Triple Gallblader

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Clinical Journal of Gastroenterology (2023) 16:629–640

https://doi.org/10.1007/s12328-023-01829-3

CLINICAL REVIEW

Triple gallbladder: radiological review


Eliseo Picchi1 · Paola Leomanni1 · Vito Bruno Dell’Olio1 · Noemi Pucci1 · Francesca Di Giuliano2 ·
Valentina Ferrazzoli2 · Silvia Minosse1 · Maurizio Rho3 · Marcello Chiocchi1 · Francesco Garaci2 · Roberto Floris1

Received: 8 February 2023 / Accepted: 1 July 2023 / Published online: 11 August 2023
© The Author(s) 2023

Abstract
Triple gallbladder represents a rare congenital anatomical abnormality that can be a diagnostic challenge in reason to its rarity
and consequential difficulties with diagnosis and identification. A systematic review of all published literature between 1958
and 2022 was performed. We identified 20 previous studies that provided 20 cases of triple gallbladder; our case was also
included in the analysis, making a total of 21 patients. All patients underwent on diagnostic imaging examinations. After
1985, 9 patients underwent US examination which allowed prompt recognition of triple gallbladder in 2 patients only. CT
was performed in 3 patients and allowed the correct diagnosis in a case. In 4 patients, was performed MRCP which allowed
the correct diagnosis of triple gallbladder in all patients. Preoperative imaging allows the recognition of triple gallbladder
in 9 of 21 patients (43%); in 12 patients (57%) the diagnosis was intraoperative. On patients considered, 16/21 underwent
cholecystectomy. In 15 cases, the excised gallbladders were submitted for histopathological characterization with detection
of metaplasia of the mucosa in 3 patients, while papillary adenocarcinoma was found in one. Imaging plays a key role in the
identification of the anatomical variants of gallbladder, especially triple gallbladder, as modern imaging techniques allow
a detailed assessment of the course of the biliary tract for a correct preoperative diagnosis. It is also crucial to be aware of
the association between this condition and the metaplasia phenomena with the development of adenocarcinoma, as this may
influence the patient’s course of treatment.

Keywords Triple gallbladder · Multiple gallbladders · Triple cholecyst · Multiple cholecyst

Introduction matter of fact, most of the extrahepatic biliary system abnor-


malities come to medical attention only when symptoms,
Triple gallbladder, also called vesica fellea triplex, was first that are mainly related to cholelithiasis and cholecystitis,
reported by Huber in 1752 during an autopsy [1]; it is an occur.
uncommon congenital and often undetected abnormality The aim of this study was to evaluate the cross-sectional
of the biliary system and, up to now, only 20 cases have imaging findings in patients with triple gallbladder through
been reported in the literature. Therefore, the identification a literature review as it is associated with an increased rate
of some congenital gallbladder anomalies, due to their rar- of gallbladder metaplasia, dysplasia, and adenocarcinoma:
ity, might represent a significant clinical challenge [2]. As a for these reasons, the prompt identification of this anatomi-
cal variant is crucial.

* Eliseo Picchi
eliseo.picchi@ptvonline.it Case report
1
Diagnostic Imaging Unit, Department of Biomedicine
and Prevention, University of Rome Tor Vergata, Viale
A 56-year-old female patient reported acute abdominal pain
Oxford 81, 00133 Rome, Italy in the right hypochondrium and mild nausea after a large
2
Department of Biomedicine and Prevention, Neuroradiology
meal; the pain spontaneously regressed in about 24 h after
Unit, University of Rome Tor Vergata, Viale Oxford 81, onset. The patient had no clinical history of either biliary
00133 Rome, Italy colic or biliary tract disease, never had any kind of abdomi-
3
Department of Surgical Science, University of Rome “Tor nal surgery; no comorbidity were reported.
Vergata”, 00133 Rome, Italy

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630 Clinical Journal of Gastroenterology (2023) 16:629–640

