Acute Cholecystitis - CECity

Acute CholecystitisView online at http://pier.acponline.org/physicians/diseases/d642/d642.htmlModule Updated: 2013-02-20CME Expiration: 2016-02-20AuthorBadri Man Shrestha, MS, MPhil, MD, FRCSTable of Contents1. Prevention .........................................................................................................................22. Diagnosis ..........................................................................................................................43. Consultation ......................................................................................................................84. Hospitalization ...................................................................................................................115. Therapy ............................................................................................................................126. Patient Education ...............................................................................................................167. Follow-up ..........................................................................................................................17References ............................................................................................................................19Glossary................................................................................................................................23Tables ...................................................................................................................................25Figures .................................................................................................................................30Quality Ratings: The preponderance of data supporting guidance statements are derived from:level 1 studies, which meet all of the evidence criteria for that study type;level 2 studies, which meet at least one of the evidence criteria for that study type; orlevel 3 studies, which meet none of the evidence criteria for that study type or are derived from expert opinion, commentary, or consensus.Study types and criteria are defined at http://smartmedicine.acponline.org/criteria.htmlDisclaimer: The information included herein should never be used as a substitute for clinical judgement and does not represent an official position ofthe American College of Physicians. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete.Therefore, PIER users should compare the module updated date on the offical web site with any printout to ensure that the information is the mostcurrent available.CME Statement: The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to providecontinuing education for physicians. The American College of Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1Credit TM . Physicians should claim only credit commensurate with the extent of their participation in the activity. Purpose: This activity has beendeveloped for internists to facilitate the highest quality professional work in clinical applications, teaching, consultation, or research. Upon completionof the CME activity, participants should be able to demonstrate an increase in the skills and knowledge required to maintain competence, strengthentheir habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Badri Man Shrestha, MS, MPhil, MD,FRCS, current author of this module, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-carerelated organizations. Deborah Korenstein, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies, biomedicaldevice manufacturers, or health-care related organizations. Richard B. Lynn, MD, FACP, Co-Editor, PIER, has no financial relationships withpharmaceutical companies, biomedical device manufacturers, or health-care related organizations.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.

Acute Cholecystitis• A 2008 systematic review and meta-analysis that included seven randomized, controlled trials(n=349 patients) comparing the efficacy of NSAIDs with other analgesic agents in the treatment ofbiliary colic showed NSAIDs to be the analgesics of choice for biliary colic in limiting the progressionof colic to acute cholecystitis (7).• A randomized, double-blind study of diclofenac showed satisfactory pain relief and decrease inprogression to acute cholecystitis. Four of 27 patients treated with diclofenac developed acutecholecystitis compared with 11 of 26 placebo patients (P=0.04) (8).• A randomized, double-blind study of diclofenac vs. hyoscine for acute biliary colic showed fasterand more effective pain relief in the diclofenac arm. A smaller percentage of patients in thediclofenac group (16.7%) progressed to acute cholecystitis compared with the hyoscine group(52.8%) (9).Rationale• Diclofenac provides pain relief in biliary colic and decreases the risk for acute cholecystitis.1.3 Consider cholecystectomy for symptomatic gallstones.Recommendations• Consider laparoscopic cholecystectomy for patients with symptomatic gallstones.Evidence• A randomized, prospective study showed that in patients with biliary colic, 38% per year hadrecurrent biliary pain and 2% per year required cholecystectomy for significant biliary symptoms(10).• Based on simulation modeling, prophylactic cholecystectomy may decrease mortality more thanconservative management in patients with symptomatic gallstones (11).• There are no randomized trials comparing cholecystectomy vs. no cholecystectomy in patients withsilent gallstones. Further evaluation of observational studies, which measure such outcomes asobstructive jaundice, gallstone-associated pancreatitis, and/or gallbladder cancer for sufficientduration of follow-up, is necessary before randomized trials are designed to evaluate whethercholecystectomy or no cholecystectomy is better for asymptomatic gallstones (12).• The need for cholecystectomy was demonstrated in a study comparing outcomes in nongangrenous(n=174) vs. gangrenous cholecystitis (n=106). Mortality was significantly higher in thelatter group (0% vs. 4%; P=0.017). The risk factors associated with gangrenous cholecystitisincluded older age (69 years vs. 57 years; P=0.001) and diabetes (19% vs. 10%; P=0.049). Therewas no overall difference in complication rates between the non-gangrenous and gangrenouscholecystitis groups (22% vs. 14%; P=0.102) when treated in a specialized unit (13).Rationale• A large percentage of patients with symptomatic gallstones will have recurrent symptoms and maydevelop more serious complications.Comments• Surgical removal of the gallbladder and gallstones is the definitive therapy for preventing acutecholecystitis.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 3 of 32

Acute Cholecystitis2. DiagnosisBase the diagnosis of acute cholecystitis on the history, physicalexam, laboratory data, and radiologic studies.2.1 Obtain patient history for features suggestive of acute cholecystitis.Recommendations• Ask about:Details of pattern, duration, location, and radiation of painRelated symptoms, such as fever, chills, nausea, or vomitingDark urinePrevious biliary colicPatient's agePresence of diabetes• Note that the typical pain is mid-epigastric, progressing to right upper quadrant. Pain may alsoradiate to right scapula, right shoulder, back, or lower abdomen.Evidence• A retrospective study showed that 73.5% of patients with acute cholecystitis had pain persistingless than 24 hours, 54% had right upper quadrant pain, and 34% had mid-epigastric pain (14).• A prospective study showed that 32.2% of patients with acute cholecystitis had fever, and 75%had previous episodes of biliary colic (15).• A retrospective study showed that in acute acalculous cholecystitis, advanced age was associatedwith the presence of severe gallbladder complications (16).• A retrospective study showed that a history of diabetes was significantly associated with thedevelopment of gangrenous cholecystitis (17).Rationale• The history of acute cholecystitis often includes previous episodes of biliary colic, mid-epigastricvisceral pain radiating to the right upper quadrant, parietal pain, fever, chills, nausea, andvomiting.• Advanced age may correlate with the development of complications in acute cholecystitis.• Diabetes may play a role in the development of complications in acute cholecystitis.Comments• In elderly patients (especially those with diabetes) with leukocytosis and acute cholecystitis,consider early surgical evaluation owing to the increased risk for developing gallbladdercomplications (16).2.2 Perform physical exam for features suggestive of acute cholecystitis.Recommendations• Look for:Abdominal tendernessMurphy's sign (palpation of the right upper quadrant causing pain and arrest of inspiration)Right upper quadrant massFeverJaundicePeritoneal signsSigns of hemodynamic instabilityTopPIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 4 of 32

