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1.  Acute cholecystitis 
BMJ Clinical Evidence  2014;2014:0411.
Introduction
Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. Up to the age of 50 years, acute calculous cholecystitis is three times more common in women than in men, and about one and a half times more common in women than in men thereafter. About 95% of people with acute cholecystitis have gallstones. Optimal therapy for acute cholecystitis, based on timing and severity of presentation, remains controversial.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute cholecystitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 18 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: early cholecystectomy, laparoscopic cholecystectomy, observation alone, open cholecystectomy, and percutaneous cholecystostomy.
Key Points
Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the cystic duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.
Early cholecystectomy within 7 days of onset of symptoms is the treatment of choice for acute cholecystitis. Early surgery reduces the duration of hospital admission compared with delayed surgery, but does not reduce mortality or complications.Up to one quarter of people scheduled for delayed surgery may require urgent operations because of recurrent or worsening symptoms.
Laparoscopic cholecystectomy may reduce the duration of hospital admission and improve some intra-operative and postoperative outcomes compared with open cholecystectomy, but it may increase the risk of bile duct injury. Up to one quarter of people having laparoscopic cholecystectomy may need conversion to open surgery because of risks of complications or uncontrolled bleeding.
We found limited evidence from one small RCT that percutaneous cholecystostomy plus early cholecystectomy may reduce time to symptomatic improvement and duration of hospital stay compared with medical treatment plus delayed cholecystectomy in people at high surgical risk. However, evidence was weak. We found no studies in people at normal surgical risk.
Routine abdominal drainage in both uncomplicated laparoscopic and open cholecystectomy is associated with an increase in wound infections compared with no drainage.
PMCID: PMC4140413  PMID: 25144428
2.  Acute cholecystitis 
BMJ Clinical Evidence  2011;2011:0411.
Introduction
Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. Up to the age of 50 years, acute calculous cholecystitis is three times more common in women than in men, and about 1.5 times more common in women than in men thereafter. About 95% of people with acute cholecystitis have gallstones. Optimal therapy for acute cholecystitis, based on timing and severity of presentation, remains controversial.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute cholecystitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: early cholecystectomy, laparoscopic cholecystectomy, minilaparoscopic cholecystectomy, observation alone, open cholecystectomy, and percutaneous cholecystostomy.
Key Points
Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.
Early cholecystectomy within 7 days of onset of symptoms is the treatment of choice for acute cholecystitis. Early surgery reduces the duration of hospital admission compared with delayed surgery, but does not reduce mortality or complications.Up to one quarter of people scheduled for delayed surgery may require urgent operations because of recurrent or worsening symptoms.
Laparoscopic cholecystectomy may reduce the duration of hospital admission and improve intra-operative and postoperative outcomes compared with open cholecystectomy, but it may increase the risk of bile duct injury. Up to one quarter of people having laparoscopic cholecystectomy may need conversion to open surgery because of risks of complications or uncontrolled bleeding. Minilaparoscopic surgery may be associated with slightly longer operative times than laparoscopic surgery, although it may reduce pain scores and the need for postoperative analgesia.
Routine abdominal drainage in both uncomplicated laparoscopic and open cholecystectomy is associated with an increase in wound infections compared with no drainage.
PMCID: PMC3275134  PMID: 22186260
3.  Acute Calculous Cholecystitis: What is new in diagnosis and therapy? 
HPB Surgery  1992;6(2):69-78.
The management of patients with acute calculous cholecystitis has changed during recent years. The etiology of acute cholecystitis is still not fully understood. Infection of bile is relatively unimportant since bile and gallbladder wall cultures are sterile in many patients with acute cholecystitis. Ultrasonography is first choice for diagnosis of acute cholecystitis and cholescintigraphy is second best. Percutaneous puncture of the gallbladder that can be used for therapeutic drainage has also diagnostic qualities. Early cholecystectomy under antibiotic prophylaxis is the treatment of choice, and has been shown to be superior to delayed surgery in several prospective trials. Mortality can be as low as 0.5% in patients younger than 70–80 years of age, but a high mortality has been reported in octogenerians. Selective intraoperative cholangiography is now generally accepted and no advantage of routine cholangiography was shown in clinical trials. Percutaneous cholecystostomy can be successfully performed under ultrasound guidance and has a place in the treatment of severely ill patients with acute cholecystitis. Laparoscopic cholecystectomy can be done safely in patients with acute cholecystitis, but extensive experience with this technique is necessary. Endoscopic retrograde drainage of the gallbladder by introduction of a catheter in the cystic duct is feasible but data are still scarce.
doi:10.1155/1992/46529
PMCID: PMC2443024  PMID: 1292590
4.  The outcome of early laparoscopic surgery to treat acute cholecystitis: a single-center experience 
Aim: The aim of this study was to prospectively assess the outcome of early laparoscopic cholecystectomy (LC) in patients with acute cholecystitis. Materials and methods: Between July 2005 and December 2012, of 623 patients who had symptoms of acute cholecystitis during the first 72 h of hospital admission and who did not respond to non-operative treatment, 302 underwent surgical treatment. After initial treatment, all patients were followed up for 21 months on average (range: 5-27 months). The clinical, biochemical, radiological, and operative data of the 302 consecutive patients with acute cholecystitis were recorded and analyzed prospectively. Results: Of the 302 patients who underwent LC for acute cholecystitis, 169 were females and 133 males. Their mean ages were 47.8 years (range: 17-79 years) and 53.3 years (range: 27-90 years) respectively. Conversion to open surgery was required in 32 patients (10.5%). The mean postoperative length of hospital stay was 2 days (range: 1-3 days) in the LC group and 3 days (range: 2-6 days) in the conversion group. Significant differences between the successful LC group and the conversion group were evident terms of the length of postoperative hospitalization and gallbladder wall thickness (P=0.023). Factors associated with conversion were male gender, pericholecystic collection observed via ultrasound, gangrenous cholecystitis, and gallbladder wall thickness >1 cm. We experienced two minor bile duct injury complications that were treated via T tube placement. No mortality occurred. Ten patients suffered infections at the incisional locations, and eight patients developed lung infections. Conclusion: Early LC is safe in patients with acute cholecystitis. Male gender, pericholecystic collection determined via ultrasound, gangrenous cholecystitis, and gallbladder wall thickness >1 cm are associated with a higher risk of conversion to open surgery.
