Langenbecks Arch Surg DOI 10.1007/s00423-015-1300-4
Laparoscopic cholecystectomy: consensus conference-based guidelines Ferdinando Agresta 1 & Fabio Cesare Campanile 2 & Nereo Vettoretto 3 & Gianfranco Silecchia 4 & Carlo Bergamini 5 & Pietro Maida 6 & Pietro Lombari 7 & Piero Narilli 8 & Domenico Marchi 9 & Alessandro Carrara 10 & Maria Grazia Esposito 6 & Stefania Fiume 11 & Giuseppe Miranda 12 & Simona Barlera 13 & Marina Davoli 14 & on the behalf of The Italian Surgical Societies Working Group on the behalf of The Italian Surgical Societies Working Group
Received: 5 January 2015 / Accepted: 24 March 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Introduction Laparoscopic cholecystectomy (LC) is the gold standard technique for gallbladder diseases in both acute and elective surgery. Nevertheless, reports from national surveys still seem to represent some doubts regarding its diffusion. There is neither a wide consensus on its indications nor on its possible related morbidity. On the other hand, more than 25 years have passed since the introduction of LC, and we have all witnessed the exponential growth of knowledge, skill and technology that has followed it. In 1995, the EAES published its consensus statement on laparoscopic cholecystectomy in which seven main questions were answered, according to the available evidence. During the following 20 years, there have been several additional guidelines on LC, mainly focused on some particular aspect, such as emergency or concomitant biliary tract surgery.
Methods In 2012, several Italian surgical societies decided to revisit the clinical recommendations for the role of laparoscopy in the treatment of gallbladder diseases in adults, to update and supplement the existing guidelines with recommendations that reflect what is known and what constitutes good practice concerning LC.
* Ferdinando Agresta [email protected]
A.O.R.N. Caserta, Chirurgia generale oncologica, Caserta, Italy
Nuova Itor General Hospital, General Surgery, Rome, Italy
New S. Agostino Estense Hospital N.O.C.S.A.E. Baggiovara, General Surgery Modena, Modena, Italy
Department of Surgery, Presidio Ospedaliero di Adria (RO), Adria, RO, Italy
Division of Surgery, Ospedale Civita Castellana, ASL VT, Civita Castellana, VT, Italy
Keywords Cholecystectomy . Laparoscopy . Guidelines . Consensus conference
Introduction Laparoscopic Cholecystectomy (LC) is the gold standard technique for gallbladder disease in both acute and elective surgery. Nevertheless, reports from national surveys still seem
S. Chiara Hospital, General Surgery I, Trento, Italy
A.O. Brotzu, Division of Emergency Surgery, Cagliari, Italy
UOC Chirurgia Generale e d’Urgenza, Asur Marche Area Vasta N. 1, Urbino, Italy
Laboratory of Medical Statistics, Department of Cardiovascular Research, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
Az. Osp. M. Mellini, General and Vascular Surgery, Chiari, Brescia, Italy
Division of general Surgery & Bariatric Center of Excellence, Sapienza University of Rome - School of Pharmacy and Medicine, Latina, Italy
Department of General and Emergency Surgery, University Hospital of Careggi, Florence, Italy
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
Evangelic Hospital Villa Betania, General, Oncologic and Advanced Laparoscopic, Surgery Unit, Naples, Italy
Department of General Surgery, ULSS19 del Veneto, 45011 Adria, RO, Italy
Langenbecks Arch Surg
to represent some doubts regarding its diffusion. There is neither a wide consensus on its indications nor on its possible related morbidity [1, 2]. On the other hand, more than 25 years have passed since the introduction of LC, and we have all witnessed the exponential growth of knowledge, skill and technology that has followed it. In 1995 , the EAES published its consensus statement on laparoscopy cholecystectomy in which seven main questions were answered, according to the available evidence: 1. 2. 3. 4. 5. 6. 7.
Who should undergo LC? How should common bile stones be managed? In what stage of technological development is LC? Is LC safe and feasible? Is it beneficial to the patients? What are the special aspects to be considered during LC? What are the training recommendations for LC?