Acute CholecystitisEvidence• A retrospective study showed that a positive Murphy's sign had a sensitivity of 97.2% and washighly predictive (93.3%) of a positive hepatobiliary scintigraphic scan in the diagnosis of acutecholecystitis (14).• A retrospective study showed that 85% of patients with acute cholecystitis had right upperquadrant tenderness, and 40% had tenderness elicited in other regions (18).• A retrospective study showed that 23% of patients with acute cholecystitis had a palpablegallbladder (19).Rationale• Classic findings on the exam of acute cholecystitis include right upper quadrant or mid-epigastrictenderness with Murphy's sign.• A right upper quadrant mass (palpable gallbladder) may be present.• Peritoneal signs imply a perforated viscus.Comments• Peritoneal signs require immediate surgical evaluation.2.3 Recognize the clinical setting of acute acalculous cholecystitis.Recommendations• Consider the diagnosis of acute acalculous cholecystitis in critically ill patients.• Understand that the classic signs and/or symptoms of acute cholecystitis may be absent inacalculous disease.Evidence• A retrospective study showed that 14% of all cases of acute cholecystitis were acalculous; 63% ofthe patients had had surgery, 52% were in the ICU, 37% were on a ventilator, 33% werehypotensive, 33% were fasting, and 18% were on TPN (20).• A retrospective study showed that only 66.7% of patients with acute acalculous cholecystitis hadright upper quadrant pain (21).Rationale• Five percent to 15% of cases of acute cholecystitis are acalculous.• Acute acalculous cholecystitis generally occurs in critically ill, septic patients.• The classic findings of right upper quadrant pain, Murphy's sign, and fever may be absent inintubated, unresponsive patients.2.4 Use laboratory data to establish the diagnosis.Recommendations• Look for evidence of leukocytosis.• Evaluate LFTs.• Use laboratory data to exclude other diseases.• See table Laboratory and Other Studies for Acute Cholecystitis.Evidence• A prospective study showed that 41% of patients with acute cholecystitis had elevated bilirubinlevels, 26% had elevated alkaline phosphatase levels, 12% had elevated ALT levels, and 51% hadleukocytosis (>10,000 10 3 /µL) (15).• A prospective study showed that 29% of patients with acute cholecystitis had hyperbilirubinemia.The average bilirubin level in patients without common bile-duct stones was 2.7 mg/dL. Theaverage bilirubin level in patients with common bile-duct stones was 6.7 mg/dL (22).• Two retrospective studies showed that leukocytosis was present in 60% and 63% of patients withacute cholecystitis (14; 23).PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 5 of 32

Acute Cholecystitis• In a review of 216 patients with acute calculous cholecystitis, elevated serum γ-glutamyltranspeptidase >90 U/L was associated with a 33% chance of having choledocholithiasis (24).• In a retrospective review of 177 patients aged 16 to 65 years who had right hypochondrial pain,statistically significant predictors of acute cholecystitis were alkaline phosphatase, Murphy's sign,elevated leukocyte count, and elevated bilirubin level (25).Rationale• Leukocytosis, mild LFT abnormalities, and mild hyperbilirubinemia are common in acutecholecystitis.• Leukocytosis may correlate with outcome in acute cholecystitis.• Bilirubin >4 mg/dL is not a feature of uncomplicated acute cholecystitis.Comments• Bilirubin levels >4 mg/dL suggest possible common bile-duct stone, cholangitis, or Mirizzi'ssyndrome, a rare condition in which a gallstone impacting the cystic duct obstructs the commonbile duct by edema and extrinsic compression.• In elderly patients with acute cholecystitis and leukocytosis, consider early surgical evaluationowing to the increased risk for developing gallbladder complications (16; 17).2.5 Use imaging studies to establish the diagnosis.Recommendations• Obtain the following:Transcutaneous ultrasound to diagnose acute cholecystitisCholescintigraphy scans (e.g., HIDA scan) as an alternative to diagnose acute cholecystitis or whenultrasound is equivocalCT scan when other studies are equivocal or when complications of acute cholecystitis are suspectedMRCP scan if there is suspicion of calculi in the bile duct• See table Laboratory and Other Studies for Acute Cholecystitis.• See figure Gallbladder Ultrasound Showing Gallstones.• See figure Acalculous Cholecystitis.• See figure Normal Gallbladder Ultrasound.• See figure Gallstone Ileus.Evidence• A prospective study showed that when ultrasound revealed gallstones and a positive sonographicMurphy's sign, the positive predictive value for acute cholecystitis was 92.2%. When the patienthad gallstones and gallbladder-wall thickening (≥3 mm), the positive predictive value was 95.2%for acute cholecystitis (26).• Multiple (>20) prospective and retrospective studies have showed ultrasound to have 81% to 98%sensitivity and 70% to 98% specificity for acute cholecystitis (26; 27; 28; 29; 30).• Various retrospective and prospective trials have compared ultrasound with HIDA scanning for thediagnosis of acute cholecystitis. A retrospective analysis of patients with acute cholecystitis showedultrasound scans to be less sensitive than HIDA scans for initial diagnosis (48% vs. 86%) (30).• A retrospective study showed ultrasound to have a sensitivity of 86% vs. 97% for HIDA scans (28).• A retrospective study showed ultrasound to have an accuracy of 94% vs. 93% for HIDA scans (27).• A meta-analysis from 1994 of 30 articles showed ultrasound to have 94% sensitivity and 78%specificity, compared with HIDA scans, which have a 97% sensitivity and a 90% specificity for thediagnosis of acute cholecystitis (29).• A retrospective study showed that 50.9% of patients with acute cholecystitis showed evidence of athickened gallbladder wall on unenhanced CT scan. In addition, 66.7% of patients with this findinghad gangrenous cholecystitis on histology (31).• A 2003 meta-analysis of 67 studies including 4711 patients showed that MRCP is a non-invasiveimaging test with excellent overall sensitivity (95%) and specificity (97%) for showing the levelPIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 6 of 32

Acute CholecystitisRationaleand presence of biliary obstruction, although it was less sensitive for identifying stones (88%) andmalignant lesions (92%) (32).• Both ultrasound and HIDA scans are accurate for the diagnosis of acute cholecystitis. The generalrecommendation has been to obtain an ultrasound scan first, followed by an HIDA scan, ifnecessary.• The classic findings of acute cholecystitis on ultrasound are pericholecystic fluid and a thickenedgallbladder wall of 3 mm to 4 mm; sonographic Murphy's sign further confirms the diagnosis.• The classic finding of acute cholecystitis on HIDA scan is non-visualization of the gallbladder.• An enhanced CT scan can show gallstones, gallbladder-wall thickening, gallbladder distension,pericholecystic fluid, and inflammation of the pericholecystic fat. An unenhanced CT scan can showgallstones and a hyperdense gallbladder wall, which can suggest the presence of gangrenouscholecystitis.Comments• Despite most organizations recommending ultrasound as the primary diagnostic tool for acutecholecystitis, the literature shows that an HIDA scan has equal or better sensitivity and specificity;however, cost and ease of access favor the use of ultrasound.• Ultrasound can be less accurate in patients with ascites, hypoalbuminemia, hepatitis, obesity, andheart failure.• HIDA scans can give false-positive results in critically ill, fasting patients. Furthermore, HIDA scansare not accurate with bilirubin levels >5 mg/dL, in which case more specialized tests, such asDISIDA scan, can be used.• CT scan should be reserved for cases of diagnostic dilemma and to detect possible complications ofacute cholecystitis (31).• MRCP is commonly used to diagnose obstruction of the biliary tree caused by stones or malignantlesions.2.6 Consider the broad differential diagnosis.Recommendations• When considering the differential diagnosis of acute cholecystitis, include acute disease processeson both sides of the diaphragm.• See table Differential Diagnosis of Acute Cholecystitis.Evidence• Consensus.Rationale• Many intra-abdominal and thoracic conditions can mimic acute cholecystitis.• The correct diagnosis must be made to separate routine conditions from emergent conditions.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 7 of 32

