Klinični oddelek za abdominalno kirurgijo, Kirurška klinika, Univerzitetni klinični center Ljubljana, Ljubljana 
Correspondence: 
Jurij Janež, 
e: jurij.janez@gmail.com 

Key words: 
acute cholecystitis; laparoscopic cholecystectomy; open cholecystectomy; percutaneous cholecystostomy; tokyo Guidelines; World society of emergency surgery guidelines 

Cite as: 
Zdrav Vestn. 2017; 86(11–12):532–43. 
received: 20. 2. 2017 Accepted: 23. 6. 2017 
Doi 10.6016/ ZdravVestn.2496 

Acute cholecystitis – early surgery or an attempt at conservative treatment? 
Jurij Janež 

Abstract 

Acute cholecystitis is a common disease, which often requires admission to hospital and surgical treatment. Acute cholecystitis is defined as inflammation of the gallbladder and usually occurs due to cystic duct obstruction from stones or sludge. It is a relatively common complication of gallstones, but it can also occur without gallstones.A combination of relevant clinical symptoms and ultrasound evidence is required to make a diagnosis of acute cholecystitis. Early surgery is recommended for all patients who are in good physical condition. There is still a debate how to treat high-risk and critically-ill patients. Laparoscopic cholecystectomy is the method of choice for treatment of patients with acute cholecystitis. Early laparoscopic cholecystectomy should be done within 72 hours from the onset of symptoms. 
This article presents current guidelines according to the Tokyo guidelines and the World Society of Emergency Surgery guidelines, and at the end, experiences of some clinical trials. 
Cite as: Zdrav Vestn. 2017;86(11–12):532–43. 


1. Introduction 

Acute cholecystitis is a condition that represents a difficult diagnostic problem often requires admission to hospital and in diabetics, pregnant women and surgery. It occurs most commonly in immunocompromised patients because individuals with gallstones, yet it can also ofunclearclinicalmanifestations. Early develop in the absence of gallstones (1). diagnosis and early operative treatment Acalculous cholecystitis often affects are imperative in these patients, provided critically-ill patients on long-term that their general condition allows it (5). parenteral nutrition, patients with Early cholecystecomy reduces the rate of multiple trauma or severe burns and peri- and postoperative complications, patients following cardiac surgery (2). and the risk of recurrence following Acute cholecystitis is a common cause conservative treatment (3). Thanks to its of morbidity and mortality in the safety and acceptable risk of postoperative elderly, diabetic patients and pregnant complications, early laparoscopic women (3). Factors associated with cholecystectomy is recommended in cholelithiasis include obesity, old elderly patients. Early surgery, compared age and some drugs, such as oral with delayed operation, significantly contraceptives.(4) Acute cholecysitis decreases morbidity, hospital stay and recovery time, and therefore significantly lowers the costs of treatment (6). There is still a debate about how to treat patients with concomitant diseases and high-risk patients. In the latter, percutanous gallbladder drainage is used as a bridge to surgery until the patient’s general condition improves to permit surgical intervention. In some cases, percutaneous transhepatic gallbladder drainage can be considered a definitive treatment (7-9). 

2. Complications of acute cholecystitis 
The rate of complications in ad­vanced forms of cholecystitis ranges from 7.2 % to 26 % (4). In patients with acute cholecystitis, gallbladder perfora­tion most often occurs due to impaired circulation and necrosis of the gallblad­der wall. The resulting leakage of bile into the abdominal cavity causes biliary peritonitis, or localised peritonitis with the formation of pericholecystic abscess may occur (6,10), Acute inflammation of the gallbladder may be complicated by the formation of biliary fistula, i.e. an abnormal connection between the gall­bladder and the biliary tree or a nearby hollow structure, most commonly the duodenum (cholecysto–duodenal fis­tula), the colon (cholecysto-colic fistula) and the stomach (cholecysto-gastric fis­tula) (10). Cholecyto-duodenal fistulas are most commonly due to the erosion of a large gallstone through the wall of the gallbladder and the duodenum. The stone may enter into the duodenum and then migrate through the digestive tract. A very large gallstonestone may become impacted in the terminal ileum on the ileocecal valve, causing mechanical ob­struction of the intestine, called biliary ileus. Proximal ileus due to impaction of a gallstone in the duodenum is referred to as Bouveret’s syndrome (10). Biliary fistulas fall roughly into two categories: primary fistulas related to gallstones, and secondary fistulas related to surgical complications (11). The incidence of pri­mary biliary fistulas is 1 to 2 %. Second­ary biliary fistulas most frequently occur following open or laparoscopic chole­cystectomy. The incidence of secondary biliary fistulas is low (0.3–0.6 % of all cholecystectomies). Secondary biliary fistulas are characterized by bile leakage in the abdominal cavity or through the abdominal drain. If abdominal drainage is not used after surgery, bile collection in the abdominal cavity may lead to the development of biliary peritonitis (11). Patients with a suspected biliary fistula should have an abdominal ultrasound to assess the presence of free fluid or larger fluid collections in the abdominal cav­ity. The next step is contrast-enhanced imaging of the biliary tree, either by en­doscopic retrograde cholangiopancrea­tography (ERCP) or magnetic resonance cholangiopancreatography (MRCP). These investigations allow visualization of the biliary system anatomy and dem­onstrate possible biliary leak by visual­izing the contrast agent pooling outside the biliary tree due to biliary fistula or iatrogenic bile duct injury. Patients with bile duct leaks are treated by ERCP with biliary stent placement to bridge areas of the damaged bile duct wall. The biliary stent is removed at a later date (11). 