During the following 20 years, there have been several additional guidelines on LC, mainly focused on some particular aspect, such as emergency or concomitant biliary tract surgery [4–9]. In January 2012, the Scientific and Educational Committee and the Young Chapter of the A.C.O.I. (Associazione Chirurghi Ospedalieri Italiani—ACOI—The Italian Society of Hospital Surgeons) decided to revisit the clinical recommendations for the role of laparoscopy in the treatment of gallbladder diseases in adults, to update and supplement the existing guidelines on specific topics, in order to: 1. Establish the preferred diagnostic procedures, selection of patients—if any—and the suitability of the laparoscopic approach for gallbladder and CBD stones in scheduled and in emergency situations; 2. Analyze indications, morbidity/mortality (and their prevention), learning curve/training, new technologies, technical aspects and outcome of LC; 3. Define an optimal practice and provide recommendations that reflect what is known and what constitutes good practice concerning LC.
the entire Italian surgical community. The Consensus was held under the auspices of the EAES. A multidisciplinary panel is critical in order to achieve both guidelines and recommendations [10, 11]. Therefore, radiologists (SIRM: Italian Society of Radiology), epidemiologists, nurses (IPASVI—the Italian National Federation Nursing Council), health-services researchers, endoscopists (SIED—Italian Society of Digestive Endoscopy), emergency doctors (SIMEU—Italian Society of Emergency Medicine) were also involved. A patient’s association was also invited and participated (Cittadinanzattiva Active Citizenship). No pediatric surgeon was included in the panel because only adult surgery was taken into consideration. For each topic/questions previously analyzed by the EAES, the topic editors appraised the available literature and drafted a preliminary evidence report. According to the Delphi method, the panel produced key statements followed by a commentary to explain the rationale and the level of evidence behind the statement. All key statements obtained a 100 % consensus. Next, the statements were presented to the Annual Congress of the ACOI in May 2013 and at the Annual Congress of the SICE in Naples in September 2013. The audiences of both Congresses acted as a jury; Grades of recommendations (GoR) were approved.
Literature searches and appraisal A systematic literature review was made on Pubmed including papers from 1994 to February 2013. Cross-link control was performed with Google Scholar and Cochrane library databases. Pediatric literature was excluded. The 2011 Oxford hierarchy for grading the Level of Evidence (LE) of the outcomes was used. Studies on the same patients or containing severe methodological flaws were excluded or downgraded as necessary. For each intervention, the validity and homogeneity of study results, effect sizes, safety issues and economic consequences were considered. A modified GRADE system was adopted to categorize the issued recommendations: a moderate grade was added to the strong and weak, in order to obtain a system more useful and applicable to daily practice: BStrong recommendation^ BModerate recommendation^ BWeak recommendation^
Consensus development In order to better analyze the existing Bevidence^ on the subject, several Italian surgical societies (here defined as BItalian Surgical Societies Working Group^) were invited to join the ACOI in the Promoting Committee and selected a panel of eight topic editors, surgeons expert in laparoscopic and open surgery. The involved scientific societies represented almost
The methodology was reviewed by Dr. S. Balera—Laboratory of Medical Statistics; Department of Cardiovascular Research; IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milano (Italy) and Dr. M. Davoli—Department of Epidemiology, Lazio Regional Health Service, National Outcome Evaluation Programme BPiano Nazionale Esiti^— Agenas
Langenbecks Arch Surg
