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1.  Acute cholecystitis 
Clinical Evidence  2011;2011:0411.
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).
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.
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
2.  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.
PMCID: PMC2443024  PMID: 1292590
3.  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.
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.
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).
Fluoroscopy-guided percutaneous gallstone removal using a 12-Fr sheath is technically feasible and clinically effective in high-risk surgical patients with acute cholecystitis.
PMCID: PMC3052612  PMID: 21430938
Gallbladder stone; Acute cholecystitis; Percutaneous cholecystolithotomy
4.  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.
PMCID: PMC4066164  PMID: 16521227
Sphincterotomy; Choledocholithiasis; Acute cholecystitis; Cholecystectomy
5.  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.
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.
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).
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%.
Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis.
Trial registration NCT00448786
PMCID: PMC3688238  PMID: 23679351
6.  A Case of Emphysematous Cholecystitis Managed by Laparoscopic Surgery 
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.
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.
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.
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
7.  Endoscopic gallbladder stenting for acute cholecystitis: a retrospective study of 46 elderly patients aged 65 years or older 
BMC Gastroenterology  2013;13:65.
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.
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.
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).
EGS can be effective for elderly patients with acute cholecystitis who are poor surgical candidates and can provide a solution for several years.
PMCID: PMC3675408  PMID: 23586815
Endoscopic gallbladder stenting; Cholecystitis; Percutaneous transhepatic gallbladder drainage; percutaneous transhepatic gallbladder aspiration; Endoscopic transpapillary naso-gallbladder drainage; Elderly patients
8.  Acute cholecystitis 
Clinical Evidence  2008;2008:0411.
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).
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.
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
9.  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.
PMCID: PMC3664294  PMID: 23717743
Systemic inflammation; Immune response; Laparoscopy; Cholecystectomy; Bile peritonitis
10.  Routine histopathology of gallbladder after elective cholecystectomy for gallstones: waste of resources or a justified act? 
BMC Surgery  2013;13:26.
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.
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.
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.
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.
PMCID: PMC3710513  PMID: 23834815
Gallbladder malignancy; Cholelithiasis; Cholecystectomy
11.  Outcomes of Xanthogranulomatous cholecystitis in laparoscopic era: A retrospective Cohort study 
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.
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.
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.
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.
PMCID: PMC3764653  PMID: 24019688
Bile duct injury; laparoscopic cholecystectomy; xanthogranulomatous cholecystitis
12.  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.
PMCID: PMC2675099  PMID: 19399941
Percutaneous cholecystostomy; Cholecystitis; Biliary stenting; Alcohol; Chemical therapy
13.  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.
PMCID: PMC2937116  PMID: 20818819
Gallbladder volume; Pathophysiology; Gallbladder ejection fraction; Gallstone formation; Acute cholecystitis
14.  Acute acalculous cholecystitis complicated by MRCP-confirmed Mirizzi syndrome: A case report 
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.
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.
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.
To the best of our knowledge, this is the first reported case of MRCP-confirmed Mirizzi syndrome in acute acalculous cholecystitis.
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
15.  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.
PMCID: PMC2784499  PMID: 17252302
Acute cholecystitis; Cholecystectomy; Laparoscopic cholecystectomy; Open surgery; Cholecystostomy; Guidelines
16.  Perfidious Gallbladders – A Diagnostic Dilemma with Xanthogranulomatous Cholecystitis 
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.
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.
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.
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.
PMCID: PMC1964568  PMID: 17346415
Xanthogranulomatous cholecystitis; Gallbladder carcinoma; Laparoscopic cholecystectomy
17.  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
18.  Endoscopic transpapillary gallbladder drainage with replacement of a covered self-expandable metal stent 
Endoscopic self-expandable metal stent (SEMS) placement has become a standard palliative therapy for patients with malignant biliary obstruction. Acute cholecystitis after SEMS placement is a serious complication. We report a patient with an acute cholecystitis after covered SEMS placement, who was managed successfully with endoscopic transpapillary gallbladder drainage (ETGBD) and replacement of the covered SEMS. An 85-year-old man with pancreatic cancer suffered from acute cholecystitis after covered SEMS placement. It was impossible to perform percutaneous transhepatic gallbladder drainage. After removal of the covered SEMS with a snare, a 7Fr double pigtail stent was placed between the gallbladder and duodenum, subsequently followed by another covered SEMS insertion into the common bile duct beside the gallbladder stent. The cholecystitis improved immediately after ETGBD. ETGBD with replacement of the covered SEMS thus proved to be effective for treatment of patients with acute cholecystitis after covered SEMS placement.
