Differential Diagnosis for Gallstones: A Comprehensive Guide for Clinicians

Introduction

Gallstones, also known as cholelithiasis, are a prevalent condition characterized by the formation of hardened deposits within the gallbladder. These formations, primarily composed of cholesterol, bilirubin, and bile salts, can range from asymptomatic to causing significant abdominal distress and severe complications. While gallstones are a common cause of right upper quadrant pain and gastrointestinal issues, their clinical presentation can overlap with a multitude of other conditions. Therefore, establishing an accurate Differential Diagnosis For Gallstones is crucial for effective patient management and to avoid unnecessary interventions. This article aims to provide a comprehensive guide to the differential diagnosis of gallstones, enhancing the clinician’s ability to distinguish gallstone-related pathology from other mimicking conditions.

Understanding Gallstones: Etiology, Pathophysiology, and Epidemiology

Gallstone formation is a complex process influenced by metabolic, environmental, and genetic factors. Bile, produced by the liver, aids in digestion by emulsifying fats. Gallstones arise when bile components become imbalanced, leading to supersaturation and crystallization. Cholesterol stones are the most common type, especially in Western countries, linked to factors like obesity, diabetes, dyslipidemia, and rapid weight loss. Pigment stones, composed of calcium bilirubinate, are associated with hemolysis and biliary infections. Brown stones are often related to bacterial infections within the bile ducts.

Epidemiologically, gallstones are a significant health concern globally, particularly in developed nations. In the United States, millions of adults are affected, with prevalence increasing with age, especially in women and certain ethnic groups like Indigenous Americans and Hispanics. While many individuals remain asymptomatic, a substantial portion will develop symptoms or complications over time, necessitating accurate diagnosis and management strategies.

Clinical Presentation of Gallstones

The clinical spectrum of gallstone disease is wide, varying from incidental findings on imaging to severe, life-threatening conditions. Asymptomatic gallstones often require no immediate intervention but necessitate patient education and monitoring for symptom development. Symptomatic gallstones, however, typically manifest as biliary colic, characterized by episodic, intense right upper quadrant or epigastric pain. This pain is often triggered by fatty meals and may radiate to the back or right shoulder, frequently accompanied by nausea and vomiting.

When gallstones obstruct the cystic duct for prolonged periods, acute cholecystitis can develop. This condition presents with more constant and severe right upper quadrant pain, often associated with fever, tenderness to palpation (Murphy’s sign), and potentially a palpable gallbladder mass. Migration of gallstones into the common bile duct can lead to choledocholithiasis, causing jaundice, elevated liver enzymes, and potentially ascending cholangitis, a severe infection of the biliary system characterized by Charcot’s triad (right upper quadrant pain, fever, and jaundice) and in severe cases Reynold’s pentad (Charcot’s triad plus altered mental status and shock). Gallstone pancreatitis arises when a stone obstructs the pancreatic duct at the ampulla of Vater, leading to epigastric pain, nausea, and vomiting.

Alt text: Point-of-care ultrasound image clearly visualizing a gallstone within the gallbladder, indicated by a bright echogenic focus and a distinct posterior acoustic shadow, which is a hallmark sign for gallstone diagnosis.

Differential Diagnosis of Gallstones

Given the variability in presentation and the non-specific nature of abdominal pain, a robust differential diagnosis for gallstones is essential. Many conditions can mimic gallstone disease, and a thorough evaluation is necessary to ensure accurate diagnosis and appropriate management. The differential diagnoses can be broadly categorized into gastrointestinal, cardiovascular, pulmonary, musculoskeletal, renal, and other conditions.

Gastrointestinal Conditions

Several gastrointestinal disorders can present with symptoms similar to gallstones, particularly right upper quadrant or epigastric pain.

• Peptic Ulcer Disease (PUD): Both gastric and duodenal ulcers can cause epigastric pain, which may radiate to the back. However, PUD pain is often related to meals (eating may worsen gastric ulcer pain, while it may relieve duodenal ulcer pain), and may have a burning or gnawing character, unlike the colicky nature of biliary pain. Endoscopy is the definitive diagnostic tool.

• Gastroesophageal Reflux Disease (GERD): GERD can cause epigastric and chest pain, often described as burning. While it can be exacerbated by fatty meals, like gallstone symptoms, GERD pain is typically associated with heartburn, regurgitation, and acid reflux symptoms, which are less common in biliary colic. Upper endoscopy and pH monitoring can aid in diagnosis.