3. Clinical classification 
According to the Tokyo guidelines, the severity of local and systemic signs of inflammation in acute cholecystitis is classified into three grades: mild (Grade I), moderate (Grade II) and severe (Grade III) (Table 1). 
In 2016, the World Society of Emer­gency Surgery (WSES) defined recom­mendations for the management of pa­tients with acute calculous cholecystitis. These recommendations are based on the review and analysis of the most re­cent literature and include the Tokyo guidelines. However, the recommen­dations are limited to patients who are good candidates for surgical treatment. The management of critically-ill pa­tients or high-risk surgical patients with acute cholecystitis still remains unde­fined (14,15). 

4. Clinical features and diagnosis 

Diagnosis of acute cholecystits is based on symptoms and clincial signs in patients with abdominal pain felt in the upper right quadrant bellow the right costal margin (RCM) (16). Acute cholecystitis is differentiated from biliary colics by the constant pain in the right upper quadrant bellow RCM and by positive Murphy’s sign (i.e. pain elicited by pressure on the right upper quadrant bellow RCM with the patient taking a deep breath). Patients with acute cholecystitis may present with a history of biliary colics or they may have been asymptomatic until the presenting episode (16). Laboratory tests in patients with acute cholecystitis show elevated inflammation markers (WBC and CRP levels), while in patients presenting with biliary colics, as a rule, these markers are within the normal reference range (3,4,16). Abdominal ultrasound examination is the first-line imaging modality in these cases. In acute cholecystitis ultrasound usually discloses pericholecystic fluid, and enlarged and distended gallbladder with a thickened, layered and hyperemic wall; and occasionally calculi in the gallbladder. X-ray of the abdomen reveals radiopaque gallstones in 10 % of patients with acute cholecystitis, and shows gas in the gallbladder wall in patients with emphysematous cholecystitis (17). 
If the diagnosis remains unclear after ultrasound examination, the patient is further assessed by computed tomography of the abdomen performed with or without contrast media or by gallbladder scintigraphy using hydroxy-iminodiacetic acid (HIDA scan) (16). 

Table 1:classification of acute cholecystitis according to tokyo guidelines (13). 


5. Treatment options in acute cholecystitis 
5.1. Conservative management 
Conservative management of acute cholecystitis involves supportive treatment with intravenous fluids, analgesics and antibiotics. In the acute phase of inflammation nil per os for 2 to 3 days is recommended to block stimuli for gallbladder contractions elicited by feeding, and to allow the gallbladder adequate rest during acute inflammation process. In the course of treatment the patient’s general clinical condition and the dynamics of inflammation markers (WBC, CRP) are monitored. Conservative treatment for acute cholecystitis is considered to be effective if the patient’s clinical condition has improved and the levels of inflammation markers have decreased (18). 
While the results of cultures and anti­microbial sensitivity testing are awaited, the patient with suspected infection is treated empirically with antibiotics se­lected with the intent to cover pathogens most commonly associated with the spe­cific disease. Acute cholecystitis is most commonly caused by pathogens from the upper digestive tract (19). Once the results of bacterial cultures and antimi­crobial susceptibility tests are available, targeted antibiotic treatment is institut­ed. The patient is initially given empiric therapy with an antibiotic considered to be effective against pathogens most commonly associated with the disease, yet once the results of cultures are avail­able, the patient is given antibiotics se­lected on the basis of antimicrobial sus­ceptibility testing (19). Unnecessary and prolonged therapy with broad-spectrum antibiotics should be avoided because of the risk of antibiotic resistance. Ac­cording to Tokyo guidelines, antibiot­ics should be selected in accordance with the severity grade classified in the guidelines (19). Slovene national recom­mendations have been formulated in line with the international and Japanese guidelines. In addition, national guide­lines point out that antibiotics should be selected based on current epidemiologi­cal situation and susceptibility of most common pathogens to antibiotics. Mild (Grade I) inflammation is usually caused by Escherichia coli., therefore treatment with a single antibiotic is sufficient (Ta­ble 2). Oral amoxicillin-clavulanic acid is recommended (19,20). Intravenous or oral ciprofloxacin in combination with metronidazol or intravenous ertapenem can be used.The therapy of choice for moderate (Grade II) and severe (Grade 
III) acute cholecystitis is treatment with a broad-spectrum antibiotic (second generation-cephalosporin) (Table 3). In patients with severe most often polymi­crobial disease, empiric treatment with third-generation cephalosporins, fluo­roquinolones and carbapenems is rec­ommended. It should be pointed out, however, that misuse or overuse of third and fourth generation-cephalosporins and carbapenemes leads to the creation of multidrug-resistant forms of bacte­ria (19). Immediate institution of broad-spectrum antibiotic therapy is particu­larly important in high-risk patients with comorbidities, in immunocompromised patients, diabetics, in patients with im­plants (vascular stents, grafts and inter­nal fixation materials) and in patients infected with antibiotic-resistant strains of bacteria (19,20). 
After surgical removal of the in-flammed gallbladder, it is recommended to stop antibiotic therapy 24 hours post­operatively, except in patients with overt signs of pericholecystitis (1). Intraop­erative swab cultures of pericholecystic fluid, gallbladder contents or gallblad­der wall should be taken. The cultures are sent to the microbiology laboratory, so that after the operation targeted an­tibiotic therapy based on susceptibility testing can be initiated. In patients with perycholecystic abscess, gallbladder perforation, emphysematous and gan­grenous cholecystitis, Tokyo guidelines recommend prolonged antibiotic treat­ment for 4 to 5 days postoperatively, or targeted antibiotic therapy based on an­timicrobial susceptibility testing for at least 14 days in confirmed gram-positive bacteremia (1). 
According to meta-analysis of multiple studies, conservative treatment of acute cholecystitis is successful in 87 % of all patients with acute calculous cholecystitis, and in 96 % of patients with Grade I disease. In patients with a confirmed diagnosis of acute cholecystitis, immediate institution of antibiotic therapy is necessary. Delayed antibiotic treatment is associated with increased risk of complications, such as gangrene and perforation of the gallbladder. If there is no improvement after 3 days of conservative therapy, cholecystectomy or percutaneous cholecystostomy should be considered in high-risk surgical patients (18). 

