Diagnosis of gallbladder perforation by ultrasound Mika Shapira-Rootman, Ahmad Mahamid, Nadir Reindorp, Alicia Nachtigal, Abdel-Rauf Zeina PII: DOI: Reference:
S0899-7071(15)00120-5 doi: 10.1016/j.clinimag.2015.05.008 JCT 7835
To appear in:
Journal of Clinical Imaging
Received date: Revised date: Accepted date:
7 February 2015 1 May 2015 13 May 2015
Please cite this article as: Shapira-Rootman Mika, Mahamid Ahmad, Reindorp Nadir, Nachtigal Alicia, Zeina Abdel-Rauf, Diagnosis of gallbladder perforation by ultrasound, Journal of Clinical Imaging (2015), doi: 10.1016/j.clinimag.2015.05.008
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Diagnosis of gallbladder perforation by ultrasound
AC
CE
PT
ED
MA NU
SC
RI P
T
Mika Shapira-Rootman MD PhD1, Ahmad Mahamid MD2, Nadir Reindorp MD1, Alicia Nachtigal MD1, Abdel-Rauf Zeina MD1 1Department of Radiology, 2Division of Surgery, Hillel Yaffe Medical Center, Hadera, Israel. Affiliated with the Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel Short Title: Ultrasound diagnosis of gallbladder perforation Corresponding author: Abdel-Rauf Zeina, MD Department of Radiology , Hillel Yaffe Medical Center , P.O.B. 169, Hadera 38100, Israel Tel. + 972-4-6304621 Fax. +972-4-6304884 [email protected] Conflict of interest: The authors report no conflicts of interest
1
ACCEPTED MANUSCRIPT
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Abstract: Purpose: The aim of this study was to identify possible pitfalls in the sonographic evaluation of perforated gallbladders. Methods: This is a retrospective analysis of sonograms of 11 patients diagnosed by surgery or pathology with perforated gallbladder. Sonograms were evaluated for multiple sonographic features. Results: Only 3 patients (27%) were diagnosed correctly with gallbladder perforation by ultrasonography prior to surgery. Gangrenous cholecystitis was reported in 10 cases (90%). Visualization of a wall defect was demonstrated in only 5 cases (45%) and was associated with a focal echogenic soft-tissue mass. Conclusion: Missed perforations by ultrasound may partially result from technical inadequacies.
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Keywords: Gallbladder; perforation; cholecystitis; ultrasound; gangrenous cholecystitis.
2
ACCEPTED MANUSCRIPT
Introduction
T
Gallbladder (GB) perforation is a rare complication of cholecystitis, and is associated
RI P
with increased rates of morbidity and mortality [1, 2]. Since the condition can be life threatening, rapid diagnosis and treatment are required. Known risk factors include
SC
male gender, older age, gallstones and diseased GB, systemic disease (cardiovascular disease, diabetes mellitus), and corticosteroid administration [2, 3]. Observations
MA NU
made by Niemeier in the 1930s still provide the basis of the current classification [35]. Accordingly, type 1 represents an acute perforation with signs of peritonitis. Type 2 is defined as sub-acute perforation with sealing of the inflammatory process and abscess formation. Type 3 is a chronic process with fistulous communication between
ED
the GB and adjacent viscous. Type 2 is the most common, followed by Type 1[3-6].
PT
Ultrasound (US) is generally the initial imaging modality for diagnosing
CE
complications of cholecystitis, as well as other GB pathologies. The primary and most specific sonographic feature is the direct visualization of a wall defect, also known as
AC
the "sonographic-hole" sign [3, 7]. Another indication of wall rupture is the demonstration of gallstones outside the GB [3]; however, this is rarely seen, and a less reliable sign. The diagnosis is often very challenging, with a relatively small percentage of patients detected prior to surgery [5]. From a radiological perspective, this may partially result from the fact that the direct visualization of a GB wall defect is not always feasible [8,9]. In this study we retrospectively reviewed the sonograms of 11 patients with perforated GB. The main objectives were (1) to further characterize this condition, by assessing established and new sonographic features and (2) to reveal possible recurring mistakes, as well as clues that may promote the diagnosis. 3
ACCEPTED MANUSCRIPT Materials and methods Patients
T
A search of the surgical database at our institution was performed to identify all
RI P
patients who were diagnosed with perforated GB between January 2010 and August 2014. Medical records were retrospectively reviewed for clinical data, imaging
SC
studies, and surgical and pathological reports. Clinical data accessed included white blood cell (WBC) levels and neutrophil counts at presentation, and comorbidities
MA NU
including diabetes mellitus and cardiovascular disease. Institutional review board approval was obtained for the study. Imaging studies
ED
All sonograms were performed by using one of two scanners (ACUSON S2000, Siemens medical solutions; or ATL HDI 5000, Philips Healthcare). In 6 of 11 cases, a
PT
complementary computed tomography (CT) was performed. Intravenous contrast
CE
material was administered in five cases. CT was performed using 64-MDCT scanner (Brilliance-64, Philips Healthcare, Cleveland, Ohio, USA).