Blood tests performed 7 days after the acute episode walls and multiple parietal thickenings with polypoid-like
revealed an increase in total (2.56 mg/dl) and indirect biliru- appearance. The largest wall thickening was at the fun-
bin (0.65 mg/dl); serum tumor markers (CEA and CA 19.9) dus (6 mm). The cystic duct arising from this gallblad-
were negative. der showed mild ectasia (5 mm) and confluence on the
The patient underwent ultrasound (US) examination, per- posterior wall of the middle third of the choledochal duct
formed with a high-definition multiband convex probe. The (Figs. 6, 7).
US showed three closely adjacent gallbladders in the chol- - the two posterior gallbladders had regular walls and
ecystic fossa. One of the gallbladders was hypo-distended, their respective cystic ducts converged into a single duct
with diffuse thickened and irregular hyperechogenic walls which joined the choledochal duct at the level of the pos-
with focal thickening at the fundus (Fig. 1). No dilation of tero-medial wall, just below the insertion of the cystic duct
intra- and extrahepatic biliary system was detected. How- of the anterior gallbladder (Figs. 2, 3, 4, 5, 6, 7).
ever, ultrasonographic examination did not allow a detailed According to the Harlaftis classification [3], the pre-
study of the anatomy of the cystic ducts and their relation- sented triple gallbladders had Y + H morphology (Fig. 4).
ship with the extrahepatic biliary tree, neither of all the three MRCP showed a focal filling defect in the intrapancre-
gallbladders: for these reasons, magnetic resonance cholan- atic choledochal duct immediately downstream the con-
giopancreatography (MRCP) was performed. fluence of the cystic ducts, with ectasia of the upstream
The MR examination was performed using a high-field segment (7 mm); the pre-papillary segment of the chole-
magnetic scanner (1.5 Tesla) with axial T2-weighted (w) dochal duct showed a maximum diameter of 5 mm with no
and T2w-SPAIR sequences, T1w-DUAL FFE sequence, dif- evidence of endoluminal signal abnormalities (Figs. 2, 7).
fusion weighted imaging and completed with MRCP study Patient underwent to surgical examination during which
obtained with radial, volumetric and gradient and spin echo she was informed about the clinical risks associated with
(GRaSE) sequences. this rare condition and even though laparoscopic cholecys-
The study confirmed the presence of three distinct gall- tectomy was proposed to remove the triple gallbladder, and
bladders located in the cystic fossa (Figs. 2, 3, 4, 5, 6, 7): the patient refused surgery.
- the most anterior gallbladder had a more hyperintense
endoluminal T2 signal and was characterized by irregular

Fig. 1  Ultrasound examination showed three different gallbladders (numbers 1, 2, 3 in panels A and C) in the cholecysticfossa. To note the dif-
fuse thickened, irregular and hyperechogenic wall of the most anterior gallbladder (panel B, number 1). PV portal vein

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Clinical Journal of Gastroenterology (2023) 16:629–640 631

Fig. 2  A Coronal balanced turbo-field-echo (BTFE) sequence showed higher T2 signal than two others. C Posterior view of 3D-MIP mag-
three different gallbladder one of which with irregular wall. B Ante- netic resonance cholangiopancreatography (MRCP) with gradient and
rior view of 3D-MIP magnetic resonance cholangiopancreatography spin echo (GRASE) technique; to note the confluence of the two pos-
(MRCP) with gradient and spin echo (GRASE) technique; to note the terior cystic ducts into a single duct (*)
anterior gallbladder with irregular wall, fundal thickness (arrow) and

Fig. 3  A Coronal balanced turbo-field-echo (BTFE) and B transverse T2-Spectral Adiabatic Inversion Recovery (SPAIR) sequence: to note the
gallbladder with nodular thickness at fundus (white arrow)

Methods The study was conducted according to local ethical stand-


ards and Helsinki Declaration’s principles.
We performed a literature search for case description of
triple gallbladder in humans published up to September
2022, using the keywords “triple cholecyst”, “triple gall-
bladder”, “multiple cholecysts” and “multiple gallblad- Results
der” without additional filters. Eligible articles were fully
reviewed for compliance with the research objectives and From the literature review, we identified 20 previous stud-
adequacy of data. Studies reporting a clear description of ies that provided 20 cases of triple gallbladder; our case of
the triple gallbladder found during radiological examina- triple gallbladder was also included in the analysis, making
tions or following cholecystectomy surgery were consid- a total of 21 patients with triple gallbladder. The clinical
ered eligible. In addition, we included the present case and anamnestic characteristics of the patients, radiological
report. Radiological features and clinical data were col- examinations, laboratory tests, surgeries performed, and his-
lected and analyzed by descriptive statistics. topathological findings are summarized in Table 1.

