Imaging findings of acute and chronic cholecystitis

Imaging findings of acute and chronic cholecystitis Award: I-MED Best Emergency Radiology Scientific Exhibit Prize Poster No.: R-0010 Congress: 2017 ASM Type: Educational Exhibit Authors: J. Lim, C. Hewavitharana; WA/AU Keywords: Biliary Tract / Gallbladder, Abdomen, Gastrointestinal tract, CT, Ultrasound, MR, Cholangiography, Education, Calcifications / Calculi, Education and training DOI: 10.1594/ranzcr2017/R-0010 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply RANZCR's endorsement, sponsorship or recommendation of the third party, information, product or service. RANZCR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold RANZCR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies,.ppt slideshows,.doc documents and any other multimedia files are not available in the pdf version of presentations. Page 1 of 28

Learning objectives 1. 2. 3. To illustrate and describe the findings of acute and chronic cholecystitis, highlighting the complementary role of Ultrasound (US) and Computed Tomography (CT). To illustrate complications of acute cholecystitis namely gangrenous cholecystitis, haemorrhagic cholecystitis, perforated cholecystitis, emphysematous cholecystitis, gallbladder empyema and acute cholecystitis with hepatic abscess. To illustrate other associated conditions namely choledocholithiasis, choledochoduodenal fistula, gallstone ileus, Mirizzi syndrome and dropped gallstones Background Cholecystitis is inflammation of the gallbladder, most often secondary to cholelithiasis[1]. Acute acalculous cholecystitis is inflammation of the gallbladder in the absence of cholelithiasis which occurs in approximately 10% of all cases of acute cholecystitis, usually in patients who are diabetic, critically ill or with prolonged illness[2]. The multiple forms of cholecystitis are the most common surgical entity encountered in developed countries[3]. Approximately 380 000 medical presentations per year in Australia are attributed to gallbladder disease[4]. Disorders of the gallbladder, biliary tree and liver may cause right upper quadrant abdominal pain. Imaging plays a key role in discerning the aetiology and establishing a prompt diagnosis. US is the initial imaging modality of choice but CT, Magnetic Resonance Imaging (MRI) and radionuclide imaging play complementary roles[2]. Imaging findings OR Procedure details Fig. 1 ACUTE CHOLECYSTITIS Acute cholecystitis is acute inflammation of the gallbladder and is often caused by gallstones, leading to outflow obstruction[1, 2]. It has a mortality rate of 4%[5]. Page 2 of 28

Plain abdominal radiographs are of limited value as only 20% of gallstones are radioopaque[3] and gallbladder inflammation cannot be visualised. US is the imaging modality of choice and findings include the following with the first two being the most specific ( Fig. 1 on page 10 )[2]: Gallstones which appear as mobile and highly reflective echoes with posterior acoustic shadowing Sonographic Murphy's sign: painful replication of biliary colic by probe pressure on the gallbladder in real time Gallbladder distention Wall thickening greater than 3 mm. However this feature may also be associated with chronic inflammation, ascites, hypoalbuminaemia, congestive cardiac failure and sepsis Pericholecystic fluid CT, although not first-line imaging, may be performed if the diagnosis is not suspected or uncertain and is a useful adjunct to US when findings are equivocal or if a complication is suspected. CT findings are similar to US with pericholecystic stranding being the most specific. However, it has a sensitivity of 75% for gallstones as some calculi are difficult to detect as they may be isoattenuating to the surrounding bile[6]. MRI is performed when other imaging findings are equivocal or if the clinical picture is uncertain. The excellent soft tissue contrast provides better detail of the biliary tract and allows identification of inflammatory changes. On non-contrast T2-weighted imaging, gallstones appear as signal voids in the high-signal-intensity bile[2] and pericholecystic free fluid appears as high signal intensity around the gallbladder. Post-contrast T1 imaging demonstrates gallbladder wall thickening. ACUTE ACALCULOUS CHOLECYSTITIS (AAC) AAC is an acute necro-inflammatory disease in the absence of gallstones and accounts for approximately 10% of all cases of acute cholecystitis. It usually occurs in critically ill patients post trauma, surgery, burns or those with shock, sepsis, on total parenteral nutrition or prolonged fasting. AAC has higher complication rates including gangrene, perforation and empyema which occur in 40% of cases resulting in a higher mortality rate of 30%. The diagnosis is often difficult as there are no specific findings and patients are usually critically ill with no ability to corroborate findings whilst intubated or sedated. Although no Page 3 of 28