AC
For the purpose of the current study, sonographic reports were reviewed for documentation of positive sonographic Murphy's sign and final diagnoses given by radiologists. In all cases, the original study was performed by a sonologist followed by a radiologist with at least three years of experience. All sonographic reports and final diagnoses were approved by certified radiologists that practice daily on the US unit. An US expert radiologist retrospectively reviewed all sonograms for wall defects, GB short axis diameter, wall thickness and striations, presence of gallstones, presence of echogenic content within the bladder (debris or sludge), free fluid around the GB and in the abdomen, complicated fluid collections (suspected abscess), pleural effusions, signs of periportal tracking, and local inflammatory fat changes. A 4
ACCEPTED MANUSCRIPT qualitative analysis of all sonograms was also performed by an US expert. Each study was evaluated for its technical adequacy including proper selection of transducers and
T
frequency range, correct focal zone placement, appropriate gain, maximal imaging
RI P
depth, and overall image quality. In addition, adherence to the standard protocol used in our institution for GB pathologies was evaluated. This includes proper assessment
SC
of the entire GB and its surroundings with long-axis and transverse views.
MA NU
Surgical and pathological data
Surgical reports were reviewed for major observations, including type and location of perforation and additional pathologies of the GB. In addition, type of surgery (open versus laparoscopic) was recorded. Pathological reports were reviewed for final
ED
diagnosis and additional histologic features including fibrosis, erosions, hemorrhage,
PT
and inflammatory changes of the adjacent fat such as fat necrosis. Results
CE
Eleven patients were diagnosed with GB perforation during the study period. Mean age was 67 years, with male predominance (81%). Major comorbidities were
AC
cardiovascular disease (5 patients), hyperlipidemia (4 patients), diabetes mellitus (3 patients) and morbid obesity (2 patients). One patient had liver cirrhosis. The mean level of WBCs at presentation was 13.9 x 109/L; the percentage of neutrophils was increased (mean 85.7%). The mean time between the US study and surgery was 3 days (range of 0-8 days). Three patients (27%) were diagnosed correctly with GB perforation by US prior to surgery. In all three, the perforation was sub-acute (type 2) with sonographic demonstration of abscesses. The mean short axis diameter of the 11 patients in the cohort was 4.6 cm (SD 1) and the wall width 6 mm (SD 1.7). The classical "sonographic hole" sign, with direct visualization of a wall defect, was retrospectively appreciated in 5 cases (45%). Of these, 3 perforations involved the 5
ACCEPTED MANUSCRIPT fundus and 2 the bladder neck. Additional sonographic findings of perforated GB are summarized in table 1. A qualitative analysis of all sonograms revealed that in 5 cases
T
there was an inadequate demonstration of the fundus. In these cases, the fundal area
RI P
was only partially demonstrated with inadequate use of technical parameters as focal zone placement. In all cases where a wall defect was demonstrated, a focal area of
SC
increased fat echogenicity was noticed near the tear (Figure 1), probably representing a thickened and inflamed omentum.
MA NU
All surgeries were open (rather than laparoscopic). Surgeons reported gangrenous cholecystitis in 10 cases (90%) and empyema of the GB in 8 (72%). Three patients were diagnosed with acute perforation (type 1) with spillage of pus and bile into the
ED
abdominal cavity. Seven were diagnosed with sub-acute perforation. In one patient, a fistulous tract between the GB and duodenum (type 3 perforation) was observed.
PT
Histologic features associated with perforated GB included inflammatory fat changes
(18%).