• Appendicitis: While classically presenting with right lower quadrant pain, early appendicitis can manifest as periumbilical or epigastric pain, potentially mimicking early biliary colic. As appendicitis progresses, pain migrates to the right lower quadrant. Fever, anorexia, and right lower quadrant tenderness are more suggestive of appendicitis. CT scan of the abdomen and pelvis is often used for diagnosis.

• Pancreatitis: Acute pancreatitis, regardless of etiology (gallstone-induced or other causes like alcohol), can present with severe epigastric pain radiating to the back, nausea, and vomiting, similar to gallstone complications. However, pancreatitis pain is typically more constant and severe than biliary colic. Elevated serum lipase and amylase levels are key diagnostic indicators. CT scan is also crucial to assess pancreatic inflammation and rule out other causes.

• Cholangitis: Ascending cholangitis, often caused by common bile duct stones, shares symptoms with complicated gallstone disease, including right upper quadrant pain, jaundice, and fever. However, cholangitis is a more severe, systemic illness with potential for rapid deterioration. Blood cultures and imaging (ultrasound, MRCP) are essential for diagnosis and to identify biliary obstruction.

• Cholangiocarcinoma: Cancer of the bile ducts can cause biliary obstruction, leading to jaundice and abdominal pain, which may be confused with choledocholithiasis. However, cholangiocarcinoma often presents with progressive, painless jaundice initially, and pain may develop later. Imaging (CT, MRI, MRCP) and tumor markers (CA 19-9) are important for differentiation. Biopsy is required for definitive diagnosis.

• Irritable Bowel Syndrome (IBS): IBS can cause abdominal pain, bloating, and altered bowel habits. While IBS pain is typically more diffuse and related to bowel movements, some patients may experience upper abdominal discomfort, leading to diagnostic confusion. IBS is a diagnosis of exclusion, based on Rome criteria, and lacks specific diagnostic tests.

• Inflammatory Bowel Disease (IBD): Crohn’s disease and ulcerative colitis can cause abdominal pain, although more commonly in the lower abdomen. However, IBD-related complications such as sclerosing cholangitis can mimic biliary disease. IBD usually presents with diarrhea, bloody stools, and systemic symptoms. Colonoscopy and imaging studies are used for diagnosis.

• Gastritis: Inflammation of the stomach lining can cause epigastric pain and nausea. Gastritis pain is often described as burning or gnawing and may be related to meals, similar to PUD. Upper endoscopy with biopsy is the diagnostic method of choice.

• Hepatitis: Liver inflammation from viral, alcoholic, or other causes can cause right upper quadrant discomfort and jaundice, mimicking gallstone disease. However, hepatitis typically presents with more systemic symptoms like fatigue, malaise, and dark urine. Liver function tests and viral serology are crucial for diagnosis.

Cardiovascular Conditions

Certain cardiac conditions can present with epigastric or chest pain that can be mistaken for gallstone symptoms.

• Myocardial Infarction (MI): Inferior wall myocardial infarction, in particular, can present with epigastric pain, nausea, and vomiting, mimicking biliary colic or even acute cholecystitis. It’s crucial to consider cardiac etiology, especially in patients with risk factors for coronary artery disease. ECG and cardiac enzyme tests are essential to rule out MI in patients presenting with upper abdominal pain, particularly if it is atypical for biliary colic.

• Angina: Stable or unstable angina can sometimes manifest as epigastric discomfort, especially exertional angina. This pain is typically related to physical activity and relieved by rest or nitroglycerin, unlike biliary colic which is often postprandial. ECG and stress testing are used to evaluate for angina.

• Aortic Dissection: Although less common, aortic dissection can present with sudden, severe chest or abdominal pain that may radiate to the back. This is a life-threatening emergency and must be considered in the differential diagnosis of acute abdominal pain, particularly in patients with hypertension or Marfan syndrome. CT angiography or MRI is used for rapid diagnosis.

• Pericarditis: Inflammation of the pericardium can cause chest pain that may radiate to the abdomen and mimic upper abdominal pain. Pericarditis pain is often sharp, pleuritic, and positional, worsened by lying down and relieved by sitting up and leaning forward, which differs from biliary colic. ECG, echocardiogram, and inflammatory markers are used to diagnose pericarditis.