Acute Cholecystitis3. ConsultationObtain surgical and possibly GI consultation to aid in the diagnosis.Consult a surgeon and a gastroenterologist as needed formanagement of patients.3.1 Obtain surgical consultation for suspected cases of acute cholecystitis.Recommendations• Obtain surgical consultation to aid in diagnosing acute calculous and acalculous cholecystitis.Evidence• Consensus.Rationale• The differential diagnosis of acute cholecystitis is extensive; several surgical conditions can mimicacute cholecystitis.• Acute acalculous cholecystitis can present with subtle signs and symptoms in critically ill patients.• A surgical consultant can establish a diagnosis and formulate a treatment plan.3.2 Obtain GI consultation in certain cases.Recommendations• Obtain GI consultation in cases of suspected acute cholecystitis with a bilirubin level >4 mg/dLand/or significantly elevated LFTs.Evidence• A prospective study of patients with acute cholecystitis who had hyperbilirubinemia and subsequentbiliary-tract exploration showed that 68.4% had common bile-duct stones (22).Rationale• Acute cholecystitis is generally not associated with significant jaundice or elevation of LFTs; thesefindings suggest either common bile-duct stones or Mirizzi's syndrome, a rare condition in which agallstone impacting the cystic duct obstructs the common bile duct by edema and extrinsiccompression.• MRC is useful in detecting stones in the common bile duct before or after cholecystectomy and maybe indicated.• Endoscopic evaluation of the biliary tree may be warranted.3.3 Obtain joint surgical and obstetric consultations in cases of suspectedacute cholecystitis during pregnancy.Recommendations• Obtain joint surgical and obstetric consultations in cases of suspected acute cholecystitis duringpregnancy.Evidence• In a study of 6221 women with gallstone-related hospitalization during pregnancy and postpartum,76% were diagnosed with uncomplicated cholelithiasis, 16% with pancreatitis, 9% with acutecholecystitis, and 8% with cholangitis. Seventy-three percent of the hospitalized women underwentcholecystectomy and 5% underwent ERCP (39).• In a prospective observational study of 122 patients with biliary disease (41 with acutecholecystitis), conservative treatment failed in 69 (56.5%) patients and 54 of this group underwentlaparoscopic cholecystectomy during second trimester with no fetal or maternal mortality (40).TopPIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 8 of 32

Acute Cholecystitis• In a study of 49 patients admitted with an acute abdomen in pregnancy due to cholecystitis, 15patients (31%) had emergency cholecystectomy within the first week. Thirty-four patients (69%)were treated conservatively, of whom 24 relapsed many times and had to be readmitted to thehospital. Of the remaining 10 patients on conservative management, 3 had emergencycholecystectomy and 7 reached term safely. Maternal morbidity was significantly less in thesurgically treated group (P

Acute CholecystitisRationale• Cholecystectomy is definitive therapy in most patients with acute cholecystitis.• Early laparoscopic cholecystectomy can be safely done in most patients with acute cholecystitis.• Inoperable and high-risk surgical candidates may need interventions, such as cholecystostomy,which can be coordinated by a surgical consultant.3.5 Consult a gastroenterologist in certain cases.Recommendations• Consult a gastroenterologist in patients for possible ERCP with acute cholecystitis and:EvidenceJaundiceCommon bile-duct dilationSignificantly elevated LFT levelsSignificantly elevated pancreatic enzymes• A prospective, randomized study showed that 100% of patients presenting with acute cholangitishad successful biliary drainage by ERCP. There was a trend toward fewer complications in the ERCPgroup vs. the surgery group (P>0.05), and there was less mortality in the ERCP group (P

Acute Cholecystitis4. HospitalizationTopHospitalize patients with acute cholecystitis.4.1 Hospitalize patients with acute cholecystitis for definitive diagnosis andtreatment.Recommendations• Hospitalize patients to:Provide analgesia, hydration, supportive care, and possibly antibioticsObtain surgical consultationPrepare patient for possible cholecystectomy• See Therapy.Evidence• Consensus.Rationale• Many patients with acute cholecystitis will have nausea, vomiting, or anorexia requiring ivhydration and supportive care, and many will also require parenteral analgesia.• Most patients will require definitive surgical therapy.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 11 of 32

Acute Cholecystitis5. TherapyTopConsider cholecystectomy as definitive therapy.5.1 Consider the use of antibiotics in certain patients.Recommendations• Consider using broad-spectrum antibiotics in acute cholecystitis patients with sepsis, fever,leukocytosis, or evidence of complications.• See table Drug Treatment for Acute Cholecystitis.Evidence• A prospective study of 467 patients with acute cholecystitis showed positive bile cultures in 46%;the most common organisms were E. coli, Klebsiella sp., group D Streptococcus sp., andEnterobacter sp. Patients aged over 60 years had the highest rate of biliary infection (43).• Cases of acute cholecystitis are reported to be caused by such organisms as Vibrio cholerae (44),Haemophilus influenzae (45), Moellerella wisconsensis (46), Salmonella sp. (47), Cytomegalovirus(48), Cellulomonas denverensis (49), and Candida lusitaniae (50).• A retrospective study of 302 patients with acute cholecystitis showed no difference in local septiccomplications, such as empyema or pericholecystic abscess, in those treated with or withoutantibiotics. There was a lower incidence of wound infections and postoperative bacteremia inpatients treated with antibiotics (51).Rationale• A significant percentage of patients with acute cholecystitis will have positive blood and bilecultures. Antibiotics would be expected to benefit this group.Comments• Definitive evidence regarding the use of antibiotics in acute cholecystitis is lacking; however, itwould seem prudent to consider using antibiotics in toxic-appearing patients.• The recommended regimens vary from single- to triple-coverage; the choice of antibiotic should bebased on suspected organisms and local antibiotic resistance patterns.5.2 Ensure appropriate use of pain medications.Recommendations• Consider using:NSAIDs in patients with biliary colic or acute cholecystitis with mild to moderate abdominal painNarcotic analgesics in patients with moderate to severe abdominal pain• See module Pain.Evidence• Retrospective studies of patients presenting with acute cholecystitis show that abdominal painoccurs in 73.5% (14) and abdominal tenderness occurs in 85% (18).• A randomized, double-blind study of diclofenac showed satisfactory pain relief and decrease inprogression to acute cholecystitis. Four of 27 patients who received diclofenac developed acutecholecystitis compared with 11 of 26 patients who received placebo (P=0.04) (8).• A 2008 systematic review and meta-analysis that included seven randomized, controlled trials(n=349 patients) assessing the efficacy of NSAIDs in comparison to other analgesic agents in thetreatment of biliary colic showed NSAIDs to be the analgesics of choice for biliary colic in limitingthe progression of colic to acute cholecystitis (7).• A randomized, double-blind study evaluated the efficacy of iv ketorolac compared with butorphanolfor the treatment of biliary colic pain in the emergency department. Patients presenting withabdominal pain suspected to be biliary colic were randomized to receive either ketorolac, 30 mg iv,PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 12 of 32

Acute CholecystitisRationaleor butorphanol, 1 mg iv. The mean (+/- SD) pain score (visual analogue scale) in the butorphanolgroup decreased from 7.1 (+/-1.7) to 2.1 (+/-2.2) after 30 minutes. The mean (+/-SD) pain scorein the ketorolac group decreased from 7.4 (+/-2.0) to 3.1 (+/-3.3) after 30 minutes. This studyshowed that both ketorolac and butorphanol provide pain relief in biliary colic and were suitableespecially in patients who require HIDA scan (52).• Over 80% of patients with acute cholecystitis present with abdominal pain or tenderness, and painmedications can provide analgesia while awaiting definitive therapy.• NSAIDs provide pain relief in biliary colic and may decrease the risk for progression to acutecholecystitis.Comments• A prospective, non-blinded study using sphincter of Oddi manometry showed that morphineincreased sphincter phasic wave amplitude and basal pressure (P