specific clinical factor will lead to the diagnosis, there should be high clinical suspicion for AAC in critically ill patients for whom no etiology for their condition is found. The sensitivity and specificity of US ranges widely from 30-100% ( Fig. 2 on page 11 ). CT may be a useful adjunct for establishing the diagnosis. Major and minor diagnostic criteria have been described as follows with the diagnosis requiring 2 major or 1 major and 2 minor criteria[7]. Major criteria 3.5-4 mm (or more) thick wall (if at least 5 cm distended longitudinally with no ascites or hypoalbuminemia) Pericholecystic fluid (halo)/subserosal oedema Intramural gas Sloughed mucosal membrane Minor criteria Echogenic bile (sludge) Hydrops distension greater than 8 cm longitudinally or 5 cm transversely COMPLICATED ACUTE CHOLECYSTITIS Gangrenous cholecystitis Severe form of acute cholecystitis associated with vascular compromise, intramural haemorrhage, necrosis and abscess formation. The incidence ranges from 2-30% with higher incidence in males, the elderly and those with cardiovascular diseases. This condition is often caused by stone impaction in the cystic duct leading to progressive gallbladder distension and ultimately ischaemic necrosis of the wall[1, 2]. US features include heterogenous striated thickening and irregularity of the gallbladder wall and intraluminal membranes from ulceration, haemorrhage, necrosis or microabscess formation. Other signs include pericholecystic fluid collection, liver or pericholecystic abscess following perforation ( Fig. 3 on page 12 )[8]. The sonographic Murphy's sign may be absent secondary to denervation of the gallbladder wall[2]. CT findings are similar to US but an additional finding on contrast-enhanced CT is irregular or absent gallbladder wall enhancement[9]. Page 4 of 28

Haemorrhagic cholecystitis This is an uncommon complication of acute cholecystitis with a high mortality rate. It usually occurs in cases of cholelithiasis and gangrenous cholecystitis where transmural inflammation causes mural necrosis and ulceration, resulting in haemorrhage into the gallbladder lumen. On US, blood in the gallbladder lumen appears hyperechoic and is generally more hyperechoic than biliary sludge ( Fig. 4 on page 12 ). However, clotted blood may appear as heterogenous echogenic material adherent to the gallbladder wall and may simulate a mass. A fluid-fluid level with a high attenuation-dependent component may be observed on CT[10]. Perforated cholecystitis Perforated cholecystitis is a potentially life-threatening condition often as a complication in 0.8-3.2 % of cases of acute cholecystitis or trauma. Gallstone impaction within the cystic duct leads to obstruction and bile accumulation within the gallbladder causing distension. Progressive distension causes vascular compromise leading to perforation. Gallbladder perforation can be classified into 3 types: Type 1: acute free perforation of the gallbladder into the peritoneal cavity without protective adhesions (highest mortality) Type 2: subacute perforation surrounded by a pericholecystic abscess walled off by adhesions (most common) Type 3: chronic perforation with presence of a fistulous communication between the gallbladder and a viscus Imaging plays a vital role as symptoms are non-specific and urgent cholecystectomy is needed. The "sonographic-hole" sign which is the direct visualization of a gallbladder wall defect on US, CT or MRI is very specific but not always visualized ( Fig. 5 on page 13 ). Other signs include identification of gallstones outside the gallbladder in the correct clinical setting, focal gallbladder wall bulge, pericholecystic abscesses and cholecystoenteric fistula in chronic cases[11]. Emphysematous cholecystitis Emphysematous cholecystitis is a complication of acute cholecystitis characterised by gas within the gallbladder wall or lumen in the absence of an abnormal biliaryenteric communication. Cystic artery compromise leads to proliferation of gas-producing Page 5 of 28