AC
Discussion
CE
(63%), hemorrhage (36%), fat necrosis (27%), fibrosis (27%), and wall erosions
This retrospective study highlights the diagnostic challenge of GB perforation, specifically the high rate of false negatives in ultrasound studies. The most specific and reliable sign of perforation is a wall defect. Yet, a wall defect was demonstrated in only 5 patients (45%). The characteristics of this cohort of patients with perforated GB were similar to those reported by others [2, 3]: older age (mean 67 years), mostly men (81%), and with additional comorbidities, chiefly cardiovascular. Patients presented with elevated WBC levels (mean 13.9 x 109/L) and with a high percentage of neutrophils (mean 85.7%), a known feature of complicated cholecystitis [1, 10]. 6
ACCEPTED MANUSCRIPT Since almost all perforated GBs are gangrenous (90% in this study), sonographic signs of gangrenous cholecystitis, such as severe inflammation, coexist. As described
T
here, perforated GBs were found to be distended (mean 4.6 cm) and with thickened
RI P
walls (mean 6 mm), which are findings that have been described for gangrenous cholecystitis [10, 11]. In addition, most GBs contained gallstones and all of them
SC
contained debris or sludge. In 72%, the wall had a striated appearance. The association between this finding and gangrenous cholecystitis is not clear. While once
MA NU
considered a sign suggestive of gangrenous cholecystitis [12], in a recent publication by Teefey et al [10], there was no association. Interestingly, in most cases of the current cohort, additional sonographic findings in the surrounding area (rather than in
ED
the GB itself) were demonstrated. This included free fluid around the GB and in the abdominal cavity. In two patients (18% of cases), pleural effusions were demonstrated
PT
as well. Additional sonographic signs that may clinch the diagnosis are those related to the type of perforation. For example, demonstration of cholecystitis together with
CE
an adjacent abscess, suggests a type 2 perforation.
AC
In the 5 cases presented here that had an obvious wall defect (the "sonographic hole" sign), a focal area of increased fat echogenicity was observed near the tear (Figure 1). This is a meaningful finding that may facilitate diagnosis and help in localizing the perforation. Inflammatory fat changes around the GB were mentioned in the pathological reports of 7 patients (63%) and fat necrosis in three of them. The literature concerning fat necrosis associated with GB pathologies is sparse, with reports of this finding mainly in the context of gallstone pancreatitis [13]. These changes may reflect extensive local inflammation with involvement of neighboring organs.
7
ACCEPTED MANUSCRIPT Evaluation of inflammatory fat changes may be most accurate and informative in the fundus, since this is the only part of the GB that is covered entirely by peritoneum,
T
contrasting with the body and neck of the GB, which are covered by peritoneum only
RI P
at their inferior border. However, most sonograms of the GB focus on the body neck area.
SC
We believe that some cases of GB perforation are "missed" due to technical
MA NU
inadequacies such as suboptimal demonstration of the fundus. As the fundus is located in a relatively anterior and caudal location, it does not always appear in the same plane as the other parts of the GB. Thus, a part of the GB's body may be falsely perceived as a "blind end" or as the fundus. In addition, due to its marginal location,
ED
the fundus is frequently seen on the edge of the image and out of focus. Nonetheless, the demonstration of the fundus is of paramount importance. As shown here, and by
PT
others [3, 4, 14, 15], most GB perforations involve this area. The propensity of the
CE
fundus to perforate is related mainly to a relatively poor blood supply [3, 15]. We suggest that in cases of suspected perforation (based on clinical grounds, risk factors,
AC
leukocytosis, and a sonogram of severe/gangrenous cholecystitis), a thorough inspection of the fundal area be performed. Assessment of this area with linear transducer may be of benefit to better look at this area. This study suffers from several drawbacks. First, this is a retrospective analysis without a control group. In order to evaluate the possible contribution of the ultrasonographic features discussed here, a prospective study is warranted. In addition, all images were reviewed only by a single sonographer. In conclusion, the sonographic detection of GB perforation is tricky, with direct visualization of a wall discontinuity possible in only a minority of cases. Focal areas
8
ACCEPTED MANUSCRIPT of increased fat echogenicity may help in detection and localization of the wall defect. Better delineation of the fundal area may improve the detection of GB perforation,
T
since most perforations occur in the fundus, and since inflammatory fat changes can
AC
CE
PT
ED
MA NU
SC
RI P
be most accurately assessed in this area.