Acute Cholecystitis• A 2008 Cochrane review, which included five trials with 429 patients randomly assigned to the daycasegroup (n=215) and overnight-stay group (n=214), showed no significant difference betweenthe two groups regarding morbidity, prolongation of hospital stay, readmission rates, pain, qualityof life, patient satisfaction, and return to normal activity and work. The day-case electivelaparoscopic cholecystectomy was safe and effective in selected patients with symptomaticgallstones who had no or minimal systemic disease and were within easy reach of the hospital(59).• In a prospective study from the UK that included 106 patients who had day-case laparoscopiccholecystectomy, 84% were discharged on the day of surgery. Mean surgery time was 62 minutes,with an average total stay on the day-case unit of 426 minutes. Both the readmission rate aftersurgery and rate of conversion to open surgery were 2%. Introduction of day-case laparoscopiccholecystectomy in the UK was feasible and acceptable to patients (60).• Cholecystectomy using rigid-hybrid transvaginal natural orifice transluminal endoscopic surgeryreduces abdominal-wall incisions and might decrease surgical trauma by combining endoluminalaccess and laparoscopic techniques. In one study, 102 of 137 consecutive patients (74.5 %) withsymptomatic cholecystolithiasis (n=74) or cholecystitis (n=28) were scheduled for this type ofsurgery. There were no intraoperative complications. At 6 weeks postoperatively, there were fewerdyspareunia symptoms than preoperatively (P=0.049). This technique is feasible and safe inroutine practice for symptomatic cholecystolithiasis and acute cholecystitis (61).• Percutaneous transhepatic gallbladder drainage is a procedure to resolve acute cholecystitis, whichdecreases the technical difficulty of laparoscopic cholecystectomy and facilitates successful surgerywhen a patients' condition improves. Early laparoscopic cholecystectomy (within 72 hours, n=21)vs. delayed (after 72 hours; n=46) laparoscopic cholecystectomy after percutaneous transhepaticgallbladder drainage showed a higher complication rate and longer operating time, but shorterhospital stay in the former group (62).• In a retrospective study involving 809 patients with acute cholecystitis, laparoscopiccholecystectomy (done in 82% of patients) was associated with significantly better outcomes,including shorter postsurgical stay and fewer complications compared with open cholecystectomyand cholecystostomy (63).Rationale• Laparoscopic cholecystectomy is safer, less expensive, and associated with shorter hospitalizationsthan open procedures.• Early cholecystectomy is associated with a shorter recovery period and fewer complications, suchas gangrene and empyema of the gallbladder.• Acute cholecystitis and/or other serious complications of gallstone disease can recur in untreatedpatients.Comments• The exact surgical approach may vary based on local surgical expertise.• Patients should understand that conversion from a laparoscopic to an open procedure may benecessary.• Day-case laparoscopic cholecystectomy is not suitable for acute cholecystitis.• Natural orifice transluminal endoscopic surgery is being increasingly practiced with encouragingresults.• Single-incision laparoscopic cholecystectomy is a variation in which trocar scars are hidden in theumbilicus. In a study including 205 cases of single-incision laparoscopic cholecystectomy, the meanoperating time was 60 minutes and complications occurred in 4% of cases. Single-incisionlaparoscopic cholecystectomy can be done safely and offers a better cosmetic result, which maylead to greater patient satisfaction (64).5.4 Consider cholecystostomy in certain patients.RecommendationsPIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 14 of 32

Acute Cholecystitis• Consider cholecystostomy as temporizing or definitive therapy for inoperable or high-risk patientswith calculous or acalculous cholecystitis.Evidence• A retrospective study of inoperable patients treated with percutaneous cholecystostomy showed98% successful biliary drainage; 96% of these patients showed clinical improvement within 72hours, and 93% were discharged from the hospital with plans for a subsequent cholecystectomy(65).• A prospective study showed that 92.3% of patients with acute acalculous cholecystitis treated withpercutaneous cholecystostomy had good clinical response. All patients had subsequent catheterremoval without the need for cholecystectomy (66).• A prospective study showed that 93.3% of patients with acute acalculous cholecystitis treated withpercutaneous cholecystostomy had significant clinical improvement; 13 of 14 patients whoresponded had catheter removal and required no further therapy (67).• A retrospective study of 45 patients having cholecystostomy for acute cholecystitis showed a 100%technically successful gallbladder drainage rate. 78% of the patients improved clinically within 5days (68).• A prospective study randomizing patients with acute calculous cholecystitis into those havingpercutaneous cholecystostomy followed by an early laparoscopic cholecystectomy (n=31) andthose having an initial conservative treatment followed by a delayed laparoscopic cholecystectomy(n=30) showed significantly shorter hospital stay and lower cost in the first group (69).• In a study involving 106 patients with acute cholecystitis, percutaneous cholecystostomy led toclinical improvement in 72 patients (68%), whereas 34 (32%) showed no improvement or clinicaldeterioration. Patients who presented to the emergency department primarily with acutecholecystitis fared better (84% of patients showed improvement) than inpatients (34% showedimprovement; P

Acute Cholecystitis6. Patient EducationInform patients of the natural history of acute cholecystitis.6.1 Inform patients of the natural history and therapeutic options for acutecholecystitis.Recommendations• Explain the natural course of acute cholecystitis.• Inform the patient of the treatment options available.• Explain why surgical options are preferred in most cases.Evidence• A retrospective study of patients at initial presentation with acute cholecystitis showed 7.1% hadgangrenous cholecystitis, 6.3% had empyema of the gallbladder, 3.3% had gallbladder perforation,and 0.5% had emphysematous cholecystitis (71).• A prospective, randomized trial compared early cholecystectomy with delayed cholecystectomy inpatients with acute cholecystitis. In the delayed group, 13% of patients required emergent surgerywithin 90 days owing to cholangitis, empyema, or peritonitis. Another 15% of patients developedacute recurrent symptoms within the 90-day period (54).• A prospective, randomized clinical trial compared the outcomes of early (within 7 days of onset ofsymptoms) with delayed (6 to 8 weeks after initial conservative treatment) laparoscopiccholecystectomy. Twenty-six percent of patients in the delayed cholecystectomy group requiredemergency cholecystectomy for failure of conservative treatment. There was no significantdifference in the conversion rate, operating time, or complications. The greatest advantage was areduced length of hospital stay in the early cholecystectomy group (72).• A 2008 meta-analysis of 20 randomized, controlled trials including 3860 patients showed day-caselaparoscopic cholecystectomy to be safe in a selected group of patients who do not have acutecholecystitis, bile-duct stones, or previous upper-abdominal surgery (73).• In 185 adult patients admitted with acute cholecystitis (mean age 71 years; 80% had more thanone comorbidity), percutaneous cholecystostomy was done in 78% of cases and open surgicalcholecystostomy was done in 22%. In both groups, 85% patients underwent laparoscopiccholecystectomy as definitive treatment, thereby confirming that cholecystostomy is a usefulalternative to open cholecystectomy in patients with acute cholecystitis that allows patients toundergo laparoscopic cholecystectomy at a later date (74).Rationale• The risk for advanced disease and complications at the time of presentation is significant.• The risk for recurrent acute cholecystitis in the untreated patient is significant.• Surgical therapies are definitive, effective, and safe.TopPIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 16 of 32