organisms such as C. perfringens, E. coli and Klebsiella species causing local ischaemia. It is more common in males, many of whom have diabetes mellitus. The mortality rate of 15-20% is reduced by broad-spectrum antibiotics and early emergency cholecystectomy[12]. US findings depend on the amount and location of gas. Small amounts of gas appear as echogenic foci with posterior acoustic shadowing or a posterior ring-down artefact ( Fig. 6 on page 15, Fig. 7 on page 15 ). Large amounts of gas appear as a wide band of acoustic shadowing. However, it may be difficult to differentiate emphysematous cholecystitis from porcelain gallbladder or a highly contracted gallbladder filled with gallstones[13]. CT is more sensitive than US and findings include intraluminal or intramural gallbladder gas and complications such as pericholecystic inflammatory changes, abscess formation or perforation[14]. Gallbladder empyema Gallbladder empyema ( Fig. 8 on page 16, Fig. 9 on page 17 ) is an uncommon but serious complication, usually seen in adults with diabetes. It occurs when pus accumulates within an obstructed gallbladder. Initial symptoms as similar to cholecystitis but high fevers develop as the disease progresses. It can lead to perforation and sepsis if not promptly treated. US is the modality of choice but pus within the gallbladder may resemble sludge. However, intraluminal gas suggests empyema rather than simple cholecystitis. CT plays a complementary role by providing more anatomical detail and gas within the empyema. Percutaneous cholecystostomy are often performed rather than cholecystectomy as these patients are too unwell to tolerate a general anaesthetic. Aspiration of pus during the procedure also allows the establishment of the definite diagnosis[15]. Acute cholecystitis with hepatic abscess A hepatic abscess is a localized collection of purulent material within the liver with associated destruction of hepatic parenchyma and stroma with pyogenic ones being the most common in developed countries. This could be secondary to ascending cholangitis from biliary obstruction, direct or haematogenous spread[16]. Page 6 of 28

On US, pyogenic abscesses appear hypoechoic or echogenic, poorly defined with irregular walls, demonstrate posterior acoustic enhancement and contain fluid-debris levels ( Fig. 10 on page 17 ). However, appearances are variable and diffusely echogenic abscesses with little posterior enhancement may mimic solid lesions[16]. As necrosis and liquefaction occurs, the abscess becomes increasingly cystic with septations, internal echoes and debris. Doppler may show surrounding hyperaemia[2]. On post-contract CT, abscesses appear as low-density lesions with thick enhancing rims[2]. Septations may also be seen. OTHER ASSOCIATED CONDITIONS Choledocholithiasis Biliary calculi that form de novo within the biliary tree are referred to as primary stones whilst those that migrate through the cystic duct or a cholecystocholedochal fistula are referred to as secondary stones, which form the majority. Impacted stones within the common bile duct may lead to potentially life-threatening suppurative cholangitis and necrotizing pancreatitis[17]. Although the normal common bile duct calibre is slightly increased in the elderly, a diameter greater than 8 mm raises the concern of ductal obstruction[3]. US ( Fig. 11 on page 18 ) has a sensitivity ranging from 22-75%, limited by the ability to visualize the entire common bile duct, especially the distal part which may be obscured by bowel gas[18]. Unenhanced helical CT ( Fig. 12 on page 18 ) has a sensitivity of 88%[18] with 4 criteria described[2]: 1. 2. 3. 4. Target sign: central density within the bile duct (calculus) with surrounding low density (bile or mucosa) Rim sign: refers to the calculus outlined by a rim of increased density Crescent sign: bile eccentrically outlining the calculus, creating a low attenuation crescent Indirect signs: include abrupt termination of the dilated distal common bile duct without visible surrounding mass or biliary dilatation CT Cholangiography with intravenous iodinated cholangiographic agents have a higher sensitivity of 85-89%[18]. Intraductal calculus appear as filling defects within the biliary tree which has been opacified by contrast. Page 7 of 28

