaints. Physical examin ation showed no abnor-
malities. Laboratory analysis showed elevated inflam-
mation markers and signs of cholestasis (Table 1).
Abdominal ultrasound as well as CT-scan revealed an
abscess located in the right liver lobe (Figure 4), with a
slender biliary duct, sludge in both the gallbladder and
biliary duct. The abscess was drained. Cultures showed
an E. coli, for which Amoxicillin/clavulanic acid was
administered for 6 weeks. The patient made a complete
recovery.
Several months later she was admitted again, this time
septic due to cholang itis. An ERCP showed several large
bile duct stones with clear dilation (Figure 5). After
papillotomy the stones were removed with a basket. A
second ERCP was performed because of renewed signs
of inflammation and cholestasis. No more ductal stones
were found. A regimen of amoxicillin/clavulanic acid
was administered for 2 days, after which patient re-
covered.
Due to the extensive choledocholithiasis, it was
concluded that the previous liver abscess was a com-
plication of gall stone disease, as well. Remarkably, both
ultrasound and CT-scan had not revealed any stones or
Figure 2. CT scan showing the intestinally located gallstone.
(a) (b)
Figure 3. (a) and (b) preoperative photographs of gallstone
ileus (note the prestenotic dilated and congestive loops with
intraluminal stone en lean postobstructive bowel loops).
Copyright © 2012 SciRes. OPEN ACCESS
S. Janssen et al. / Open Journal of Internal Medicine 2 (2012) 19-26 21
Figure 4. Liver abcess and cysts.
Figure 5. ERCP with multiple biliary duct stones.
bile duct dilation. It is highly unlikely for the patient to
have formed multiple new gall stones so soon after the
liver abcess.
Cholecystectomy was proposed, but patient refused.
No new complications have been seen in a 1 year follow
up.
2.3. Patient C
An 83-year old male was referred to our hospital for a
second opinion. His medical history included an ab-
dominal aortic endoprothesis, atrial fibrillation and la-
paroscopic cholecystectomy three years earlier. Patient
had a weight loss of 10 kilograms, productive coughing,
dyspnea, and sometimes vomiting after a severe cough-
ing stroke. No fever was reported. Claritromycin admi-
nistered by the general practitioner for suspected res-
piratory infection had given no relief. Physical exami-
nation showed no abnormalities beyond bilateral basal
crackles and a median abdominal herniation without
signs of incarceration. Lab results showed mild leuco-
cytosis, elevated CRP and a slightly elevated gamma
(Table 1). Chest X-ray sh owed an infiltration in the right
lower quadrant, and an elevated right hemidiaphragm. A
scan had already been performed by the referring
hospital, which showed a fluid-filled cavity, positioned
dorsally in the liver. This was originally thought to be a
bilioma. A new CT scan with intravenous contrast
showed the cavity to be an abscess with two densities
inside. These were thought to be gall stones, spilled
during the cholecystectomy. The abscess was percu-
taneously drained by CT guidance, and in a second stage
evacuated by operation. During this procedure the two
densities proved to be gall stones (Figure 6). Retro-
spectively, they had also been visible on an earlier CT
scan (Figure 7).
Figure 6. Gallstones found in the abcess.
Figure 7. Careful examination of the CT scan performed at the
referring clinic already showed the gallstones.
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S. Janssen et al. / Open Journal of Internal Medicine 2 (2012) 19-26
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The infiltration in the lower right lung resulted in a
pleural empyema, which was surgically evacuated. Kle-
bsiella species were found in both sputum and the liver
abcess, but not in the empyema. Initially, cefuroxim was
administered intravenously, and later replaced by amo-
xicillin/clavulanic acid when the patient’s condition had
improved. Antibiotic treatment was given for eleven
weeks. The patient made a full recovery. The cholecys-
tectomy report confirmed there had been spill of gall-
bladder contents at the time, although spillage of stones
had not been reported.
2.4. Patient D
A 67-year old male was admitted to our hospital with
recurring fever. Medical history showed cystic kidneys,
with terminal renal insufficiency. Fifteen years earlier
patient had received his second, still functional, renal
transplant. Several episodes of urosepsis had occured in
the past years. Further medical history included an
appendectomy, atrial fibrillation and intermediate left
ventricular function. Current medication included pred-
nisolone and azathioprine.
Several episodes of fever and bacteriaemia with E Coli
had occured in the previous weeks. It was concluded that
the infection had originated in the still present cystic
kidneys. Laparoscopic nefrectomy of the left cystic kid-
ney was performed, followed by an episode of diverti-
culitis. CT scan at that time also showed a dilated biliary
tract, without an obstructing moment. It was decided to
delay nefrectomy of the right kidney for several months
in order to let patient recuperate.