Acute Cholecystitis7. Follow-upTopSchedule follow-up of patients treated for acute cholecystitis basedon hospital course.7.1 Ensure that patients who have had cholecystectomy follow-up with theirsurgeon.Recommendations• Advise patients to follow-up with their surgeon routinely, and immediately if they have right upperquadrant pain, fever, or wound-site complaints which suggest postoperative biliary tractcomplications such as retained bile-duct stone, bile leak, or infection.Evidence• Two prospective, randomized studies showed overall complication rates of 13% (75) and 9% (76)in patients having early laparoscopic cholecystectomy for acute cholecystitis.• A retrospective literature review showed that the overall risk for biliary injury during laparoscopiccholecystectomy (for any indication) is 2.58%; major bleeding occurred in 1.38% of cases, woundinfection in 0.6%, bile leak in 0.4%, biliary injury in 0.2%, and bowel injury in 0.16% (81). Aretrospective, single-center study showed bile-duct injury occurring in 0.59% of patients havinglaparoscopic cholecystectomy for any indication (82).Rationale• Laparoscopic cholecystectomy carries risk for postoperative complications; these risks are higher inpatients having the procedure for acute cholecystitis.• The surgeon should watch for signs and symptoms of biliary-tract complications and woundinfections.Comments• The surgeon should determine the postoperative follow-up schedule.7.2 Re-evaluate patients who have had cholecystostomy or medicalmanagement.Recommendations• In consultation with a surgeon, re-evaluate patients with acute cholecystitis who have had:Cholecystostomy or medical therapy alone for subsequent cholecystectomyMedical therapy with UDCA to dissolve remaining symptomatic gallstonesERCP with or without sphincterotomy to remove a retained bile-duct stone• Ask about recurrent symptoms of right upper quadrant pain and biliary colic, fever, and jaundice.Evidence• A prospective, randomized trial compared early cholecystectomy with delayed cholecystectomy inpatients with acute cholecystitis. In the delayed group, 13% of patients required emergent surgerywithin 90 days owing to cholangitis, empyema, or peritonitis. Another 15% of patients developedacute recurrent symptoms within the 90-day period (54).• A retrospective study showed that 61.5% of patients with acute calculous cholecystitis who weretemporized with a cholecystostomy tube were able to have subsequent elective cholecystectomy.Surgical morbidity was 12.5% with no mortalities (83).Rationale• Many patients treated conservatively for acute calculous cholecystitis will have recurrent significantcomplications.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 17 of 32

Acute Cholecystitis• Cholecystectomy provides definitive therapy.Comments• Extremely poor-risk surgical candidates can be maintained with a permanent cholecystostomydrainage tube.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 18 of 32

Acute CholecystitisReferencesTop1. May GR, Sutherland LR, Shaffer EA. Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials.Aliment Pharmacol Ther. 1993;7:139-48. (PMID: 8485266)2. Erlinger S, Le Go A, Husson JM, Fevery J. Franco-Belgian cooperative study of ursodeoxycholic acid in the medical dissolution ofgallstones: a double-blind, randomized, dose-response study, and comparison with chenodeoxycholic acid. Hepatology.1984;4:308-14. (PMID: 6706305)3. Fischer S, Muller I, Zundt BZ, Jungst C, Meyer G, Jungst D. Ursodeoxycholic acid decreases viscosity and sedimentable fractionsof gallbladder bile in patients with cholesterol gallstones. Eur J Gastroenterol Hepatol. 2004;16:305-11. (PMID: 15195895)4. Uy MC, Talingdan-Te MC, Espinosa WZ, Daez ML, Ong JP. Ursodeoxycholic acid in the prevention of gallstone formation afterbariatric surgery: a meta-analysis. Obes Surg. 2008;18:1532-8. (PMID: 18574646)5. Cho JY, Han HS, Yoon YS, Ahn KS. Risk factors for acute cholecystitis and a complicated clinical course in patients withsymptomatic cholelithiasis. Arch Surg. 2010;145:329-33; discussion 333. (PMID: 20404281)6. Venneman NG, Besselink MG, Keulemans YC, Vanberge-Henegouwen GP, Boermeester MA, Broeders IA, et al. Ursodeoxycholicacid exerts no beneficial effect in patients with symptomatic gallstones awaiting cholecystectomy. Hepatology. 2006;43:1276-83. (PMID: 16729326)7. Basurto Oña X, Robles Perea L. [Anti-inflammatory drugs for biliary colics: systematic review and meta-analysis of randomizedcontrolled trials.] Gastroenterol Hepatol. 2008;31:1-7. (PMID: 18218271)8. Akriviadis EA, Hatzigavriel M, Kapnias D, Kirmlidis J, Markantas A, Garyfallos A. Treatment of biliary colic with diclofenac: arandomized, double-blind, placebo-controlled study. Gastroenterology. 1997;113:225-31. (PMID: 9207282)9. Kumar A, Deed JS, Bhasin B, Kumar A, Thomas S. Comparison of the effect of diclofenac with hyoscine-N-butylbromide in thesymptomatic treatment of acute biliary colic. ANZ J Surg. 2004;74:573-6. (PMID: 15230794)10. Thistle JL, Cleary PA, Lachin JM, Tyor MP, Hersh T. The natural history of cholelithiasis: the National Cooperative GallstoneStudy. Ann Intern Med. 1984;101:171-5. (PMID: 6742647)11. Ransohoff DF, Gracie WA. Treatment of gallstones. Ann Intern Med. 1993;119(7 Pt 1):606-19. Review. (PMID: 8363172)12. Gurusamy KS, Samraj K. Cholecystectomy versus no cholecystectomy in patients with silent gallstones. Cochrane DatabaseSyst Rev. 2007;(1):CD006230. (PMID: 17253585)13. Nikfarjam M, Niumsawatt V, Sethu A, Fink MA, Muralidharan V, Starkey G, et al. Outcomes of contemporary management ofgangrenous and non-gangrenous acute cholecystitis. HPB (Oxford). 2011;13:551-8. (PMID: 21762298)14. Singer AJ, McCracken G, Henry MC, Thode HC Jr, Cabahug CJ. Correlation among clinical, laboratory, and hepatobiliaryscanning findings in patients with suspected acute cholecystitis. Ann Emerg Med. 1996;28:267-72. (PMID: 8780468)15. Raine PA, Gunn AA. Acute cholecystitis. Br J Surg. 1975;62:697-700. (PMID: 1174813)16. Wang AJ, Wang TE, Lin CC, Lin SC, Shih SC. Clinical predictors of severe gallbladder complications in acute acalculouscholecystitis. World J Gastroenterol. 2003;9:2821-3. (PMID: 14669342)17. Fagan SP, Awad SS, Rahwan K, Hira K, Aoki N, Itani KM, et al. Prognostic factors for the development of gangrenouscholecystitis. Am J Surg. 2003;186:481-5. (PMID: 14599611)18. Staniland JR, Ditchburn J, De Dombal FT. Clinical presentation of acute abdomen: study of 600 patients. Br Med J. 1972;3:393-8. (PMID: 4506871)19. Halasz NA. Counterfeit cholecystitis, a common diagnostic dilemma. Am J Surg. 1975;130:189-93. (PMID: 1155733)20. Kalliafas S, Ziegler DW, Flancbaum L, Choban PS. Acute acalculous cholecystitis: incidence, risk factors, diagnosis, andoutcome. Am Surg. 1998;64:471-5. (PMID: 9585788)21. Eggermont AM, Lameris JS, Jeekel J. Ultrasound-guided percutaneous transhepatic cholecystostomy for acute acalculouscholecystitis. Arch Surg. 1985;120:1354-6. (PMID: 3904672)22. Dumont AE. Significance of hyperbilirubinemia in acute cholecystitis. Surg Gynecol Obstet. 1976;142:855-7. (PMID: 936028)23. Gruber PJ, Silverman RA, Gottesfeld S, Flaster E. Presence of fever and leukocytosis in acute cholecystitis. Ann Emerg Med.1996;28:273-7. (PMID: 8780469)24. Peng WK, Sheikh Z, Paterson-Brown S, Nixon SJ. Role of liver function tests in predicting common bile duct stones in acutecalculous cholecystitis. Br J Surg. 2005;92:1241-7. (PMID: 16078299)25. Mills LD, Mills T, Foster B. Association of clinical and laboratory variables with ultrasound findings in right upper quadrantabdominal pain. South Med J. 2005;98:155-61. (PMID: 15759944)PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 19 of 32