9
ACCEPTED MANUSCRIPT References 1. Ausania F, Guzman Suarez S, Alvarez Garcia H, Senra Del Rio P, Casal
RI P
prediction. Surg Endosc. 2014 [Epub ahead of print].
T
Nuñez E Gallbladder perforation: morbidity, mortality and preoperative risk
2. Stefanidis D, Sirinek KR, Bingener J. Gallbladder perforation: risk factors and
SC
outcome. J Surg Res 2006;131:204-8.
3. Seyal AR, Parekh K, Gonzalez-Guindalini FD, Nikolaidis P, Miller
Imaging 2014;39:853-74.
MA NU
FH, Yaghmai V . Cross-sectional imaging of perforated gallbladder. Abdom
4. Swayne LC, Filippone A. Gallbladder perforation: correlation of
ED
cholescintigraphic and sonographic findings with the Niemeier classification. J Nucl Med 1990;31:1915-20.
PT
5. Date RS, Thrumurthy SG, Whiteside S, Umer MA, Pursnani KG, Ward JB, Mughal MM. Gallbladder perforation: case series and systematic review.
CE
Int J Surg 2012;10:63-8.
AC
6. Fletcher AG, Ravdin IS. Perforation of the gallbladder. Am J Surg 1951;81:178-85.
7. Chau WK, Na AT, Feng TT, Li YB. Ultrasound diagnosis of perforation of the gallbladder: real-time application and the demonstration of a new sonographic sign. J Clin Ultrasound 1988;16:358-60. 8. Derici H, Kara C, Bozdag AD, Nazli O, Tansug T, Akca E. Diagnosis and treatment of gallbladder perforation. World J Gastroenterol 2006;12:7832-6. 9. Kim PN, Lee KS, Kim IY, Bae WK, Lee BH. Gallbladder perforation: comparison of US findings with CT. Abdom Imaging 1994;19:239-42.
10
ACCEPTED MANUSCRIPT 10. Teefey SA, Dahiya N, Middleton WD, Bajaj S, Dahiya N, Ylagan L, Hildebolt CF. Acute cholecystitis: do sonographic findings and WBC count predict
T
gangrenous changes? AJR Am J Roentgenol 2013;200:363-9.
RI P
11. Bennett GL, Rusinek H, Lisi V, Israel GM, Krinsky GA, Slywotzky CM, Megibow A. CT findings in acute gangrenous cholecystitis. AJR Am J
SC
Roentgenol 2002;178:275-81.
12. Teefey SA, Baron RL, Radke HM, Bigler SA. Gangrenous cholecystitis: new
MA NU
observations on sonography. J Ultrasound Med 1991;10:603-6. 13. Chitkara YK. Pathology of the gallbladder in gallstone pancreatitis. Arch Pathol Lab Med 1995; 119:355-9.
ED
14. Chowksey SR, Baghel H, Sharma P, Singh B. Diagnosis of Gallbladder Perforation-a Puzzle!. Indian J Surg 2014; 76:247-50.
PT
15. Morris BS, Balpande PR, Morani AC, Chaudhary RK, Maheshwari M, Raut
AC
901.
CE
AA. The CT appearances of gallbladder perforation. Br J Radiol 2007;80:898-
11
ACCEPTED MANUSCRIPT Figure legends Figure 1. Perforated GB. A 53 year old woman presented with right upper quadrant
T
abdominal pain. US of the GB revealed signs of inflammation with multiple stones.
RI P
(A,B) Around the fundus appears a localized area of increased echogenicity (A-B thin arrow), in addition to a small amount of fluid that is tracking anteriorly (thick arrow,
SC
B). (C,D) Further inspection with longitudinal (C) and transverse (D) views revealed an obvious wall defect of approximately 9 mm (arrowhead). These findings were
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confirmed in surgery with fundal perforation with inflamed omentum adjacent to the
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PT
ED
tear.