Results Indications to laparoscopic cholecystectomy (LC) (Who should ungergo LC?) The panel of 1994 EAES Consensus Conference, stated that LC is indicated in symptomatic gallbladder disease patients who can tolerate general anesthesia including patients with porcelain gallbladder. However, the panelists identified two special subgroups of patients: (1) symptomless gallstones cases that should be followed-up closely (diabetic, sickle-cell anemia, those on long-term somatostatin treatment, etc.) and (2) patients who required Bextreme caution^ and an Bexpert surgeon^ (acute cholecystitis, pregnancy, elderly etc.). Finally, the absolute contraindications were reported. Starting from these assertions, we selected seven sub-topics related to the indications. The panel also agreed that the absolute contraindications stated in 1994 remain still valid. Asymptomatic gallbladder diseases Cholelithiasis is defined as Basymptomatic^ when gallstones do not relate to symptoms such as pain or complications such as acute cholecystitis, cholangitis, or pancreatitis [12, 13]. The estimated prevalence of gallstones is 10–25 % [12–15] and 50–80 % of the patients are asymptomatic at the diagnosis [15–18]. Several studies report a frequency of symptom development of 10 % after the first 5 years and of 20 % after 20 years [13–15, 19]. So the annual risk for severe and nonsevere events decreases with time and the annual complication rate of initially asymptomatic patients is 0.3–3 % [16, 20–23]. The majority of patients rarely develop gallstone-related complications without first having at least one episode of biliary pain [12–14]. Therefore, most authors recommend a Bwatch and wait^ policy in asymptomatic patients [12, 13, 16, 24, 25] (LE3). In 134 patients followed up for 24 years, only 6 % experienced symptoms that led to cholecystectomy, and no adverse events could be ascertained from expectant management  (LE3). In 2009, the conclusion of the Cochrane Review  stated: Bthere is no evidence in literature to either recommend or refuse surgery to patients with asymptomatic gallstones (no randomized or controlled trial comparing LC vs. no-LC was available)^. In 2012, Duncan and Riall  reviewed the evidence-based current surgical practice for calculous gallbladder diseases and concluded that prophylactic LC for asymptomatic gallstone patients is still not recommended. Microcalculi/sludge Recent data suggest an association between acute pancreatitis and small gallbladder stones or sludge [29–32]. This association is not unexpected: microcalculi might migrate into the common bile duct easier
than larger stones, especially if gallbladder motility is preserved. This evidence (LE 4–5) supports prophylactic LC. Porcelain gallbladder (PGB) A recent review states that PGB is only weakly associated with gallbladder cancer (0– 12 %) (LE4). Thus, prophylactic LC is not indicated for PGB and that it should be performed only in patients with conventional indications for LC [33–35] (LE4). Diffuse intramural calcifications should be distinguished from selective mucosal calcifications. The latter seem to be at a higher risk for association with gallbladder cancer  (LE4). Risk of gallbladder cancer (GBC) There is no indication for prophylactic LC in Western countries as the incidence of GBC in asymptomaticpatients with gallbladder stones is less than 1 %. Patients with calculi >3 cm  or multiple calculi seem to be at higher risk for GBC, but evidence is not sufficient to advise prophylactic LC [15, 16, 21, 26, 35–37] (LE4). A study conducted on the Shanghai population stated that there is a great variety of GBC incidence in the various ethnic groups, and China has a much higher GBC incidence than Western Europe  (LE4). There is no data whether immigrants from high incidence countries (China, India, Pakistan, Eastern Europe, South American) have the same cancer risk as the resident population. A recent controlled follow-up study on 134 patients who were asymptomatic in 1983 and followed up for 24 years did not detect any cancer cases  (LE3). Incidental gallstones Several experts suggest LC for asymptomatic cholelithiasis during other abdominal procedures, as long as the surgeon is comfortable performing it, and no prosthetic material is being used [15, 21, 24, 25] (LE 5) Diabetes Prophylactic LC is not indicated in diabetic patients with asymptomatic gallstones [16, 21, 24] (LE 5). Diabetic patients should be treated like every other gallstone patient because there is no evidence to support an increased risk of gallstone-related complications. Patients on long-term somatostatin treatment No data is available as to whether these patients are at higher risk of complication than other gallstone populations [30, 31, 37] (LE 5). Patients on long-term somatostatin treatment should be treated like every other asymptomatic gallstones patient. Prophylactic LC is not recommended. Transplant patients Prophylactic LC is to be considered in cardiac transplant recipients with asymptomatic gallstones, due to increased mortality and morbidity when compared with the general population  (LE3). Instead, an expectant management is to be preferred in kidney, pancreas, and/or pulmonary transplant recipients [39–41] (LE 3).