Acute Cholecystitis26. Ralls PW, Colletti PM, Lapin SA, Chandrasoma P, Boswell WD Jr, Ngo C, et al. Real-time sonography in suspected acutecholecystitis. Prospective evaluation of primary and secondary signs. Radiology. 1985;155:767-71. (PMID: 3890007)27. Matolo NM, Stadalnik RC, McGahan JP. Comparison of ultrasonography, computerized tomography, and radionuclide imaging inthe diagnosis of acute and chronic cholecystitis. Am J Surg. 1982;144:676-81. (PMID: 7149126)28. Fink-Bennett D, Freitas JE, Ripley SD, Bree RL. The sensitivity of hepatobiliary imaging and real-time ultrasonography in thedetection of acute cholecystitis. Arch Surg. 1985;120:904-6. (PMID: 3893388)29. Shea JA, Berlin JA, Escarce JJ, Clarke JR, Kinosian BP, Cabana MD, et al. Revised estimates of diagnostic test sensitivity andspecificity in suspected biliary tract disease. Arch Intern Med. 1994;154:2573-81. (PMID: 7979854)30. Kalimi R, Gecelter GR, Caplin D, Brickman M, Tronco GT, Love C, et al. Diagnosis of acute cholecystitis: sensitivity ofsonography, cholescintigraphy, and combined sonography-cholescintigraphy. J Am Coll Surg. 2001;193:609-13. (PMID:11768676)31. Cheng SM, Ng SP, Shih SL. Hyperdense gallbladder wall sign: an overlooked sign of acute cholecystitis on unenhanced CTexamination. Clin Imaging. 2004;28:128-31. (PMID: 15050226)32. Romagnuolo J, Bardou M, Rahme E, Joseph L, Reinhold C, Barkun AN. Magnetic resonance cholangiopancreatography: a metaanalysisof test performance in suspected biliary disease. Ann Intern Med. 2003;139:547-57. (PMID: 14530225)33. Working Party of the British Society of Gastroenterology; Association of Surgeons of Great Britain and Ireland; PancreaticSociety of Great Britain and Ireland; Association of Upper GI Surgeons of Great Britain and Ireland. UK guidelines for themanagement of acute pancreatitis. Gut. 2005;54 Suppl 3:iii1-9. (PMID: 15831893)34. Mergen H, Genç H, Tavusbay C. Assessment of liver hydatid cyst cases--10 years experience in Turkey. Trop Doct.2007;37:54-6. (PMID: 17326896)35. Wani I. Gallbladder ascariasis. Turk J Gastroenterol. 2011;22:178-82. (PMID: 21796555)36. Kelly TR. Benign liver tumors: presenting profiles and treatment. Am Surg. 1981;46:398-402. (PMID: 7447174)37. Boer J, Boerma D, de Vries Reilingh TS. A gallbladder torsion presenting as acute cholecystitis in an elderly woman: A casereport. J Med Case Rep. 2012;5:588. (PMID: 22185300)38. Choi YS. Gallbladder hemorrhage mimicking acute cholecystitis in a patient under antiplatelet therapy. Z Gastroenterol.2012;50:285-7. (PMID: 22383284)39. Ko CW. Risk factors for gallstone-related hospitalization during pregnancy and the postpartum. Am J Gastroenterol.2006;101:2263-8. (PMID: 17032191)40. Chiappetta Porras LT, Nápoli ED, Canullán CM, Quesada BM, Roff HE, Alvarez Rodríguez J, et al. Minimally invasivemanagement of acute biliary tract disease during pregnancy. HPB Surg. 2009;2009:829020. (PMID: 19606252)41. Elamin Ali M, Yahia Al-Shehri M, Abu-Eshy S, Cheema MA, Mustafa Z, Sadek A. Is surgical intervention in acute cholecystitis inpregnancy justified? J Obstet Gynaecol. 2004;17:435-8. (PMID: 15511915)42. Kuy S, Roman SA, Desai R, Sosa JA. Outcomes following cholecystectomy in pregnant and nonpregnant women. Surgery.2009;146:358-66. (PMID: 19628096)43. Csendes A, Burdiles P, Maluenda F, Diaz JC, Csendes P, Mitru N. Simultaneous bacteriologic assessment of bile from gallbladderand common bile duct in control subjects and patients with gallstones and common duct stones. Arch Surg. 1996;131:389-94.(PMID: 8615724)44. Vogt AP, Doshi RK, Higgins JE, Burd EM, Ribner BS, Kraft CS. Acute cholecystitis caused by nontoxigenic Vibrio cholerae O1Inaba. J Clin Microbiol. 2010;48:1002-4. (PMID: 20053858)45. Matsubayashi T, Tobayama S, Machida H. Acute cholecystitis caused by Haemophilus influenzae in a child. J Infect Chemother.2009;15:325-7. (PMID: 19856072)46. Aller AI, Castro C, Medina MJ, González MT, Sevilla P, Morilla MD, et al. Isolation of Moellerella wisconsensis from blood culturefrom a patient with acute cholecystitis. Clin Microbiol Infect. 2009;15:1193-4. (PMID: 19732083)47. khan FY, Elouzi EB, Asif M. Acute acalculous cholecystitis complicating typhoid fever in an adult patient: a case report andreview of the literature. Travel Med Infect Dis. 2009;7:203-6. (PMID: 19717100)48. Drage M, Reid A, Callaghan CJ, Baber Y, Freeman S, Huguet E, et al. Acute cytomegalovirus cholecystitis following renaltransplantation. Am J Transplant. 2009;9:1249-52. (PMID: 19422351)49. Ohtaki H, Ohkusu K, Sawamura H, Ohta H, Inoue R, Iwasa J, et al. First report of acute cholecystitis with sepsis caused byCellulomonas denverensis. J Clin Microbiol. 2009;47:3391-3. (PMID: 19656981)50. Yildirim M, Ozaydin I, Sahin I, Yasar M. Acute calculous cholecystitis caused by Candida lusitaniae: an unusual causativeorganism in a patient without underlying malignancy. Jpn J Infect Dis. 2008;61:138-9. (PMID: 18362405)PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 20 of 32