Magnetic Resonance Cholangiopancreatography (MRCP) is a non-invasive and lowrisk technique with sensitivities higher than US and CT and almost equal to that of Endoscopic Retrograde Cholangiopancreatography (ERCP) at 88%-95% and 89%-96% respectively[18]. MRCP include heavily T2 weighted sequences. Stones generally appear as well circumscribed low signal intensity filling defects within the biliary tract. MR is also helpful for differentiation of non-calcified stone from a soft tissue mass[2]. ERCP is highly sensitive and specific for choledocholiathiasis and allow therapeutic intervention but carries a 4% complication risk including pancreatitis, haemorrhage and death. Therefore, it is generally reserved for those who require stone removal[19] such as those with cholangitis or biliary obstruction. Gallstone ileus Gallstone ileus results from chronic cholelithiasis causing gallbladder perforation and cholecystoenteric fistula formation with the duodenum being the most common, followed by the colon and stomach[18]. If the migrated gallstone is larger than 2.5 cm, it usually lodges within the lumen of the small bowel causing mechanical bowel obstruction. The most common site is the narrow ileocaecal junction and it accounts for 1% of all small bowel obstructions. Bouveret syndrome ( Fig. 13 on page 19 ) occurs when an obstructing gallstone within the duodenum causes gastric outlet obstruction[3]. On plain radiographs, the Rigler's triad of the obstructing gallstone, pneumobilia and small bowel obstruction may be seen but CT ( Fig. 14 on page 20 ) is superior as it allows identification of the location of the obstructing calculus and choledochoenteric fistula ( Fig. 15 on page 21, Fig. 16 on page 22 )[20]. Mirizzi syndrome Mirizzi syndrome is partial obstruction of the common hepatic duct secondary to calculus impaction causing chronic inflammation in the adjacent Hartmann's pouch[3]. It is an uncommon complication and occurs in 0.05-2.7% of patients with longstanding cholelithiasis[21]. Preoperative diagnosis is important as it leads to an increased risks of bile duct injury (up to 22%) and conversion to open cholecystectomy[3]. Diagnosis may be made by US, CT or MRI with the hallmark being intrahepatic and common hepatic duct dilatation to the level of the porta hepatis with normal distal common bile duct calibre. A stone may be identified in the gallbladder neck or cystic duct. Multiplanar imaging with CT or MRI may be helpful in differentiating the extrinsic nature of the obstruction ( Fig. 17 on page 23 )[2]. Page 8 of 28

Dropped gallstones Spillage of gallstones occur in 2.3% - 40 % of cholecystectomies, with 1-40% of them retrieved. Microscopic evaluation of stones confirmed the presence of viable bacteria in pigmented stones which may lead to abscesses. Due to the indolent nature of inflammation secondary to these spilled gallstones, complications may occur from the immediate post-operative period to an interval of 20 years. In laparoscopic cholecystectomy, creation of pneumoperitoneum and irrigation of the peritoneal cavity can disperse the spilled gallstones to the subhepatic space, right subphrenic space, port sites, right flank, retroperitoneum, pelvis or thorax. US and CT are the modalities of choice. In CT, gallstones may appear as hypoattenuating or hyperattenuating nodules resembling peritoneal seeding with the perihepatic area being the most common location ( Fig. 18 on page 23 ). Imaging-guided percutaneous drainage and antibiotics are customary management options if there is abscess formation but definitive recovery of stones is often better[22]. CHRONIC CHOLECYSTITIS Chronic cholecystitis involves an evolving inflammatory process occurring with repeated episodes of gallbladder obstruction leading to focal ulceration and/or necrosis of the mucosa. 88% of cases are associated with gallstones but other causes include tumour, fibrosis or external cystic duct compression[3]. US findings include gallstones, thickened gallbladder wall and gallbladder contraction persisting with fasting. CT findings include dystrophic calcification and pericholecystic inflammatory change[2, 3]. Porcelain gallbladder Porcelain gallbladder is a rare condition characterized by gallbladder wall calcification found in 0.06-0.08% of autopsies. It is associated with increased risk of gallbladder malignancy of 5-12% and cholecystectomy should be considered[23]. However, more recent studies are questioning this association[24]. On plain radiograph, the calcifications appear as linear or curvilinear in the right upper quadrant or mid abdomen in the shape of the gallbladder. Page 9 of 28