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632 Clinical Journal of Gastroenterology (2023) 16:629–640

manifested either as a single episode of biliary colic or as


repeated self-limited episodes occurring over a variable
period of weeks, months or even years.
Only in one patient the diagnosis of triple gallbladder
occurred without abdominal pain, and it was found inciden-
tally through radiological examinations performed following
an episode of hematemesis [5].
In addition to abdominal pain, 9/21 (43%) patients pre-
sented with nausea and/or vomiting, 4/21 (19%) patients
presented fever, and 3/21 (14%) had a clinical history of
cholelithiasis or choledocholithiasis.
In 13 patients, blood chemistry tests were performed after
the onset of symptoms; in particular, we evaluated indices of
liver function (aspartate aminotransferase-AST, alanine ami-
notransferase-ALT, total bilirubin), cholestasis (Gamma-glu-
tamyl Transferase-GGT, Alkaline Phosphatase-ALP, direct
bilirubin) and leukocytosis as the main inflammatory index.
Among these 13 patients, 4 had normal blood tests; in the
Fig. 4  Illustration on coronal plane of our case showing the Y + H tri- remaining 9 patients, cholestasis and leukocytosis indices
ple gallbladder morphology following the Harlaftis classification and were abnormal. 6 patients (46%) had at least one increased
the focal fundus wall thickness cholestasis index value and 4 patients (31%) had leukocy-
tosis. An increase in liver function indices was detected in
First case of triple gallbladder was reported by Boni in only in 3 patients (23%).
1958 [4]. The triple gallbladder is more common in women All patients underwent further diagnostic investigation
(12 women and 9 men), with a female/male ratio of 1.33; the by imaging examinations. Specifically, all the 11 patients
mean age at diagnosis was 34 years, specifically 36 years in reported between 1958 and 1985 underwent cholangio-
women and 32 years in men. graphy: this exam allowed the recognition of the triple gall-
The clinical manifestations of triple gallbladder are bladder in 5 cases while in 3 cases revealed two gallbladders
related to non-specific gastrointestinal symptoms: most and in the last 3 cases it was not diagnostic. However, a
patients (20/21 patients—95%) had at least one episode correct depiction of the extrahepatic biliary anatomy was
of abdominal pain before diagnosis. The abdominal pain achieved in 3 patients only.

Fig. 5  3D volume rendering reconstruction showing three different supero-posterior; IRP infero-right-posterior, RAS right-antero-supe-
gallbladders one of which with irregular wall. RIA right-infero-ante- rior, SLA supero-left-anterior, LPI left-postero-inferior
rior; SRP supero-right-posterior, ILA infero-left-anterior, LSP left-

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Clinical Journal of Gastroenterology (2023) 16:629–640 633

Fig. 6  A Transverse T2 show-


ing three distinct gallblad-
ders (numbers 1, 2 and 3) [123].
B Infero-lateral view of 3D-MIP
magnetic resonance cholan-
giopancreatography (MRCP)
with gradient and spin echo
(GRASE) technique; to note the
fundus of the three distinct gall-
bladders [123], the anterior with
fundal thickness (*) and higher
T2 signal than two others

In the cases published after 1985, 9 patients underwent patients (43%) only; in the remaining 12 patients (57%), the
US as the first-level imaging examination: US allowed diagnosis was intraoperative.
prompt recognition of triple gallbladder in 2 patients only, All reported cases of triple gallbladder were classified
while in 4 patients, it was wrongly identified a duplicate according to the anatomy of the cystic ducts [3], specifically
gallbladder. Moreover, US rarely allows correct biliary tree the most frequently encountered anatomical variant was type
anatomy depiction. I (11/20 patients, 55%) followed by type II (6/20 patients,
CT was performed only in 3 patients and allowed the cor- 30%) and type III (3/20 patient 15%).
rect diagnosis of triple gallbladder in a case. Only for a patient, the anatomy of cystic ducts was not
In 4 patients, the study of the biliary tract was performed defined and for this reason, it has not been reported [6].
by MRCP which allowed the correct diagnosis of triple Of the total 21 patients considered, 16 underwent to chol-
gallbladder in all patients, even though in a single patient, ecystectomy. In 15 cases, the surgical samples of the excised
it gave incomplete information about the anatomy of the gallbladder were submitted for histopathological characteri-
biliary tree. zation and the most common histologic finding was chronic
ERCP was performed in only in 2 patients, and in both cholecystitis (11/15 patients, 73%). In 2 patients, the walls
cases, it was non-diagnostic. of the excised gallbladder had necrotic and hemorrhagic
Considering the available data, preoperative imag- features. Only a patient had no histological changes of gall-
ing allows the recognition of triple gallbladder in 9 of 21 bladder [7].