Acute Cholecystitis51. Kune GA, Burdon JG. Are antibiotics necessary in acute cholecystitis? Med J Aust. 1975;2:627-30. (PMID: 1207539)52. Olsen JC, McGrath NA, Schwarz DG, Cutcliffe BJ, Stern JL. A double-blind randomized clinical trial evaluating the analgesicefficacy of ketorolac versus butorphanol for patients with suspected biliary colic in the emergency department. Acad EmergMed. 2008;15:718-22. (PMID: 18637080)53. Helm JF, Venu RP, Geenen JE, Hogan WJ, Dodds WJ, Toouli J, et al. Effects of morphine on the human sphincter of Oddi. Gut.1988;29:1402-7. (PMID: 3197985)54. Jarvinen HJ, Hastbacka J. Early cholecystectomy for acute cholecystitis: a prospective randomized study. Ann Surg.1980;191:501-5. (PMID: 6445180)55. Navez B, Mutter D, Russier Y, Vix M, Jamali F, Lipski D, et al. Safety of laparoscopic approach for acute cholecystitis:retrospective study of 609 cases. World J Surg. 2001;25:1352-6. (PMID: 11596902)56. Kiviluoto T, Siren J, Luukkonen P, Kivilaakso E. Randomised trial of laparoscopic versus open cholecystectomy for acute andgangrenous cholecystitis. Lancet. 1998;351:321-5. (PMID: 9652612)57. Siddiqui T, MacDonald A, Chong PS, Jenkins JT. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis: ameta-analysis of randomized clinical trials. Am J Surg. 2008;195:40-7. (PMID: 18070735)58. Gurusamy K, Samraj K, Gluud C, Wilson E, Davidson BR. Meta-analysis of randomized controlled trials on the safety andeffectiveness of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg. 2010;97:141-50. (PMID:20035546)59. Gurusamy KS, Junnarkar S, Farouk M, Davidson BR. Day-case versus overnight stay for laparoscopic cholecystectomy.Cochrane Database Syst Rev. 2008;(3):CD006798. (PMID: 18677781)60. Briggs CD, Irving GB, Mann CD, Cresswell A, Englert L, Peterson M, et al. Introduction of a day-case laparoscopiccholecystectomy service in the UK: a critical analysis of factors influencing same-day discharge and contact with primary careproviders. Ann R Coll Surg Engl. 2009;91:583-90. (PMID: 19558787)61. Linke GR, Tarantino I, Hoetzel R, Warschkow R, Lange J, Lachat R, et al. Transvaginal rigid-hybrid NOTES cholecystectomy:evaluation in routine clinical practice. Endoscopy. 2010;42:571-5. (PMID: 20432208)62. Han IW, Jang JY, Kang MJ, Lee KB, Lee SE, Kim SW. Early versus delayed laparoscopic cholecystectomy after percutaneoustranshepatic gallbladder drainage. J Hepatobiliary Pancreat Sci. 2012;19:187-93. (PMID: 21938408)63. Wiseman JT, Sharuk MN, Singla A, Cahan M, Litwin DE, Tseng JF, et al. Surgical management of acute cholecystitis at a tertiarycare center in the modern era. Arch Surg. 2010;145:439-44. (PMID: 20479341)64. Vemulapalli P, Agaba EA, Camacho D. Single incision laparoscopic cholecystectomy: a single center experience. Int J Surg.2011;9:410-3. (PMID: 21515426)65. Spira RM, Nissan A, Zamir O, Cohen T, Fields SI, Freund HR. Percutaneous transhepatic cholecystostomy and delayedlaparoscopic cholecystectomy in critically ill patients with acute calculus cholecystitis. Am J Surg. 2002;183:62-6. (PMID:11869705)66. Sugiyama M, Tokuhara M, Atomi Y. Is percutaneous cholecystostomy the optimal treatment for acute cholecystitis in the veryelderly? World J Surg. 1998;22:459-63. (PMID: 9564288)67. Shirai Y, Tsukada K, Kawaguchi H, Ohtani T, Muto T, Hatakeyama K. Percutaneous transhepatic cholecystostomy for acuteacalculous cholecystitis. Br J Surg. 1993;80:1440-2. (PMID: 8252358)68. Byrne MF, Suhocki P, Mitchell RM, Pappas TN, Stiffler HL, Jowell PS, et al. Percutaneous cholecystostomy in patients with acutecholecystitis: experience of 45 patients at a US referral center. J Am Coll Surg. 2003;197:206-11. (PMID: 12892798)69. Akyürek N, Salman B, Yüksel O, Tezcaner T, Irkörücü O, Yücel C, Oktar S, Tatlicioglu E. Management of acute calculouscholecystitis in high-risk patients: percutaneous cholecystotomy followed by early laparoscopic cholecystectomy. SurgLaparosc Endosc Percutan Tech. 2005 Dec;15(6):315-20. (PMID: 16340560)70. Joseph T, Unver K, Hwang GL, Rosenberg J, Sze DY, Hashimi S, et al. Percutaneous cholecystostomy for acute cholecystitis:ten-year experience. J Vasc Interv Radiol. 2012;23:83-8.e1. (PMID: 22133709)71. Bedirli A, Sakrak O, Sozuer EM, Kerek M, Guler I. Factors effecting the complications in the natural history of acutecholecystitis. Hepatogastroenterology. 2001;48:1275-8. (PMID: 11677945)72. Johansson M, Thune A, Blomqvist A, Nelvin L, Lundell L. Management of acute cholecystitis in the laparoscopic era: results of aprospective, randomized clinical trial. J Gastrointest Surg. 2003;7:642-5. (PMID: 12850677)73. Tenconi SM, Boni L, Colombo EM, Dionigi G, Rovera F, Cassinotti E. Laparoscopic cholecystectomy as day-surgery procedure:current indications and patients' selection. Int J Surg. 2008;6 Suppl 1:S86-8. (PMID: 19167938)74. Cherng N, Witkowski ET, Sneider EB, Wiseman JT, Lewis J, Litwin DE, et al. Use of cholecystostomy tubes in the managementof patients with primary diagnosis of acute cholecystitis. J Am Coll Surg. 2012;214:196-201. (PMID: 22192897)PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 21 of 32

Acute Cholecystitis75. Lo CM, Liu CL, Fan ST, Lai EC, Wong J. Prospective randomized study of early versus delayed laparoscopic cholecystectomy foracute cholecystitis. Ann Surg. 1998;227:461-7. (PMID: 9563529)76. Lai PB, Kwong KH, Leung KL, Kwok SP, Chan AC, Chung SC, et al. Randomized trial of early versus delayed laparoscopiccholecystectomy for acute cholecystitis. Br J Surg. 1998;85:764-7. (PMID: 9667702)77. Chang L, Moonka R, Stelzner M. Percutaneous cholecystostomy for acute cholecystitis in veteran patients. Am J Surg.2000;180:198-202. (PMID: 11084129)78. Lai EC, Mok FP, Tan ES, Lo CM, Fan ST, You KT, Wong J. Endoscopic biliary drainage for severe acute cholangitis. N Engl J Med.1992;326:1582-6. (PMID: 1584258)79. Leung JW, Chung SC, Sung JJ, Banez VP, Li AK. Urgent endoscopic drainage for acute suppurative cholangitis. Lancet.1989;1:1307-9. (PMID: 2566834)80. Ke ZW, Zheng CZ, Li JH, Yin K, Hua JD. Prospective evaluation of magnetic resonance cholangiography in patients withsuspected common bile duct stones before laparoscopic cholecystectomy. Hepatobiliary Pancreat Dis Int. 2003;2:576-80.(PMID: 14627523)81. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am CollSurg. 1995;180:101-25. (PMID: 8000648)82. Mahatharadol V. Bile duct injuries during laparoscopic cholecystectomy: an audit of 1522 cases. Hepatogastroenterology.2004;51:12-4. (PMID: 15011821)83. Werbel GB, Nahrwold DL, Joehl RJ, Vogelzang RL, Rege RV. Percutaneous cholecystostomy in the diagnosis and treatment ofacute cholecystitis in the high-risk patient. Arch Surg. 1989;124:782-5. (PMID: 2742479)PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 22 of 32

