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316 Hepatobiliary Pancreat Dis IntVol 13No 3 June 152014 www.hbpdint.com Original Article / Biliary Author Affiliations: Department  of  General  Surgery  (Karakayali  FY,  Akdur A, Kirnap M, Ekici Y and Moray G), and Department of Radiology  (Harman A), Baskent University School of Medicine, Ankara, Turkey Corresponding Author: Feza  Y  Karakayali,  MD,  Department  of  General  Surgery,  Baskent  University  School  of  Medicine,  Ankara,  Turkey  (Tel:  90-532-6455407; Fax: 90-532-6455312; Email: [email protected]) © 2014, Hepatobiliary Pancreat Dis Int. All rights reserved. doi: 10.1016/S1499-3872(14)60045-X Published online March 27, 2014. BACKGROUND: In  low-risk  patients  with  acute  cholecystitis  who  did  not  respond  to  nonoperative  treatment,  we  prospectively compared treatment with emergency laparoscopic  cholecystectomy or percutaneous transhepatic cholecystostomy  followed by delayed cholecystectomy. METHODS: In 91 patients (American Society of Anesthesiologists  class I or II) who had symptoms of acute cholecystitis 72 hours  at hospital admission and who did not respond to nonoperative  treatment  (48  hours),  48  patients  were  treated  with  emergency  laparoscopic  cholecystectomy  and  43  patients  were  treated  with  delayed  cholecystectomy  at  4  weeks  after  insertion  of  a  percutaneous  transhepatic  cholecystostomy  catheter.  After  initial  treatment,  the  patients  were  followed  up  for  23  months  on average (range 7-29). RESULT: Compared  with  the  patients  who  had  emergency  laparoscopic  cholecystectomy,  the  patients  who  were  treated  with  percutaneous  transhepatic  cholecystostomy  and  delayed  cholecystectomy  had  a  lower  frequency  of  conversion  to  open  surgery  [19  (40%)  vs  8  (19%);  P=0.029],  a  frequency  of  intraoperative bleeding  100 mL [16 (33%) vs 4 (9%);  P=0.006],  a  mean  postoperative  hospital  stay  (5.3±3.3  vs  3.0±2.4  days;  P=0.001), and a frequency of complications [17 (35%) vs 4 (9%);  P=0.003].  CONCLUSION: In  patients  with  acute  cholecystitis  who  presented to the hospital 72 hours after symptom onset and did  not respond to nonoperative treatment for 48 hours, percutaneous  transhepatic  cholecystostomy  with  delayed  laparoscopic  chole- cystectomy  produced  better  outcomes  and  fewer  complications  than emergency laparoscopic cholecystectomy.  (Hepatobiliary Pancreat Dis Int 2014;13:316-322) KEY WORDS: acute abdomen; acute cholecystitis; complications; laparoscopy; surgery; biliary tract Introduction A cute  cholecystitis  is  commonly  treated  with  laparoscopic  cholecystectomy,  which  has  a  surgical  mortality  of  less  than  0.8%. [1] Acute  cholecystitis  was  considered  a  contraindication  for  laparoscopic  cholecystectomy  because  of  frequent  complications,  but  results  may  have  improved  because  of increased laparoscopic experience and improvements  in  laparoscopic  instruments. [2,  3] A  meta-analysis  of  10  prospective,  randomized  trials  concluded  that  patients  who had emergency laparoscopic cholecystectomy (24 to  96 hours after onset of symptoms) had a shorter hospital  stay and a similar frequency of complications compared  with those who had open cholecystectomy. [4] The  Tokyo  guidelines  of  the  Japanese  Society  of  Hepato-Biliary-Pancreatic  Surgery  include  diagnostic  criteria,  therapeutic  strategies,  and  clinical  flowcharts  for acute cholangitis and cholecystitis. [5] The severity of  acute cholecystitis is graded as mild (grade I), moderate  (grade  II),  or  severe  (grade  III),  and  surgical  treatment  options vary with grade. Emergency cholecystectomy is  indicated for patients with symptoms >72 hours (grade  II), and patients with grade II concomitant local severe  inflammation may be treated with emergency or urgent  gallbladder  drainage,  medical  treatment,  and  delayed  cholecystectomy. [5] Laparoscopic cholecystectomy may be recommended  at  6  to  12  weeks  after  the  onset  of  symptoms. [6-10] In  patients  with  acute  cholecystitis,  laparoscopic  cholecystectomy  is  technically  feasible  and  safe  within  72 to 96 hours after the onset of symptoms. [10-14] Within  Emergency cholecystectomy vs percutaneous cholecystostomy plus delayed cholecystectomy for patients with acute cholecystitis Feza Y Karakayali, Aydincan Akdur, Mahir Kirnap, Ali Harman, Yahya Ekici and Gökhan Moray Ankara, Turkey