PMCID: PMC4443219  PMID: 26064385
Acute cholecystitis; laparoscopic cholecystectomy; conversion to open surgery
5.  Fluoroscopy-Guided Percutaneous Gallstone Removal Using a 12-Fr Sheath in High-Risk Surgical Patients with Acute Cholecystitis 
Korean Journal of Radiology  2011;12(2):210-215.
Objective
To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic cholecystolithotomy under fluoroscopic guidance in high-risk surgical patients with acute cholecystitis.
Materials and Methods
Sixty-three consecutive patients of high surgical risk with acute calculous cholecystitis underwent percutaneous transhepatic gallstone removal under conscious sedation. The stones were extracted through the 12-Fr sheath using a Wittich nitinol stone basket under fluoroscopic guidance on three days after performing a percutaneous cholecystostomy. Large or hard stones were fragmented using either the snare guide wire technique or the metallic cannula technique.
Results
Gallstones were successfully removed from 59 of the 63 patients (94%). Reasons for stone removal failure included the inability to grasp a large stone in two patients, and the loss of tract during the procedure in two patients with a contracted gallbladder. The mean hospitalization duration was 7.3 days for acute cholecystitis patients and 9.4 days for gallbladder empyema patients. Bile peritonitis requiring percutaneous drainage developed in two patients. No symptomatic recurrence occurred during follow-up (mean, 608.3 days).
Conclusion
Fluoroscopy-guided percutaneous gallstone removal using a 12-Fr sheath is technically feasible and clinically effective in high-risk surgical patients with acute cholecystitis.
doi:10.3348/kjr.2011.12.2.210
PMCID: PMC3052612  PMID: 21430938
Gallbladder stone; Acute cholecystitis; Percutaneous cholecystolithotomy
6.  Risk factors of acute cholecystitis after endoscopic common bile duct stone removal 
AIM: To evaluate the risk factors of acute cholecystitis after endoscopic common bile duct (CBD) stone removal.
METHODS: A total 100 of patients who underwent endoscopic CBD stone removal with gallbladder (GB) in situ without subsequent cholecystectomy from January 2000 to July 2004 were evaluated retrospectively. The following factors were considered while evaluating risk factors for the development of acute cholecystitis: age, gender, serum bilirubin level, GB wall thickening, cystic duct patency, presence of a GB stone, CBD diameter, residual stone, lithotripsy, juxtapapillary diverticulum, presence of liver cirrhosis or diabetes mellitus, a presenting illness of cholangitis or pancreatitis, and procedure-related complications.
RESULTS: During a mean 18-mo follow-up, 28 (28%) patients developed biliary symptoms; 17 (17%) acute cholecystitis and 13 (13%) CBD stone recurrence. Of patients with acute cholecystitis, 15 (88.2%) received laparoscopic cholecystectomy and 2 (11.8%) open cholecystectomy. All recurrent CBD stones were successfully removed endoscopically. The mean time elapse to acute cholecystitis was 10.2 mo (1-37 mo) and that to recurrent CBD stone was 18.4 mo. Of the 17 patients who received cholecystectomy, 2 (11.8%) developed recurrent CBD stones after cholecystectomy. By multivariate analysis, a serum total bilirubin level of
<1.3 mg/dL and a CBD diameter of <11 mm at the time of stone removal were found to predict the development of acute cholecystitis.
CONCLUSION: After CBD stone removal, there is no need for routine prophylactic cholecystectomy. However, patients without a dilated bile duct (<11 mm) and jaundice (<1.3 mg/dL) at the time of CBD stone removal have a higher risk of acute cholecystitis and are possible candidates for prophylactic cholecystectomy.
doi:10.3748/wjg.v12.i6.956
PMCID: PMC4066164  PMID: 16521227
Sphincterotomy; Choledocholithiasis; Acute cholecystitis; Cholecystectomy
7.  The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors 
BMC Cancer  2013;13:242.
Background
Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function.
Methods
Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment).
Results
Forty-nine patients received ≥1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary “sludge” in Arms A/B/C was 39%/36%/27%.
Conclusions
Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis.
Trial registration
ClinicalTrials.gov NCT00448786
doi:10.1186/1471-2407-13-242
PMCID: PMC3688238  PMID: 23679351
8.  A Case of Emphysematous Cholecystitis Managed by Laparoscopic Surgery 
Background:
Emphysematous cholecystitis is a rare condition caused by ischemia of the gallbladder wall with secondary gas-producing bacterial proliferation. The pathophysiology and epidemiology of this condition differ from that in gallstone-related acute cholecystitis. This report illustrates a case of emphysematous cholecystitis successfully treated by laparoscopic surgery.
Methods:
An 83-year-old female patient was admitted to the hospital with acute abdominal syndrome. Clinical examination and blood tests suggested acute cholecystitis. Plain radiography revealed a circular gas pattern in the right upper quadrant suggestive of emphysematous cholecystitis. Subsequent computed tomography confirmed the presence of gas in the gallbladder wall and a gas-fluid level within the organ.