Fig. 7  Anterior view of 3D-MIP magnetic resonance cholangiopan- thickness (arrow) and higher T2 signal than two others and the con-
creatography (MRCP) with gradient and spin echo (GRASE) tech- fluence of the two posterior cystic ducts into a single duct (*)
nique; to note the anterior gallbladder with irregular wall, fundal

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Table 1  The table, sorted by data, shows a comprehensive review of the demographical, symptoms, blood test values, radiological and histopathological findings of patients with triple gallblad-
634

der

Authors Age/gender Symptoms Blood tests Radiological findings Type Surgery Histopathological findings

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Our report 56 F -Abdominal pain ↑ Total bilirubin (2.56 mg/ US revealed: three gall- II NP NP
dL) bilirubin (0.56 mg/ bladders in the cholecys-
dL) tic fossa
MRCP revealed: confirmed
the presence of three
gallbladders and evalu-
ate the anatomy of the
biliary tract
Chen X, Yi B [12] 5F -Abdominal pain ↑ ALT (465 U/L) CT and MRCP revealed: I Laparoscopic cholecys- -Chronic cholecystitis
a) Triple gallbladder tectomy -Wall edema
b) Three cystic ducts -Gallbladder adhesion
c) A shared common bile
duct
d) Choledocholithiasis
e) Dilated pancreatic duct
Ott L et al 2F -Abdominal pain ↑ ALT (359 U/L) US revealed: I Laparoscopic cholecys- -Chronic cholecystitis
[8] -Emesis ↑ AST (146 U/L) a) Intrahepatic and extrahe- tectomy -Gastric metaplasia with
↑ ALP (549 U/L) patic biliary dilation oxyntic cells
↑ GGT (515 U/L) b) Tubular cystic structure
anterior to the gallblad-
der that communicated
with the common bile
duct
MRCP revealed:
a) Mild dilation of the cen-
tral intrahepatic biliary
ducts
b) Two tubular cystic
structures superior to the
gallbladder communicat-
ing with the common
bile duct
Copeland-Halperin LR 30 M -Abdominal pain ↑ Total bilirubin (12.2 mg/ US revealed: I Cholecystectomy Intraop- -Gallbladder hydrops
et al. [26] -Icterus dL) a) Cholelithiasis erative diagnosis of triple -Necrotic and hemorrhagic
-Fever ↑ Direct bilirubin (7.9 mg/ b) Gallbladder sludge gallbladder walls
-History of cholelithiasis dL) b) Wall thickening
and choledocholithiasis ↑ ALP (218 U/L) CT revealed:
↑ ALT (105 U/L) a) Mass in the gallbladder
↑ AST (38 U/L) fossa
Khadim MT et al. [1 30F -Abdominal pain Leukocytosis US revealed: II Open cholecystectomy -Fibrosis
-Nausea ↑ ALP a) Duplicated gallbladder Intraoperative diagnosis -Mononuclear cell infiltrate
b) Thickened wall of triple gallbladder -Multiple gallstones
c) Multiple gallstones
Clinical Journal of Gastroenterology (2023) 16:629–640
Table 1  (continued)
Authors Age/gender Symptoms Blood tests Radiological findings Type Surgery Histopathological findings

Alicioglu B [16] 54 F -Abdominal pain Leukocytosis US and CT revealed: I Cholecystectomy - Ulcerated active chronic
-Nausea ↑ ALT (167 U/L) a) Duplicated gallbladder, cholecystitis
-Dyspepsia with thickened wall and
considerable sludge in
one gallbladder
b) Tortuous cystic in the
last gallbladder
ERCP: two cystic ducts,
normal common hepatic
duct
Barnes S el al [7] 15 F -Epigastric pain Within the limits US revealed: 3 fluid-filled III Laparoscopic cholecys- -Non-inflamed triple GB
-Emesis structures in the GB tectomy
fossa. GB triplication Each of the GBs had its
was suggested own small cystic duct,
Clinical Journal of Gastroenterology (2023) 16:629–640

MRCP revealed: 3 separate and all converged into a


GB. Two of the cystic larger cystic duct, which
ducts could be visualized entered a single CBD
becoming a common
cystic duct. This common
cystic duct was shown to
enter a normal-looking
CBD
Mottin CC et al. [27] 36 F -Abdominal pain Within the limits US revealed: gallbladder I Cholecystectomy: three NP
stones independent gallbladders
were identified, each
one communicating with
the common bile duct
through its own cystic
duct
Schroeder C [28] 38 M -Biliary colic -Leukocytosis (14,000 US revealed: two gallblad- I Laparoscopic cholecystec- -Chronic inflammatory
-Fever ­mm3) ders with stones tomy: the diagnosis was disease;
intraoperative -Lithiasis
Nanthakumaran S et al. [6] 50 F -Biliary colic NA US and ERCP revealed: I Laparoscopic cholecys- -Lithiasis
-Clinical history of chole- a) lithiasis tectomy: intraoperative -Chronic cholecystitis
docholithiasis b) no abnormality of diagnosis
biliary tract
Gruk M et al. [29] 29 M -Abdominal pain No abnormalities Cholecystography: non- I Cholecystectomy -Lithiasis
diagnostic examination