Emergency cholecystectomy vs percutaneous cholecystostomy plus delayed cholecystectomy for patients with acute cholecystitis

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Hepatobiliary & Pancreatic Diseases International

316 • Hepatobiliary Pancreat Dis Int,Vol 13,No 3 • June 15,2014 • www.hbpdint.com

Original Article / Biliary

Author Affiliations: Department  of  General  Surgery  (Karakayali  FY, Akdur A, Kirnap M, Ekici Y and Moray G), and Department of Radiology (Harman A), Baskent University School of Medicine, Ankara, Turkey

Corresponding Author: Feza  Y  Karakayali,  MD,  Department  of  General Surgery,  Baskent  University  School  of  Medicine,  Ankara,  Turkey  (Tel: 90-532-6455407; Fax: 90-532-6455312; Email: [email protected])

© 2014, Hepatobiliary Pancreat Dis Int. All rights reserved.doi: 10.1016/S1499-3872(14)60045-XPublished online March 27, 2014.

BACKGROUND:  In  low-risk  patients  with  acute  cholecystitis who  did  not  respond  to  nonoperative  treatment,  we prospectively compared treatment with emergency laparoscopic cholecystectomy or percutaneous transhepatic cholecystostomy followed by delayed cholecystectomy.

METHODS:  In 91 patients (American Society of Anesthesiologists class I or II) who had symptoms of acute cholecystitis ≥72 hours at hospital admission and who did not respond to nonoperative treatment (48 hours), 48 patients were treated with emergency laparoscopic  cholecystectomy  and  43  patients  were  treated with  delayed  cholecystectomy  at  ≥4  weeks  after  insertion  of a  percutaneous  transhepatic  cholecystostomy  catheter.  After initial  treatment,  the  patients  were  followed  up  for  23  months on average (range 7-29).

RESULT:  Compared  with  the  patients  who  had  emergency laparoscopic  cholecystectomy,  the  patients  who  were  treated with  percutaneous  transhepatic  cholecystostomy  and  delayed cholecystectomy  had  a  lower  frequency  of  conversion  to open  surgery  [19  (40%)  vs  8  (19%);  P=0.029],  a  frequency  of intraoperative bleeding ≥100 mL [16 (33%) vs 4 (9%); P=0.006], a  mean  postoperative  hospital  stay  (5.3±3.3  vs  3.0±2.4  days; P=0.001), and a frequency of complications [17 (35%) vs 4 (9%); P=0.003]. 

CONCLUSION:  In  patients  with  acute  cholecystitis  who presented to the hospital ≥72 hours after symptom onset and did not respond to nonoperative treatment for 48 hours, percutaneous transhepatic  cholecystostomy  with  delayed  laparoscopic  chole-cystectomy  produced  better  outcomes  and  fewer  complications than emergency laparoscopic cholecystectomy. 

(Hepatobiliary Pancreat Dis Int 2014;13:316-322)

KEY WORDS:  acute abdomen;                                 acute cholecystitis;                                 complications;                                 laparoscopy;                                 surgery;                                 biliary tract

Introduction

Acute  cholecystitis  is  commonly  treated  with laparoscopic  cholecystectomy,  which  has  a surgical  mortality  of  less  than  0.8%.[1]  Acute 

cholecystitis  was  considered  a  contraindication  for laparoscopic  cholecystectomy  because  of  frequent complications,  but  results  may  have  improved  because of increased laparoscopic experience and improvements in  laparoscopic  instruments.[2,  3]  A  meta-analysis  of  10 prospective,  randomized  trials  concluded  that  patients who had emergency laparoscopic cholecystectomy (24 to 96 hours after onset of symptoms) had a shorter hospital stay and a similar frequency of complications compared with those who had open cholecystectomy.[4]