Results:
Emergency laparoscopic cholecystectomy was successfully performed during which bubbling of the gall-bladder wall was observed. Intraoperative cholangiography revealed no bile duct stones or biliary obstruction. The patient made an unremarkable recovery from surgery with no postoperative complications or admission to the intensive care unit. Pathological analysis revealed full-thickness infarctive necrosis of the gallbladder. Bacterial cultures grew Clostridium perfringens.
Conclusions:
This case illustrates a typical case of emphysematous cholecystitis successfully treated by laparoscopic surgery. It contributes to suggestions from other reports that this condition can be safely treated by the laparoscopic approach.
PMCID: PMC3015641  PMID: 16381372
Emphysematous cholecystitis; Laparoscopy; Management
9.  Outcome of gallbladder preservation in surgical management of primary bile duct stones 
AIM: To evaluate the methods and outcome of gallbladder preservation in surgical treatment of primary bile duct stones.
METHODS: Thirty-five patients with primary bile duct stones and intact gallbladders received stone extraction by two operative approaches, 23 done through the intrahepatic duct stump (RBD-IDS, the RBD-IDS group) after partial hepatectomy and 12 through the hepatic parenchyma by retrograde puncture (RBD-RP, the RBD-RP group). The gallbladders were preserved and the common bile duct (CBD) incisions were primarily closed. The patients were examined postoperatively by direct cholangiography and followed up by ultrasonography once every six months.
RESULTS: In the RBD-IDS group, residual bile duct stones were found in three patients, which were cleared by a combination of fibrocholedochoscopic extraction and lithotripsy through the drainage tracts. The tubes were removed on postoperative day 22 (range: 16-42 days). In the RBD-RP group, one patient developed hemobilia and was cured by conservative therapy. The tubes were removed on postoperative day 8 (range: 7-11 days). Postoperative cholangiography showed that all the gallbladders were well opacified, contractile and smooth. During 54 (range: 6-120 months) months of follow-up, six patients had mildly thickened cholecystic walls without related symptoms and further changes, two underwent laparotomies because of adhesive intestinal obstruction and gastric cancer respectively, three died of cardiopulmonary diseases. No stones were found in all the preserved gallbladders.
CONCLUSION: The intact gallbladders preserved after surgical extraction of primary bile duct stones will not develop gallstones. Retrograde biliary drainage is an optimal approach for gallbladder preservation.
doi:10.3748/wjg.v9.i8.1871
PMCID: PMC4611565  PMID: 12918142
10.  Endoscopic gallbladder stenting for acute cholecystitis: a retrospective study of 46 elderly patients aged 65 years or older 
BMC Gastroenterology  2013;13:65.
Background
Endoscopic transpapillary pernasal gallbladder drainage and endoscopic gallbladder stenting (EGS) have recently been reported to be useful in patients with acute cholecystitis for whom a percutaneous approach is contraindicated. The aim of this study was to evaluate the efficacy of permanent EGS for management of acute cholecystitis in elderly patients who were poor surgical candidates.
Methods
We retrospectively studied 46 elderly patients aged 65 years or older with acute cholecystitis who were treated at Japan Labour Health and Welfare Organization Niigata Rosai Hospital. In 40 patients, acute cholecystitis was diagnosed by transabdominal ultrasonography and computed tomography, while 6 patients were transferred from other hospitals after primary management of acute cholecystitis. All patients underwent EGS, with a 7Fr double pig-tail stent being inserted into the gallbladder. If EGS failed, percutaneous transhepatic gallbladder drainage or percutaneous transhepatic gallbladder aspiration was subsequently performed. The main outcome measure of this study was the efficacy of EGS.
Results
Permanent EGS was successful in 31 patients (77.5%) with acute cholecystitis, without any immediate postprocedural complications such as pancreatitis, bleeding, perforation, or cholangitis. The most common comorbidities of these patients were cerebral infarction (n=14) and dementia (n=13). In 30 of these 31 patients (96.7%), there was no recurrence of cholecystitis and 29 patients (93.5%) remained asymptomatic until death or the end of the study period (after 1 month to 5 years).
Conclusions
EGS can be effective for elderly patients with acute cholecystitis who are poor surgical candidates and can provide a solution for several years.
doi:10.1186/1471-230X-13-65
PMCID: PMC3675408  PMID: 23586815
Endoscopic gallbladder stenting; Cholecystitis; Percutaneous transhepatic gallbladder drainage; percutaneous transhepatic gallbladder aspiration; Endoscopic transpapillary naso-gallbladder drainage; Elderly patients
11.  Acute cholecystitis 
BMJ Clinical Evidence  2008;2008:0411.
Introduction
Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. Up to the age of 50 years, acute calculous cholecystitis is three times more common in women than in men, and about 1.5 times more common in women than in men thereafter. About 95% of people with acute cholecystitis have gallstones. Optimal therapy for acute cholecystitis, based on timing and severity of presentation, remains controversial.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute cholecystitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: early cholecystectomy, laparoscopic cholecystectomy, minilaparoscopic cholecystectomy, observation alone, and open cholecystectomy.
Key Points
Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.
Early cholecystectomy within 7 days of onset of symptoms is the treatment of choice for acute cholecystitis. Early surgery reduces the duration of hospital admission compared with delayed surgery, but does not reduce mortality or complications.Up to a quarter of people scheduled for delayed surgery may require urgent operations because of recurrent or worsening symptoms.