12
ACCEPTED MANUSCRIPT Table 1 Sonographic findings associated with gallbladder perforation (N=11) Number (%)
Wall striations
8 (72%)
T
Finding
RI P
Gallstones Debris/sludge
SC
Pericholecystic fluid
MA NU
Free intra-peritoneal fluid
10 (90%) 11 (100%) 8 (72%) 7 (63%)
Complicated fluid collections (suspected abscess)
4 (36%)
Pleural fluid
2 (18%) 3 (27%)
Periportal tracking
5 (45%)
ED
Positive sonographic Murphy's sign
11 (100%)
AC
CE
PT
Inflammatory fat changes around the GB
13
SC R
IP T
ACCEPTED MANUSCRIPT
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PT
ED
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Fig. 1a
14
SC R
IP T
ACCEPTED MANUSCRIPT
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Fig. 1b
15
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IP T
ACCEPTED MANUSCRIPT
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Fig. 1c
16
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ACCEPTED MANUSCRIPT
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Fig. 1d
17
S0899-7071(15)00120-5 doi: 10.1016/j.clinimag.2015.05.008 JCT 7835
To appear in:
Journal of Clinical Imaging
Received date: Revised date: Accepted date:
7 February 2015 1 May 2015 13 May 2015
Please cite this article as: Shapira-Rootman Mika, Mahamid Ahmad, Reindorp Nadir, Nachtigal Alicia, Zeina Abdel-Rauf, Diagnosis of gallbladder perforation by ultrasound, Journal of Clinical Imaging (2015), doi: 10.1016/j.clinimag.2015.05.008
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Diagnosis of gallbladder perforation by ultrasound
AC
CE
PT
ED
MA NU
SC
RI P
T
Mika Shapira-Rootman MD PhD1, Ahmad Mahamid MD2, Nadir Reindorp MD1, Alicia Nachtigal MD1, Abdel-Rauf Zeina MD1 1Department of Radiology, 2Division of Surgery, Hillel Yaffe Medical Center, Hadera, Israel. Affiliated with the Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel Short Title: Ultrasound diagnosis of gallbladder perforation Corresponding author: Abdel-Rauf Zeina, MD Department of Radiology , Hillel Yaffe Medical Center , P.O.B. 169, Hadera 38100, Israel Tel. + 972-4-6304621 Fax. +972-4-6304884 [email protected] Conflict of interest: The authors report no conflicts of interest
1
ACCEPTED MANUSCRIPT
SC
RI P
T
Abstract: Purpose: The aim of this study was to identify possible pitfalls in the sonographic evaluation of perforated gallbladders. Methods: This is a retrospective analysis of sonograms of 11 patients diagnosed by surgery or pathology with perforated gallbladder. Sonograms were evaluated for multiple sonographic features. Results: Only 3 patients (27%) were diagnosed correctly with gallbladder perforation by ultrasonography prior to surgery. Gangrenous cholecystitis was reported in 10 cases (90%). Visualization of a wall defect was demonstrated in only 5 cases (45%) and was associated with a focal echogenic soft-tissue mass. Conclusion: Missed perforations by ultrasound may partially result from technical inadequacies.
AC
CE
PT
ED
MA NU
Keywords: Gallbladder; perforation; cholecystitis; ultrasound; gangrenous cholecystitis.
2
ACCEPTED MANUSCRIPT
Introduction
T
Gallbladder (GB) perforation is a rare complication of cholecystitis, and is associated
RI P
with increased rates of morbidity and mortality [1, 2]. Since the condition can be life threatening, rapid diagnosis and treatment are required. Known risk factors include
SC
male gender, older age, gallstones and diseased GB, systemic disease (cardiovascular disease, diabetes mellitus), and corticosteroid administration [2, 3]. Observations
MA NU
made by Niemeier in the 1930s still provide the basis of the current classification [35]. Accordingly, type 1 represents an acute perforation with signs of peritonitis. Type 2 is defined as sub-acute perforation with sealing of the inflammatory process and abscess formation. Type 3 is a chronic process with fistulous communication between
ED
the GB and adjacent viscous. Type 2 is the most common, followed by Type 1[3-6].