5.2. Surgical treatment 
Acute cholecystitis is treated by minimally invasive surgery (laparoscopic cholecystectomy) or classical open cholecystectomy (1). 

Table 2: Antibiotic therapy for mild acute cholecystitis (Grade i) according to tokyo guidelines (19). 

Table 3: Antibiotic therapy for moderate (Grade ii) and severe (Grade iii) acute cholecystitis according to tokyo guidelines (19). 
Moderate disease (Grade II) 

broad-spectrum penicillin with beta-lactamase piperacillin/tazobactam, ampicillin/sulbactam, inhibitor cefmetazole, cefotiam, oxacefem, flomoxef cephalosporine of 2nd generation 
Severe disease (Grade III) – first-line antibiotic cefoperazon/sulbactam, ceftriaxon, ceftazidim, cephalosporine of 3rd or 4th generation monobactams cefepime, cefazopran aztreonam 
one of the above listed antibiotics+metronidazole (in suspected or confirmed infection with anae-robic bacteria) 

Severe disease (Grade III) – second line antibiotic one of the above listed antibiotics+metronidazole fluoroquinolones (in suspected or confirmed infection with carbapenems anaerobic bacteria) ciprofloxacin, levofloxacin, 
pazufloxacin+metronidazol (in suspected or confirmed infection with anaerobic bacteria) meropenem, imipenem/cilastatin, panipenem/ betamipron 