Langenbecks Arch Surg
Sickle-cell anaemia and beta thalassemia The incidence of cholelithiasis is reported to be increased in these patients [42, 43]. LC is safe in sickle cell disease patients without preoperatory transfusion and by maintaining a low insufflation pressure [43–46]. Statement 1.1 Although a systematic prophylactic LC for asymptomatic cholelithiasis is not generally indicated (GoR strong), it might be advisable in some subgroups of patients: incidental (concomitant) cholecystectomy during another laparoscopic operation; chronic hemolytic conditions; risk of malignancy (ethnicity, geographic area, gallbladder imaging); microcalculi/biliary sludge in presence of functioning gallbladder; post-cardiac transplant patient 5) (GoR weak) Obesity The diffusion of laparoscopic bariatric surgery during the last 10 years changed the attitude and confidence of surgeons towards morbid obesity, once considered a relative contraindication . Comparative data suggest that obesity, even morbid obesity (BMI>40), does not result in an increase in morbidity, mortality, and conversion rates when compared to the nonobese population [47–55] (LE 3). Instead Rosen  and Chandio  found BMI as a predicting factor of conversion in acute cholecystitis. A recent review by Hussain  stated that the triad of obesity, acute cholecystitis, and previous upper abdominal surgery leads to higher morbidity, longer operating time and higher conversion rate. Statement 1.2 LC is safe in obese patients (BMI >30 kg/m2). As it carries a low risk of conversion and perioperative complications, it should be the standard of care when indicated. The association of obesity and acute cholecystitis leads to increased conversion rates (LE3) (GoR moderate) Pregnancy Laparoscopy can be performed safely during any trimester of pregnancy with minimal morbidity to the fetus and mother. The significant morbidity and mortality associated with untreated benign gallbladder diseases in the gravid patient favours surgical treatment [57–61]. LC is the treatment of choice in the pregnant patient with benign gallbladder disease [57, 62]. The delay in surgical management results in increased rates of hospitalization, spontaneous abortion, preterm labour, and preterm delivery [57, 60, 64]. Non-operative management of symptomatic gallstones in gravid patients results in recurrent symptoms in more than 50 % of patients, and 23 % develop acute cholecystitis or gallstone pancreatitis [57, 58]. Gallstone pancreatitis results in fetal loss in 10 to 60 % of pregnant patients [57, 59]. Gravid patients who are candidates for LC should be placed in the left lateral
recumbent position to minimize compression of the vena cava and the aorta . To establish a pneuoperitoneum, both the Hasson technique and Veress needle can be safely and effectively used, via a subcostal approach [57–59, 62–64]. Statement 1.3 LC is the treatment of choice in the pregnant patient with benign gallbladder disease. LC can be safely performed in any trimester of pregnancy. Early elective LC is encouraged. The delay of surgical management of symptomatic gallbladder disease increase spontaneous abortion and pre-term delivery (GoR strong). Elderly Laparoscopy is the treatment of choice in uncomplicated disease in the elderly, as results are better than OC regarding morbidity, length of surgery, and mean postoperative hospitalization [64–70] (LE3). Nevertheless, Tucker et al., in a recent case-matched study, evidenced that LC is safe but underused in the elderly  (LE3). LC in older patients is indeed associated with increased rates of conversion to laparotomy, longer operation time, longer hospital stay and more operative complications, such as bile duct injury and hemorrhage, than in younger patients . Moreover, the elderly experience a higher incidence of choledocholithiasis and gallstone pancreatitis and have a higher frequency and severity of associated cardiopulmonary disease [66, 73]. Kim et al. stated that the peri-operative outcomes in the elderly seem to be influenced by the severity of gallbladder disease and not by chronological age  (LE3). On the basis of these observations, early elective LC should be encouraged in symptomatic elderly patients [65–67] (LE3) due to a higher complication, mortality, and conversion rates especially in complicated disease [64, 66, 74]. Statement 1.4 Elective LC is safe and effective in patients over 65 years old with uncomplicated gallbladder stone disease. LC in the elderly should be performed at the early onset of symptoms, particularly in patients aged 80 and over, because this group has a higher rate of complications and conversion to OC. The perioperative outcomes are influenced more by the severity of gallbladder disease, than by the chronological age (GoR strong) Gallbladder polypoid lesions (GPL) The treatment and surveillance of GPL are still controversial as a result of the lack of RCTs . There is no evidence from trials to recommend surgery or not for patients with GPL smaller than 10 mm  (LE1). LC offers good pain relief in more than 90 % of the cases if GPL is associated with pain . The primary goal in GPL management is to prevent gallbladder carcinoma  with an appropriate balance
Langenbecks Arch Surg