Laparoscopic cholecystectomy reduces the duration of admission and may improve intraoperative and postoperative outcomes compared with open cholecystectomy, but increases the risk of bile duct injury. Up to a quarter of people having laparoscopic cholecystectomy may need conversion to open surgery because of risks of complications or uncontrolled bleeding.We don't know whether minilaparoscopic surgery leads to further reductions in duration of admission or improved outcomes compared with laparoscopic surgery.
PMCID: PMC2907986  PMID: 19445789
12.  Overlap of Acute Cholecystitis with Gallstones and Squamous Cell Carcinoma of the Gallbladder in an Elderly Patient 
Case Reports in Surgery  2015;2015:767196.
Introduction. The incidence of gallbladder cancer presenting with acute cholecystitis is 2.3%, squamous cell carcinoma is rarely seen, and overlap of acute cholecystitis and squamous cell carcinoma is a very rare condition in the literature. Presentation of Case. A 75-year-old woman was admitted to emergency service with a pain in the right upper quadrant, nausea, and vomiting. The patient was considered as having acute cholecystitis. During the exploration because Hartman's pouch was not dissected, it was adhered to the cystic duct and had fibrotic adhesion. It could not be understood whether this adhesion was a tumor or a fibrotic tumor and thus we performed cholecystectomy with a 1 cm resection of the choledochus. Pathological examination revealed the presence of (R0), T1 N0 M0 squamous cell carcinoma with clean resection borders and there was no in tumor five dissected lymph nodes. The patient has been followed up for about two years and no clinical problem has been observed throughout the follow-up. Discussion. Acute cholecystitis with gallstones may overlap with gallbladder cancer and generally presents nonspecific symptoms. No additional imaging techniques were performed since no clinical sign except for the wall thickening was detected and no suspected malignancy such as mass was detected on USG. Squamous cell carcinoma of the gallbladder shows poor diagnosis, but since its overlap with cholecystitis presents early symptoms and thus leads to early diagnosis and effective treatment, the localization of the carcinoma is of prime importance. Conclusion. Gallbladder cancer should be kept in mind in elderly patients with acute cholecystitis.
doi:10.1155/2015/767196
PMCID: PMC4556822  PMID: 26356191
13.  Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis 
AIM: To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach.
METHODS: From January 2002 to May 2012, we conducted a prospective randomized study on 45 consecutive patients (27 women, 18 men; mean age 58 years). These subjects were taken from a total of 681 patients who were hospitalised presenting similar preoperative findings: acute upper abdominal pain with tenderness, involuntary guarding under the right hypochondrium and/or in the flank; fever higher than 38 °C, leukocytosis greater than 10 × 109/L or both, and ultrasonographic evidence of calculous cholecystitis possibly complicated by peritonitis. These patients had undergone cholecystectomy for acute calculous cholecystitis, complicated by bile peritonitis. Randomly, 23 patients were assigned to laparoscopic cholecystectomy (LC), and 22 patients to open cholecystectomy (OC). Blood samples were collected from all patients before operation and at days 1, 3 and 6 after surgery. Serum bacteraemia, endotoxaemia, white blood cells (WBCs), WBC subpopulations, human leukocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin-1 (IL-1) and IL-6, and C-reactive protein (CRP) were measured at 0, 30, 60, 90, 120 and 180 min, at 4, 6, 12, 24 h, and then daily (8 A.M.) until post-op day 6.
RESULTS: The two groups were comparable in the severity of peritoneal contamination as indicated by the viable bacterial count (open group = 90% of positive cultures vs laparoscopic group = 87%) and endotoxin level (open group = 33.21 ± 6.32 pg/mL vs laparoscopic group = 35.02 ± 7.23 pg/mL). Four subjects in the OC group (18.1%) and 1 subject (4.3%) in the LC group (P < 0.05) developed intra-abdominal abscess. Severe leukocytosis (range 15.8-19.6/mL) was observed only after OC but not after LC, mostly due to an increase in neutrophils (days 1 and 3, P < 0.05). This value returned to the normal range within 3-4 d after LC and 5-7 d after OC. Other WBC types and lymphocyte subpopulations showed no significant variation. On the first day after surgery, a statistically significant difference was observed in HLA-DR expression between LC (13.0 ± 5.2) and OC (6.0 ± 4.2) (P < 0.05). A statistically significant change in plasma elastase concentration was recorded post-operatively at days 1, 3, and 6 in patients from the OC group when compared to the LC group (P < 0.05). In the OC group, the serum levels of IL-1 and IL-6 began to increase considerably from the first to the sixth hour after surgery. In the LC group, the increase of serum IL-1 and IL-6 levels was delayed and the peak values were notably lower than those in the OC group. Significant differences between the groups, for these two cytokines, were observed from the second to the twenty-fourth hour (P < 0.05) after surgery. The mean values of serum CRP in the LC group on post-operative days (1 and 3) were also lower than those in the OC group (P < 0.05). Systemic concentration of endotoxin was higher in the OC group at all intra-operative sampling times, but reached significance only when the gallbladder was removed (OC group = 36.81 ± 6.4 ρg/mL vs LC group = 16.74 ± 4.1 ρg/mL, P < 0.05). One hour after surgery, microbiological analysis of blood cultures detected 7 different bacterial species after laparotomy, and 4 species after laparoscopy (P < 0.05).
CONCLUSION: OC increased the incidence of bacteraemia, endotoxaemia and systemic inflammation compared with LC and caused lower transient immunological defense, leading to enhanced sepsis in the patients examined.
doi:10.4240/wjgs.v5.i4.73
PMCID: PMC3664294  PMID: 23717743
Systemic inflammation; Immune response; Laparoscopy; Cholecystectomy; Bile peritonitis
14.  Routine histopathology of gallbladder after elective cholecystectomy for gallstones: waste of resources or a justified act? 