The  Tokyo  guidelines  of  the  Japanese  Society  of Hepato-Biliary-Pancreatic  Surgery  include  diagnostic criteria,  therapeutic  strategies,  and  clinical  flowcharts for acute cholangitis and cholecystitis.[5] The severity of acute cholecystitis is graded as mild (grade I), moderate (grade  II), or  severe  (grade  III),  and  surgical  treatment options vary with grade. Emergency cholecystectomy is indicated for patients with symptoms >72 hours (grade II), and patients with grade II concomitant  local severe inflammation may be treated with emergency or urgent gallbladder  drainage,  medical  treatment,  and  delayed cholecystectomy.[5]

Laparoscopic cholecystectomy may be recommended at  6  to  12  weeks  after  the  onset  of  symptoms.[6-10] In  patients  with  acute  cholecystitis,  laparoscopic cholecystectomy  is  technically  feasible  and  safe  within 72 to 96 hours after the onset of symptoms.[10-14] Within 

Emergency cholecystectomy vs percutaneous cholecystostomy plus delayed cholecystectomy for patients with acute cholecystitisFeza Y Karakayali, Aydincan Akdur, Mahir Kirnap, Ali Harman, Yahya Ekici and Gökhan Moray

Ankara, Turkey

Treatment of acute cholecystitis

Hepatobiliary Pancreat Dis Int,Vol 13,No 3 • June 15,2014 • www.hbpdint.com • 317

72  hours  after  the  onset  of  symptoms  and  before  the development  of  fibrosis,  laparoscopic  cholecystectomy may be a safe procedure because the anatomy usually is clear  and dissection may be guided by  edema.[15, 16]  For patients who are admitted more than 72 hours after the onset of symptoms, however,  treatment  is controversial and  results  are  unclear.  Laparoscopic  cholecystectomy 72  hours  after  the  onset  of  symptoms  may  be  difficult and the risk of complications may increase.[17] However, some  studies[18-21]  showed  no  difference  in  frequency of  conversion  to  open  surgery,  morbidity,  or  length of  postoperative  hospital  stay  between  patients  with symptoms more or less than 72 hours. 

Many  patients  with  acute  cholecystitis  may  not respond  to  nonoperative  treatment  but  require  urgent surgery to avoid gallbladder gangrene or perforation. In this situation, laparoscopic surgery may have limited safety and a high-risk of complications, and such patients may need conversion  to open cholecystectomy.[22-24] Most patients with acute cholecystitis more than 72 hours may have severe inflammation and dense adhesions that increase the risk of  complications  of  laparoscopic  cholecystectomy  and conversion to open surgery. Therefore, these patients are frequently  treated  nonoperatively,  discharged  from  the hospital when the acute attack has subsided, and treated with cholecystectomy 4 to 8 weeks later.[25-27] Conversion from  laparoscopic  to  open  surgery  is  associated  with more  surgical  complications  than  laparoscopic  surgery alone.[28]

Percutaneous  transhepatic  cholecystostomy  is  a treatment option for patients with acute cholecystitis.[29] This  minimally  invasive  procedure  guided  by  imaging methods  is  an  alternative  treatment  for  patients  with acute  or  complicated  cholecystitis,  who  require  urgent treatment.[30]  This  procedure  could  help  critically  ill and complex patients to recover from the acute episode before  delayed  elective  laparoscopic  cholecystectomy is  performed.  Despite  the  use  of  percutaneous cholecystostomy  in  high-risk  patients  with  acute cholecystitis, other indications for this procedure are not clear. Although emergency laparoscopic cholecystectomy is suitable for surgery low-risk patients without response to  nonoperative  treatment,  percutaneous  transhepatic cholecystostomy is preferred in some centers. 

Literature  search  showed  no  prospective  studies evaluating preferred treatment for low-risk patients with acute cholecystitis who had no response to nonoperative treatment.  The  present  study  was  undertaken  to compare  emergency  laparoscopic  cholecystectomy  and percutaneous transhepatic cholecystostomy followed by delayed  laparoscopic  cholecystectomy  in  patients  with low-risk  acute  cholecystitis  who  had  no  response  to nonoperative treatment. 