between the risk of malignancy (ranging between 45 and 67 % in polyps between 10 and 15 mm in size [79–82]), and the risks associated to LC (LE4). The evidence of multiple polyps per se is not an indication for surgery  (LE4). In patients with age ≥60, sessile polyp morphology, and polyp size ≥10 mm, EUS or CT for accurate characterization is advised  (LE4). If there are no signs of malignancy, for polyps 6– 9 mm in diameter, an ultrasound (US) follow-up is recommended after 6 months and after 1 year in case of no change. No further follow-up of a stable lesion is recommended  (LE4). GPL smaller than 6 mm do not require follow-up in the absence of suspicions of malignancy [78, 83]. A GPL greater than 18 mm has a high likelihood of gallbladder cancer: open cholecystectomy, partial liver resection, and lymph node dissection are advised  (LE5). Statement 1.5 Any symptomatic patient with GPL, with or without concurrent stones, should be a candidate for LC. Elective LC is indicated for patients with asymptomatic gallbladder polypoid lesions between 10 and 18 mm. OC is advised for polyps greater than 18 mm (GoR moderate) Cirrhosis Cholelithiasis in patients with cirrhosis occurs twice as often as in the general population. Five systematic reviews comparing outcomes of open cholecystectomy (OC) versus LC for symptomatic cholelithiasis in Child-Pugh A or B cirrhotic patients, show fewer overall postoperative complications, shorter hospital stay, shorter operative time and faster resumption of a regular diet for the LC group [84–89] (LE1). Due to the high risk of liver failure and dangerous hemorrhage in Child-Pugh C patients, surgery should be avoided . In such patients, cholecystostomy or percutaneous drainage of the gallbladder should be considered as alternative options . The increased risk of a major complication, however, demands more attention than usual. The morbidity rates for OC in these patients are between 30 and 35 % compared to 13–33 % in LC , with a 3.4-fold higher risk of mortality [87, 91]. Statement 1.6 Elective LC is the first choice treatment for symptomatic cholelithiasis in patients with compensated cirrhosis (grade A or B Child-Pugh) (GoR strong) Gallbladder dyskinesia Gallbladder dyskinesia is a motility disorder of an acalculous gallbladder associated with intermittent right upper quadrant pain (classic symptoms) . Recently Corrazziari and Cotton published a flow chart to assess the diagnostic criteria and treatment options . The incidence of negative US examination in patients complaining of biliary pain differs between
the two sexes, ranging from 7.6 % in males to 20.7 % in females . Preoperative diagnostic evaluation includes serial dynamic ultrasonography, upper ultrasound-endoscopy (to rule out microlithiasis), and dynamic cholescintigraphy [95–97] even if a recommendation regarding its use is not definitive  (LE2). Recently, an evidenced-based review  concluded that despite the widespread acceptance of CCK-HIDA provocative test and its’ standardization, highquality data indicating efficacy of cholecystectomy in the treatment of this condition are still lacking. Clinical signs and symptoms still remain the most important criteria for surgical treatment: LC alleviates symptoms (98 vs. 32 % of nontreated) in patients with biliary dyskinesia; those with longlasting symptoms were more likely to be satisfied [94–96] A meta-analysis showed 98 % symptomatic relief in the cholecystectomy group vs. 32 % in the control group (no treatment)  (LE2). In 2009, a Cochrane Review stated that the evidence of the benefits and harms of cholecystectomy in the treatment of gallbladder dyskinesia is based on a single small randomized controlled clinical trial (21 patients, 11 open cholecystectomy vs. control); therefore, the results could be biased. Thus, a wait and see policy is recommended for patients with atypical symptoms . If symptoms persist, a cholecystectomy can be considered after a careful explanation of the pros and cons without a guaranteed success. Statement 1.7 Elective LC for patients with gallbladder dyskinesia should be recommended in cases of recurrent Bclassic^ biliary symptoms with a normal ultrasound. Decreased gallbladder ejection fraction in CCK-HIDA scintigraphy might not predict a good outcome (GoR moderate) Acute cholecystitis The use of laparoscopy for the treatment of acute cholecystitis has been recently examined in a consensus conference endorsed by several scientific societies; a consensus statement was published in 2012 . The present review is an update of that work and takes into consideration the entire bibliographic search, used for that consensus conference. Indications for laparoscopy The safety of laparoscopic cholecystectomy for acute cholecystitis has been shown in several studies. The EAES Consensus Conference recommended that laparoscopic cholecystectomy be the treatment of choice for acute cholecystitis. That recommendation considered the evidence obtained from two randomized trials [101, 102] (LE2), a population-based outcome research (LE3)  and numerous comparative studies demonstrating that laparoscopic cholecystectomy was associated with faster recovery and shorter hospital stay compared to open cholecystectomy. The populationbased outcome research showed also lower morbidity and mortality . An additional trial, published after that consensus
Langenbecks Arch Surg