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635
Table 1  (continued)
636

Authors Age/gender Symptoms Blood tests Radiological findings Type Surgery Histopathological findings

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Foster DR [15] 46 M -Abdominal pain NA Cholecystography and CT II NP NP
revealed:
a) three separate gallblad-
ders
b) there were calculi
present in one of the
gallbladders
c) single cystic duct drain-
ing into the common duct
d) the cystic ducts of the
other two gall bladders
fused prior to insertion
into the common bile
duct
Kurzweg FT el al [5] 34 M -Hematemesis NA Cholecystography III NP NP
revealed: triple gallblad-
der with a common
cystic duct
Roeder WJ et al. [11] 36 M -Abdominal pain -Leukocytosis (11,500/ Oral cholecystogra- I Open cholecystectomy: Examination of the “first”
-Icterus mm3) phy revealed: poorly intraoperative diagnosis gallbladder showed the
-Fever functioning gallbladder The “third” gallbladder mucosal surface was
-History of fever containing a solitary was not removed hemorrhagic
round calcific density -Cholelithiasis and subacute
measuring 3 cm and chronic cholecystitis
-Papillary adenocarcinoma
Aroca Ruiz-Funes J.M. 43 F -Chronic abdominal pain ↑ ALP Cholecystography III Cholecystectomy -Acute cholecystitis
et al. [20] -Nausea ↑ GGT​ revealed: triplication of
-Fever ↑ Direct bilirubin the gallbladder
Ross RJ & Sachs MD [30] 51 M -Abdominal pain NA Cholecystography II NP NP
revealed: triplication
of the gallbladder; the
largest and independ-
ent gallbladder seemed
to empty directly into a
large cystic duct. Two
smaller gallbladders
near the infundibulum
appeared to join the
common duct in a cluster
close together
Clinical Journal of Gastroenterology (2023) 16:629–640
Table 1  (continued)
Authors Age/gender Symptoms Blood tests Radiological findings Type Surgery Histopathological findings

Kelly A [9] 12 M -Biliary colic NA Cholecystography II Cholecystectomy: the In the two gallbladders,
-Emesis revealed: two gallblad- diagnosis was intraop- which have a common
ders each with a cystic erative cystic duct, there was
duct. These ducts unite chronic inflammation
just prior to entering the -Lithiasis
common duct -Duodenal metaplasia
Hause WA [31] 69 F -Abdominal pain NA Cholecystography I Cholecystectomy: the Dissection revealed there
-Nausea revealed: numerous diagnosis was intraop- were three separate
-Emesis calculi erative chambers and a separate
cystic duct
-The mucosa was coarsened
and irregular and the wall
thick and tough
-Lithiasis
Clinical Journal of Gastroenterology (2023) 16:629–640

-Chronic inflammation
Skielboe B [32] 54 F -Abdominal pain NA Cholecystography I Open cholecystectomy; the -Edema
-History of cholelithiasis revealed: duplicated diagnosis was intraop- -Lymphocytic cellular
gallbladder erative infiltration
Casey EW [10] 12 M -Abdominal pain NA Cholecystography II Cholecystectomy: intraop- -Lithiasis
-Chronic dyspepsia revealed: two gallblad- erative diagnosis -Duodenal metaplasia
ders, each with a separate
cystic duct, the ducts
apparently uniting just
before they entered the
common bile duct
Boni R [4] 32 F -Abdominal pain Within the limits Cholecystography NA NP NP
revealed: three gallblad-
ders; lithiasis

ALP alkaline phosphatase, ALT alanine transaminase, AST aspartate transaminase, CT computed tomography, ERCP endoscopic retrograde cholangiopancreatography, F female, GGT​ Gamma-
glutamyl Transferase M male, MRCP magnetic resonance cholangiopancreatography, NA not available, NP not performed; US ultrasound

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638 Clinical Journal of Gastroenterology (2023) 16:629–640