Pulmonary Conditions

Pulmonary conditions, particularly those affecting the lower lobes of the lungs, can sometimes cause referred pain to the upper abdomen.

• Pneumonia: Lower lobe pneumonia, especially right-sided, can cause pleuritic chest pain that may be referred to the right upper quadrant, mimicking acute cholecystitis or biliary colic. Cough, fever, and respiratory symptoms are more indicative of pneumonia. Chest X-ray is essential for diagnosis.

• Pleurisy: Inflammation of the pleura can cause sharp, localized chest pain that can be referred to the abdomen, particularly the upper quadrants. Pleuritic pain is typically worsened by breathing and coughing. Chest X-ray and clinical examination can help diagnose pleurisy.

• Pulmonary Embolism (PE): While less common, PE can present with pleuritic chest pain and sometimes abdominal pain, particularly in cases of diaphragmatic pleurisy. Shortness of breath, tachycardia, and risk factors for thromboembolism should raise suspicion for PE. CT pulmonary angiography is the gold standard for diagnosis.

Musculoskeletal Conditions

Musculoskeletal pain in the chest wall or upper abdomen can mimic biliary colic.

• Costochondritis: Inflammation of the costochondral cartilage can cause localized chest wall pain that may radiate to the upper abdomen. Costochondritis pain is typically reproducible on palpation of the costochondral junctions and is not related to meals, unlike biliary colic.

• Muscle Strain: Strain of the abdominal or intercostal muscles can cause localized pain that can be exacerbated by movement or palpation. Muscle strain pain is typically related to recent physical activity or trauma and lacks the typical episodic, colicky nature of biliary pain.

Renal Conditions

Renal colic from kidney stones can cause flank pain that may radiate to the abdomen and be confused with biliary colic.

• Renal Calculi (Kidney Stones): Renal colic typically presents with severe, colicky flank pain that may radiate to the groin or abdomen. While flank pain is more characteristic, anterior abdominal pain is possible, particularly with proximal ureteral stones. Hematuria, urinary frequency, and urgency are suggestive of renal colic. CT scan of the abdomen and pelvis (non-contrast) is the preferred diagnostic modality.

• Pyelonephritis: Kidney infection can cause flank pain, fever, and urinary symptoms. While flank pain is primary, referred abdominal pain is possible. Urinalysis showing pyuria and bacteriuria, along with fever and CVA tenderness, points towards pyelonephritis.

Other Conditions

• Esophageal Spasm: Esophageal spasm can cause sudden, severe chest pain that may radiate to the abdomen, mimicking biliary colic. Esophageal spasm pain is often described as squeezing or crushing and may be triggered by hot or cold liquids. Esophageal manometry and upper endoscopy can be used for diagnosis.

• Herpes Zoster (Shingles): Pre-eruptive phase of herpes zoster can cause localized pain along a dermatomal distribution in the chest or abdomen, which may mimic visceral pain. The development of vesicular rash along the dermatome is diagnostic.

• Biliary Dyskinesia: Dysfunction of the sphincter of Oddi or gallbladder motility issues can cause biliary-type pain in the absence of gallstones. This condition, often termed biliary dyskinesia, can present with recurrent biliary colic-like pain, but imaging studies will be negative for gallstones. HIDA scan with CCK stimulation can assess gallbladder ejection fraction and sphincter of Oddi manometry can evaluate sphincter function.

Alt text: Abdominal CT scan illustrating acute cholecystitis, characterized by gallbladder wall thickening, pericholecystic fluid accumulation, and the presence of gallstones within the gallbladder lumen, critical findings for confirming acute inflammation.

Diagnostic Approach to Rule Out Gallstones and Differential Diagnoses

A systematic approach is crucial to differentiate gallstones from other conditions presenting with similar symptoms. The diagnostic process typically involves:

1. History and Physical Examination: Detailed history focusing on pain characteristics (onset, location, radiation, duration, aggravating/relieving factors), associated symptoms (nausea, vomiting, jaundice, fever, urinary symptoms, respiratory symptoms), and risk factors (age, sex, obesity, diabetes, previous medical history). Physical examination should include abdominal palpation (Murphy’s sign, tenderness, guarding, rebound), vital signs (fever, tachycardia), and assessment for jaundice.

