Challenging situations in cholecystectomy and strategies to overcome them

There was a long-lasting controversy in surgery whether early or delayed cholecystectomy should be the preferred strategy in patients with acute cholecystitis. This discussion did not change with the introduction of laparoscopic cholecystectomy. Series of the early period of laparoscopic cholecystectomy described an advantage with respect to postoperative pain and length of stay for early cholecystectomy at arguable conversion rates [5]. Today, the debate has subsided to patients with specific risk factors. There is high evidence that early cholecystectomy is the superior surgical strategy in patients with acute cholecystitis [6]. In a randomized multicenter trial from Germany, early laparoscopic cholecystectomy was associated with less morbidity (11.8 vs. 34.4%, p  0.01), shorter length of stay (5.4 vs. 10 days, p  0.01), and fewer costs for hospitalization (2919 vs. 4262 €, p  0.01). This study did not find a significant difference in conversion to open cholecystectomy (9.9 vs. 11.9%) [7].

Mostly, early cholecystectomy is defined as cholecystectomy within 72 h from onset, which is the recommendation of the Tokyo guidelines [8]. However, it may be difficult to determine precisely how many hours from onset have passed. So other definitions of early cholecystectomy used in trials encompass 24 h from admission to 1 week since onset. In contrast, delayed was generally defined as cholecystectomy after 6 weeks. Last amended in 2018, the Tokyo guidelines introduced a severity assessment of acute cholecystectomy. According to the local and systemic status of inflammation and the presence of organ dysfunction, three grades of acute cholecystitis are discriminated (Table 1). Based on this grading system, therapeutic recommendations were published and reevaluated regularly [9, 10]. While the Tokyo guidelines helped to establish the role of early laparoscopic cholecystectomy in grade I, the therapeutic strategy remained less clear for grades II and III. Loozen et al. demonstrated similar results of emergency cholecystectomy with respect to conversion rate (6 vs. 6%), complication rate (7 vs. 9%), mortality (1 vs. 1%), and length of stay (4 vs. 4 days) in patients with grade I and grade II acute cholecystitis [11]. Indeed, the Tokyo guidelines’ update of 2018 recommends early laparoscopic cholecystectomy in moderate acute cholecystitis (grade II) for patients with limited risk factors (Charlson comorbidity index ≤5 or ASA ≤2) in advanced centers by experienced laparoscopic surgeons. Moreover, for severe acute cholecystitis (grade III), early laparoscopic cholecystectomy is an option if the patient is estimated to be fit for surgery and a setting of intensive care management and extensive laparoscopic experience is provided. Clearly, the Tokyo guidelines’ therapeutic recommendations for moderate and severe acute cholecystitis indicate the need for an institutionalized concept for surgical departments, depending on the hospital setting and surgical experience. Patients who are decided to be unfit for early cholecystectomy due to high individual risk factors need urgent gallbladder drainage for source control. In practice, these interventions are provided in centers with high institutional experience and a continuous case load. Aside from guideline recommendations, it is clearly proven that time matters in surgical therapy of acute cholecystitis. An analysis of the Swedish GallRiks Registry demonstrates a correlation of the rate of bile duct injuries with acute cholecystitis. Overall, the incidence in acute cholecystitis was 0.43 vs. 0.28% in patients without cholecystitis. The rate for patients with acute cholecystitis increased markedly from 0.17% in cholecystectomies on the day of admission to 0.67% for 3 days after admission to 0.93% for 5 days and longer. Interestingly, there was also a significantly increased 30- and 90-day mortality when operations were performed after the fourth day of admission [12].

The timing of laparoscopic cholecystectomy in patients with mild biliary pancreatitis is another item of debate in clinical routine. Mostly, patients were discharged following the episode of biliary pancreatitis and scheduled for an interval cholecystectomy. The background for this strategy was an estimated higher risk for cholecystectomy-related complications in early surgery. However, the PONCHO trial, a multicenter randomized controlled trial from the Netherlands, could prove that cholecystectomy during the same hospital admission is superior to interval cholecystectomy regarding the rate of recurrent gallstone-related complications without increasing the surgical risk [13]. Patients were randomized 5 days after admission for mild biliary pancreatitis and operated on day one in the same admission or day 27 in the interval group. The primary endpoint of readmission for gallstone-related complications or mortality was significantly lower when cholecystectomy was performed in the same admission (5 vs. 17%, p  0.002). Nevertheless, the fear of a difficult cholecystectomy with increased complication rates may hinder consequent implementation of a same admission cholecystectomy. The Dutch Pancreatitis Study Group analyzed the rate of difficult cholecystectomies in their PONCHO trial [14]. They defined difficult cholecystectomy as one or more of the three factors, enhanced score of difficulty to perform laparoscopic cholecystectomy, operating time 75 min, and conversion or subtotal cholecystectomy. Overall, 33% of patients fulfilled the criteria of difficult cholecystectomy, 26% in the same admission and 39% in the interval group (p = 0.037). Male sex, prior sphincterotomy, and delaying cholecystectomy for at least 14 days were identified to increase the probability of a difficult cholecystectomy.