Two weeks later, patient presented again with abdo-
minal dyscomfort, anorexia with 10 kg of weight loss
and a fever. Abdominal ultrasound showed no signs of an
abscess, nor any other focu s of inflammation. Blood cul-
tures remained negative. No antibiotics were adminis-
tered, but the dosage of prednisolone was temporarily
increased. Patient made a recovery, after which he was
released.
Three weeks later, patient again presented with fever,
anorexia, weight loss and abdominal dyscomfort, mostly
in the lower right quadrant. Physical examination showed
a low blood pressure (80/50 mmHg, pulse 70 beats per
minute under beta blockade). Laboratory tests showed
moderately elevated CRP (Table 1). Abdominal ultra-
sound showed no signs of an abscess or inflammation.
The left intrahepatical biliary duct system and the cho-
ledochal duct were dilated. An abdominal CT scan with
iv contrast was performed, without any new findings.
Because it was now believed the dilated biliary system
might indicate an obstructive moment such as a pan-
creatic mass, even though there were no laboratory
findings present indicative of cholestasis, an MRCP
(Figure 8) was performed. This showed multiple biliary
stones in the pancreatic region, without any sign of a
pancreatic mass. An ERCP was performed, which
confirmed choledocholithiasis. After papillotomy, extrac-
tion of multiple stones was performed. During a second
and third ERCP, performed because of persistent fever
after the first intervention , no residual stones were found.
Patient made a good recovery on amoxycillin/clavulanic
acid administered for three weeks in total.
Whilst waiting for an elective cholecystectomy, patient
developed an acute cholecystitis, for which cholecystec-
tomy was performed. Patient has had several recurrences
of choledocholithiasis afterwards.
2.5. Patient E
An 82-year old man presented at our Emergency unit
with acute epigastric pain, naus ea and vomiting. Medical
history included COPD and a pulmonary embolism two
years before presentation. Physical examination showed
a septic patient, with an almost silent bowel, epigastric
tenderness and muscular defence. Laboratory tests re-
vealed iron deficiency anaemia, severe leukocytosis,
slightly elevated CRP, as well as elevated serum and
urine amylase. Liver tests were all in the normal range
(Table 1). An abdominal ultrasound was performed,
which showed aerobilia, a dilated choledochal duct and
an enlarged pancreas. No biliary stones were visualized.
Abdominal CT scan showed a pancreatitis and aerobilia
(Figure 9). The gallbladder was located adjacent to the
duodenum (Figure 10). A cholecystoduodenal fistula
was suspected, and later confirmed by esophago-gas-
troscopy and ERCP. Several gallstones, as well as food,
were removed from the distal choledochal duct after
papillotomy was performed.
In the following days patient developed a full blown
sepsis due to infected necrotic pancreatitis, for which
drainage was achieved percutaneously under CT guid-
ance. Gentamycin, cefuroxim and metronidazole were
Figure 8. The MRCP shows biliary stones, as pointed out by
the arrow.
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S. Janssen et al. / Open Journal of Internal Medicine 2 (2012) 19-26 23
Figure 9. CT scan showing aerobilia.
Figure 10. Same CT scan, showing the close relation between
gallbladder and duodenum, respectively on the left and right
side of the circle, within an inflamed region.
administered. Cultures of the drain fluids showed mul-
tiple enteric bacteriae. Blood cultures showed Strepto-
coccus anginosus. Antibiotic treatment was then swit-
ched to tazobactam/piperacillin.
In the following weeks, the patient’s condition fluc-
tuated. Via endoscopic ultrasound an enteral drainage of
the abscess was achieved several times. In spite of this,
his condition eventually deteriorated, and the patient
died.
3. DISCUSSION
With a prevalence of 5% - 25%, and in some groups even
up to 75%, gallston e disease is a common illness [1,3-5].
A wide variety of risk factors is currently known (Table
2), amongst which are obesity, female gender, in-
creasing age, pregnancy and age. Despite their high
Table 2. Risk factors for biliary disease [1,3-5].
Increased age
Hormonal effects
Female gender
Pregnancy
Exogenous estrogens
Metabolic disorders
Obesity
Diabetes mellitus
Insulin resistance
Dyslipidemia
Dietary factors
High calorie diet
High cholesterol diet
High carbohydrate diet
Low-fiber diet
Loss of bile salts
Crohn’s disease
Rapid weight loss (>1.5 kg/wk)
Liver disease
Liver cirrhosis,
Hepatitis C virus infection
Gallbladder stasis
Medication: Octreotide, Fibrates, Ceftriaxon
Autonomic neuropathy
Spinal cord injury
Prolonged fasting
Long-term total parenteral nutrition
Low physical activity
Genetic factors
Family history
Ethnicity
Lithogenic gene mutation/polymorphism
Miscellaneous
Hyperparathyroidism
Hemolytic diseases
Down’s syndrome
Cystic Fibrosis
prevalence, only 10% - 30% of gallstones are sym-
ptomatic [1,5].
