TG13: Updated Tokyo guidelines for acute cholecystitis

Only Internationally recognized guidelines regarding acute cholecystitis

1. TG13: Updated Tokyo guidelines for acute cholecystitis Jibran Mohsin Resident, Surgical Unit I SIMS/Services Hospital, Lahore

2. Background Before TG07, there were no practical guidelines through out the world primarily targeting acute cholecystitis TG07 was updated after total 35 meetings of Tokyo Guidelines Revision Committee for revision of TGO7(TGRC) email exchanges with c o authors abroad e.g. USA, Netherlands, UK, Germany, New Zealand, India, Korea, China, Greece, Hong Kong, Italy, Philippines, Taiwan, Singapore, Argentina, Australia and Malaysia 3 International Meetings for the Clinical Assessment and Revision of Tokyo Guidelines

3. OUTLINE Terminology, Etiology and Epidemiology Diagnostic Criteria Severity assessment criteria/grading Differential Diagnosis Management Antimicrobial therapy Gallbladder drainage Surgical management Summary Management bundle Acute Cholecystitis Bundle Checklist

4. Terminology, Etiology and Epidemiology Definition Acute inflammatory disease of gallbladder, often attributable to gallstones, but many factors such as ischemia, motility disorders, direct chemical injury, infections by microorganism, protozoon and parasites, collagen disease, and allergic reaction are also involved

5. Terminology, Etiology and Epidemiology Pathophysiology Gallstones are the cause of acute cholecystitis in majority of cases Involves physical obstruction at neck or in cystic duct by gallstone Leading to increased pressure in GB Determined by degree of obstruction and duration of obstruction i.e. partial and short duration  biliary colic Complete and long duration  Acute cholecystitis If early treatment not given  severe disease and risk of complications

6. Terminology, Etiology and Epidemiology Pathological Classification STAGE FINDINGS Edematous Cholecystitis 1 st Stage 2-4 days Interstitial fluid with dilated capillaries and lymphatics Edematous wall (sub serosal layer) of GB Intact GB tissue Necrotizing Cholecystitis 2 nd Stage 3-5 days Edematous changes with areas of hemorrhage and scattered necrosis (superficial, not full thickness) Vascular thrombosis and occlusion Suppurative Cholecystitis 3 rd Stage 7-10 days WBC infiltration with areas of necrosis and suppuration Active repairing process of inflammation Contracted and thick wall due to fibrosis Intramural (not entire thickness) and pericholecystic abscesses Chronic Cholecystitis Repeated attacks of mild cholecystitis Mucosal atrophy and fibrosis of GB wall Chronic irritation by large gallstones Acute on chronic cholecystitis Neutrophil invasion + lymphocyte/plasma cell infiltration

7. Terminology, Etiology and Epidemiology Special forms of acute cholecystitis Acalculous Cholecystitis Acute cholecystitis wtihout cholecystoithiasis Xanthogranulomatous cholecystits Cholecystitis with xanthogranulomatous thickening of GB wall and raised GB pressure due to stones with rupture of Rokitansky-Aschoff sinuses. Leakage and entry of bile into GB wall, ingested by histiocytes to form granulomas containing foamy histiocytes Emphysematous Cholecystitis Air in GB wall due to gas-forming anaerobes including Clostridium perfringens Often seen in diabetes and likely to progress to sepsis and gangrenous cholecystitis Torsion of GB INHERITED FACTORS : floating GB ACQURIED FACTORS: splanchoptosis , senile humpback, scoliosis, weight loss PHYSICAL FACTORS : sudden change in intraperitoneal pressure, sudden change of body position, pendulum-like movement in anteflexion position, hyperperistalsis of organs near GB, defecation, and blow to abdomen

8. Terminology, Etiology and Epidemiology Advanced forms of and the type of complications of acute cholecystitis Perforation of gallbladder Due to acute cholecystitis , injury or tumors Most frequently due to ischemia and necrosis of GB wall Biliary Peritonitis Due to cholecystitis-induced GB perforation, trauma, and detached catheter during biliary drainage and incomplete suture after biliary operation Pericholecystitic abscess Perforation of GB covered by surrounding tissue along with formation of abscesses around GB Biliary fistula Between GB and duodenum following an episode of acute cholecystitis Due to large stone eroding through GB wall into duodenum Can also cause gallstone ileus (mechanical obstruction by stone at ileocecal valve)