BMC Surgery  2013;13:26.
Background
Selective approach for sending cholecystectomy specimens for histopathology results in missing discrete pathologies such as premalignant benign lesions such as porcelain gallbladder, carcinoma-in-situ, and early carcinomas. To avoid such blunders therefore, every cholecystectomy specimen should be routinely examined histologically. Unfortunately, the practice of discarding gallbladder specimen is standard in most tertiary care hospitals of Pakistan including the primary investigators’ own institution. This study was conducted to assess the feasibility or otherwise of performing histopathology in every specimen of gallbladder.
Methods
This cohort study included 220 patients with gallstones for cholecystectomy. All cases with known secondaries from gallbladder, local invasion from other viscera, traumatic rupture of gallbladder, gross malignancy of gallbladder found during surgery was excluded from the study. Laparoscopic cholecystectomy was performed in majority of cases except in those cases where anatomical distortion and dense adhesions prevented laparoscopy. All gallbladder specimens were sent for histopathology, irrespective of their gross appearance.
Results
Over a period of two years, 220 patients with symptomatic gallstones were admitted for cholecystectomy. Most of the patients were females (88%). Ninety two per cent patients presented with upper abdominal pain of varying duration. All specimens were sent for histopathology. Two hundred and three of the specimens showed evidence chronic cholecystitis, 7 acute cholecystitis with mucocele, 3 acute cholecystitis with empyema and one chronic cholecystitis associated with poly. Six gallbladders (2.8%) showed adenocarcinoma of varying differentiation along with cholelithiasis.
Conclusion
The histopathological spectrum of gallbladder is extremely variable. Incidental diagnosis of carcinoma gall bladder is not rare; if the protocol of routine histopathology of all gallbladder specimens is not followed, subclinical malignancies would fail to be identified with disastrous results. We strongly recommend routine histopathology of all cholecystectomy specimens.
doi:10.1186/1471-2482-13-26
PMCID: PMC3710513  PMID: 23834815
Gallbladder malignancy; Cholelithiasis; Cholecystectomy
15.  Outcomes of Xanthogranulomatous cholecystitis in laparoscopic era: A retrospective Cohort study 
INTRODUCTION:
Xanthogranulomatous cholecystitis (XGC) is a rare variant of cholecystitis and reported incidence of XGC varies from different geographic region from 0.7% -9%. Most of the clinicians are not aware of the pathology and less evidence is available regarding the optimal treatment of this less common form of cholecystitis in the present era of laparoscopic surgery.
MATERIALS AND METHODS:
A retrospective cohort study was conducted in a tertiary care university hospital from 1989 to 2009. Histopathologically confirmed XGC study patients (N=27) were compared with non-Xanthogranulomatous cholecystitis (NXGC) control group (N=27). The outcomes variables were operative time, complication rate and laparoscopic to open cholecystectomy conversion rate. The study group (XGC) was further divided in to three sub groups; group I open cholecystectomy (OC), laparoscopic cholecystectomy (LC) and laparoscopic converted to open cholecystectomy (LCO) for comparative analysis to identify the significant variables.
RESULTS:
During the study period 6878 underwent cholecystectomy including open cholecystectomy in 2309 and laparoscopic cholecystectomy in 4569 patients. Histopathology confirmed xanthogranulomatous cholecystitis in 30 patients (0.43% of all cholecystectomies) and 27 patients qualified for the inclusion criterion. Gallbladder carcinoma was reported in 100 patients (1.45%) during the study period and no association was found with XGC. The mean age of patients with XGC was 49.8 year (range: 29-79), with male to female ratio of 1:3. The most common clinical features were abdominal pain and tenderness in right hypochondrium. Biliary colic and acute cholecystitis were the most common preoperative diagnosis. Ultrasonogram was performed in all patients and CT scan abdomen in 5 patients. In study population (XGC), 10 were patients in group I, 8 in group II and 9 in group III. Conversion rate from laparoscopy to open was 53 % (n=9), surgical site infection rate of 14.8% (n=4) and common bile duct injury occurred one patient in open cholecystectomy group (3.7%). Statistically significant differences between group I and group II were raised total leukocyte count: 10.6±3.05 vs. 7.05±1.8 (P-Value 0.02) and duration of surgery in minutes: 248.75±165 vs. 109±39.7 (P-Value 0.04). The differences between group III and group II were duration of surgery in minutes: 208.75±58 vs. 109±39.7 (P-Value 0.03) and duration of symptoms in days: 3±1.8 vs. 9.8±8.8 (P-Value 0.04). The mean hospital stay in group I was 9.7 days, group II 5.6 days and in group III 10.5 days. Two patients underwent extended cholecystectomy based on clinical suspicion of carcinoma. No mortality was observed in this study population. Duration of surgery was higher in XGC group as compared to controls (NXGC) (203±129 vs.128±4, p-value=0.008) and no statistically significant difference in incidence proportion of operative complication rate were observed among the group (25.9% vs. 14.8%, p-value=0.25. Laparoscopic surgery was introduced in 1994 and 17 patients underwent laparoscopic cholecystectomy and higher conversion rate from laparoscopic to open cholecystectomy was observed in 17 study group (XGC) as compared to 27 Control group (NXGC) 53%vs.3.3% with P-value of < 0.023.