In the past, acute cholecystitis was considered to be a contraindication of laparoscopic cholecystectomy, therefore treatment by open cholecystectomy was recommended (21). With advances in minimally invasive surgery, laparoscopic cholecystectomy was gradually adopted as the method of choice for the operative management of acute gallbladder inflammation. Early laparoscopic removal of the inflammed gallbladder, performed as early as possible after the onset of symptoms or hospital admission is recommended in the majority of cases (22,23). The only exception are patients at increased risk for postoperative complications. Those advocating early surgical treatment believe that delayed surgery increases the risk of biliary sepsis and secondary complications in patients with unsuccessful conservative therapy. They maintain that even with successful conservative treatment, biliary colics or inflammation are very likely to recur (21). Early surgery is also believed to be associated with shorter hospital stay and lower rate of readmissions, and hence with lower costs of treatment. Many authors recommend that early laparoscopic cholecystectomy be done within 72 hours of the onset of symptoms, stressing that delayed surgery is associated with increased risk for early and late postoperative complications (1). 
The Tokyo guidelines recommend treatment by early laparoscopic cholecystectomy for all patients with mild (Grade I) cholecystitis. If initial acute inflammation subsides with conservative treatment, delayed elective laparoscopic cholecestectomy is recommended after 8 to 12 weeks in order to prevent recurrence (23).According to the updated guidelines, laparoscopic approach is also recommended in moderate (Grade II) inflammation because several studies have shown that there is no difference in the rate of peri- and postoperative complications between patients with mild inflammation and those with moderate disease (12). Surgery should be performed by an experienced surgeon, as it has been shown that in the hands of experienced operating surgeons, laparoscopic approach is safe even in advanced forms of gallbladder inflammation (21-23). In severe (Grade 
III) acute cholecystitis, single or multiple organ failure may develop. In addition to supportive treatment, these patients with biliary peritonitis due to gallbladder perforation require emergency cholecystectomy. High-risk surgical patients can be treated initially by percutaneous drainage of the gallbladder or by percutaneous cholecystostomy. Once the patient is stable and shows improvement, elective cholecystectomy is done (24). 
According to the updated recom­mendations of the World Society of Emergency Surgery (WSES), early lapa­roscopic cholecystectomy is the therapy of choice in patients with acute inflam­mation of the gallbladder. Patients with uncomplicated inflammation do not need postoperative antibiotic therapy. Therapeutic strategies for patients who are poor surgical candidates have not yet been established, and there is no agree­ment on how to define the risks for peri-operative complications. In high-risk patients, conservative treatment or per-cutanous cholecystostomy may be con­sidered (14,15). 
A treatment algorithm for the man­agement of acute calculous cholecystitis was developed by WSES to estimate the probability of concurrent common bile duct stones on the basis of clinical fea­tures, abdominal ultrasound and liver enzyme tests (14,15). In low probabil­ity patients, treatment by early laparo­scopic cholecystectomy is recommend­ed (14,15). In patients with moderate or high probability, endoscopic ultrasound or MRCP should be done prior to the procedure. In patients with confirmed choledocholythiasis, optimum manage­ment involves endoscopic removal of stones using ERCP, followed by imme­diate laparoscopic cholecystectomy. An­other option is intraoperative bile duct exploration and removal of bile stones during cholecystectomy. In these cases the procedure is technically demand­ing and requires great surgical expertise. Bile duct stones can also be removed following surgical procedure using ERCP (14,15). 
In Slovenia, WSES and Tokyo guide­lines have been adopted for the manage­ment of patients with acute cholecysti-tis (13-15). Our policy is to operate on patients with confirmed acute cholecys­titis as soon as possible after their admis­sion to hospital (22). The only exception are high-risk surgical patients, who are treated conservatively and sometimes with percutaneous drainage of the gall­bladder. Patients suspected of harboring concurrent common bile duct stones are assessed by preoperative endoscopic ul­trasound to either confirm or refute the diagnosis of choledocholithiasis, where-after ERCP may be done. At our institu­tion, early laparoscopic cholecystectomy is the method of choice for treating pa­tients with acute cholecystitis (23). 
5.3. Percutanous gallbladder drainage – percutaneous cholecystostomy 

Critically-ill patients and high-risk surgical patients with acute cholecystitis can be treated by percutaneous drainage of the gallbladder or percutaneous cholecystostomy. This minimally invasive procedure under ultrasound control is carried out by the interventional radiologist (24). The recommended option is transhepatic biliary drainage, 
i.e. drainage of the gallbladder with the catheter advanced through the liver parenchyma in order to prevent spillage of the gallbladder contents into the abdominal cavity and thereby reduce the risk of biliary peritonitis (24). Placement of the drainage catheter into the gallbladder is a brief and minimally invasive procedure, which can improve the patient’s condition in a very short time. In the hands of an experienced interventional radiologist the procedure is technically feasible in 95 to 100 % of patients(24). The estimated mortality rate following percutanous cholecystostomy is 0 to 3 %; mild complications occur in 4 to 18 % of patients. The most common complication of percutaneous cholecystostomy is leakage of bile into the abdominal cavity and the resulting biliary peritonitis (25,26). Drainage of the gallbladder through the liver parenchyma is recommended to reduce complications after the procedure. The anterior transperitoneal approach can be used in patients with a greatly enlarged gallbladder, or when transhepatic approach is considered to be contraindicated because of liver disease or coagulation disorders (25,26). 



6. Results of meta-analyses of clinical studies 
According to the literature data, approximately 20 % of patients with acute cholecystitis require emergency surgical treatment. Surgery is necessary when the patient’s clinical condition deteriorates despite conservative treatment, and when there are signs of generalized peritonitis or emphysematous cholecystitis (14), indicating a risk of gangrene or gallblader perforation. Optimal timing of surgery in stable patients without signs of gangrene or gallbladder perforation has not yet been established. In the past, classical open cholecystectomy used to be done 6 to 12 weeks after initial symptoms and tissue inflammation have cleared up, thus providing more propitious conditions for delayed interval surgery (14). Acute inflammation of the bladder was considered a contraindication of laparoscopic management, therefore classical cholecystecomy was the recommended therapeutic option in those patients (22). The experience of the operating surgeon is an important factor that impacts the length of the procedure and the rate of postoperative complications in patients with acute cholecystitis (1). Patients with acute inflammation of the gallbladder are most often examined and operated on by duty surgeons, who lack experience in laparoscopic hepatobiliary surgery. The learning curve in laparoscopic cholecystectomies is considered to be 30 procedures, as 75 % of the documented complications ocurred during the learning curve (27). Even after completion of their learning curve, surgeons differ in the level of expertise needed to perform laparoscopic cholecystectomy in unfavourable conditions. It is therefore recommended that patients with acute cholecystitis be operated on by surgeons who have the largest experience with laparoscopic and hepatobiliary procedures (1). 