On US, the calcifications are curvilinear and echogenic with posterior acoustic shadowing in the gallbladder fossa. Other conditions that may appear similar include emphysematous cholecystitis and the wall-echo-shadow complex in cholelithiasis in a collapsed gallbladder. CT is the most sensitive for identification of gallbladder wall calcification ( Fig. 19 on page 25 )[24]. Images for this section: Fig. 1: Ultrasound longitudinal (a) and transverse (b, c and d) images of a patient with right upper quadrant pain. There are calculi (arrow) within the gallbladder lumen causing acoustic shadowing. Sonographic Murphy's sign is positive. The gallbladder wall Page 10 of 28

is thickened at 12 mm with significant pericholecystic oedema and mild hyperemia in keeping with acute calculous cholecystitis. Fig. 2: Ultrasound longitudinal (a) and transverse (b) images of a patient with right upper quadrant pain. There is extensive debris within the gallbladder but no calculus Page 11 of 28

identified. The gallbladder wall is thickened with pericholecystic fluid in keeping with acute acalculous cholecystitis. Fig. 3: Ultrasound transverse (a and b) and longitudinal (c and d) images of an 89 year old nursing home resident with suprapubic pain and right upper quadrant mass on examination. The gallbladder wall is avascular and thickened with thick septa (orange arrow) and focal irregularity (thin arrows). There are calculi (thick arrow) and layering of echogenic fluid within the grossly distended gallbladder in keeping with gangrenous cholecystitis. Page 12 of 28

Fig. 4: A and b: Ultrasound longitudinal image (a) of a patient with right upper quadrant pain and guarding on a background of diffuse large B cell lymphoma demonstrates nonmobile heterogenous hyperechoic material within the gallbladder (thin arrows) in keeping with intraluminal haemorrhage in haemorrhagic cholecystitis. These findings are also demonstrated on the CT Abdomen Portal Venous phase axial image (b). C: Ultrasound longitudinal image of the same patient 7 days later with decreased echogenicity of the gallbladder contents (thin arrow) in keeping with the expected evolution of haemorrhage. Page 13 of 28

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Fig. 5: A: Ultrasound longitudinal images of a patient with epigastric pain on a background of pancreatic carcinoma with hepatic metastases. There is a 6 mm defect within the anteroinferior gallbladder wall (orange arrow) in keeping with perforated cholecystitis. B: CT Portal Venous phase axial image of the same patient demonstrating the gallbladder wall defect (long thin arrow), hepatic metastasis (short thin arrow), biliary stent (thick arrow) and perihepatic ascites (blue arrow). Fig. 6: Erect abdominal radiograph of a diabetic patient with abdominal pain demonstrates intraluminal (thin arrow) and intramural gallbladder gas (thick arrows) in keeping with emphysematous cholecystitis. Page 15 of 28

Fig. 7: A and b: Ultrasound longitudinal images of a patient with right upper quadrant pain and vomiting. There is gas (thin arrows) within the non-dependent portion of the gallbladder which is thick-walled in keeping with emphysematous cholecystitis. Page 16 of 28

Fig. 8: A and b: Ultrasound longitudinal and axial images of a patient with 3 days of right upper quadrant pain and vomiting. The gallbladder is distended, thick walled and hyperaemic. There are intraluminal septation (arrows) in keeping with empyema. Fig. 9: A and b: CT Abdomen Portal Venous phase coronal and axial images of a patient 1 month post stent insertion for cholecystitis and cholangitis demonstrating pericholecystic septated fluid collection (thin arrow) communicating with the distended gallbladder (thick arrow) in keeping with empyema. Page 17 of 28