Metaplasia of the gallbladder mucosa was found in 3 Based on the number and morphology of the cystic ducts,
patients [8–10], of which 2 had duodenal mucosa [9, 10] three different types of triple gallbladder have been identi-
and one had gastric mucosa and ossicular cells [8]. fied by Alicioglu [16]:
Dysplastic mucosa with papillary adenocarcinoma was
found in one patient [11]. The presence of endoluminal lithi- a) the first type is characterized by the presence of three
asis was found in 9 patients (43%). gallbladders each with its own independent cystic duct
hat drains separately into the bile duct;
b) the second type is characterized by the presence of two
Discussion gallbladders with a common cystic duct draining into the
common bile duct and a third gallbladder with independ-
During the 4th week of gestation, hepatobiliary and pancre- ent cystic duct;
atic organogenesis begins from the endodermal bud origi- c) the third type is characterized by the presence of three
nating from the anterior intestine [12]; specifically, its upper gallbladders sharing a single cystic duct.
segment gives rise to the liver and intrahepatic bile ducts
and its lower segment to the gallbladder, cystic duct, and From our analysis, the most common type of triple gall-
common bile duct [13]. Between the 4th and 5th week of bladder was type I (55%) followed by type II (30%) and
gestation, the gallbladder primordium begins to form, which finally type III, the most rarely encountered variant (15%).
will give rise to the gallbladder and cystic duct: interruption Multiple gallbladder is a very uncommon condition
or alteration of the development process at this stage may and, usually, its clinical presentation is non-specific [2,
result in malformations of the gallbladder and extrahepatic 16]. Colic abdominal pain is the most commonly reported
bile ducts [12]. In 1926, Boyden hypothesized that multiple symptom and it is related to cholecystitis and cholelithiasis
gallbladders represented an outgrowth of a secondary vesicle [13]. Accessory gallbladders may be found incidentally in
from a portion of the bile duct system after the formation of asymptomatic patients during a routine radiological exami-
the definitive gallbladder [14]. In the human embryo, this nation [16].
small cellular opening, called the rudimentary bile duct, usu- Preoperative diagnosis of the triple gallbladder condition
ally regresses, and disappears [15]; however, the failure of is crucial, as it allows proper planning of surgery and conse-
the rudimentary bile ducts to regress can lead to the forma- quently also a reduction of possible intra- and post-operative
tion of extroversions along the biliary system, and when it complications.
occurs along the extrahepatic pathways, it can result in the Until 1979, preoperative imaging of the biliary tract was
development of accessory gallbladders [8]. performed by oral or intravenous cholecystography, fat meal
Depending on the location of these accessory sacs, dif- studies and conventional tomography. Currently, preopera-
ferent anatomical relationships between gallbladders, cystic tive imaging uses high-resolution techniques such as US,
ducts and common hepatic duct will take place: if the buds spiral or multilayer CT, MRCP, and ERCP.
that give rise to the accessory gallbladders originate from the The most frequently performed first-level examination in
common hepatic duct, the gallbladders will have independ- the case of patients with colic symptoms related to gallblad-
ent and separate cystic ducts; on the other hand, if the sacs der is US, as it is highly available and low cost [16]. How-
originate from a cystic duct there will be gallbladders with ever, US is an operator-dependent imaging modality and has
a common cystic duct draining into the common hepatic a low sensitivity (65%), so this anatomical variation could
duct [1]. be missed or misdiagnosed [2, 13].
In 1977, Harlaftis et al. proposed an anatomical classifi- Both US and CT are able to assess the anatomical features
cation of multiple gallbladder based on the embryogenetic of the gallbladder such as number, wall thickness and pres-
mechanism [3]: ence of endoluminal lithiasis, although they may not depict
the exact anatomy of the biliary tree [16].
– -type I consists of a double gallbladder with more or less Therefore, further investigations are recommended.
separate cystic ducts jointly discharging into the common MRCP allows a non-invasive study of the anatomy of the
hepatic duct; biliary system and its abnormalities, accurately describing
– -type II consists of a double gallbladder with two inde- the number, the position of cystic ducts and their relation-
pendent cystic ducts discharging separately into the ship to the common bile duct [13, 17].
biliary tree; in this case, the accessory gallbladder may ERCP allows detailed assessment of the anatomy of the
reach the common hepatic duct (ductular type) or an biliary system, but it is an invasive method that requires
intrahepatic bile duct (trabecular type); general anesthesia, exposes patients to radiation and it could
– -type III includes gallbladder with anatomical anomalies be associated with the development of serious complica-
that do not fit the previous two groups. tions [2].