, confirmed those findings. A further randomized controlled study demonstrated that the laparoscopic cholecystectomy caused less surgical trauma and immunosuppression (by measuring serum C-reactive protein and tumor necrosis factor-a -TNF-a- secretion of peripheral blood mononuclear cells) and also confirmed that it was associated with a shorter hospital stay  (LE2). Severe (gangrenous, empyematous) cholecystitis (LE2)  and advanced age (LE3) [67, 69, 107, 108] do not preclude the indication for laparoscopic cholecystectomy. The preference for laparoscopic cholecystectomy is also expressed in the Tokyo guidelines, recently published ; however, the Bseverity^ tailored approach suggested in those guidelines, limits the indication for surgery only to the mildest forms of acute cholecystitis and takes in consideration only in part the above evidence (LE5). Timing of surgery The optimal timing of surgical treatment of acute cholecystitis has been extensively debated after earlier reports suggested an increased risk of conversion and complications, in particular bile duct injury, when early treatment of acute cholecystitis was carried out by laparoscopic cholecystectomy [109, 110]. The EAES Consensus Conference examined five meta-analyses (LE1) [111–116] (including six randomized controlled trials) and one trial comparing early versus delayed laparoscopic cholecystectomy for acute cholecystitis. A more detailed analysis of those papers can be found in that Consensus report ; all the studies show that an early treatment reduces the total hospital stay and does not increase the complication or conversion rates. In particular, the rate of bile duct injury has been shown to be higher in the delayed treated patients, but the difference was not statistically significant due to the small numbers analyzed in the trials. An update of the Chochrane review , two RCTs not included in any systematic review [118, 119] and six population-based outcome researches [120–125] were published after the EAES Consensus Conference; they confirmed the above-described findings. The evidence reported above does not identify, however, an optimal delay for surgery after the onset of symptoms. A subgroup analysis in one of the above-mentioned systematic reviews [114, 116], compared data from the trials that included only patients treated less than 4 days from the onset of symptoms to those whose treatment was delayed beyond that limit. No statistically significant difference between the two groups could be demonstrated. One of the large population-based studies mentioned above detailed the differences in the outcome of the patients who received a cholecystectomy within each of the first four days of admission. Patients hospitalized for two or more days before surgery sustained longer operative times and were significantly more likely to require open cholecystectomy compared with patients who received operation on the day of admission, but no difference in morbidity or mortality was found . if patients are fit for emergency surgery laparoscopic cholecystectomy is the treatment of choice for acute cholecystitisThe available
literature allows us to state that early cholecystectomy is indicated whenever possible for acute cholecystitis; it should be performed as soon as feasible after the onset of symptoms, but a cut-off delay, after which the outcome is significantly worse, is not yet defined. In particular, early cholecystectomy even in the severe forms of the disease [106, 126–128] or in the elderly population [129–131] has been shown to be safe and effective in several recent studies. The possibility to differentiate the timing of the treatment for acute cholecystitis according to the comorbidities and clinical conditions of the patients has not been addressed in the current literature . Therefore, if patients are fit for emergency surgery, early laparoscopic cholecystectomy is the treatment of choice. Percutaneous cholecystostomy (PC) Among the several alternatives proposed for the emergency treatment in septic high-risk patients, percutaneous tube cholecystostomy (followed or not by surgery) is extensively reported in the recent literature. A recent systematic review performed a detailed examination of 53 papers about cholecystostomy as an option in acute cholecystitis (LE3). It found no evidence to support the recommendation of percutaneous drainage rather than early emergency cholecystectomy even in critically ill patients. It actually suggested that cholecystectomy seems to be a better option for treating acute cholecystitis in the elderly and/or critically ill population . The comparison of the mortality rate after PC (15.4 %) with that after acute cholecystectomy (4.5 %) reported in the published series of similar patients, shows a significant difference (p8–10 mm) and multiple stones, proximal ductal stones inside the common hepatic duct and unfavorable cystic duct anatomy (small, friable, low common bile duct junction). The latter procedure is associated with an increased risk of biliary complications (bile leakage, T tube displacement) and prolonged hospital stay  (LE1). Therefore, when the laparoscopic trans-cystic stone clearance is not successful, intra-operative or postoperative endoscopic sphincterotomy may be the appropriate alternative option, especially in the presence of smalldiameter common bile duct and inflamed tissues [154, 155] (LE2). The primary closure of the common bile duct seems to be as effective as the BT-tube^ drainage after choledochotomy in the prevention of post-operative complications. Discomfort and complications related to T-tube drainage, including bile leakage and bile infection, may be avoided with a trans-cystic LCBDE  (LE1). However, laparotomic procedures seem to have a higher clearance rate than endoscopic or laparoscopic methods, without mortality and morbidity differences . Nevertheless, open surgery being more invasive, it should be considered for patients not eligible for laparoscopic or endoscopic common bile duct clearance, when the surgical team has no expertise in advanced laparoscopy, or whenever the local resources are scanty. Statement 3 ERCP is as safe as total laparoscopic removal for the treatment of concomitant gallbladder and common bile duct stones (GoR strong). ERCP should be performed preoperatively, whereas laparoendoscopic Brendez-vous^ should be reserved to patients with incidental intraoperative evidence of CBDS, in a highly complex organizational context (GoR