MethodsPatients and grouping

From  May  2007  to  September  2012,  a  total  of  1814 patients  were  admitted  to  our  surgery  department because  of  their  clinical,  radiographic,  and  laboratory findings of calculous cholecystitis. Acute cholecystitis was diagnosed by the clinical criteria including local (Murphy sign or right upper quadrant mass, pain, or  tenderness) and  systemic  (fever,  elevated  C-reactive  protein,  or elevated  white  blood  cell  count)  signs  of  inflammation in addition to imaging findings. Emergency laparoscopic cholecystectomy  was  recommended  for  patients  with symptoms at 0 to 72 hours before admission and was not included in this study. 

In  369  patients  (20%)  with  symptoms  which appeared  more  than  72  hours  before  admission, recommended  nonoperative  treatment  included  fasting, use  of  ceftriaxone,  a  third  generation  broad  spectrum antibiotic,  intravenous  anti-inflammatory  drugs,  and intravenous  fluids.  After  48  hours  of  nonoperative treatment,  symptoms  persisted  or  worsened  in  122 patients (33%), and radiographic evaluation was repeated (ultrasonography  in  all  patients;  computed  tomography in  12  patients  who  had  inconclusive  ultrasonographic studies).  Thirty-one  patients  were  excluded  because  of high surgical risk [American Society of Anesthesiologists (ASA)  class  III  to  V]  or  severe  comorbidity  (chronic obstructive  pulmonary  disease,  ischemic  heart  disease, cerebrovascular disease, cancer, age >80 years, previous abdominal surgery, choledocholithiasis, acute cholangitis, pancreatitis, free biliary perforation, or intra-abdominal abscess). The remaining 91 patients were included in the study  (Fig. 1).  The  study  protocol  was  approved  by  the 

Fig. 1. Flowchart showing the study design for the evaluation of treatment options for acute cholecystitis.

Hepatobiliary & Pancreatic Diseases International

318 • Hepatobiliary Pancreat Dis Int,Vol 13,No 3 • June 15,2014 • www.hbpdint.com

Institutional  Review  Board  of  Baskent  University,  and informed consent was obtained from all patients. 

The  91  patients  were  consecutively  allocated  to two  treatment  groups:  one  for  emergency  laparoscopic cholecystectomy  (48  patients)  and  the  other  for percutaneous transhepatic cholecystostomy with delayed laparoscopic  cholecystectomy  from  4  to  8  weeks  after cholecystostomy (43 patients) (Fig. 1). The patients were allowed  to  change  assigned  treatment  based  on  their preference.  Patients  in  both  groups  were  followed  up after treatment for an average of 23 months (range 7-29).

Laparoscopic cholecystectomy

Laparoscopic  cholecystectomy  was  performed  by two  qualified  surgeons  using  a  4-port  method.  The decisions  to  convert  to  open  cholecystectomy  or  use abdominal  drains  were  made  according  to  the  clinical factors  including  the  difficulty  of  dissection,  poor control  of  intraoperative  hemorrhage,  and  adhesions of  the  Calot  triangle  and  the  liver  bed.  The  difficulty in  dissecting  the  Calot  triangle  was  assessed  according to  an  adhesion  scoring  system  previously  described (presence of adhesions, 1; absence of adhesions, 0).[31]

Percutaneous transhepatic cholecystostomy 

A  percutaneous  transhepatic  cholecystostomy  was performed  by  a  specialized  interventional  radiology team  under  the  ultrasonographic  guidance,  with  or without  fluoroscopy,  in  the  interventional  radiology unit.  The  gallbladder  fundus  was  visualized  with ultrasonography  and  accessed  from  a  transhepatic approach  with  an  18-gauge  needle.  The  needle  was advanced  to  avoid  puncturing  the  anterior  wall  of  the gallbladder. Bile samples were taken from all patients for anaerobic and aerobic cultures. After placing a guidewire (Amplatz Super Stiff Guide Wire, Boston Scientific Corp, Natick,  MA,  USA)  and  sequentially  dilating  the  track, an 8- to 10-French lockable, all purpose, pigtail catheter was  introduced  into the gallbladder. A small volume of contrast agent was injected and fluoroscopy was used to confirm the position of the catheter and determine the patency  of  the  biliary  ductal  system.  The  catheter  was secured  to  the  abdominal  wall  with  2-0  silk  sutures  at the puncture site and allowed to drain with gravity. At 24  hours  after  placement,  the  position  of  the  catheter was  checked  with  ultrasonography  or  fluoroscopy  with water-soluble contrast solution injection.