According to the most recent guidelines, early laparoscopic cholecystectomy is the recommended treatment option in all patients with acute inflammation of the gallbladder who are fit for surgery, provided that it is done within 72 to 96 hours of the onset of symptoms (16). These patients had lower complication rates, shorter hospital stay and less conversions to open surgery than patients treated by delayed (interval) cholecystectomy (16). Early surgery (within 72 hours of the onset of symptoms) is associated with lower conversion rates compared with delayed operative treatment undertaken after several days of unsuccesful conservative management. Longer duration of symptoms before hospital admission is statistically significantly correlated with advanced forms of gallbladder inflammation (16). Complications most commonly associated with delayed surgery include bile duct injury, abscess, hematoma in the gallbladder resection bed and need for prolonged antibiotic therapy. Minor bile duct injuries leading to biliary fistulas can be managed by ERCP and placement of a plastic prosthesis. If this treatment option is not feasible, surgical exploration and repair of the injured bile duct with primary suture of the bile duct and biliary drainage, or creation of a bilioenteric anastomosis should be considered (27). Abscess collections or hematomas in the gallbladder resection bed are mostly amenable to conservative treatment that includes percutaneous drainage performed by an interventional radiologist, and prologed antibiotic therapy (16). Meta-analysis of the studies by Indar and Beckingham showed that early laparoscopic cholecystectomy for acute cholecystitis is a safe and feasible therapeutic modality, especially if performed within 72 hours of the onset of symtpoms (16). The updated 2013 Tokyo guidelines too recommend early laparoscopic cholecystectomy within 72 hours of the onset of symptoms (13). 
Shinke et al., in their retrospective study, analyzed a group of 233 patients with acute cholecystitis subjected to emergency laparoscopic cholecystectomy within 7 days of the onset of symptoms. They were divided into a group operated on within 72 hours of the onset of symptoms (early phase group), and a group of patients who underwent surgery between day 4 and day 7 after the onset of symptoms (late phase group) (27). The rate of conversions to open surgery in the early-phase group was 3 %, compared with 8 % documented in the late-phase group. There were no statistically significant differences between the groups in the operation time, postoperative complications and length of hospital stay (27). Patients undergoing surgery within 4 to 7 days of the onset of symptoms showed increased rate of conversions to open surgery (8 %) and nearly a twofold increase in intraoperative blood loss. Within a few days, the progressing local inflammation leads to fibrosis of the gallbladder wall with indistinct anatomic layers. Resection is therefore hindered by poor visualization of the indinstinct, normally present, avascular part of the subserosal layer, which accounts for increased intraoperative blood loss (27). Increased blood loss, however, was found to have no influence on the postoperative course and the authors maintain that it is a clinically and hemodynamically insignificant factor (27). 
Advanced inflammation impedes identification of the anatomical structures within Calot’s triangle required for accurate recognition and safe ligation of the cytic duct and cystic artery (28). Poor recognition of these structures is responsible for increased rates of common bile duct injuries and iatrogenic biliary fistulas, and the resulting increase in postoperative morbidity and mortality rates (29). Patients who were initially treated conservatively and had elective surgery several weeks later showed more conversions to open surgery (12–24 %), more overall postoperative complications (29–34 %), and longer hospital stay. The authors threfore conclude that delayed elective laparoscopic cholecystectomy following initial conservative management is not superior to emergency laparoscopic cholecystectomy perfomed 4 to 7 days after the onset of symptoms. Early laparoscopic cholecystectomy is therefore considered to be a safe and feasible therapeutic option in patients with acute cholecystitis, even in the late phase, i.e. 4 to 7 days after the onset of symtpoms (27). 
Blohm et al. analyzed data from the Swedish national registry gathered for for 87,108 patients operated on for acute cholecystitis (30), with a focus on postoperative complications. They found that patients undergoing surgery within 4 days of hospital admission were at a significantly lower risk for postoperative complications, and that they needed less conversions to open surgery. Conversions from laparoscopic to classical surgery were documented in 
16.6 % of patients operated on within 4 days of hospital admission compared to 
27.8 % in the group of delayed surgery patients (30). Intraoperative blood loss was comparable in both groups, yet patients undergoing delayed surgery sustained more bile duct injuries. The authors conclude that optimal timing for operation is within 48 hours of admission to hospital. Surgery performed later than 96 hours after admission carries higher risk of postoperative complications (30). 
A retrospective study of 967 patients admitted to hospital because of acute cholecystitis by Gonzalez-Munoz showed that patients operated on soon after admission stayed in hospital less time than patients who underwent delayed surgery (31). Conservative treatment too was associated with shorter hospital stay compared with delayed surgery. Also, patients undergoing delayed surgery had higher rates of postoperative complications, especially biliary fistulas (31). The authors recommend that all patients with acute gallbladder inflammation be operated on as soon as possible, the only exception being patients with comorbidities and high-risk surgical patients, who are candidates for conservative management. Delayed surgery is disadvised because of longer hospital stay, more peri- and postoperative complications and higher costs of treatment (31). 