9. Terminology, Etiology and Epidemiology Incidence Around 10 % of general population have gallstones 20-40 % of asymptomatic gallstone have risk for developing some type of S/S. (1-3 % annually) 1-2 % asymptomatic and 1-3 % mild symptomatic gallstones annually present with severe symptoms or complications (acute cholecystitis/cholangitis/ pancreatitis and severe jaundice)

10. Terminology, Etiology and Epidemiology Incidence Acute cholecystitis – most frequent complication of cholelithiasis (3.8 - 12 %) 6.0 % cases are of severe (accompanying organ dysfunction- Grade III) acute cholecystitis 0.2 – 1.0 % cases of ERCP develop acute cholystitis

11. Terminology, Etiology and Epidemiology Etiology 90-95 % gallstones 3.7 – 14 % acalculous cholecysytitis Mechanism Gallstone  Cystic duct obstruction  bile stasis  activation of inflammatory mediators and mucosal injuries

12. Terminology, Etiology and Epidemiology Risk Factors “4Fs” ( forties, female, fat, fair) and “5Fs” ( 4Fs + fecund or fertile) associated with lithogenesis in GB but no established association with acute cholecystitis except obesity Drugs: Hormone replacement therapy (2X), thiazides?, Hepatic artery chemotherapy, statins (protective) AIDS (AIDS cholangiopathy and acute acalculous cholecystitis) Parenteral Nutrition, thermal burn, infection, surgery, trauma, long term ICU stay

13. Terminology, Etiology and Epidemiology Prognosis Mortality rate Grade I 0.6 % Grade II 0 % Grade III 21.4 % overall 1.7 %

14. Terminology, Etiology and Epidemiology

15. Diagnostic Criteria Murphy’s (1903) sign shows high specificity( 79 – 96 %), however the sensitivity has been reported low ( 50-65 %), thus not applicable in making a diagnosis of acute cholecystitis due to low sensitivity TG13 Diagnostic criteria for acute cholecystitis A. Local signs of inflammation etc. Murphy’s sign RUQ mass/pain/tenderness B. Systemic signs of inflammation etc. Fever Elevated CRP Elevated WBC count C. Imaging findings Characteristic of acute cholecystitis SUSPECTED DIAGNOSIS: one item in A + one item in B DEFINITE DIAGNOSIS: one item in A + one item in B + C Sensitivity (91 %) Specificity (97%) IMAGING: USG CT Tc-HIDA scans

16. Diagnostic Criteria Most typical clinical sign of acute cholecystitis is abdominal pain ( RHC or epigastric) -72-93 % Followed in frequency by nausea and vomiting Fever >38 O C only in 30 % cases Muscular defense (guarding) in 50 % cases Palpable tumors, rebound tenderness, stiffness (rigidity) are rare

17. Diagnostic Criteria

18. Diagnostic Criteria No specific blood tests for making a diagnosis of acute cholecystitis General inflammatory findings (> 10,000 mm 3 / dL TLC, > 3 mg/ dL CPR level) Mild increase of serum enzymes in hepatobiliary system Raised bilirubin (up to 4 mg/ dL ) even in absence of complications

19. Diagnostic Criteria Ultrasonography should be performed at the initial consultation for all cases for which acute cholecystitis is suspected (satisfactory diagnostic capability even if done by ER physicians) Ultrasonography shows 50-88 % sensitivity and 80-88 % specificity Diagnostic if all of following are present Thickening of GB wall (5mm or more) Pericholecystic fluid Direct tenderness when probe is pushed against GB ( ultrasonographic Murphy’s sign – superior to ordinary Murphy’s sign in that it is possible to press GB accurately i.e 90 % sensitivity and specificity)

20. Diagnostic Criteria Others GB enlargement, GB stones(13 % cases), debris echo and gas imaging sonolucent(hypoechoic) layer, referred to as a low-echo zone (8 % sensitivity, 71 % specificity) Low-echoic area with an irregular multiple structure (62 % sensitivity, 100 % specificity)