2. Laboratory Investigations:

   • Complete Blood Count (CBC): To assess for leukocytosis, indicating infection or inflammation (e.g., cholecystitis, cholangitis, appendicitis, pyelonephritis).
   • Liver Function Tests (LFTs): Elevated bilirubin, alkaline phosphatase, and transaminases can suggest biliary obstruction or liver inflammation (e.g., choledocholithiasis, cholangitis, hepatitis).
   • Lipase and Amylase: To rule out pancreatitis.
   • Urinalysis: To assess for hematuria and signs of infection (e.g., renal calculi, pyelonephritis).
   • Cardiac Enzymes (Troponin): If cardiac etiology is suspected (e.g., myocardial infarction).
   • ECG: To rule out cardiac ischemia or infarction.

3. Imaging Studies:

   • Ultrasound: First-line imaging for gallstones due to its high sensitivity and specificity for detecting gallstones and signs of cholecystitis (wall thickening, pericholecystic fluid, sonographic Murphy’s sign).
   • CT Scan of the Abdomen and Pelvis: Useful for evaluating acute abdominal pain, especially when differential diagnosis includes appendicitis, pancreatitis, renal calculi, aortic dissection, or other intra-abdominal pathology. Can detect gallstones, but ultrasound is more sensitive for small stones and gallbladder sludge. CT is better for assessing complications of cholecystitis and ruling out other conditions.
   • MRCP (Magnetic Resonance Cholangiopancreatography): Highly sensitive and specific for detecting common bile duct stones (choledocholithiasis) and biliary obstruction. Useful when choledocholithiasis is suspected or if ultrasound findings are inconclusive.
   • Chest X-ray: To rule out pulmonary causes of abdominal pain (e.g., pneumonia, pleurisy).
   • HIDA Scan (Hepatobiliary Iminodiacetic Acid Scan): Used to assess gallbladder function and diagnose acute cholecystitis (non-visualization of gallbladder). Also useful in evaluating biliary dyskinesia (CCK-stimulated ejection fraction).
   • Upper Endoscopy (EGD): To evaluate for peptic ulcer disease, gastritis, GERD, and esophageal spasm, especially if upper GI symptoms are prominent.

4. Specialized Tests (if indicated):

   • ERCP (Endoscopic Retrograde Cholangiopancreatography): Both diagnostic and therapeutic for choledocholithiasis. Used to visualize and remove common bile duct stones.
   • Esophageal Manometry and pH Monitoring: To evaluate for esophageal spasm and GERD, respectively, if suspected.
   • Colonoscopy: If IBD or lower GI pathology is considered in the differential.

Treatment and Management of Gallstones

Treatment strategies for gallstones depend on the presence and severity of symptoms. Asymptomatic gallstones often require no treatment other than observation and patient education about potential symptoms and complications. Symptomatic gallstones, particularly biliary colic and acute cholecystitis, generally warrant intervention.

Laparoscopic cholecystectomy is the gold standard treatment for symptomatic gallstones and acute cholecystitis. This minimally invasive surgical procedure involves removing the gallbladder and is highly effective in resolving symptoms and preventing complications. For patients with choledocholithiasis, ERCP with sphincterotomy and stone extraction is typically performed to clear the common bile duct before or after cholecystectomy.

Non-surgical management options, such as oral bile acid dissolution therapy (ursodeoxycholic acid), are available but have limited efficacy and are generally reserved for select patients with small cholesterol stones and contraindications to surgery. Lithotripsy, mechanical or extracorporeal shockwave, is rarely used due to limited efficacy and potential complications.

Prognosis and Complications

The prognosis for gallstone disease is generally favorable, especially with timely diagnosis and appropriate treatment. Asymptomatic gallstones may remain silent for years, but a proportion of individuals will develop symptoms or complications. Symptomatic gallstones, if left untreated, can lead to significant morbidity due to complications like acute cholecystitis, cholangitis, pancreatitis, and gallbladder cancer (though rare).

Laparoscopic cholecystectomy is a safe and effective procedure with low mortality rates. Post-cholecystectomy syndrome, characterized by persistent abdominal symptoms, can occur in some patients but is usually mild and manageable. Long-term prognosis after cholecystectomy is generally excellent, with improved quality of life and resolution of gallstone-related symptoms.