PMCID: PMC3055944  PMID: 21403817
Self-expandable metal stent; Cholecystitis; Endoscopic transpapillary gallbladder drainage
19.  Predicting the success of endoscopic transpapillary gallbladder drainage for patients with acute cholecystitis during pretreatment evaluation 
Although endoscopic transpapillary gallbladder drainage (ETGBD) has been reported to be an effective treatment for acute cholecystitis, technical difficulties have precluded more widespread use of this technique. Case evaluations that can predict the occurrence of such difficulties should increase the acceptance of ETGBD for acute cholecystitis treatment.
To establish a pretreatment evaluation protocol for patients with acute cholecystitis.
Eleven patients with acute cholecystitis who received ETGBD in 2003 or 2004 were enrolled in the present retrospective study. The frequency of success, complications and overall effectiveness of ETGBD for treatment of cholecystitis were measured. Factors that could affect ETGBD success, including clinical and laboratory parameters, and gallbladder ultrasonograms, were also evaluated.
ETGBD was successful in seven of 11 patients (success rate 63.6%). All seven patients who underwent ETGBD successfully were afebrile and asymptomatic within a few days. No clinical or laboratory variables were significantly associated with the success of ETGBD. In contrast, ultrasonographic measures of gallbladder minor-axis length and wall thickness in successful cases were significantly shorter (27.4 mm versus 38.0 mm; P=0.008) and thinner (4.2 mm versus 9.0 mm; P=0.041) relative to unsuccessful cases.
Ultrasonographic measures of gallbladder minor-axis length and wall thickness can serve as important predictors of ETGBD technical difficulties during pretreatment evaluation of patients with acute cholecystitis.
PMCID: PMC2661289  PMID: 18701945
Acute cholecystitis; Endoscopic transpapillary gallbladder drainage
20.  The value of percutaneous ultrasound in predicting conversion from laparoscopic to open cholecystectomy due to acute cholecystitis 
Surgical Endoscopy  2013;27(7):2561-2568.
Laparoscopic cholecystectomy has become the treatment of choice for gallstone disease. Advantages of the laparoscopic approach include lower morbidity and mortality rates, reduced length of hospital stay, and earlier return to work. In acute cholecystitis, severe inflammation makes laparoscopic dissection technically more demanding, with a higher risk of related complications that require conversion to open cholecystectomy.
We reviewed the records of 5,596 patients who underwent cholecystectomy between 1993 and 2011 in a single institution. A laparoscopic approach was undertaken in 4,105 patients (73.4 %). The ultrasound signs of acute cholecystitis were found in 542 patients (13.2 %) who underwent laparoscopic cholecystectomy. We analyzed the ultrasound presentations of acute cholecystitis in patients who required conversion to open cholecystectomy and compared them with the ultrasound signs of acute cholecystitis in patients who had a completed laparoscopic cholecystectomy.
A conversion to open cholecystectomy in patients with acute cholecystitis was necessary in 24 % (n = 130) of the patients compared to 3.4 % of the patients with uncomplicated gallstone disease. The most frequent ultrasound findings in patients requiring conversion were a pericholecystic exudate in 42 %, a difficult identification of anatomical structures due to local severe inflammation in 34 %, and gallbladder wall thickening of >5 mm in 31 %. Additionally, when the duration of symptoms exceeded 3 days, more than half of the patients required conversion to open cholecystectomy and the conversion rate was fivefold higher than for those with a shorter duration of acute cholecystitis.