Fig. 10: A: Ultrasound longitudinal image of a patient with acute pancreatitis post alcoholic binge. The gallbladder is totally collapsed with no calculus identified (thin arrow). B: CT Abdomen Portal Venous phase axial image demonstrating gallbladder (thin arrow) wall thickening and pericholecystic inflammatory change with an adjacent hepatic abscess in segment V (thick arrow). Fig. 11: A and b: Ultrasound longitudinal images of a 72 year old man with 3 days of constant right upper quadrant abdominal pain. There are multiple calculi within the dilated common bile duct (thin arrows) in keeping with choledocholithiasis. The gallbladder is distended, thick-walled and contains a calculus (A) and some sludge (thick arrow). Sonographic Murphy's sign was positive. Page 18 of 28

Fig. 12: A, b and c: CT Abdomen Portal Venous phase axial and coronal images of a patient with abdominal pain and deranged liver function tests. The images demonstrate gallstones within the gallbladder (thick arrows) and common bile duct (thin arrows) in keeping with cholelithiasis and choledocholithiasis. Page 19 of 28

Fig. 13: A: Supine abdominal radiograph of a patient with right upper quadrant pain and deranged liver function tests demonstrating the gallstone (thick arrow) within the distal stomach. B, c and d: CT Abdomen Portal Venous phase coronal and axial images demonstrating a gallstone within the duodenal bulb (thick arrows) and pneumobilia (thin arrows) in keeping with Bouveret's syndrome. Page 20 of 28

Fig. 14: A, b and c: CT Abdomen Portal Venous phase axial and coronal images of a patient with abdominal pain and vomiting. The images demonstrate a gallstone within the ileum (thick arrows), dilated small bowel loops (thin arrows) and pneumobilia (blue arrows) in keeping with gallstone ileus. Page 21 of 28

Fig. 15: A: CT Abdomen Portal Venous phase coronal image of a patient with 1 week of abdominal pain and vomiting demonstrating gas within the choledochoduodenal fistula (thin arrows). B: Axial image of the same patient demonstrating pneumobilia (thin arrow). C: Axial image of the same patient demonstrating an oedematous gallbladder containing calculus (thick arrow) and gas (thin arrow), with surrounding fluid and fat stranding. Page 22 of 28

Fig. 16: A and b: CT Abdomen Portal Venous phase axial and coronal images of a patient with abdominal pain demonstrating intramural gallbladder gas (thin arrow).this patient had a known choledochoenteric fistula. Fig. 17: A, b, c and d: Ultrasound transverse images of a patient with obstructive jaundice with known choledocholithiasis in keeping with Mirizzi syndrome. A: Dilated non-vascular linear intrahepatic duct in keeping with intrahepatic biliary dilatation. B: The known 29 mm calculus (thin arrow) is seen at the junction of the common bile duct and cystic duct. The proximal common bile duct is dilated at 13 mm. C: Intrahepatic duct dilatation with a plastic biliary stent (thick arrow) in situ as the calculus could not be removed on previous ERCP. D: The gallbladder is thick-walled but no sonographic Murphy's sign or pericholecystic free fluid to suggest acute cholecystitis. E: ERCP image demonstrating large filling defect within the cystic duct in keeping with a calculus (thin arrows). Page 23 of 28

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Fig. 18: A, b and c: CT Abdomen Portal Venous phase axial and coronal images of a patient with epigastric pain and deranged liver function tests on a background of previous cholecystectomy. The images demonstrate speckled calcification within the hepatic capsule adjacent to segment VII representing gallstones (thin arrows). There is a surgical clip (thick arrows) amongst the dropped gallstones. Ultrasound performed 3 days before this CT was normal but limited by patient body habitus. Fig. 19: A: Ultrasound transverse image of a patient with right upper quadrant abdominal pain and deranged liver function tests demonstrates gallbladder wall calcification (thin arrow). B and c: CT Abdomen Portal Venous phase axial and coronal images of the same patient demonstrating the gallbladder wall calcification (thin arrows). Page 25 of 28