PT
Ultrasound (US) is generally the initial imaging modality for diagnosing
CE
complications of cholecystitis, as well as other GB pathologies. The primary and most specific sonographic feature is the direct visualization of a wall defect, also known as
AC
the "sonographic-hole" sign [3, 7]. Another indication of wall rupture is the demonstration of gallstones outside the GB [3]; however, this is rarely seen, and a less reliable sign. The diagnosis is often very challenging, with a relatively small percentage of patients detected prior to surgery [5]. From a radiological perspective, this may partially result from the fact that the direct visualization of a GB wall defect is not always feasible [8,9]. In this study we retrospectively reviewed the sonograms of 11 patients with perforated GB. The main objectives were (1) to further characterize this condition, by assessing established and new sonographic features and (2) to reveal possible recurring mistakes, as well as clues that may promote the diagnosis. 3
ACCEPTED MANUSCRIPT Materials and methods Patients
T
A search of the surgical database at our institution was performed to identify all
RI P
patients who were diagnosed with perforated GB between January 2010 and August 2014. Medical records were retrospectively reviewed for clinical data, imaging
SC
studies, and surgical and pathological reports. Clinical data accessed included white blood cell (WBC) levels and neutrophil counts at presentation, and comorbidities
MA NU
including diabetes mellitus and cardiovascular disease. Institutional review board approval was obtained for the study. Imaging studies
ED
All sonograms were performed by using one of two scanners (ACUSON S2000, Siemens medical solutions; or ATL HDI 5000, Philips Healthcare). In 6 of 11 cases, a
PT
complementary computed tomography (CT) was performed. Intravenous contrast
CE
material was administered in five cases. CT was performed using 64-MDCT scanner (Brilliance-64, Philips Healthcare, Cleveland, Ohio, USA).
AC
For the purpose of the current study, sonographic reports were reviewed for documentation of positive sonographic Murphy's sign and final diagnoses given by radiologists. In all cases, the original study was performed by a sonologist followed by a radiologist with at least three years of experience. All sonographic reports and final diagnoses were approved by certified radiologists that practice daily on the US unit. An US expert radiologist retrospectively reviewed all sonograms for wall defects, GB short axis diameter, wall thickness and striations, presence of gallstones, presence of echogenic content within the bladder (debris or sludge), free fluid around the GB and in the abdomen, complicated fluid collections (suspected abscess), pleural effusions, signs of periportal tracking, and local inflammatory fat changes. A 4
ACCEPTED MANUSCRIPT qualitative analysis of all sonograms was also performed by an US expert. Each study was evaluated for its technical adequacy including proper selection of transducers and
T
frequency range, correct focal zone placement, appropriate gain, maximal imaging
RI P
depth, and overall image quality. In addition, adherence to the standard protocol used in our institution for GB pathologies was evaluated. This includes proper assessment
SC
of the entire GB and its surroundings with long-axis and transverse views.
MA NU
Surgical and pathological data
Surgical reports were reviewed for major observations, including type and location of perforation and additional pathologies of the GB. In addition, type of surgery (open versus laparoscopic) was recorded. Pathological reports were reviewed for final
ED
diagnosis and additional histologic features including fibrosis, erosions, hemorrhage,
PT
and inflammatory changes of the adjacent fat such as fat necrosis. Results
CE
Eleven patients were diagnosed with GB perforation during the study period. Mean age was 67 years, with male predominance (81%). Major comorbidities were
AC
cardiovascular disease (5 patients), hyperlipidemia (4 patients), diabetes mellitus (3 patients) and morbid obesity (2 patients). One patient had liver cirrhosis. The mean level of WBCs at presentation was 13.9 x 109/L; the percentage of neutrophils was increased (mean 85.7%). The mean time between the US study and surgery was 3 days (range of 0-8 days). Three patients (27%) were diagnosed correctly with GB perforation by US prior to surgery. In all three, the perforation was sub-acute (type 2) with sonographic demonstration of abscesses. The mean short axis diameter of the 11 patients in the cohort was 4.6 cm (SD 1) and the wall width 6 mm (SD 1.7). The classical "sonographic hole" sign, with direct visualization of a wall defect, was retrospectively appreciated in 5 cases (45%). Of these, 3 perforations involved the 5
ACCEPTED MANUSCRIPT fundus and 2 the bladder neck. Additional sonographic findings of perforated GB are summarized in table 1. A qualitative analysis of all sonograms revealed that in 5 cases
T
there was an inadequate demonstration of the fundus. In these cases, the fundal area
RI P
was only partially demonstrated with inadequate use of technical parameters as focal zone placement. In all cases where a wall defect was demonstrated, a focal area of
SC
increased fat echogenicity was noticed near the tear (Figure 1), probably representing a thickened and inflamed omentum.
MA NU
All surgeries were open (rather than laparoscopic). Surgeons reported gangrenous cholecystitis in 10 cases (90%) and empyema of the GB in 8 (72%). Three patients were diagnosed with acute perforation (type 1) with spillage of pus and bile into the
ED
abdominal cavity. Seven were diagnosed with sub-acute perforation. In one patient, a fistulous tract between the GB and duodenum (type 3 perforation) was observed.