Clinical improvement after percutaneous transhepatic cholecystostomy  was  defined  as  (1)  resolution  of pain  or  tenderness  of  the  right  upper  quadrant,  (2) body  temperature  ≤37.5 ℃  during  a  24-hour  period, and  (3)  resolution  of  leukocytosis.  After  the  patient 

Table 1. Demographic and clinical characteristics of patients with acute cholecystitis

Variables

Emergency  laparoscopic   cholecystectomy  (n=48)

Percutaneous  transhepatic  cholecystostomy and  delayed laparoscopic   cholecystectomy  (n=43)

P value

Age (yr)   60±10 (35-78)   65±9 (41-80) 0.02

Gender (male/female)    25/23    29/14 NS

ASA I/II    16/32      9/34 NS

Time from the onset of   symptoms to  admission (d)

 5.2±1.3 (3-8)  4.8±1.4 (3-9) NS

Temperature >37.5 ℃    20 (42%)   22 (51%) NS

White blood cell count  (×109/L)

  12±4 (6-23)   12±4 (6-27) NS

C-reactive protein  (mg/dL)

148±72 (56-303) 154±79 (43-344) NS

Radiographic findings

  Gallbladder wall    thickness (mm)

 3.4±0.9 (2-7)  3.3±0.6 (2-5) NS

  Pericholecystic fluid    40 (83%)   36 (84%) NS

  Ultrasonographic    Murphy sign

  31 (65%)   23 (53%) NS

  Pericholecystic abscess     4 (8%)     3 (7%) NS

ASA: American Society of Anesthesiologists; NS: not significant.

was  discharged  from  the  hospital,  the  catheter  was monitored twice weekly at the outpatient surgery clinic. Transcatheter  cholangiography  was  performed  2  weeks after  the  percutaneous  transhepatic  cholecystostomy. In  patients  with  obstruction  of  the  cystic  duct,  a percutaneous transhepatic cholecystostomy catheter was left  open  until  delayed  cholecystectomy  was  performed; in patients with a patent cystic duct, the catheter was left in place, closed, and secured under wound dressings. All patients had  laparoscopic  cholecystectomy at  less  than 4 weeks after discharge from the hospital.

Statistical analysis

Data analysis was performed with statistical software (SPSS  15.0,  SPSS  Inc.,  Chicago,  IL,  USA).  Quantitative data  were  analyzed  with  the  Mann-Whitney  U  test. Proportions were compared using the Chi-square test. A P<0.05 was considered statistically significant. 

ResultsThe mean age of the patients was lower in the emergency laparoscopic  cholecystectomy  group  than  in  the percutaneous transhepatic cholecystostomy and delayed cholecystectomy group  (Table 1). The  two groups were 

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similar  in  gender,  ASA  class,  time  from  the  onset  of symptoms  to  admission,  temperature,  white  blood cell  count,  C-reactive  protein  level,  and  radiographic findings (Table 1). 

Percutaneous  transhepatic  cholecystostomy  was technically  successful  in  all  43  patients  without  any early complications. In two patients with abscess of the gallbladder bed, drainage of the abscess was observed on imaging studies when the gallbladder was aspirated with the percutaneous transhepatic cholecystostomy catheter; in  another  patient  who  did  not  have  communication between  the  abscess  and  gallbladder,  an  additional percutaneous  transhepatic  aspiration  was  performed. After  percutaneous  transhepatic  cholecystostomy placement,  40  patients  (93%)  had  early  resolution  of cholecystitis  symptoms  (within  24  hours),  and  the  3 patients  with  pericholecystic  abscess  had  improvement within 48 hours. All of the 43 patients were discharged after  complete  resolution  of  symptoms,  and  the  mean time  from  percutaneous  transhepatic  cholecystostomy to discharge was 4.7±2.0 days (range 3-11).

During follow-up, bile leak around the cholecystostomy catheter  was  observed  in  two  patients  and  was  treated with  repeat  catheterization  with  a  larger  catheter. Two  weeks  after  the  placement  of  the  percutaneous transhepatic  cholecystostomy  catheter,  all  patients underwent cholangiography; in 9 patients (21%) the cystic duct  was  obstructed,  and  the  cholecystostomy  catheter was left open until surgery (Fig. 2). Although there were no  clinical  symptoms,  common  bile  duct  stones  were observed by cholangiography in 3 patients; these stones were  successfully  removed  by  endoscopic  retrograde cholangiopancreatography and sphincterotomy before the operation.  In all patients,  laparoscopic cholecystectomy was performed at an average of 5 weeks (range 4-7) after percutaneous transhepatic cholecystostomy. 