In patients with severe acute cholecystitis found on ultrasound, combined with gallbladder wall thickening to >5 mm, pericholecystic exudates or abscess adjacent to the gallbladder, difficulty identifying anatomical structures within Calot’s triangle, specifically when the duration of symptoms exceeds 3 days, cholecystectomy should be done as an open approach because of the high risk of conversion.
PMCID: PMC3679415  PMID: 23371022
Acute cholecystitis; Laparoscopic cholecystectomy; Open cholecystectomy; Conversion; Percutaneous ultrasound
21.  Surgical options in the management of cystic duct avulsion during laparoscopic cholecystectomy 
Avulsion of cystic duct during laparoscopic cholecystectomy (LC) is not a common intraoperative complication, but may be encountered by any laparoscopic surgeon. Surgeons are rarely familiar with management of this condition.
Patients with gall stone related problems who were scheduled for LC at the minimal invasive surgery unit of a tertiary referral hospital during a 5 years period (April 2002–April 2007) were prospectively enrolled.
12 cases were identified (incidence: 1.15%). All 12 patients had gallbladder inflammation. Five patients had acute and seven patients had chronic cholecystitis. The avulsed cystic duct (ACD) was managed by clipping in 4, intracorporeal suturing in 3, converting to open surgery with suture ligation in 2, and lonely external drainage in 3 patients. Bile leakage had ceased within 3 days in 2, 14 days in one, and 20 days in the other patient. Bile volume increased gradually in one of the patients, which stopped only after endoscopic sphincterotomy (ES) at 25th postoperative day. No major late complication or mortality occurred.
ACD during LC is a rare complication. Almost all standard methods of treatment yield to successful outcomes with low morbidity. According to the situation, ACD may be successfully managed laparoscopically. Available cystic stump remnant was clipped. Intracorporeal suture ligation was performed when short length of stump precluded clipping. Deeply retracted cystic duct with active bile leak led to conversion to open surgery. With minimal or no bile leak at ACD stump, closed tube drainage of sub-hepatic area was attempted. Persistent bile leak was assumed to be controlled by ES, successfully accomplished in one patient.
PMCID: PMC2442050  PMID: 18565237
22.  Cystic artery pseudo-aneurysm: a complication of xanthogranulomatous cholecystitis 
The British Journal of Radiology  2010;83(992):e165-e167.
A 54-year-old man presented for radiology with pain and a feeling of fullness in the upper abdomen and an epigastric mass. Ultrasound revealed a large cystic mass with internal echoes, lying posterior and inferior to left lobe of the liver. The gallbladder was thick-walled and contracted, and contained a calculus and echogenic sludge. A cystic structure that produced swirling flow signals on colour Doppler was demonstrated within the gallbladder. The CT scan showed a thickened gallbladder with adjacent inflammation and a 2-cm pseudo-aneurysm in its wall. High-density material was present in the gallbladder lumen, in the extra-hepatic bile ducts and around the gastrohepatic ligament. A thick haemorrhagic pus, from which Escherichia coli was cultured, was drained from the gastrohepatic collection. An elective coeliac angiogram demonstrated a solitary pseudo-aneurysm of the medial branch of the cystic artery. Selective catheterisation of this artery with a micro-catheter enabled complete exclusion of the pseudo-aneurysm by a single micro-coil. Histological examination of the gallbladder, which was ultimately removed at open cholecystectomy, demonstrated xanthogranulomatous cholecystitis.
PMCID: PMC3473518  PMID: 20675459
23.  Laparoscopic Cholecystectomy: a Safe Approach for Management of Acute Cholecystitis 
Background and Objectives:
Laparoscopic cholecystectomy (LC) is increasingly being used as an appropriate early treatment in patients with cholecystitis. This study evaluated the safety, effectiveness, and complications of LC in all cases of acute cholecystitis.
A retrospective study involved the patients who underwent LC for acute cholecystitis within 72 hours of admission. The preoperative diagnosis was based on clinical, laboratory, and echographic examinations, while the final diagnosis was confirmed by histopathological examination of the excised gallbladder.