Langenbecks Arch Surg
moderate). In cases of acute cholangitis or severe acute biliary pancreatitis with persistent biliary obstruction, ERCP should be performed as soon as possible (GoR strong). Intra-operative cholangiography is recommended only for those patients who are likely to have common bile duct stones, not detected before surgery. In these cases, laparoscopic ultrasonography is likely to be accurate (GoR moderate). Three vs. standard four port technique, techniques of dissection from the liver bed and occlusion of cystic duct and artery, intraoperative cholangiography, drainage, analgesia (What are the special aspects to be considered during LC) Three vs. standard four port technique Standard laparoscopic cholecystectomy is mainly done using four trocars. With increasing surgeon experience, laparoscopic cholecystectomy has undergone many refinements including reduction in size and number of ports. Several studies have reported that three port LC is technically feasible and safe also on acute and chronic cholecystitis, although it does not reduce the analgesia requirements, and there is no significant differences between the three port group and four port groups in terms of operating time, success rate and postoperative hospital stay  (LE1) Statement 4.1 The three-port technique outcomes are similar to the conventional four-port technique (GoR strong) Technology for the dissection from the liver bed and occlusion of cystic duct and artery The occlusion of the cystic duct is one of the main steps in laparoscopic cholecystectomy. Usually, metal clips are used, but several methods are available (absorbable clips, clipless with ultrasonic dissector or stapler). Currently, monopolar electrosurgical energy is the most commonly used energy for dissection of the liver bed. However, its application is associated with numerous risks, such as biliary complications and thermal injuries. The application of ultrasound within the harmonic frequency range, limits lateral energy spread and reduces the risk of distant tissue damage compared with highfrequency electrosurgery, and has been suggested as an alternative to conventional electrosurgical energy. Non-absorbable clips Traditionally, non-absorbable metal clips are adopted to occlude the cystic duct permanently. Usually three large clips are applied, and the cystic duct is transected between the proximal and middle clips. However, applying multiple clips is neither feasible nor safe for a dilated (>1 cm) and difficult CD. Clip-related complications are
described with both metallic  and Hem-o-lok clips  (LE4). Absorbable materials There is a reduced inflammatory reaction to absorbable clips, as compared with metallic clips  (LE3). A recent review could not determine the benefits and harms of different methods of cystic duct occlusion because of the small sample sizes, short period of follow-up, and lack of reporting of important outcomes in the included trials  (LE1). Monopolar electrocautery for the cystic artery Many surgeons feel that the electrocautery is an unsafe method of controlling the cystic artery because of concerns over both adequacy of hemostasis and collateral tissue damage Katri et al. reported their experience with the use of monopolar electrocautery to control small and medium (15) or pigment stones in order to avoid abscess formation [GoR moderate]
Langenbecks Arch Surg
Quality of life after laparoscopic cholecystectomy (Is it beneficial to the patients?) Besides mortality and complications, health-related quality of life (HRQoL) (symptoms resolution, duration of convalescence, patient satisfaction and well-being) has become, in recent years, an important outcome measure. Instruments for measuring HRQoL may be disease-specific or generic. Quality of life (QoL) after laparoscopic cholecystectomy has been measured using the BGastrointestinal Quality of Life Index^ (GIQLI), the GI gallbladder symptom surveys (GISS) and the BShort-Form 36-Item Health Survey^ (SF36). We directed out our attention to the QoL about these main issues: (1) Efficacy of LC; (b) Comparison to OC; (c) Comparison to Minilaparotomic Cholecystectomy (MLTC); (d) Impact of iatrogenic Bile Duct Injury (BDI). QoL after laparoscopic cholecystectomy: is the operation effective? Three non-comparative prospective cohort studies concerned QoL after LC [260–262]. Gastrointestinal symptoms were evaluated by either the GIQLI or the GISS scores, the SF-36 was adopted for generic QoL. From their data, it could be deduced that: & & & &
LC significantly improved other GI symptoms as well as QoL in subjects with symptomatic gallstone disease; Best results may be achieved by appropriate selection of patients, in terms of discrimination between biliary disease-related symptoms and other GI disorders; Patients with a worse preoperative health condition are shown to benefit from greater QoL improvements following LC surgery; Preoperative functional status scores are the best predictors of postoperative HRQoL.