There exist several strategies to treat patients with cholecystolithiasis and bile duct stones. Amongst these concepts, therapeutic splitting with prior clearance of the bile ducts by endoscopic sphincterotomy and subsequent laparoscopic cholecystectomy is most commonly applied. In a large population-based analysis in British Columbia, in 44.4% timing followed an early cholecystectomy strategy within 2 days after sphincterotomy and in 55.6% a delayed cholecystectomy [15]. This survey reflects clinical practice to some extent, with a wide variation in scheduling laparoscopic cholecystectomy. As in mild biliary pancreatitis, early laparoscopic cholecystectomy may be seen as a more difficult operation with increased complication rates. Furthermore, increased serum amylase as an indicator of a mild post-sphincterotomy pancreatitis may delay surgery. Indeed, several reports found a higher conversion rate compared to standard laparoscopic cholecystectomy [16, 17]. In contrast, overall conversion rates for laparoscopic cholecystitis after endoscopic sphincterotomy are most often lower (4–23% for early vs. 8–55% for delayed) and recurrent biliary events less frequent (2–10% early vs. 24–47% delayed) for early cholecystectomy [18‐20]. In an RCT comparing laparoscopic cholecystectomy within 3 days and 6–8 weeks after endoscopic sphincterotomy, no significant difference in conversion rates (4.3 early vs. 8.7% delayed), operating times, or length of stay was detected. But there was a marked difference in biliary events in the waiting period, with 2% in the early and 36.2% in the delayed group. Consequently, the ESGE guidelines recommend laparoscopic cholecystectomy within 2 weeks from endoscopic sphincterotomy. This is quoted as a strong recommendation with moderate-quality evidence [21].

According to the above-cited Swedish Registry for Gallstone Surgery (GallRiks), only 0.12% of cholecystectomies are performed in patients with liver cirrhosis [22]. Compared with noncirrhotic patients, the incidence of postoperative complications was higher (16.9 vs. 9.2%, p  0.05). However, the conclusion of the registry is that cholecystectomy should not be delayed in patients with an adequate indication. One of the largest series of laparoscopic cholecystectomies in cirrhotic patients was recently published by Gad et al. [23]. In a cohort of 213 cirrhotic patients operated between 2011 and 2019, 30-day morbidity and mortality were 22.1 and 2.3%. Nevertheless, Child–Pugh class, MELD score, and acuity increase perioperative mortality significantly. In a survey of herniorrhaphies and cholecystectomies in cirrhotic patients, mortality was zero, 8.8, and 10.7% for Child A, B, and C, respectively [24]. Emergency surgery raised mortality to 20%.

The number of patients with antithrombotic therapy undergoing surgery is increasing steadily. Preoperatively, this raises the question of whether this therapy should be maintained, adopted, or withdrawn to keep perioperative hemorrhagic complications low. Especially in acute surgery, this problem needs urgent consideration. In general, the incidence of postoperative bleeding complications is determined by the intensity of antithrombotic therapy. In a review of 1075 patients undergoing abdominal laparoscopic surgery, no increase in hemorrhagic complications was found in patients with continued antiplatelet therapy compared to patients with preoperatively suspended or without therapy [25]. A recently published analysis of the effect of antithrombotic therapy in emergency cholecystectomy by the same authors underlines the need of a differentiated approach. Multiple antiplatelet therapy, anticoagulation, male sex, limited performance status, and grade II and III acute cholecystitis were independent risk factors for increased intraoperative blood loss and postoperative bleeding. Single antiplatelet therapy was not associated with hemorrhagic complications [26]. An individual approach balancing each patient’s risk of thrombotic or bleeding complications is therefore crucial.

Morbid obesity seems to be a clear risk factor for a difficult cholecystectomy. Indeed, a recent review on risk factors for conversion of laparoscopic to open cholecystectomy found that 8 of 19 studies analyzing BMI found that conversion was significantly higher in patients with a BMI above 30 kg/m² [27]. Going into detail, there may be a variety of reasons why the conversion rate is higher according to this review. All of them are technical issues, like the length and positioning of trocars, fatty infiltration of Calot’s triangle, and unclear anatomy. However, it remains unclear whether obesity is really a reason for a difficult cholecystectomy. A retrospective comparison of day-case cholecystectomy in patients with a BMI 30 kg/m² and obese patients indicated by a BMI above 30 kg/m² revealed a technically more demanding procedure in the obese group. However, there were no strong indicators for a major impact of obesity. Conversion rates, overall complications, and the incidence of readmission were not markedly different [28].