As shown by a French multicentric study, patients with acute cholecystitis operated on within 3 days of hospital admission had significantly lower rates of postoperative complications (32). The analysis of results showed higher complications rates also in patients operated on immediately on admission or within 24 hours of admission. These findings indicate that optimal timing for the operation is 2 to 3 days after hospital admission, provided that there are no reservations about surgery (32). Similar results, based on the data from the national registry of patients operated on for acute cholecystitis, were reported by the researchers from the United States (33). 
Bile duct injury, leading to biliary fistula formation is the worst complication of cholecystectomy. A meta-analysis by Oneil Machado indicates that bile duct injuries occur in 0.3 to 0.6 % of all laparoscopic cholecystectomies (34). Duca et al. report on the results of their retrospective analysis of 9,542 patients undergoing cholecystectomy (35). Emergency surgery for acute cholecystitis was required in 13.9 % of the patients. Seventeen (0.1 %) patients sustained intraoperative bile duct injuries, and 184 (1.9 %) needed conversion to open surgery because of unclear anatomical situation and severe inflammation (35). According to other studies the rate of conversions in patients undergoing emergency surgery was 6 to 35 % (1). A retrospective study by Terho et al. found significantly more conversions in patients with advanced inflammation and high CRP levels (36). As reported by Ackerman et al. in their retrospective study, delayed-surgery patients and patients with initial conservative treatment showed higher rates of overall postoperative complications and conversions, and longer hospital stay than patients who underwent early surgery (37). Studies by Yuval and Kmalapurkar have shown that early cholecystectomy is a safe and effective option even for patients with advanced inflammation (38,39). As reported by Mizrahi et al., patients treated by delayed surgery and previous percutaneous biliary drainage had increased rates of complications, including infections, conversions, biliary fistulas, hospital readmissions and longer duration of hospital stay (40). 

7. Conclusions 
Early laparoscopic cholecystectomy is recomended for all patients with acute gallbladder inflammation who are fit for surgery, except for patients with comorbidities who are identified as high-risk for operative treatment and are therefore candidates for conservative therapy. If no improvement occurs after 3 days of conservative treatment, or if the patient’s clinical condition deteriorates, percutaneous cholecystostomy should be performed. In patients who fail to improve after 3 days of percutaneous biliary drainage of the gallbladder, emergency cholecystectomy should be done. Early surgery represents definitive therapy of acute cholecystitis. The results of multiple clinical studies, meta-analyses and the accumulated experience indicate 
Profession Al Article  
that early cholecystectomy is the method  laparoscopic cholecystectomy should be  
of  choice in the treatment of  acute  performed as early as possible, i.e. within  
cholecystitis. Whenever possible, early  72 hours of the onset of symptoms.  


References 

1. 
Koti RS, Davidson CJ, Davidson BR. Surgical management of acute cholecystitis. Langenbecks Arch Surg. 2015 May;400(4):403–19. https://doi.org/10.1007/s00423–015–1306-y PMID:25971374 

2. 
Markota A, Strdin Košir A, Sinkovič A. Akutni holecistitis pri bolniku, sprejetem v intenzivno enoto zaradi drugih vzrokov. In Podbregar M, Gradišek P, Grosek Š. Šola intenzivne medicine 2015. Letn 3. Sepsa in bolnišnične okužbe, akutna ledvična odpoved, bolezni prebavil, prehrana: učbenik–Ljubljana: Slovensko združenje za intenzivno medicino: Medicinska fakulteta, Katedra za anesteziologijo in reanimatologijo, 2015. p. 146–148. 

3. 
Hatzidakis AA, Prassopoulos P, Petinarakis I, Sanidas E, Chrysos E, Chalkiadakis G, et al. Acute cholecystitis in high-risk patients: percutaneous cholecystostomy vs conservative treatment. Eur Radiol. 2002 Jul;12(7):1778–84. https://doi.org/10.1007/s00330–001–1247–4 PMID:12111069 

4. 
Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K, Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):15–26. https://doi.org/10.1007/s00534–006–1152-y PMID:17252293 

5. 
Gavrić A, Štabuc B, Steblovnik L. Žolčni kamni med nosečnostjo. Gastroenterolog. 2016;20(1):29–38. 

6. 
Caglia P, Costa S, Tracia A, Veroux M, Luca S, Zappulla E, et al. Can laparoscopic cholecystectomy be safety performed in the elderly? Ann Ital Chir. 2012 Jan-Feb;83(1):21–4. PMID:22352211 

7. 
Bagla P, Sarria JC, Riall TS. Management of acute cholecystitis. Curr Opin Infect Dis. 2016 Oct;29(5):508–13. https://doi.org/10.1097/QCO.0000000000000297 PMID:27429137 