CONCLUSION:
XGC is a rare entity of cholecystitis and preoperative diagnosis is a challenging task. Difficult dissection was encountered in open as well in laparoscopic cholecystectomy with increased operation time. Laparoscopic cholecystectomy was carried out with high conversion rate to improve the safety of procedure. Per operative clinical suspicion of malignancy was high but no association of XGC was found with gallbladder carcinoma, therefore frozen section is recommended before embarking on radical surgery.
doi:10.4103/0972-9941.115368
PMCID: PMC3764653  PMID: 24019688
Bile duct injury; laparoscopic cholecystectomy; xanthogranulomatous cholecystitis
16.  Chemical ablation of the gallbladder using alcohol in cholecystitis after palliative biliary stenting 
Chemical ablation of the gallbladder is effective in patients at high risk of complications after surgery. Percutaneous gallbladder drainage is an effective treatment for cholecystitis; however, when the drain tube cannot be removed because of recurrent symptoms, retaining it can cause problems. An 82-year-old woman presented with cholecystitis and cholangitis caused by biliary stent occlusion and suspected tumor invasion of the cystic duct. We present successful chemical ablation of the gallbladder using pure alcohol, through a percutaneous gallbladder drainage tube, in a patient who developed intractable cholecystitis with obstruction of the cystic duct after receiving a biliary stent. Our results suggest that chemical ablation therapy is an effective alternative to surgical therapy for intractable cholecystitis.
doi:10.3748/wjg.15.2041
PMCID: PMC2675099  PMID: 19399941
Percutaneous cholecystostomy; Cholecystitis; Biliary stenting; Alcohol; Chemical therapy
17.  Pathophysiological significance of gallbladder volume changes in gallstone diseases 
AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.
METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 53 healthy subjects who received health examinations were measured by abdominal ultrasonography. Proper adjustments were made after the correction factors were calculated by comparing the preoperative and postoperative measurements. Pathological correlations between gallbladder changes in patients with acute calculous cholecystitis and the stages defined by the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student’s t tests were used. P < 0.05 was deemed statistically significant.
RESULTS: The fasting GBV was larger in late stage than in early/second stage acute cholecystitis gallbladders (84.66 ± 26.32 cm3, n = 12, vs 53.19 ± 33.80 cm3, n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders in chronic cholecystitis were larger/lower than those of normal subjects (28.77 ± 15.00 cm3 vs 6.77 ± 15.75 cm3, P < 0.0001)/(34.6% ± 10.6%, n = 65, vs 53.3% ± 24.9%, n = 53, P < 0.0001).
CONCLUSION: GBV increases as acute cholecystitis progresses to gangrene and/or empyema. Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones.
doi:10.3748/wjg.v16.i34.4341
PMCID: PMC2937116  PMID: 20818819
Gallbladder volume; Pathophysiology; Gallbladder ejection fraction; Gallstone formation; Acute cholecystitis
18.  Acute acalculous cholecystitis complicated by MRCP-confirmed Mirizzi syndrome: A case report 
INTRODUCTION
Acute acalculous cholecystitis can be complicated by extrinsic compression of the common hepatic/common bile duct by the enlarged and inflamed gallbladder followed by jaundice. Its mechanism is very similar to that of Mirizzi syndrome, when the bile duct is compressed from outside due to a stone impacted in the gallbladder neck or cystic duct. This complication of acalculous cholecystitis is rare, with very little number of published cases.
PRESENTATION OF A CASE
We present a patient with compression of the common hepatic duct by an inflamed and enlarged gallbladder in the absence of stones as confirmed by magnetic resonance cholangiopancreatography (MRCP). Acute cholecystitis and jaundice resolved after conservative treatment, and the changes were shown by a follow-up MRCP five months later.
DISCUSSION
We were able to find only three similar cases reported in the literature. In these cases, compression of the common hepatic/common bile duct by the inflamed gallbladder was confirmed by endoscopic retrograde cholangiopancreatography and intraoperatively. Terminology to describe this condition has not been agreed upon. We consider it as a special kind of Mirizzi syndrome.
CONCLUSION
To the best of our knowledge, this is the first reported case of MRCP-confirmed Mirizzi syndrome in acute acalculous cholecystitis.
doi:10.1016/j.ijscr.2011.11.006
PMCID: PMC3312057  PMID: 22406001
MS, Mirizzi syndrome; AAC, acute acalculous cholecystitis; ERCP, endoscopic retrograde cholangiopancreatography; MRCP, magnetic resonance cholangiopancreatography; US, ultrasonography; Acute acalculous cholecystitis; Mirizzi syndrome; Magnetic resonance cholangiopancreatography
19.  Surgical treatment of patients with acute cholecystitis: Tokyo Guidelines 
Cholecystectomy has been widely performed in the treatment of acute cholecystitis, and laparoscopic cholecystectomy has been increasingly adopted as the method of surgery over the past 15 years. Despite the success of laparoscopic cholecystectomy as an elective treatment for symptomatic gallstones, acute cholecystitis was initially considered a contraindication for laparoscopic cholecystectomy. The reasons for it being considered a contraindication were the technical difficulty of performing it in acute cholecystitis and the development of complications, including bile duct injury, bowel injury, and hepatic injury. However, laparoscopic cholecystectomy is now accepted as being safe for acute cholecystitis, when surgeons who are expert at the laparoscopic technique perform it. Laparoscopic cholecystectomy has been found to be superior to open cholecystectomy as a treatment for acute cholecystitis because of a lower incidence of complications, shorter length of postoperative hospital stay, quicker recuperation, and earlier return to work. However, laparoscopic cholecystectomy for acute cholecystitis has not become routine, because the timing and approach to the surgical management in patients with acute cholecystitis is still a matter of controversy. These Guidelines describe the timing of and the optimal surgical treatment of acute cholecystitis in a question-and-answer format.
doi:10.1007/s00534-006-1161-x
PMCID: PMC2784499  PMID: 17252302
Acute cholecystitis; Cholecystectomy; Laparoscopic cholecystectomy; Open surgery; Cholecystostomy; Guidelines
20.  Percutaneous cholecystostomy in acute cholecystitis; a retrospective analysis of a large series of 104 patients 
BMC Surgery  2015;15:17.