Conversion from laparoscopic to open surgery (most commonly  because  of  difficulty  with  dissection  at  the gallbladder  and  Calot  triangle)  was  significantly  more frequent  in  patients  who  were  treated  with  emergency laparoscopic cholecystectomy than cholecystostomy and delayed  cholecystectomy  (40%  vs  19%;  P=0.029).  In 19  of  the  48  emergency  laparoscopic  cholecystectomy patients,  conversion  to  open  surgery  decision  was realized because of difficulty with dissection(15 patients) and uncontrolled bleeding (4) (Table 2).  Intraoperative bleeding  ≥100  mL  was  also  more  frequent  in  patients undergoing  emergency  laparoscopic  cholecystectomy than  in  those  having  cholecystostomy  and  delayed cholecystectomy  (33%  vs  9%;  P=0.006);  bleeding was  stopped  in  most  patients  undergoing  hemostatic laparoscopic procedures without open surgery (Table 2). 

Table 2. Results of treatment of acute cholecystitis in the two groups

Variables

Emergency  laparoscopic  cholecystectomy  (n=48)

Percutaneous  transhepatic  cholecystostomy  and delayed  cholecystectomy   (n=43)

P value

Conversion to open surgery   19 (40%)     8 (19%) 0.029

  Difficulty with dissection   15     7

  Uncontrolled bleeding     4     1

Operative time (min) 114±38 (55-190) 106±27 (50-163) NS

Intraoperative bleeding   ≥100 mL

  16 (33%)     4 (9%) 0.006

Intraoperative   cholangiography

    4 (8%)     1 (2%) NS

Drain use   27 (56%)     8 (19%) 0.001

Postoperative hospital  stay (d)

  5.3±3.3 (3-23)  3.0±2.4 (1-14) 0.001

Complications   17 (35%)     4 (9%) 0.003

  Bile leakage     5     1

  Subhepatic fluid collection     4     2

  Wound infection     3     1

  Atelectasis     2     0

  Choledocholithiasis     3     0

NS: not significant.

Intraoperative  cholangiography  was  required  in several  patients  because  of  difficulty  in  evaluating  the anatomy  of  Calot  triangle  after  conversion  to  open surgery  (Table 2).  Abdominal  drains  were  used  in each  complicated  operation  that  had  intraoperative bleeding, difficulty with dissection, or bile leakage from the  gallbladder  bed.  Patients  who  had  had  emergency laparoscopic  cholecystectomy  had  more  frequent  use of  abdominal  drains  and  longer  postoperative  hospital stay  than  those  who  had  had  initial  treatment  with percutaneous transhepatic cholecystostomy (Table 2). 

Fig. 2. Cholecystography at 2 weeks after percutaneous transhepatic cholecystostomy showing complete obstruction of the cystic duct.

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There  were  no  patients  with  bile  duct  injury  or deaths.  Overall  postoperative  complications  were  more frequent  in  patients  undergoing  emergency  laparoscopic cholecystectomy,  and  the  most  frequent  complications were  bile  leakage  and  subhepatic  fluid  collection (Table  2).  In  6  patients  with  bile  leakage  (5  in  the emergency  laparoscopic  cholecystectomy  group  and 1  in  the  percutaneous  transhepatic  cholecystostomy and  delayed  laparoscopic  cholecystectomy  group),  the diagnosis was made by CT or the drainage results from the  drain  placed  at  surgery.  Endoscopic  retrograde cholangiopancreatography was performed in all 6 patients. Cystic duct  stump  leakage was  found  in 5 of  them (the emergency  laparoscopic  cholecystectomy  group)  and was  treated  with  sphincterotomy  and  either  stenting  (3 patients) or  stone extraction (2). Bile  leakage caused by an open duct of Luschka was observed in one patient who underwent  percutaneous  transhepatic  cholecystostomy and  delayed  cholecystectomy,  and  treatment  included sphincterotomy  and  percutaneous  drainage  of  biloma. In  6  patients  with  postoperative  abdominal  subhepatic fluid collection (Table 2), 5 recovered spontaneously and one  had  percutaneous  drainage  of  the  biloma.  On  the long-term  follow-up,  choledocholithiasis  was  diagnosed with  magnetic  resonance  cholangiopancreatography  in one  patient  at  9  months  after  emergency  laparoscopic cholecystectomy.  Treatment  of  this  patient  included hospital  admission,  endoscopic  retrograde  cholangio-pancreatography, and stone extraction. 