21. Diagnostic Criteria Findings on contrast enhanced CT characteristic of acute cholecystitis GB distension (41 %) Pericholecystic fat stranding/density (52 %) GB wall thickening (59 %) Subserosal edema (31 %) Mucosal enhancement Transient focal enhancement of liver adjacent to gallbladder due to increased venous flow in cholecystic vein draining directly into liver parenchyma ( during arterial phase of dynamic CT, disappears during portal and equilibrium phase) Pericholecystic fluid collection (31 %) Pericholecystic abscess Gas collection within GB High- attenuation GB bile (24 %)

22. Diagnostic Criteria Tc-HIDA scan GB normally visualized within 30 min if cystic duct is patent i.e. no cholecystitis Failure of GB to fill within 60 min after administration of tracer  obstructed cystic duct 80-90 % sensitivity for acute cholecystitis False positive largely explained by cystic duct obstruction induced by chronic inflammation and some cases normal GB don’t fill due to SOD “Rim sign” = blush of increased pericholecystic radioactivity (30 % cases) Significantly higher specificity and accuracy than US

23. Diagnostic Criteria US versus Tc-HIDA scan Gold standard is Tc-HIDA scan BUT initial investigation of choice is US Immediate availability Easy access Lack of interference by elevated serum bilirubin levels (cholestasis interferes with biliary excretion of agents used for scintigraphy) Absence of ionizing radiation Information regarding presence of stone

24. Severity assessment criteria/grading

25. Differential Diagnosis Gastric and Duodenal ulcer Hepatitis Pancreatitis GB cancer Hepatic abscess Fitz-Hugh-Curtis syndrome Right lower lobar pneumonia Angina pectoris/MI UTI

26. Flowchart for management 1 st Line T/M Surgical risk 1 st Line T/M

27. Management Initial medical treatment while considering for surgery and ER drainage Nill By Mouth IV hydration and electrolytes correction Antimicrobial Analgesic Respiratory and hemodynamic monitoring Appropriate organ support in severe acute cholecystitis Artificial respiration, intubation and vasopressors along with ER drainage/cholecystectomy

28. Management Analgesics should be initiated in early stage as it doesn’t affect positive rate of sonographic Murphy’s sign NSAID (diclofenac 75 mg IM) administration is effective for impacted stones attack for PREVENTING acute cholecystitis NSAID also effective for improvement of GB function in chronic cholecystitis NOT effective to improve the course of cholecystitis after its acute onset

29. Antimicrobial therapy Primary Goal To limit both systemic septic response and local inflammation To prevent SSI (superficial, deep, organ space) To prevent intrahepatic abscess formation Early and non-severe cases  Prophylactic Others with SIRS  therapeutic

30. Antimicrobial therapy

31. Antimicrobial therapy Bile cultures should be obtained at the beginning of any procedure performed. GB bile should be sent for culture in all cases of acute cholecystitis expecting those with grade I severity TG13 suggest cultures of bile and tissue when perforation, emphysematous changes, or necrosis of GB are noted during cholecystectomy Blood cultures are not routinely recommended for grade I community-acquired acute cholecystitis

32. Antimicrobial therapy Factors influencing the selection of antimicrobial agents for acute cholecystitis Targeted organisms Pharmacokinetics Pharmacodynamics Local Antibiogram (local epidemiology and susceptibility data) H/O antimicrobial usage (< 6 months, increased risk of resistance) Renal and hepatic function (Dosage adjustment) H/O of allergies and other adverse events

33. Antimicrobial therapy Initiated as soon as diagnosis of acute cholecystitis is suspected For case in septic shock, within 1 h of recognition For other cases, as long as 4 h may be spent obtaining definitive diagnostic studies prior to beginning antimicrobial therapy Should definitely be started before any procedure (endoscopic or operative) Anaerobic therapy is appropriate if biliary-enteric anastomosis is present

34. Antimicrobial therapy Velosef ( Cephradine ) Oxidil (Ceftriaxone) Zinacef (Cefuroxime) Tanzo / Tazocin (Piperacillin/ tazobactam ) Teinam (Imipenem/ cilstatin ) Meronem ( Meropenem )

35. Antimicrobial therapy Historically, biliary penetration of agents has been considered in selection of antimicrobial agents However, there is considerable lab and clinical evidence that as obstruction occurs, secretion of antimicrobial agents into bile stops. (need RCT to determine clinical relevance and significance of biliary penetration in treating acute cholecystitis)