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Clinical Journal of Gastroenterology (2023) 16:629–640 639

To now, MRCP has proven to be much more sensitive stones is 13.5%, and of these 3.5% have carcinoma in situ
than ERCP, with a sensitivity of about 97% in identifying [23].
multiple gallbladder condition [13]. This condition, depending on both genetic and acquired
Total cholecystectomy with removal of all gallbladders risk factors [23], can be driven by a condition of gallbladder
is the appropriate treatment for symptomatic gallblad- hypomotility and bile stasis [24].
der triplication. The literature suggests that benefits from Intestinal metaplasia represents a frequent finding in
removing of all gallbladders are crucial once surgery is almost the 90% of gallbladders with chronic inflammation;
decided. Several studies have been reported describing the this condition has a close relationship with gallstones and
need for a second operation because symptoms were not wall inflammation which brings to a local chronic response
relieved after the first cholecystectomy [18]. that drives to evolution in focal dysplasia and evolution in
Prophylactic surgery is not recommended for inciden- gallbladder adenocarcinoma in 3.5% of cases [25].
tally discovered asymptomatic triplication gallbladder, but
radiological follow-up is fundamental to early diagnose a
possible development of biliary dysplasia or cancer. Conclusion
Laparoscopic cholecystectomy is performed in most
cases, but open approach is preferred in case of the high Surgeons and radiologists should be aware of the existence
insertion of the cystic ducts, previous abdominal open sur- of the triple gallbladder condition and the most appropriate
gery, and poor experience in laparoscopic surgery [19]. imaging methods for proper evaluation of this condition.
Preoperative imaging study of anatomical variants is Imaging plays a key role in the identification of the ana-
essential for a safe surgery. The surgeon should know, tomical variants of gallbladder, especially triple gallbladder,
preoperatively, the shape and location of gallbladders, as modern imaging techniques allow a detailed assessment
abnormalities of the cystic artery and cystic ducts, to avoid of the course of the biliary tract for a correct preoperative
important surgical complications, such as iatrogenic bile diagnosis. This allows the surgical procedure to be planned
duct injuries and hepatic vascular injuries. appropriately to reduce intraoperative risk and patient
In most cases, patients with symptomatic multiple gall- morbidity.
bladders underwent cholecystectomy. It is also crucial to be aware of the association between
Histopathological examination of the 15 patients who this condition and the phenomena of gastric and duodenal
underwent surgery showed chronic cholecystitis in 9/15 metaplasia and with the development of adenocarcinoma, as
patients (60%) and a cholelithiasis in 12/15 patients (80%). this may influence the patient’s course of treatment.
Only one case showed a condition of acute cholecystitis at
the histopathological evaluation [20].
Funding Open access funding provided by Università degli Studi di
Moreover, the abnormal anatomy of the extrahepatic Roma Tor Vergata within the CRUI-CARE Agreement.
biliary outflow tracts can lead to biliary stasis and thus a
predisposition to the formation of endoluminal lithiasis Open Access This article is licensed under a Creative Commons Attri-
giving rise to a condition of chronic cholecystitis, which is bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
a major risk factors for the occurrence of epithelial meta- as you give appropriate credit to the original author(s) and the source,
plasia and the development of gallbladder carcinoma [21, provide a link to the Creative Commons licence, and indicate if changes
22]. were made. The images or other third party material in this article are
In fact, consistent with the literature reports [13], the included in the article's Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
triple gallbladder condition was associated with duodenal the article's Creative Commons licence and your intended use is not
metaplasia in 2/15 cases (13%) [9, 10], with gastric meta- permitted by statutory regulation or exceeds the permitted use, you will
plasia in 1/15 case (6.5%) [8] and with papillary adenocar- need to obtain permission directly from the copyright holder. To view a
cinoma in 1/15 case (6.5%) [11]. copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/.
In our analysis, intestinal metaplasia was found in 2
cases [9, 10], both associated with a chronic cholecystitis
condition, and in one case [9], associated with endoluminal References
lithiasis.
1. Khadim MT, Ijaz A, Hassan U, et al. Triple gallbladder: a rare
It is, therefore, very important to diagnose chronic chol- entity. Amer J Gastroenterol. 2011;106:1861–2.
ecystitis in those anomalies as early diagnosis allows early 2. Vezakis A, Pantiora E, Giannoulopoulos D, et al. A duplicated
intervention and prevents tumor development. gallbladder in a patient presenting with acute cholangitis a case
This represents a very important risk factor because study and a literature review. Ann Hepatol. 2019;1:240.
3. Harlaftis N, Gray SW, Skandalakis JE. Multiple gallbladders. Surg
although it is a very common pathological condition, the Gynecol Obstet. 1977;145:928.
incidence of finding dysplasia in gallbladders removed for

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640 Clinical Journal of Gastroenterology (2023) 16:629–640