Discussion In the present study, patients with persistent symptoms and  signs  of  acute  cholecystitis  after  nonoperative treatment  (48  hours)  had  better  clinical  outcomes  in the  percutaneous  transhepatic  cholecystostomy  and delayed  cholecystectomy  group  than  in  the  emergency laparoscopic cholecystectomy group. 

Initial  nonoperative  treatment  was  unsuccessful in  122  (33%)  of  369  patients,  which  was  similar  to previous  studies  (32%).[24] Treatment  for  these patients is  commonly  based  on  the  general  condition  of  the patients  (ASA  class),  and  includes  emergency  surgery for  low-risk  patients  and  percutaneous  transhepatic cholecystostomy  for  high-risk  patients.  Urgent  or  early drainage  may  be  recommended  for  patients  with  acute cholecystitis  defined  by  leukocytosis  (white  blood  cell count >18×109/L); painful and palpable mass at the right upper  quadrant;  and  symptoms  >72  hours  or  marked local inflammation (8 mm gallbladder wall thickness).[5] We  defined  72  hours  as  the  minimum  duration  of symptoms  for  inclusion  in  the  study  and  prospectively 

evaluated  the  results  of  treatment  in  low-risk  patients with acute cholecystitis. 

In  patients  with  acute  cholecystitis  who  did  not respond  to  nonoperative  treatment,  the  results  of treatment with emergency laparoscopic cholecystectomy or percutaneous  transhepatic cholecystostomy  followed by  delayed  laparoscopic  cholecystectomy  are  similar for  low-risk  (ASA  I)  patients,  but  the  conversion  rate to  open  surgery  is  significantly  higher  for  high-risk (ASA II or III) patients who are treated with emergency laparoscopic cholecystectomy.[22] However, controversial findings  have  also  been  reported  that  percutaneous transhepatic  cholecystostomy  had  a  higher  frequency of conversion to open surgery and the shorter operative time  or  shorter  postoperative  hospital  stay  than emergency cholecystectomy did.[32]

We  observed  a  shorter  mean  postoperative  hospital stay,  a  lower  frequency  of  complications,  and  a  lower frequency  of  conversion  to  open  surgery  in  patients treated  initially  with  percutaneous  transhepatic cholecystostomy  than  in  those  treated  with  emergency laparoscopic cholecystectomy. Therefore, elective delayed surgery after percutaneous transhepatic cholecystostomy may  produce  better  outcomes.  Although  the  present study was performed at a tertiary care university hospital and  the  operations  were  performed  by  experienced hepatobiliary  and  liver  transplant  surgeons,  the frequency of conversion to open surgery after emergency laparoscopic  cholecystectomy  (40%)  was  higher  than that  reported  (11%-28%).[10,  23,  33]  This  may  be  due  to the  differences  in  timing  of  emergency  laparoscopic cholecystectomy  and  disease  severity  between  studies. In  the  patients  who  were  treated  with  emergency laparoscopic  cholecystectomy,  the  mean  time  between the  onset  of  symptoms  and  admission  to  the  hospital was  5  days  and  the  duration  of  failed  nonoperative treatment was 2 days. Our results were in consistent with those of another study showing a similar high frequency of conversion to open surgery (31%) in patients operated upon 7 days after the onset of symptoms.[14]

We  did  not  find  major  perioperative  complications or  bile  duct  injuries,  but  the  overall  frequency  of complications  was  significantly  higher  in  patients undergoing  emergency  laparoscopic  cholecystectomy. The most common complication, bile  leakage  from the cystic duct stump, was likely caused by slipped surgical clips  because  of  retained  common  bile  duct  stones,  or resolution of inflammation. In 3 patients who underwent emergency  laparoscopic  cholecystectomy,  common bile duct stones were noted early (2 patients) or  late (1) after  surgery.  Early  diagnosed  retained  common  bile duct stones were a major cause of bile leakage. However, 

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in  patients  treated  with  percutaneous  transhepatic cholecystostomy,  choledocholithiasis  was  noted  in  3 patients on cholangiography before delayed laparoscopic cholecystectomy;  in  these  patients,  the  percutaneous transhepatic cholecystostomy enabled elective extraction of common bile duct stones before surgery and avoided perioperative  cholangiography  and  common  bile  duct exploration.  In  a  study,[25]  percutaneous  transhepatic cholecystostomy  was  used  for  cholangiography  in  12 of  54  patients  with  persistently  elevated  levels  of  liver enzyme, and common bile duct stones were observed in 5 patients.