Conclusion

Establishing an accurate differential diagnosis for gallstones is paramount in clinical practice. While gallstones are a common cause of abdominal pain, numerous other conditions can mimic their presentation. A thorough clinical evaluation, including history, physical exam, laboratory tests, and appropriate imaging, is essential to differentiate gallstone disease from its mimics. By considering a broad differential and employing a systematic diagnostic approach, clinicians can ensure accurate diagnoses, guide appropriate management strategies, and ultimately improve patient outcomes in individuals presenting with suspected gallstone disease.

References

1.Tsai TJ, Chan HH, Lai KH, Shih CA, Kao SS, Sun WC, Wang EM, Tsai WL, Lin KH, Yu HC, Chen WC, Wang HM, Tsay FW, Lin HS, Cheng JS, Hsu PI. Gallbladder function predicts subsequent biliary complications in patients with common bile duct stones after endoscopic treatment? BMC Gastroenterol. 2018 Feb 27;18(1):32. [PMC free article: PMC6389262] [PubMed: 29486713]

2.Shenoy R, Kirkland P, Hadaya JE, Tranfield MW, DeVirgilio M, Russell MM, Maggard-Gibbons M. Management of symptomatic cholelithiasis: a systematic review. Syst Rev. 2022 Dec 12;11(1):267. [PMC free article: PMC9743645] [PubMed: 36510302]

3.Di Ciaula A, Garruti G, Frühbeck G, De Angelis M, de Bari O, Wang DQ, Lammert F, Portincasa P. The Role of Diet in the Pathogenesis of Cholesterol Gallstones. Curr Med Chem. 2019;26(19):3620-3638. [PMC free article: PMC8118138] [PubMed: 28554328]

4.Rebholz C, Krawczyk M, Lammert F. Genetics of gallstone disease. Eur J Clin Invest. 2018 Jul;48(7):e12935. [PubMed: 29635711]

5.E S, Srikanth MS, Shreyas A, Desai S, Mehdi S, Gangadharappa HV, Suman, Krishna KL. Recent advances, novel targets and treatments for cholelithiasis; a narrative review. Eur J Pharmacol. 2021 Oct 05;908:174376. [PubMed: 34303667]

6.Unalp-Arida A, Ruhl CE. Burden of gallstone disease in the United States population: Prepandemic rates and trends. World J Gastrointest Surg. 2024 Apr 27;16(4):1130-1148. [PMC free article: PMC11056655] [PubMed: 38690054]

7.Gutt C, Schläfer S, Lammert F. The Treatment of Gallstone Disease. Dtsch Arztebl Int. 2020 Feb 28;117(9):148-158. [PMC free article: PMC7132079] [PubMed: 32234195]

8.Fujita N, Yasuda I, Endo I, Isayama H, Iwashita T, Ueki T, Uemura K, Umezawa A, Katanuma A, Katayose Y, Suzuki Y, Shoda J, Tsuyuguchi T, Wakai T, Inui K, Unno M, Takeyama Y, Itoi T, Koike K, Mochida S. Evidence-based clinical practice guidelines for cholelithiasis 2021. J Gastroenterol. 2023 Sep;58(9):801-833. [PMC free article: PMC10423145] [PubMed: 37452855]

9.Cianci P, Restini E. Management of cholelithiasis with choledocholithiasis: Endoscopic and surgical approaches. World J Gastroenterol. 2021 Jul 28;27(28):4536-4554. [PMC free article: PMC8326257] [PubMed: 34366622]

10.Di Ciaula A, Wang DQ, Portincasa P. An update on the pathogenesis of cholesterol gallstone disease. Curr Opin Gastroenterol. 2018 Mar;34(2):71-80. [PMC free article: PMC8118137] [PubMed: 29283909]

11.Kotrotsios A, Tasis N, Angelis S, Apostolopoulos AP, Vlasis K, Papadopoulos V, Filippou DK. Dietary Intake and Cholelithiasis: A Review. J Long Term Eff Med Implants. 2019;29(4):317-326. [PubMed: 32749137]

12.Shabanzadeh DM. New determinants for gallstone disease? . Dan Med J. 2018 Feb;65(2) [PubMed: 29393043]