36. Antimicrobial therapy

37. Antimicrobial therapy Patients who can tolerate oral feeding may be treated with oral therapy.

38. Antimicrobial therapy Use of Antibiotic irrigation Irrigation of surgical fields with antimicrobial agents Clearly effective in reduction of wound infection May be effective as effective as use of systemic antimicrobial agents Combined use of systemic and topical antimicrobial agents may have additive effects (especially if different agents are used)

39. GB Drainage

40. GB Drainage Percutaneous transhepatic GB drainage (PTGBD) Recommended essential Standard GB drainage method for surgically unfit patients with acute cholecystitis Safe alternative to one-shot definitive treatment in form of early cholecystectomy in surgically high risk populations e.g. mortality rate in elderly or critically ill patients up to 19 % Low complication rate 0-13 % with procedure related mortality 0.36 %

41. GB Drainage Grade II  only when patient does not respond to conservative treatment Grade III  recommended with intensive care PREDICTOR FOR FAILURE OF CONSERVATIVE TREATMENT: AT 24-h and 48-h follow-up WBC >15000 cell/µl Elevated temperature Age > 70 years AT ADMISSION Age > 70 years Diabetes Tachycardia Distended GB

42. GB Drainage 6- to 10-Fr pigtail catheter Under fluoroscopy ( Seldinger technique)

43. GB Drainage

44. GB Drainage INDICATION: end-stage liver disease (in whom percutaneous approach is difficult to perform)

45. GB Drainage

46. GB Drainage

47. GB Drainage

48. GB Drainage

49. Surgical Management Grade I (mild) EARLY laparoscopic Cholecystectomy Grade II (moderate) MOST CASES EARLY laparoscopic or open cholecystectomy (within 72 hr after onset of acute cholecystitis) in experienced centers “difficult gallbladder” ( severe local inflammation i.e. >72 h from onset, WBC count >18,000 and palpable tender mass in RUQ) continues medical treatment or drainage (PTGBD or surgical cholecystostomy ) preferable DELAYED cholecystectomy Serious local complications(biliary peritonitis, pericholecystic abscess, liver abscess, GB torsion or emphysematous/ gangrenous/ purulent cholecystitis EMERGENCY open or laparoscopic depending on experience (along with general supportive care) Grade III (severe) DELAYED cholecystectomy (2-3 months later after improvement of patient’s general condition) when indicated

50. Surgical Management OPTIMAL APPROACH Until 1 st half of 1990’s --. Open cholecystectomy was the standard technique of acute cholecystitis Open cholecystectomy with mini-incision is able to produce as good results as those obtained by laparoscopic procedure although superiority of laparoscopic procedure is now well established TG13 recommends laparoscopic cholecystectomy over open cholecystectomy However, the 1 st priority is ALWAYS patient safety

51. Surgical Management OPTIMAL TIMING Preferable to perform cholecystectomy soon after admission, particularly when less than 72 hours have been passed since the onset of symptoms Definition of early surgery  within 72-96 h from onset of symptoms (NOT time of diagnosis or admission) Definition of elective (DELAYED) surgery  6 weeks or more after onset

52. Surgical Management OPTIMAL TIME FOR CONVERSION FROM LAPAROSCOPIC TO OPEN CHOLECYSTECTOMY Surgeons should NEVER hesitate to convert to open surgery to prevent injuries when they experience difficulties in performing laparoscopic cholecystectomy i.e. low threshold

53. Surgical Management Optimal time for cholecystectomy following PTGBD Often performed after several days/2 weeks BUT remains controversial due to lack of any strong evidence(no RCT) Optimal time for cholecystectomy following endoscopic stone extraction of bile duct in patients with cholecysto-choledocholithiasis in acute cholecystitis No definitive conclusions could be made due to insufficient evidence

54. Management bundle Bundle = collection of mandatory items or procedures to be performed in clinical practice OR Group of therapies for a disease that, when implemented together, may result in better outcomes than if implemented individually

55. Management bundle

56. Management bundle

57. Management bundle

58. Acute Cholecystitis Bundle Checklist

59. Available at surgicalpresentations