8. 
Ambe PC, Kaptanis S, Papadakis M, Weber SA, Jansen S, Zirngibl H. The treatment of critically ill patients with acute cholecystitis. Dtsch Arztebl Int. 2016 Aug;113(33–34):545–51. https://doi.org/10.3238/ arztebl.2016.0545 PMID:27598871 

9. 
Weigand K, Köninger J, Encke J, Büchler MW, Stremmel W, Gutt CN. Acute cholecystitis–early laparoskopic surgery versus antibiotic therapy and delayed elective cholecystectomy: ACDC-study. Trials. 2007 Oct;8(1):29–34. https://doi.org/10.1186/1745–6215–8-29 PMID:17916243 

10. 
Golobinek R. Visoki ileus, povzročen z žolčnim kamnom (Bouveretov sindrom) – prikaz primera. Zdrav Vestn. 2006;75:843–6. 

11. 
Crespi M, Montecamozzo G, Foschi D. Diagnosis and treatment of biliary fistulas in the laparoscopic era. Gastroenterol Res Pract. 2016;2016:6293538. https://doi.org/10.1155/2016/6293538 PMID:26819608 

12. 
Loozen CS, Blessing MM, van Ramshorst B, van Santvoort HC, Boerma D. The optimal treatment of patients with mild and moderate acute cholecystitis: time for a revision of the Tokyo Guidelines. Surg Endosc. 2017 Oct;31(10):3858-63. https://doi.org/10.1007/s00464-016-5412-x PMID:28127715 

13. 
Takada T, Strasberg SM, Solomkin JS, Pitt HA, Gomi H, Yoshida M, et al.; Tokyo Guidelines Revision Committee. TG13: updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci. 2013 Jan;20(1):1–7. https://doi.org/10.1007/s00534–012–0566-y PMID:23307006 

14. 
Ansaloni L, Pisano M, Coccolini F, Peitzmann AB, Fingerhut A, Catena F, et al. 2016 WSES guidelines on acute calculous cholecystitis. World J Emerg Surg. 2016 Jun;11(1):25. https://doi.org/10.1186/s13017–016– 0082–5 PMID:27307785 

15. 
Campanile FC, Pisano M, Coccolini F, Catena F, Agresta F, Ansaloni L. Acute cholecystitis: WSES position statement. World J Emerg Surg. 2014 Nov;9(1):58. https://doi.org/10.1186/1749–7922–9-58 PMID:25422672 

16. 
Indar AA, Beckingham IJ. Acute cholecystitis. BMJ. 2002 Sep;325(7365):639–43. https://doi.org/10.1136/ bmj.325.7365.639 PMID:12242178 

17. 
Draghi F, Ferrozzi G, Calliada F, Solcia M, Madonia L, Campani R. Power Doppler ultrasound of gallbladder wall vascularization in inflammation: clinical implications. Eur Radiol. 2000;10(10):1587–90. https://doi. org/10.1007/s003300000371 PMID:11044929 

18. 
Loozen CS, Oor JE, van Ramshorst B, van Santvoort HC, Boerma D. Conservative treatment of acute cholecystitis: a systematic review and pooled analysis. Surg Endosc. 2017 Feb;31(2):504–15. https://doi. org/10.1007/s00464–016–5011-x PMID:27317033 

19. 
Yoshida M, Takada T, Kawarada Y, Tanaka A, Nimura Y, Gomi H, et al. Antimicrobial therapy for acute cholecystitis: tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):83–90. https://doi.org/10.1007/ s00534–006–1160-y PMID:17252301 

20. 
Miura F, Takada T, Kawarada Y, Nimura Y,Wada K, Hirota M, et al. Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):27–34. https://doi.org/10.1007/s00534–006–1153-x PMID:17252294 

21. 
Tomažič A, Grosek J. Akutni abdomen. Gastroenterolog. 2013;17(1):21–34. 

22. 
Hazabent M, Gorenjak N. Holecistitis in holangitis. In: Zbornik 3. šole urgence; Maribor, Slovenija; december 2015. p. 44–48. 


23. 
Shinya S,Yamashita Y, Takada T. The impact of the Japanese clinical guidelines on the clinical management of patients with acute cholecystitis. J Hepatobiliary Pancreat Sci. 2013 Aug;20(6):611–9. https://doi.org/10.1007/ s00534–013–0603–5 PMID:23564194 

24. 
Jang WS, Lim JU, Joo KR, Cha JM, Shin HP, Joo SH. Outcome of conservative percutaneous cholecystostomy in high-risk patients with acute cholecystitis and risk factors leading to surgery. Surg Endosc. 2015 Aug;29(8):2359–64. https://doi.org/10.1007/s00464–014–3961–4 PMID:25487543 