Background
The purpose of this study was to evaluate the clinical course and possible benefit of a percutaneous cholecystostomy in patients with acute cholecystitis.
Methods
Retrospective study of 104 patients with severe cholecystitis or cholecystitis not responding to antibiotic therapy treated with percutaneous drainage of the gall bladder (PC) during the period 2007 – 2013. Primary outcome was relief of cholecystitis, complications following the procedure and need for later cholecystectomy.
Results
There were 57 men and 47 women with a median age of 73,5 years (range 22 – 96). 43% of the patients were ASA III or IV and 91% had cholecystitis Grade 2 or 3. About 60% of the patients had severe comorbidity (cardiovascular disease or active cancer). Drain insertion was successful in all but one patient and complications were mild, apart from two patients that needed percutaneous drainage of intraabdominal fluid collection due to bile leakage. The drain was left in place for 1 – 75 days (median 6,5). When evaluated clinically and by blood tests (CRP and white blood cell counts) we found resolution of symptoms in 101 patients (97,2%), whereas 2 patients had no obvious effect of drainage. Four patients died within 30 days, no deaths were related to the drainage procedure. Follow-up after drainage was median 12 months (range 0 – 78). During that time cholecystectomy was performed in 30 patients and 24 patients had died. Following cholecystectomy, two had died, both from cancer and more than one year after the operation.
Conclusion
Patients with acute cholecystitis were promptly relieved from their symptoms following PC. There were only minor complications following the procedure and only about 30% of the patients had a later cholecystectomy.
doi:10.1186/s12893-015-0002-8
PMCID: PMC4357156  PMID: 25872885
Cholecystitis; Cholecystostomy; Percutaneous; Complications
21.  Perfidious Gallbladders – A Diagnostic Dilemma with Xanthogranulomatous Cholecystitis 
INTRODUCTION
Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis characterised by marked thickening of the gallbladder wall and dense local adhesions. Pre-operative and intra-operative diagnosis is difficult and it often mimics a gallbladder carcinoma (GBC). Laparoscopic cholecystectomy (LC) is frequently unsuccessful with a high conversion rate. A series of patients with this condition led us to review our experience with XGC and to try to develop a care pathway for its management.
PATIENTS AND METHODS
A retrospective review of the medical records of 1296 consecutive patients who had undergone cholecystectomy between January 2000 and April 2005 at our hospital was performed. Twenty-nine cases of XGC were identified among these cholecystectomies. The clinical, radiological and operative details of these patients have been analysed.
RESULTS
The incidence of XGC was 2.2% in our study. The mean age at presentation was 60.3 years with a female:male ratio of 1.4:1. Twenty-three patients (79%) required an emergency surgical admission at first presentation. In three patients, a GBC was suspected both radiologically and at operation (10.3%), but was later disproved on histology. Seventeen patients (59%) had obstructive jaundice at first presentation and required an endoscopic retrograde cholangiopancreatography (ERCP) before LC. Of these, five had common bile duct stones. Abdominal ultrasound scan showed marked thickening of the gallbladder wall in 16 cases (55%). LC was attempted in 24 patients, but required conversion to an open procedure in 11 patients (46% conversion rate). A total cholecystectomy was possible in 18 patients and a partial cholecystectomy was the choice in 11 (38%). The average operative time was 96 min. Three patients developed a postoperative bile leak, one of whom required ERCP and placement of a biliary stent. The average length of stay in the hospital was 6.3 days.
CONCLUSIONS
Severe xanthogranulomatous cholecystitis often mimics a gallbladder carcinoma. Currently, a correct pre-operative diagnosis is rarely made. With increased awareness and a high index of suspicion, radiological diagnosis is possible. Preoperative counselling of these patients should include possible intra-operative difficulties and the differential diagnosis of gallbladder cancer. Laparoscopic cholecystectomy is frequently unsuccessful and a partial cholecystectomy is often the procedure of choice.
doi:10.1308/003588407X155833
PMCID: PMC1964568  PMID: 17346415
Xanthogranulomatous cholecystitis; Gallbladder carcinoma; Laparoscopic cholecystectomy
22.  Endoscopic Gallbladder Drainage for Acute Cholecystitis 
Clinical Endoscopy  2015;48(5):411-420.
Background/Aims
Surgery is the mainstay of treatment for cholecystitis. However, gallbladder stenting (GBS) has shown promise in debilitated or high-risk patients. Endoscopic transpapillary GBS and endoscopic ultrasound-guided GBS (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage.
Methods
Data from patients with cholecystitis were prospectively collected from August 2004 to May 2013 from two United States academic university hospitals and analyzed retrospectively. The following treatment algorithm was adopted. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and cystic duct stenting was initially attempted. If deemed feasible by the endoscopist, EUS-GBS was then pursued.
Results
During the study period, 139 patients underwent endoscopic gallbladder drainage. Among these, drainage was performed in 94 and 45 cases for benign and malignant indications, respectively. Successful endoscopic gallbladder drainage was defined as decompression of the gallbladder without incidence of cholecystitis, and was achieved with ERCP and cystic duct stenting in 117 of 128 cases (91%). Successful endoscopic gallbladder drainage was also achieved with EUS-guided gallbladder drainage using transmural stent placement in 11 of 11 cases (100%). Complications occurred in 11 cases (8%).