Acute CholecystitisGlossaryTopALTalanine aminotransferaseASTaspartate aminotransferaseCBCcomplete blood countCDCAchenodeoxycholic acidCIconfidence intervalCTcomputed tomographyDISIDAdiisopropyl phenyl carboxymethyl iminodiacetic acidERCPendoscopic retrograde cholangiopancreatographyGIgastrointestinalHIDAhepato-iminodiacetic acidICUintensive care unitIgGimmunoglobulin GIgMimmunoglobulin MivintravenousLFTliver function testMRCmagnetic resonance cholangiographyMRCPmagnetic resonance cholangiopancreatographyNSAIDnonsteroidal anti-inflammatory drugRRrisk ratioSDstandard deviationTPNtotal parenteral nutritionUDCAursodeoxycholic acidPIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 23 of 32

Acute CholecystitisPIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 24 of 32

Acute CholecystitisTablesTopLaboratory and Other Studies for Acute CholecystitisTestComplete blood countLiver function testsSerum bilirubinSerum amylaseNotesLook for leukocytosisCan be elevated in acute cholecystitisIf >4 mg/dL, consider common bile-duct stones or Mirizzi's syndromeIf significant increases (more than three times the upper limit of normal), consider pancreatitis orcommon bile-duct stones (33)Serum alkaline phosphatase Elevation significantly predicts acute cholecystitis (25)Right upper quadrant ultrasound scan Sensitivity 81-98%Specificity 70-98%Portable, inexpensive.HIDA scan Sensitivity 85-97%Sonographic Murphy's sign (showing maximal tenderness directly over the visualized gallbladder) isover 90% predictive of acute cholecystitisSpecificity 90%CT scanMRI scan or MRCP scanExpensive; most useful to diagnose such complications as perforationSensitivity 100% for cystic-duct obstruction; 69 for gallbladder-wall thickeningSpecificity 93% for cystic-duct obstruction; 83% for gallbladder-wall thickeningCommonly used to diagnose ductal obstruction caused by stones or a malignant lesionCT = computed tomography; HIDA = hepato-iminodiacetic acid; MRCP = magnetic resonance cholangiopancreatography; MRI = magnetic resonance imaging.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 25 of 32

Acute CholecystitisDifferential Diagnosis of Acute CholecystitisDiseaseAcute cholecystitisAcute cholangitisAcute appendicitisAcute pancreatitisPyelonephritis (right)Peptic ulcer diseasePulmonary/pleural diseaseAcute viral hepatitisAcute alcoholic hepatitisInferior myocardial infarctionMesenteric ischemiaFitz-Hugh-Curtis syndrome (gonococcal perihepatitis)Hepatic abscess or tumorPre- and post-herpetic neuralgiaCharacteristicsMid-epigastric pain progressing to right upper quadrant. Pain may also radiate to right scapula, rightshoulder, back, or lower abdomen. Murphy's sign is highly specific and predictiveBilirubin >4 mg/dL is not a feature of uncomplicated acute cholecystitisCharcot triad (right upper quadrant pain, fever, jaundice)orReynold pentad (Charcot triad and shock and mental-status changes)Bilirubin generally >4 mg/dL.AST and ALT levels may exceed 1000 U/LMid-epigastric pain radiating to right lower quadrantCan mimic acute cholecystitis, especially with a high-lying cecumMid-epigastric pain radiating to the back, nausea, vomiting, elevated amylase and lipaseVomiting and hyperamylasemia are generally more pronounced than in acute cholecystitisCostovertebral angle tenderness, evidence of urinary infectionUrinalysis helps establish the diagnosisRight upper quadrant or mid-epigastric painPerforated ulcer can mimic acute cholecystitisCough, shortness of breath, chest or upper abdominal painPleuritic pain component much less common in acute cholecystitisProdromal syndrome, jaundice, AST and ALT levels generally >1000 U/LLFT and bilirubin level usually much higher than in acute cholecystitisRight upper quadrant pain, fever, jaundice, coagulopathy, leukocytosis, AST level usually two to threetimes greater than ALT levelBilirubin level generally >4 mg/dLRecent significant alcohol intakeChest/mid-epigastric pain, diaphoresis, shortness of breath, elevated cardiac enzymes, acutelyabnormal electrocardiogramPresence of cardiac risk factors.Pain characteristics generally different than acute cholecystitisPeriumbilical or mid-epigastric pain out of proportion to tendernessRight upper quadrant pain, adnexal tenderness, leukocytosisCervical smear shows gonococciRight upper quadrant pain, feverProbably requires imaging studies to differentiateRight upper quadrant pain, fever, and malaise followed by vesicular rash on the thoracic dermatomePIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 26 of 32

Acute CholecystitisVaricella IgM and IgG antibody assays helpfulBleeding or infection of hepatic hydatid cystsGall bladder ascariasisBenign liver adenomasTorsion of the gallbladderBleeding within the gallbladderRight upper quadrant pain and feverUltrasound or CT scans confirm the diagnosis (34)Right upper quadrant pain and feverUltrasound or MRC confirms the diagnosis (35)Right upper quadrant painUltrasound, CT scans, and biopsy confirm the diagnosis (36)Right upper quadrant pain and feverUltrasound or CT scans confirm the diagnosis (37)Right upper quadrant painUltrasound or CT scans confirm the diagnosis (38)ALT = alanine aminotransferase; AST = aspartate aminotransferase; CT = computed tomography; IgG = immunoglobulin G; IgM = immunoglobulin M; LFT = liver function test; MRC = magnetic resonancecholangiography.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 27 of 32

Acute CholecystitisDrug Treatment for Acute CholecystitisDrug or Drug Class Dosing Side Effects Precautions Clinical UsePenicillinsHypersensitivity reactions, hematologictoxicity, vomiting, diarrheaSeizures can occur when large dosesgiven with renal impairmentPiperacillin/tazobactam (Zosyn) 3.375 g iv q6hr Constipation, hypokalemia, headache If CrCl

Acute CholecystitisFiguresTopGallbladder Ultrasound Showing GallstonesOn ultrasonography, gallstones appear as an echogenic focus that casts an acoustic shadow.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 29 of 32

Acute CholecystitisAcalculous CholecystitisGallbladder ultrasound consistent with acalculous cholecystitis showing an absence of gallstones or sludge, thickened gallbladder wall, and pericholecystic fluid.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 30 of 32

Acute CholecystitisNormal Gallbladder UltrasoundAn ultrasound of a normal gallbladder. The gallbladder wall is denoted by a thin white line. The gallbladder is filled with fluid and appears black.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 31 of 32

Acute CholecystitisGallstone IleusPlain film of the abdomen showing air in the hepatic biliary tree (arrow) and dilated loops of bowel. Air in the biliary tree and signs of bowel obstruction support the diagnosis of fistulabetween the biliary tree and bowel, most likely created by a gallstone that obstructed the cystic duct, eroded through the wall, and is now obstructing the small bowel.PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.Page 32 of 32