13.Sun H, Warren J, Yip J, Ji Y, Hao S, Han W, Ding Y. Factors Influencing Gallstone Formation: A Review of the Literature. Biomolecules. 2022 Apr 06;12(4) [PMC free article: PMC9026518] [PubMed: 35454138]

14.Haal S, Guman MSS, Acherman YIZ, Jansen JPG, van Weeghel M, van Lenthe H, Wever EJM, Gerdes VEA, Voermans RP, Groen AK. Gallstone Formation Follows a Different Trajectory in Bariatric Patients Compared to Nonbariatric Patients. Metabolites. 2021 Oct 05;11(10) [PMC free article: PMC8541369] [PubMed: 34677397]

15.Boyang H, Yanjun Y, Jing Z, Chenxin Y, Ying M, Shuwen H, Qiang Y. Investigating the influence of the gut microbiome on cholelithiasis: unveiling insights through sequencing and predictive modeling. J Appl Microbiol. 2024 May 01;135(5) [PubMed: 38614959]

16.Hu H, Shao W, Liu Q, Liu N, Wang Q, Xu J, Zhang X, Weng Z, Lu Q, Jiao L, Chen C, Sun H, Jiang Z, Zhang X, Gu A. Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion. Nat Commun. 2022 Jan 11;13(1):252. [PMC free article: PMC8752841] [PubMed: 35017486]

17.Sharma R, Sachan SG, Sharma SR. In vitro analysis of gallstone formation in the presence of bacteria. Indian J Gastroenterol. 2020 Oct;39(5):473-480. [PubMed: 33201443]

18.Shi T, Li D, Li D, Sun J, Xie P, Wang T, Li R, Li Z, Zou Z, Ren X. Individual and joint associations of per- and polyfluoroalkyl substances (PFAS) with gallstone disease in adults: A cross-sectional study. Chemosphere. 2024 Jun;358:142168. [PubMed: 38685323]

19.Luo M, Chen P, Tian Y, Rigzin N, Sonam J, Shang F, Tai C, Li T, Sang H. Hif-1α expression targets the TMA/Fmo3/TMAO axis to participate in gallbladder cholesterol stone formation in individuals living in plateau regions. Biochim Biophys Acta Mol Basis Dis. 2024 Jun;1870(5):167188. [PubMed: 38657913]

20.Wilkins T, Agabin E, Varghese J, Talukder A. Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia. Prim Care. 2017 Dec;44(4):575-597. [PubMed: 29132521]

21.Hiwatashi K, Okumura H, Setoyama T, Ando K, Ogura Y, Aridome K, Maenohara S, Natsugoe S. Evaluation of laparoscopic cholecystectomy using indocyanine green cholangiography including cholecystitis: A retrospective study. Medicine (Baltimore). 2018 Jul;97(30):e11654. [PMC free article: PMC6078678] [PubMed: 30045318]

22.Gallaher JR, Charles A. Acute Cholecystitis: A Review. JAMA. 2022 Mar 08;327(10):965-975. [PubMed: 35258527]

23.Han JH, So H, Bang SJ, Nah YW. [Surgical Removal of a Huge Common Bile Duct Stone]. Korean J Gastroenterol. 2024 May 25;83(5):200-204. [PubMed: 38783622]

24.Hirajima S, Koh T, Sakai T, Imamura T, Kato S, Nishimura Y, Soga K, Nishio M, Oguro A, Nakagawa N. Utility of Laparoscopic Subtotal Cholecystectomy with or without Cystic Duct Ligation for Severe Cholecystitis. Am Surg. 2017 Nov 01;83(11):1209-1213. [PubMed: 29183521]

25.Ruhl CE, Everhart JE. Gallstone disease is associated with increased mortality in the United States. Gastroenterology. 2011 Feb;140(2):508-16. [PMC free article: PMC3060665] [PubMed: 21075109]

26.Thapar VB, Thapar PM, Goel R, Agarwalla R, Salvi PH, Nasta AM, Mahawar K., IAGES Research Collaborative Group. Evaluation of 30-day morbidity and mortality of laparoscopic cholecystectomy: a multicenter prospective observational Indian Association of Gastrointestinal Endoscopic Surgeons (IAGES) Study. Surg Endosc. 2023 Apr;37(4):2611-2625. [PMC free article: PMC9648883] [PubMed: 36357547]