PT
Histologic features associated with perforated GB included inflammatory fat changes
(18%).
AC
Discussion
CE
(63%), hemorrhage (36%), fat necrosis (27%), fibrosis (27%), and wall erosions
This retrospective study highlights the diagnostic challenge of GB perforation, specifically the high rate of false negatives in ultrasound studies. The most specific and reliable sign of perforation is a wall defect. Yet, a wall defect was demonstrated in only 5 patients (45%). The characteristics of this cohort of patients with perforated GB were similar to those reported by others [2, 3]: older age (mean 67 years), mostly men (81%), and with additional comorbidities, chiefly cardiovascular. Patients presented with elevated WBC levels (mean 13.9 x 109/L) and with a high percentage of neutrophils (mean 85.7%), a known feature of complicated cholecystitis [1, 10]. 6
ACCEPTED MANUSCRIPT Since almost all perforated GBs are gangrenous (90% in this study), sonographic signs of gangrenous cholecystitis, such as severe inflammation, coexist. As described
T
here, perforated GBs were found to be distended (mean 4.6 cm) and with thickened
RI P
walls (mean 6 mm), which are findings that have been described for gangrenous cholecystitis [10, 11]. In addition, most GBs contained gallstones and all of them
SC
contained debris or sludge. In 72%, the wall had a striated appearance. The association between this finding and gangrenous cholecystitis is not clear. While once
MA NU
considered a sign suggestive of gangrenous cholecystitis [12], in a recent publication by Teefey et al [10], there was no association. Interestingly, in most cases of the current cohort, additional sonographic findings in the surrounding area (rather than in
ED
the GB itself) were demonstrated. This included free fluid around the GB and in the abdominal cavity. In two patients (18% of cases), pleural effusions were demonstrated
PT
as well. Additional sonographic signs that may clinch the diagnosis are those related to the type of perforation. For example, demonstration of cholecystitis together with
CE
an adjacent abscess, suggests a type 2 perforation.
AC
In the 5 cases presented here that had an obvious wall defect (the "sonographic hole" sign), a focal area of increased fat echogenicity was observed near the tear (Figure 1). This is a meaningful finding that may facilitate diagnosis and help in localizing the perforation. Inflammatory fat changes around the GB were mentioned in the pathological reports of 7 patients (63%) and fat necrosis in three of them. The literature concerning fat necrosis associated with GB pathologies is sparse, with reports of this finding mainly in the context of gallstone pancreatitis [13]. These changes may reflect extensive local inflammation with involvement of neighboring organs.
7
ACCEPTED MANUSCRIPT Evaluation of inflammatory fat changes may be most accurate and informative in the fundus, since this is the only part of the GB that is covered entirely by peritoneum,
T
contrasting with the body and neck of the GB, which are covered by peritoneum only
RI P
at their inferior border. However, most sonograms of the GB focus on the body neck area.
SC
We believe that some cases of GB perforation are "missed" due to technical
MA NU
inadequacies such as suboptimal demonstration of the fundus. As the fundus is located in a relatively anterior and caudal location, it does not always appear in the same plane as the other parts of the GB. Thus, a part of the GB's body may be falsely perceived as a "blind end" or as the fundus. In addition, due to its marginal location,
ED
the fundus is frequently seen on the edge of the image and out of focus. Nonetheless, the demonstration of the fundus is of paramount importance. As shown here, and by
PT
others [3, 4, 14, 15], most GB perforations involve this area. The propensity of the
CE
fundus to perforate is related mainly to a relatively poor blood supply [3, 15]. We suggest that in cases of suspected perforation (based on clinical grounds, risk factors,
AC
leukocytosis, and a sonogram of severe/gangrenous cholecystitis), a thorough inspection of the fundal area be performed. Assessment of this area with linear transducer may be of benefit to better look at this area. This study suffers from several drawbacks. First, this is a retrospective analysis without a control group. In order to evaluate the possible contribution of the ultrasonographic features discussed here, a prospective study is warranted. In addition, all images were reviewed only by a single sonographer. In conclusion, the sonographic detection of GB perforation is tricky, with direct visualization of a wall discontinuity possible in only a minority of cases. Focal areas
8
ACCEPTED MANUSCRIPT of increased fat echogenicity may help in detection and localization of the wall defect. Better delineation of the fundal area may improve the detection of GB perforation,
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be most accurately assessed in this area.