The timing of delayed laparoscopic cholecystectomy after  percutaneous  transhepatic  cholecystostomy is  controversial.  Patients  treated  with  laparoscopic cholecystectomy  within  72  hours  after  percutaneous transhepatic cholecystostomy may have a  shorter mean hospital  stay  and  lower  hospital  costs  than  those  who underwent  laparoscopic  cholecystectomy  more  than  72 hours  after  percutaneous  transhepatic  cholecystostomy, but  the  latter  subjects  may  have  a  lower  frequency  of complications  and  a  shorter  operative  time.[33]  We scheduled  laparoscopic  cholecystectomy  over  4  weeks after  percutaneous  transhepatic  cholecystostomy  to avoid  marked  inflammation  that  appeared  commonly before  4  weeks.  Another  controversial  issue  is  whether the cholecystostomy catheter should be removed during or  before  delayed  laparoscopic  cholecystectomy.  In  the present  study,  we  did  not  remove  the  catheter  until delayed  laparoscopic  cholecystectomy  was  done  to decrease  the  risk  of  recurrent  acute  cholecystitis  after catheter  removal  because  of  cystic  duct  obstruction. Besides,  patients  with  complete  relief  of  symptoms may  postpone  the  scheduled  operation  after  catheter removal, and the risk of  subsequent admission because of gallstones is 50% after one year.[34] Furthermore, tract formation  may  require  2-3  weeks  before  the  catheter is  removed  safely.  The  decision  about  the  timing  of cholecystectomy  after  percutaneous  transhepatic cholecystostomy  and  catheter  removal  may  be  affected by institutional policy, surgical judgment, and experience. 

Limitations of the present study included the absence of random allocation of patients to the two study groups. After  providing  patients  with  detailed  information about the treatment options and possible complications, some  patients  insisted  on  emergency  laparoscopic cholecystectomy  being  performed  and  others  preferred to have delayed surgery.  In  these  situations,  the patient preference  was  followed;  otherwise,  the  patients  were allocated consecutively to the two treatment groups.

In summary, there is controversy about the treatment of  acute  cholecystitis  in  patients  who  are  admitted  to 

the hospital over 72 hours after the onset of symptoms. In  this  study,  nonoperative  treatment  was  given  for 48  hours,  and  the  patients  who  did  not  respond  were referred  for  emergency  laparoscopic  cholecystectomy or  percutaneous  transhepatic  cholecystostomy  and delayed  laparoscopic  cholecystectomy.  The  frequency of  conversion  to  open  surgery,  intraoperative  bleeding, drain  use,  mean  postoperative  hospital  stay,  and postoperative complications was greater in patients who underwent  emergency  laparoscopic  cholecystectomy than  in  those  who  had  percutaneous  transhepatic cholecystostomy. In addition, percutaneous transhepatic cholecystostomy  could  make  biliary  system  imaging before  delayed  cholecystectomy  possible  and  decrease the risk of retained common bile duct stones or the need for  peroperative  cholangiography  and  common  bile duct  exploration.  Therefore,  in  patients  who  presented to  the  hospital ≥72  hours  after  the  onset  of  symptoms and  did  not  respond  to  nonoperative  therapy  for  48 hours,  percutaneous  transhepatic  cholecystostomy combined with delayed cholecystectomy could produce better outcomes and fewer complications than emergency laparoscopic cholecystectomy. 

Contributors:  KFY  proposed  the  study.  AA  and  KM  collected and  analyzed  the  data.  KFY  wrote  the  first  draft.  KFY,  EY  and MG  performed  the  operations.  HA  performed  the  percutaneous cholecystostomy procedures. All  authors  contributed  to  the  study design, interpretation of study and writing the manuscript. KFY is the guarantor.Funding: None.Ethical  approval:  The  study  protocol  was  approved  by  the Institutional Review Board of Baskent University.Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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Received June 20, 2013Accepted after revision November 6, 2013