27.Nassar AHM, Khan KS, Ng HJ, Sallam M. Operative Difficulty, Morbidity and Mortality Are Unrelated to Obesity in Elective or Emergency Laparoscopic Cholecystectomy and Bile Duct Exploration. J Gastrointest Surg. 2022 Sep;26(9):1863-1872. [PMC free article: PMC9489587] [PubMed: 35641812]

28.Fagenson AM, Powers BD, Zorbas KA, Karhadkar S, Karachristos A, Di Carlo A, Lau KN. Frailty Predicts Morbidity and Mortality After Laparoscopic Cholecystectomy for Acute Cholecystitis: An ACS-NSQIP Cohort Analysis. J Gastrointest Surg. 2021 Apr;25(4):932-940. [PMC free article: PMC7222970] [PubMed: 32212087]

29.Fugazzola P, Cobianchi L, Di Martino M, Tomasoni M, Dal Mas F, Abu-Zidan FM, Agnoletti V, Ceresoli M, Coccolini F, Di Saverio S, Dominioni T, Farè CN, Frassini S, Gambini G, Leppäniemi A, Maestri M, Martín-Pérez E, Moore EE, Musella V, Peitzman AB, de la Hoz Rodríguez Á, Sargenti B, Sartelli M, Viganò J, Anderloni A, Biffl W, Catena F, Ansaloni L., S.P.Ri.M.A.C.C. Collaborative Group. Prediction of morbidity and mortality after early cholecystectomy for acute calculous cholecystitis: results of the S.P.Ri.M.A.C.C. study. World J Emerg Surg. 2023 Mar 18;18(1):20. [PMC free article: PMC10024826] [PubMed: 36934276]

30.Del Vecchio Blanco G, Gesuale C, Varanese M, Monteleone G, Paoluzi OA. Idiopathic acute pancreatitis: a review on etiology and diagnostic work-up. Clin J Gastroenterol. 2019 Dec;12(6):511-524. [PubMed: 31041651]

31.Brägelmann J, Barahona Ponce C, Marcelain K, Roessler S, Goeppert B, Gallegos I, Colombo A, Sanhueza V, Morales E, Rivera MT, de Toro G, Ortega A, Müller B, Gabler F, Scherer D, Waldenberger M, Reischl E, Boekstegers F, Garate-Calderon V, Umu SU, Rounge TB, Popanda O, Lorenzo Bermejo J. Epigenome-Wide Analysis of Methylation Changes in the Sequence of Gallstone Disease, Dysplasia, and Gallbladder Cancer. Hepatology. 2021 Jun;73(6):2293-2310. [PubMed: 33020926]

32.Sohail Z, Shaikh H, Iqbal N, Parkash O. Acute pancreatitis: A narrative review. J Pak Med Assoc. 2024 May;74(5):953-958. [PubMed: 38783446]

33.Zaher EA, Ebrahim MA, Al Salman O, Patel P, Alchalabi M. Bigger Than a Hen’s Egg: A Case of Bouveret Syndrome. Cureus. 2024 Apr;16(4):e58742. [PMC free article: PMC11110879] [PubMed: 38779279]

34.Knapik M, Okoń K, Ulatowska-Białas M. Fatal pulmonary bile embolism associated with acute pancreatitis – a case report and review of the literature. Pol J Pathol. 2024;75(1):54-57. [PubMed: 38741429]

35.Field X, Tong C, Cox S, Crichton J, Goodwin B, Welsh F, Cha R. Outcomes of asymptomatic common bile duct stones detected at intraoperative cholangiography. N Z Med J. 2024 May 17;137(1595):73-79. [PubMed: 38754115]

36.Patel SS, Kohli DR, Savas J, Mutha PR, Zfass A, Shah TU. Surgery Reduces Risk of Complications Even in High-Risk Veterans After Endoscopic Therapy for Biliary Stone Disease. Dig Dis Sci. 2018 Mar;63(3):781-786. [PubMed: 29380173]

37.Genser L, Vons C. Can abdominal surgical emergencies be treated in an ambulatory setting? J Visc Surg. 2015 Dec;152(6 Suppl):S81-9. [PubMed: 26522504]

38.Coleman J. Bile duct injuries in laparoscopic cholecystectomy: nursing perspective. AACN Clin Issues. 1999 Nov;10(4):442-54. [PubMed: 10865529]