Cholesterol stones account for 80% - 90% of all stones
in Western countries [3]. The remainder are pigment
stones.
If symptomatic, the most common presentation is that
of biliary colics or epigastric discomfort [1,3]. More
complications of gallstone disease are displayed in Table
3. Gallstone disease usually presents itself by either its
complications, or by accidental discovery during diag-
nostic investigati ons such as an abdomi nal ultrasound [ 1].
In this article we describe several uncommon pre-
sentations of gallstone disease. Both patients A and E
presented with a cholecystoduodenal fistula due to stone
erosion through the gallbladder wall. In patient A this led
to a gallstone ileus. Beyond causing iron deficiency
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S. Janssen et al. / Open Journal of Internal Medicine 2 (2012) 19-26
24
Table 3. Complications of gallstone disease [3].
Common complications: Anual Risk (%)
biliary colic
acute cholecystitis
symptomatic choledocholithiasis
cholangitis
obstructed neck of the gallbladder
mucocele
extra-hepatic cholestasis
pancreatitis
1
0.3
0.2
0.04 - 1.5
Rare complications:
gallbladder carcinoma
liver abscess
gallstone ileus
gallbladder perforation/cholecysto-duodenal fistula
anaemia due to blood loss, gall stone disease also led to
an eventually fatal pancreatitis in patient E.
Patient B showed a liver abcess, most likely as a
complication of intermittent cholestasis and cholangitis
due to gallstones. Patient C displayed a hepatic abscess
due to gallstone spill during laparoscopic cholecystec-
tomy several years earlier. Patient D had intermittent
bacteraemias and atypical abdominal complaints under
immunosuppressive therapy because of a renal transplant.
Despite nephrectomy the bacteraemia relapsed. Even-
tually cholelithiasis was revealed, for which stone re-
moval and cholecystectomy were performed. Despite this,
patient suffered recurrent gall stone disease.
Below we will elaborate on these presentations.
Gallstone ileus results from recurrent attacks of cho-
lecystitis with erosion of a gallstone through a fistula
through the adjacent duodenal wall into small intestine
[4,6,7]. Normally the fistula will be formed between a
gangrenous gallbladder and the duodenum (cholecys-
toduodenal fistula). Occasionally the fistula forms bet-
ween the gallbladder and other parts of the gastroin-
testinal tract [6,7]. Patient E presented which aerobilia on
initial imaging, which (ap art from secondary to operation
or papillotomy) can only be cau sed by such a fistula [7].
Gallstone ileus accounts for 1% - 3% of mechanical
small bowel obstruction [6] and causes up to 25% of
cases of non-strangulated small bowel obstruction in
patients over 65 years of age [6,7]. Mean age at presen-
tation is 65 - 75 years and it is 3 times more common in
women than men [6,7]. Clinical sy mptoms may be ileus,
intermittent obstipation or diarrhoea, melaena, acute
upper gastro-intestinal bleeding and aerobilia [4,6,7].
More than one-thi r d of pat ie n t s present with no history of
biliary symptoms and 40% - 50% with a history of
symptomatic cholelithiasis [6].
Overall mortality rate varies between 12% - 33% [4,7].
This may be attributed to delayed diagnosis, elderly
patients, and coexisting concomitant medical disease. An
accurate preoperative diagnosis is made in 20% - 73% of
patients [6,7]. CT scanning appears most sensitive to
reveal gall stone ileus [6]. Although other treatment
modalities, such as ERCP, are e mployed, th e treatment of
choice is surgery [6,7]. Enterolithotomy alone has been
shown to have a lower mortality rate on both the short
and long term than enterolithotomy combined with fistula
repair [6]. Re-operation rate for secondary fistula repair
or recurrence of ileus were low (10% and 5% - 9%
respectively) [6].
Liver abscess is the most common type of visceral
abcess, accounting for 48% of visceral abscesses, and
13% of all intra-abdominal abscesses [8]. The incidence
of liver abscess has been estimated at 2.3 per 100.000
citizens [9]. It is more common among men (3.3 vs 1.3
per 100.000) [9]. Biliary tract obstruction, due to either
malignancy or gallstones, accounts for 40% - 60% of
pyogenic liver abscesses [8-10]. Most abscesses are
polymicrobial, mostly due to facultative or anaerobic
species from the intestinal tract [8,9].