25. 
Ambe PC, Kaptanis S, Papadakis M,Weber SA, Zirngibl H. Cholecystectomy vs. percutaneous cholecystostomy for the management of critically ill patients with acute cholecystitis: a protocol for a systematic review. Syst Rev. 2015 May;4(1):77–81. https://doi.org/10.1186/s13643–015–0065–8 PMID:26025467 

26. 
Sugiyama M, Tokuhara M, Atomi Y. Is percutaneous cholecystostomy the optimal treatment for acute cholecystitis in the very elderly? World J Surg.1998 May;22(5):459–63.https://doi.org/10.1007/s002689900416 PMID:9564288 

27. 
Shinke G, Noda T, Hatano H, Shimizu J, Hirota M, Takata A, et al. Feasibility and safety of urgent laparoscopic cholecystectomy for acute cholecystitis after 4 days from symptom onset. J Gastrointest Surg. 2015 Oct;19(10):1787–93. https://doi.org/10.1007/s11605–015–2878–0 PMID:26129654 

28. 
Benedik T. Metode varne laparoskopske holecistektomije. Zdrav Vestn. 2003;1:3–7. 

29. 
Cagir B, Rangraj M, Maffuci L, Herz BL. The learning curve for laparoscopic cholecystectomy. J Laparoendosc Surg. 1994 Dec;4(6):419–27. https://doi.org/10.1089/lps.1994.4.419 PMID:7881146 

30. 
Blohm M, Österberg J, Sandblom G, Lundell L, Hedberg M, Enochsson L. The sooner, the better? Importance of optimal timing of cholecystectomy in acute cholecystitis: data from the National Swedish registry for gallstone surgery, GallRiks. J Gastrointest Surg. 2017 Jan;21(1):33–40. https://doi.org/10.1007/s11605–016– 3223-y PMID:27649704 

31. 
González-Munoz JI,Angoso M, Sayagués JM, Sánchez-Casado AB, Hernández A,Velasco A, et al. Improving the outcome of acute cholecystitis: the non-standardized treatment must no longer be employed. Langenbecks Arch Surg. 2014 Dec;399(8):1065–70. https://doi.org/10.1007/s00423–014–1245-z PMID:25217329 

32. 
Polo M, Duclos A, Polazzi S, Payet C, Lifante JC, Cotte E, et al. Acute cholecystitis – optimal timing for early cholecystectomy: a French nationwide study. J Gastrointest Surg. 2015 Nov;19(11):2003–10. https://doi. org/10.1007/s11605–015–2909-x PMID:26264362 

33. 
Csikesz N, Ricciardi R, Tseng JF, Shah SA. Current status of surgical management of acute cholecystitis in the United States. World J Surg. 2008 Oct;32(10):2230–6. https://doi.org/10.1007/s00268–008–9679–5 PMID:18668287 

34. 
Oneil Machado N. Biliary Complications Post Laparoscopic Cholecystectomy: Mechanism, Preventive Measures, and Approach to Management: A Review. Diagn Ther Endosc. 2011:967017. https://doi. org/10.1155/2011/967017. 

35. 
Duca S, Bala O, Al-Hajjar N, Lancu C, Puia IC, Munteanu D, et al. Laparoscopic cholecystectomy: incidents and complications.A retrospective analysis of 9542 consecutive laparoscopic operations. HPB. 2003;5(3):152– 8. https://doi.org/10.1080/13651820310015293 PMID:18332976 

36. 
Terho PM, Leppäniemi AK, Mentula PJ. Laparoscopic cholecystectomy for acute calculous cholecystitis: a retrospective study assessing risk factors for conversion and complications. World J Emerg Surg. 2016 Nov;11(1):54. https://doi.org/10.1186/s13017–016–0111–4 PMID:27891173 

37. 
Ackerman J, Abegglen R, Scaife M, Peitzman A, Rosengart M, Marsh JW, et al. Beware of the interval cholecystectomy. J Trauma Acute Care Surg. 2017 Jul;83(1):55–60. https://doi.org/10.1097/ TA.0000000000001515 PMID:28422916 

38. 
Kamalapurkar D, Pang TC, Siriwardhane M, Hollands M, Johnston E, Pleass H, et al. Index cholecystectomy in grade II and III acute calculous cholecystitis is feasible and safe. ANZ J Surg. 2015 Nov;85(11):854–9. https://doi.org/10.1111/ans.12986 PMID:25644962 

39. 
Yuval JB, Mizrahi I, Mazeh H, Weiss DJ, Almogy G, Bala M, et al. Delayed laparoscopic cholecystectomy for acute calculous cholecystitis: is it time for a change? World J Surg. 2017 Jul;41(7):1762–8. https://doi. org/10.1007/s00268–017–3928–4 PMID:28251270 

40. 
Mizrahi I, Mazeh H, Yuval JB, Almogy G, Bala M, Simanovski N, et al. Perioperative outcomes of delayed laparoscopic cholecystectomy for acute calculous cholecystitis with and without percutaneous cholecystostomy. Surgery. 2015 Sep;158(3):728–35. https://doi.org/10.1016/j.surg.2015.05.005 PMID:26094175