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ACCEPTED MANUSCRIPT References 1. Ausania F, Guzman Suarez S, Alvarez Garcia H, Senra Del Rio P, Casal
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prediction. Surg Endosc. 2014 [Epub ahead of print].
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Nuñez E Gallbladder perforation: morbidity, mortality and preoperative risk
2. Stefanidis D, Sirinek KR, Bingener J. Gallbladder perforation: risk factors and
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outcome. J Surg Res 2006;131:204-8.
3. Seyal AR, Parekh K, Gonzalez-Guindalini FD, Nikolaidis P, Miller
Imaging 2014;39:853-74.
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FH, Yaghmai V . Cross-sectional imaging of perforated gallbladder. Abdom
4. Swayne LC, Filippone A. Gallbladder perforation: correlation of
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cholescintigraphic and sonographic findings with the Niemeier classification. J Nucl Med 1990;31:1915-20.
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5. Date RS, Thrumurthy SG, Whiteside S, Umer MA, Pursnani KG, Ward JB, Mughal MM. Gallbladder perforation: case series and systematic review.
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Int J Surg 2012;10:63-8.
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6. Fletcher AG, Ravdin IS. Perforation of the gallbladder. Am J Surg 1951;81:178-85.
7. Chau WK, Na AT, Feng TT, Li YB. Ultrasound diagnosis of perforation of the gallbladder: real-time application and the demonstration of a new sonographic sign. J Clin Ultrasound 1988;16:358-60. 8. Derici H, Kara C, Bozdag AD, Nazli O, Tansug T, Akca E. Diagnosis and treatment of gallbladder perforation. World J Gastroenterol 2006;12:7832-6. 9. Kim PN, Lee KS, Kim IY, Bae WK, Lee BH. Gallbladder perforation: comparison of US findings with CT. Abdom Imaging 1994;19:239-42.
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ACCEPTED MANUSCRIPT 10. Teefey SA, Dahiya N, Middleton WD, Bajaj S, Dahiya N, Ylagan L, Hildebolt CF. Acute cholecystitis: do sonographic findings and WBC count predict
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gangrenous changes? AJR Am J Roentgenol 2013;200:363-9.
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11. Bennett GL, Rusinek H, Lisi V, Israel GM, Krinsky GA, Slywotzky CM, Megibow A. CT findings in acute gangrenous cholecystitis. AJR Am J
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Roentgenol 2002;178:275-81.
12. Teefey SA, Baron RL, Radke HM, Bigler SA. Gangrenous cholecystitis: new
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observations on sonography. J Ultrasound Med 1991;10:603-6. 13. Chitkara YK. Pathology of the gallbladder in gallstone pancreatitis. Arch Pathol Lab Med 1995; 119:355-9.
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14. Chowksey SR, Baghel H, Sharma P, Singh B. Diagnosis of Gallbladder Perforation-a Puzzle!. Indian J Surg 2014; 76:247-50.
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15. Morris BS, Balpande PR, Morani AC, Chaudhary RK, Maheshwari M, Raut
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901.
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AA. The CT appearances of gallbladder perforation. Br J Radiol 2007;80:898-
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abdominal pain. US of the GB revealed signs of inflammation with multiple stones.
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(A,B) Around the fundus appears a localized area of increased echogenicity (A-B thin arrow), in addition to a small amount of fluid that is tracking anteriorly (thick arrow,
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B). (C,D) Further inspection with longitudinal (C) and transverse (D) views revealed an obvious wall defect of approximately 9 mm (arrowhead). These findings were
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confirmed in surgery with fundal perforation with inflamed omentum adjacent to the
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tear.
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ACCEPTED MANUSCRIPT Table 1 Sonographic findings associated with gallbladder perforation (N=11) Number (%)
Wall striations
8 (72%)
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Finding
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Gallstones Debris/sludge
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Pericholecystic fluid
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Free intra-peritoneal fluid
10 (90%) 11 (100%) 8 (72%) 7 (63%)
Complicated fluid collections (suspected abscess)
4 (36%)
Pleural fluid
2 (18%) 3 (27%)
Periportal tracking
5 (45%)
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Positive sonographic Murphy's sign
11 (100%)
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Inflammatory fat changes around the GB
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Fig. 1b
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Fig. 1c
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Fig. 1d
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