Presentation of liver abscess usually includes fever
and abdominal pain, as well as nausea, vomiting, malaise,
weight loss and anorexia [9]. Depending on the size and
location of the abcess there may be hepatomegaly or
jaundice. Imaging should be performed by 4 phase CT
scan or ultrasound [8].
The best treatment for hepatic abscess is still uncertain
[8,10,11]. Current convention is that treatment should
include both drainage, either operatively or radiologically,
and long-term antibiotics. The main guide in this is the
clinical condition of the patient. Despite optimal treat-
ment, mortality of liver abscess remains high. Although
usually around 6%, it can be as high as 53% in elderly
patients [12,13].
In the case of patient B, it is remarkable that during
her first hospital stay, neither abdominal ultrasound, nor
CT scan, showed signs of gallstone disease, even though
sensitivity of these combined diagnostic tools exceeds
84% and specificity of ultrasound alone is 99% [2,5].
Laparoscopic cholecystectomy is the treatment of
choice for both acute cholecystitis and other presenta-
tions of symptomatic gallstone disease [4,14,15]. Reduced
cost, decreased hospital stay and increased patient
satisfaction are amongst the advantages of this technique
[15]. On the other hand laparoscopic cholecystectomy
has a higher rate of several complications, such as bile
duct injury. Some complications are hardly ever seen in
open cholecystectomy, such as visceral laceration or
gallstone spillage into the abdominal cavity [6]. The
incidence of gall bladder perforation during laparoscopic
surgery has been reported to be 20% - 40% [6,16,17].
Gallstone spill occurs in 7% - 16% of all laparosco pically
performed cholecystectomies [16,17].
Copyright © 2012 SciRes. OPEN ACCESS
S. Janssen et al. / Open Journal of Internal Medicine 2 (2012) 19-26 25
Not much is known about the n atural history of sp illed
gallstones. It is estimated that about 2% of all spilled
stones give rise to clinical problems [16]. This can occur
days to years after the initial surgery [6]. The usual
presentation is in the form of an abscess, either intra-
abdominally or in the operation tract [6]. Pseudocysts
have also been reported [18]. Predisposing factors for
developing complications after ston e spill are reported to
be older age, male sex, acute cholecystitis at the time of
operation, spillage of pigment stones, number of stones
(>15) or size of the stone (diameter > 1.5 cm), and
perihepatic localization of lost stones [6,17]. If possible,
spill of stones should of course be avoided, and re-
trieving spilled stones sho uld be considered [6,17].
The age of the patients presented in this article
exceeds 65 years in all cases. All of them showed serious
morbidity due to gallstone disease. In general, these
cases of relatively uncommon, but otherwise well-known
complications of gallstone disease, demonstrate that in
elderly patients with atypical abdominal complaints
gallstone disease should always be considered.
Most of the uncommon complications of gallstone
disease are more common in the elderly, as is gallstone
disease in general. Fifteen percent of men and 24% of
women have gallstones at the age of 70. At 90 years,
those numbers rise to 24% and 35% respectively [15].
Typical symptoms such as colics, local peritonitis and
fever are often absent in these patients. This also counts
for immunocompromised patients (HIV patients, use of
immunosuppressives or corticosteroids) and patients on
hemodialysis, as case D clearly demonstrates.
Although surgeons might be hesitant to operate on
elderly patients, we would advocate at least serious
consideration on a case-to-case basis. Not only is the
average patient getting older, but operating on the elderly
has been proven to be safe [14,15,19,20,21]. The main
reason for higher morbidity among the elderly is
comorbidity [14,19,20]. Careful selection and preopera-
tive optimalization can mini mize any risk s. So me authors
even state this judicous selection and preparation would
only be required in those over 80 years [14]. Furthermore,
Riall showed that in those elderly patients in whom
cholecystectomy is not performed after a first compli-
cation of gallstone disease, readmission rate is 38% in
the following two years, most of whom require chole-
cystectomy. In those operated the readmission rate is
only 4% [15] .
As mentioned, comorbidity is one of th e main reasons
not to operate on elderly patients. Although comorbidity
predicts 2-year mortality, lack of definitive therapy in
complicated gallstone disease is an independent predictor
of mortality, suggesting increased mortality rate in con-
servative treatment [15].
4. CONCLUSION
This case series describes several uncommon, but gene-
rally known complications of gallstone disease. It is
demonstrated that gallstone disease should always be
considered in case of elderly or immunocompromised
patients with atypical (abdominal) symptoms or radiolo-
gic findings. It also shows that in those patients who
present with symptomatic gallstone disease, cholecy-
stectom y should not b e d ismi ssed easily.
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