We identified 184 patients with acute cholecystitis. Intraoperative cholangiography (IOC) was not performed. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) was performed in 62 patients (33.7%), and postoperative ERCP in 13 patients (7.1%). Conversion to open cholecystectomy was necessary in 19 patients (10.3%); 16 patients for severe inflammation and adhesions and 3 patients because of uncontrolled bleeding. The mean operative time was 68 minutes. No deaths occurred. The overall complication rate was 6% with 3 postoperative bile leakages and 2 nonbilious subhepatic collections. The mean postoperative hospital stay was 2.8 days.
LC is a safe, effective procedure for the early management of patients with acute cholecystitis. LC can be safely performed without routine IOC when ERCP is performed preoperatively on the basis of specific indications. Meticulous dissection and good exposure of Calot's triangle may prevent bile duct injuries.
PMCID: PMC3015721  PMID: 17761084
Laparoscopic cholecystectomy; Acute cholecystitis; Open cholecystectomy; Intraoperative cholangiography
24.  Enhanced Expression of Cystathionine β-Synthase and Cystathionine γ-Lyase During Acute Cholecystitis-Induced Gallbladder Inflammation 
PLoS ONE  2013;8(12):e82711.
Hydrogen sulfide (H2S) has recently been shown to play an important role in the digestive system, but the role of endogenous H2S produced locally in the gallbladder is unknown. The aim of this study was to investigate whether gallbladder possesses the enzymatic machinery to synthesize H2S, and whether H2S synthesis is changed in gallbladder inflammation during acute acalculous cholecystitis (AC).
Adult male guinea pigs underwent either a sham operation or common bile duct ligation (CBDL). One, two, or three days after CBDL, the animals were sacrificed separately. Hematoxylin and eosin-stained slides of gallbladder samples were scored for inflammation. H2S production rate in gallbladder tissue from each group was determined; immunohistochemistry and western blotting were used to determine expression levels of the H2S-producing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in gallbladder.
There was a progressive inflammatory response after CBDL. Immunohistochemistry analysis showed that CBS and CSE were expressed in the gallbladder epithelium, muscular layer, and blood vessels and that the expression increased progressively with increasing inflammation following CBDL. The expression of CBS protein as well as the H2S-production rate was significantly increased in the animals that underwent CBDL, compared to those that underwent the sham operation.
Both CBS and CSE are expressed in gallbladder tissues. The expression of these enzymes, as well as H2S synthesis, was up-regulated in the context of inflammation during AC.
PMCID: PMC3857271  PMID: 24349344
25.  Acute Cholecystitis is an Indication for Laparoscopic Cholecystectomy: A Prospective Study 
Examines the issues of safety and efficacy of laparoscopic cholecystectomy for emergency treatment of acute calculous cholecystitis.
Acute cholecystitis has been considered as a relative or absolute contraindication to laparoscopic cholecystectomy. The purpose of this study is to present our experience of laparoscopic cholecystectomy as a safe and effective treatment of acute cholecystitis.
Laparoscopic cholecystectomy was offered to 34 consecutive patients with acute calculous cholecystitis, diagnosed according to strict clinical and ultrasonographic criteria. We used only three trocars. The gallbladder was routinely aspirated and sharp graspers were used. We adopted the fundus-first method of dissection when safe identification of the Calot' s triangle was difficult. The cystic duct was ligated whenever necessary.
The procedure was completed in 31 patients. The mean length of the laparoscopic procedure was 43 minutes, their mean hospital stay was 2.8 days. For the open group the mean length of the operative procedure was 66 minutes, while the mean hospital stay was 5.3 days. The overall morbidity rate was low.
The benefits of laparoscopic cholecystectomy can be safely extended to patients with acute cholecystitis. The operation must be done early in the course of the disease. The surgeon should have adequate laparoscopic experience and maintain a low threshold for conversion to open exploration. Modifications in technique should be adopted to achieve a successful outcome.
PMCID: PMC3021269  PMID: 9876658

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