Conclusions
Endoscopic gallbladder drainage techniques are safe and efficacious methods for gallbladder decompression in non-surgical patients with comorbidities.
doi:10.5946/ce.2015.48.5.411
PMCID: PMC4604280  PMID: 26473125
Transgastric; Endoscopic ultrasound-guided gallbladder drainage; Cholecystitis; Metal stent; Fully covered self-expanding metal stent
23.  Biliary levels of ceforanide. 
Ceforanide levels in plasma, gallbladder bile, gallbladder tissue, and common bile duct were studied in 10 patients with normal biliary tracts and in 35 patients with biliary disease at various intervals after intravenous injection of 1 g of the drug. Peak blood levels were obtained within 1 h of administration (mean, 67 +/- 15 micrograms/ml). Patients with a normal bilary tract, as well as patients with chronic cholecystitis and a patent cystic duct, achieved high gallbladder bile levels of ceforanide within 2 h (mean, 76 +/- 25 micrograms/ml) and attained even higher levels by 4 h (mean, 182 +/- 51 micrograms/ml). However, all patients with chronic cholecystitis and an occluded cystic duct had very low drug concentrations in the gallbladder bile (14 +/- 7 micrograms/ml at 2 h). Despite this difference in gallbladder bile levels, ceforanide levels of 21 +/- 3 micrograms/g were achieved at 1 to 3 h in gallbladder tissue in both groups with chronic cholecystitis. The concentration of ceforanide in common bile duct was 149 +/- 59 micrograms/ml at 2 h after administration, with levels over 60 micrograms/ml present from 1 to 4 h after administration. These results indicate that ceforanide reaches high levels in the biliary tract. Its potential value in the prevention and treatment of biliary infections should be assessed.
PMCID: PMC184792  PMID: 6870219
24.  Tube Cholecystostomy Before Cholecystectomy for the Treatment of Acute Cholecystitis 
Background and Objectives:
Percutaneous cholecystostomy is currently indicated for patients with cholecystitis who might be poor candidates for operative cholecystectomy. We performed a study to evaluate the long-term outcome of patients undergoing emergent tube cholecystostomy.
Methods:
This study was a retrospective chart review of patients who underwent tube cholecystostomy from July 1, 2005, to July 1, 2012.
Results:
During the study period, 82 patients underwent 125 cholecystostomy tube placements. Four patients (5%) died during the year after tube placement. The mean hospital length of stay for survivors was 8.8 days (range, 1–59 days). Twenty-eight patients (34%) required at least 1 additional percutaneous procedure (range, 1–6) for gallbladder drainage. Twenty-nine patients (34%) ultimately underwent cholecystectomy. Surgery was performed a mean of 7 weeks after cholecystostomy tube placement. Laparoscopic cholecystectomy was attempted in 25 operative patients but required conversion to an open approach in 8 cases (32%). In another 4 cases, planned open cholecystectomy was performed. Major postoperative complications were limited to 2 patients with postoperative common bile duct obstruction requiring endoscopic retrograde cholangiopancreatography, 1 patient requiring a return to the operating room for hemoperitoneum, and 2 patients with bile leak from the cystic duct stump.
Conclusions:
In high-risk patients receiving cholecystostomy tubes for acute cholecystitis, only about one third will undergo surgical cholecystectomy. Laparoscopic cholecystectomy performed in this circumstance has a higher rate of conversion to open surgery and higher hepatobiliary morbidity rate.
doi:10.4293/JSLS.2014.00200
PMCID: PMC4376213  PMID: 25848180
Acute cholecystitis; Percutaneous cholecystostomy; Cholecystectomy
25.  Unusual presentation of gallbladder perforation 
Highlights
•Percutaneous abscesses arising from the gallbladder are a rare but potentially serious consequence of acute cholecystitis, and may present in a wide variety of locations.•Silent cholecystitis is a rare but significant cause of sepsis.•It is imperative to conduct a full body inspection in the septic patient, even when a source has been identified.•Early surgical intervention is invaluable in suspected abscesses, regardless of the availability of pre-operative imaging.
Introduction
Gall bladder perforation is associated with high mortality rates and therefore must be recognised and managed promptly. We present an unusual presentation of spontaneous gall bladder perforation.
Case presentation
An elderly lady with multiple medical co-morbidities was admitted with sepsis following a fall. Initial assessment lead to a diagnosis of pneumonia, however a rapidly expanding right flank mass was incidentally noted during routine nursing care. Imaging studies were inconclusive, however incision and drainage of the mass revealed bile stained pus draining cutaneously from an acutely inflamed gallbladder. The patient made a good recovery following surgery, and was discharged with outpatient follow-up.
Discussion
Despite focussed post-hoc history taking she denied any prodromal symptoms of cholecystitis. In addition to reporting an unusual cause for a common presentation, we highlight the importance of a full body examination in the context of sepsis, regardless of whether the source has been identified. In addition, we advocate that surgical intervention in sepsis should not be delayed by imaging in cases where an abscess is suspected.
Conclusions
Percutaneous abscesses arising from the gallbladder are a rare but potentially serious consequence of acute cholecystitis, and may present in a wide variety of locations. Therefore it is imperative to conduct a full body inspection in the septic patient, even when a source has been identified.
doi:10.1016/j.ijscr.2015.11.024
PMCID: PMC4701862  PMID: 26686488
Acute cholecystitis; Gallbladder perforation; Cholecystocutaneous fistula; Sepsis

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