4. Boni R. Triple gallbladder and calcareous bile. Radiologia Med- 21. Sharma A, Sharma KL, Gupta A, et al. Gallbladder cancer epi-
ica. 1958;44:833–44. demiology, pathogenesis and molecular genetics: Recent update.
5. Kurzweg FT, Cole PA. Triplication of the gallbladder: review of World J Gastroenterol. 2017;23:2978.
literature and report of a case. Amer Surg. 1979;45:410. 22. Bojan A, Foia L, Vladeanu M, et al. Understanding the mecha-
6. Nanthakumaran S, King PM, Sinclair TS. Laparoscopic excision nisms of gallbladder lesions: A systematic review. Exp Ther Med.
of a triple gallbladder. Surg endoscopy. 2003;17:1323. 2022;24:1–4.
7. Barnes S, Nagar H, Levine C, et al. Triple gallbladder: Preopera- 23. Lazcano-Ponce EC, Miquel JF, Munoz N, et al. Epidemiology and
tive sonographic diagnosis. J Ultras Med. 2004;23:1299. Molecular Pathology of Gallbladder Cancer. CA Cancer J Clin.
8. Ott L, O’Neill J, Cameron D, et al. Triple gallbladder with hetero- 2001;51:349.
topic gastric mucosa: a case report. BMC Pediatr. 2022. https://​ 24. Apstein MD, Carey MC. Pathogenesis of cholesterol gallstones:
doi.​org/​10.​1186/​s12887-​022-​03122-7. A parsimonious hypothesis. Europ J Clin Invest. 1996;26:343.
9. Kelly A. Triple gall bladder: a case of double gall bladder with 25. Duarte I, Llanos O, Domke H, et al. Metaplasia and precursor
associated anomalous gall bladder. Med J Aust. 1959;1:124. lesions of gallbladder carcinoma Frequency, distribution, and
10. Casey EW. Triple gall bladder. Australas Radiol. 1958;2:98. probability of detection in routine histologic samples. Cancer.
11. Roeder WJ, Mersheimer WL, Kazarian KK. Triplication of the 1993;72:1878.
gallbladder with cholecystitis, cholelithiasis, and papillary adeno- 26. Copeland-Halperin LR, Kapoor K, Piper JB. Complicated triple
carcinoma. Amer J Surg. 1971;121:746. gallbladder: Clinical presentation and surgical approach. BMJ
12. Chen X, Yi B. Triple gallbladder. J Pediatr. 2022;247:173–4. Case Rep. 2016. https://​doi.​org/​10.​1136/​bcr-​2016-​215901.
13. Darnis B, Mohkam K, Cauchy F, et al. A systematic review of the 27. Mottin CC, Toneto MG, Padoin AV. Laparoscopic triple cholecys-
anatomical findings of multiple gallbladders. HPB. 2018;20:985. tectomy. Surg Laparosc Endosc Percutan Tech. 2004;14:163.
14. Boyden E. The accessory gall-bladder– an embryological and 28. Schroeder C, Draper KR. Laparoscopic cholecystectomy for triple
comparative study of aberrant biliary vesicles occurring in man gallbladder. Surg Endosc. 2003;17:1322.
and the domestic mammals. Amer J Anat. 1926;38:177–231. 29. Gruk M, Wyciślak J, Muc J, et al. Triple gallbladder as a
15. Foster DR. Triple gall bladder. Brit. J Radiol. 1981;54:817. rare development anomaly of the biliary tract. Wiad Lek.
16. Alicioglu B. An incidental case of triple gallbladder. World J Gas- 1985;38:140–2.
troenterol. 2007;13:13. 30. Ross RJ, Sachs MD. Triplication of the gallbladder. Am J Roent-
17. Morimoto M, Mori N. A Calcified Gallbladder. New Engl J Med. genol Radium Ther Nucl Med. 1968;104:656.
2020;383:86. 31. Hause WA. Triplication of gallbladder. AMA Arch Surg.
18. Gigot JF, Van Beers B, Goncette L, et al. Laparoscopic treatment 1959;104:656.
of gallbladder duplication: A plea for removal of both gallblad- 32. Skielboe B. Anomalies of the gallbladder: vesica fellea triplex;
ders. Surg Endosc. 1997;11:479. report of a case. Am J Clin Pathol. 1958;1:4.
19. Causey MW, Miller S, Fernelius CA, et al. Gallbladder dupli-
cation: evaluation, treatment, and classification. J Pediatr Surg. Publisher's Note Springer Nature remains neutral with regard to
2010;44:443. jurisdictional claims in published maps and institutional affiliations.
20. Aroca Ruiz-Funes JM, Martinez LA. Vesícula biliar triple. Rev
Esp Enferm Apar Dig. 1969;54:968.

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