Conclusion Being such a common entity, it is imperative that Sonographers, Radiology Registrars and Consultants are familiar with the different imaging findings. This project aims to portray the common presentations of cholecystitis and its complications. Additionally, Radiologists can also perform image-guided percutaneous cholecystostomies in patients unfit for cholecystectomies under general anaesthesia. Personal information Joel is a 2nd year Radiology Registrar in the Western Australia Radiology Training program. Chandra (Padmini) is a Consultant Abdominal and General Radiologist at Royal Perth Hospital. References 1. Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K, Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepato-biliary-pan. 2007;14:15-26. 2. Bennett GL. Evaluating Patients with Right Upper Quadrant Pain. Radiol Clin N Am. 2015;53:1093-1130. 3. Elwood DR. Cholecystitis. Surg Clin N Am. 2008;88:1241-52. 4. Bayram C, Valenti L, Miller G. Gallbladder disease. AFP. 2013;42(6):443. 5. Nikfarjam M, Harnaen E, Tufail F, Muralidharan V, Fink M, Starkey G, et al. Sex differences and outcomes of management of acute cholecystitis. Surg Laparosc Endosc Percutan Tech. 2013;23(1):61-5. 6. Paulson E. Acute cholecystitis: CT findings. Semin Ultrasound CT MR. 2000;21(1):56-63. 7. Huffman J, Schenker S. Acute acalculous cholecystitis: a review. Clin Gastroenterol Hepatol. 2010;8:15-22. Page 26 of 28

8. Teefey S, Baron R, Radke H, Bigler S. Gangrenous cholecystitis: New observations on Sonography. J Ultrasound Med. 1991;10:603-6. 9. Bennett G, Rusinek H, Lisi V, Israel G, Krinsky G, Slywotzky C, et al. CT Findings in acute gangrenous cholecystitis. AJR. 2002;178:275-81. 10. Jenkins M, Golding R, Cooperberg P. Sonography and computed tomography of hemorrhagic cholecystitis. AJR. 1983;140:1197-8. 11. Seyal A, Parekh K, Gonzalez-Guindalini F, Nikolaidis P, Miller F, Yaghmai V. Crosssectional imaging of perforated gallbladder. Abdom Radiol. 2014;39:853-874. 12. Rosenberg A, Cherry-Bukowiec J, Li S, Napolitano L. Emphysematous cholecystitis. Surg Infect. 2013;14(5):483-5. 13. Konno K, Ishida H, Naganuma H, Sato M, Komatsuda T, Sato A, et al. Emphysematous cholecystitis: sonographic findings. Abdom Imaging. 2002;27:191-5. 14. Chiu H, Chen C, Mo L. Emphysematous cholecystitis. Am J Surg. 2004;188:325-6. 15. Mehta V, Yarmish G, Greenstein J, Hahn B. Gallbladder empyema. The Journal of Emergency Medicine. 2016;50(6):893-4. 16. Doyle D, Hanbidge A, O'Malley M. Imaging of hepatic infections. Clin Radiol. 2006;61:737-48. 17. Liu T, Moody F. Pathogenesis and presentation of common bile duct stones. Semin Laparosc Surg. 2000;7(4):224-31. 18. Bortoff G, Chen M, Ott D, Wolfman N, Routh W. Gallbladder stones: imaging and intervention. RadioGraphics. 2000;20:751-66. 19. Ryan M. ERCP complication rates: how low can we go. Gastrointest Endosc. 2009;70(1):89-91. 20. Lassandro F, Romano S, Ragozzino A, Rossi G, Valente T, Ferrara I, et al. Role of helical CT in diagnosis of gallstone ileus and related conditions. AJF. 2005;185:1159-65. 21. Simoglou C, Simoglou L, Babalis D. Mirizzi Syndrome. Hell Cheirourgike. 2013;85:2. 22. Nooghabi A, Hassanpour M, Jangjoo A. Consequences of lost gallstones during laparoscopic cholecystectomy: a review article. Surg Laparosc Endosc Percutan Tech. 2016;26(3):183-92. 23. Ansari S. Porcelain Gallbladder. Indian J Gastroenterol. 2014;33(4):399. 24. Patel N, Caserta M, DiSantis D. Porcelain gallbladder. Abdom Radiol. 2017;42:322-3. Page 27 of 28

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