adopted the SF-36 questionnaire before and at 6 weeks after surgery . LC had better QoL outcomes than OC, but in the paper three other procedures are mixed with cholecystectomy and the population who underwent cholecystectomy in the study is very small. A prospective cohort study adopted the GIQLI and SF-36 scores and showed that 3 months after tsurgery HRQoL improvementwas significantly larger in LC than in OC patients. Additionally, preoperative health status was significantly and positively associated with each subscale of the GIQLI and SF-36 throughout the 6 months (LE3). Lastly, Matovic et al. prospectively studied 59 LC and 61 OC patients using the GIQLI score before surgery and then at 2, 5, and 10 weeks after surgery . Patients QoL at 2 and 5 weeks after the procedure were significantly better in the laparoscopic versus open group in all four domains, but 10 weeks after the procedure there was no difference in QoL total and domain score (LE 3). In conclusion, LC improves QoL faster than open surgery; however, long-term results are only slightly better or not different from OC: patients with a worse preoperative health condition may benefit from greater quality-of-life improvements following LC surgery. These results might be limited by the study design (e.g., small sample size, biased and confounding variables, low response rate to questionnaires). QoL after laparoscopic versus minilaparotomic cholecystectomy (MLTC) M LT C , a l s o c a l l e d Bs m a l l - i n c i s i o n l a p a r o t o m i c cholecystectomy^, is performed by a subcostal incision shorter than 8 cm. Several randomized controlled trials compared the QoL after MLTC and LC, study design, parameters evaluated, scale adopted and schedules were very different among the studies and some of the details are summarized in Table 1. In general, the perception of health immediately after LC is slightly better but the gain in health-related quality of life is small and of very limited duration.
QoL after laparoscopic versus open cholecystectomy
Impact of iatrogenic bile duct injury on QoL
EAES evidence-based guidelines on the evaluation of quality of life after laparoscopic surgery published in 2004 focused on the comparison of QoL after LC versus OC . Two randomized [264, 265] and eight nonrandomized trials were analyzed. Authors reported that laparoscopic cholecystectomy improves QoL faster than open surgery and that longterm results after laparoscopic cholecystectomy are slightly better or no different compared to those of open surgery. However, authors included publications that compare LC with classical OC and minilaparotomic cholecystectomy (MLTC). RCTs compared QoL after LC and MLTC . Our systematic review of the literature identified three more papers on the topic [266–268]. Velanovich prospectivestudy
The occurrence of a bile duct injury (BDI) has a significant impact on QoL. A systematic review included 831 patients from six retrospective case-controlled or case-series studies . Long-term results are conflicting. As the HRQoL surveys differed between the reports, BDI, and uncomplicated laparoscopic cholecystectomy (LC) groups, HRQOL scores were expressed as effect sizes (ES) in relation to a common general population standard. A negative ES indicated a reduced HRQoL, with a substantive reduction defined as an ES≤−0.50. Weighted logistic regression tested the effects of BDI (versus LC) and follow-up time on whether physical and mental HRQoL were substantially reduced. The analytic database comprised 90 ES computations representing 831
Langenbecks Arch Surg Table 1
Randomized controlled trials compared the QoL after MLTC and LC: study design, parameters evaluated, scale adopted, and schedules
Barkun et al.  McMahon  Squirrel et al.  Nilsson et al.  Harju et al.  Keus et al. 
37 LC+25 MLTC 151 LC+148 MLTC 50 LC+50 MLTC 364 LC+362 MLTC (non-consecutive) 72 LC+85 MLTC (non-consecutive) 120 LC+137 MLTC
GIQLI, NHP, VAS SF-36, HADS NHP EuroQol-5Da, VAS
SF-36 SF-36, GIQLI, BIQ
+, QoL is significantly better in LC than in MLTC; −, QoL is significantly better in LC than in MLTC NHP Nottingham Health Profile, VAS Visual Analogue Scale, HADS Hospital Anxiety and Depression Scale, BIQ Body image questionnaire a
Five questions concerning patient mobility, self-care, activity, pain or discomfort and mood
Significant only for role functioning/physical dimension od SF-36
Significant only for the perceived health change of SF-36, not for the rest
patients and 11 unique study groups (six BDI and five LC). After taking into account follow-up time (P