Surgical management of gallstone disease and complications from gallstone surgery
Authors: Edergren Åsa 
Published: October 2024

<p dir="ltr">Introduction</p><p dir="ltr">Surgery for gallstone disease is one of the most frequently performed surgical procedures in the world. Complications occur in 6-11% of these cases, amounting to much suffering and large expenses for healthcare systems worldwide. The aim of this thesis was to find strategies to optimize the surgical management of gallstone disease, focusing mostly on ways to avoid complications.</p><p dir="ltr">Methods</p><p dir="ltr">PAPER I and II are retrospective register-based cohort studies, using data from the Swedish register for Gallstone Surgery and ERCP, GallRiks. In PAPER I, data about all cholecystectomies performed between 2008 and 2019 were used. Multivariable logistic regression analyses were performed, with post operative abscess as outcome and intraoperative gallbladder perforation as predictor, adjusting for ASA-classification, age, sex, surgical approach, and presence of acute cholecystitis. In PAPER II, all cholecystectomies performed 2006-2020 were identified and stratified in three groups: surgeries carried out by surgeons that use FFLC in less than 20% of the cases, in 20-79% of the cases and in 80% or more of the cases. The groups were compared with logistic regression, adjusting for sex, age, surgical experience, year of surgery and history of acute cholecystitis. All surgical complications were included as outcome. A separate analysis was done with regards to operation time.</p><p dir="ltr">PAPER III is a questionnaire-based study, using data from GallRiks to select a case group (all patients in GallRiks 2007-2018 with registered suspicion of retained gallstones) and a control group without intraoperative gallbladder perforation matched 1:2. Cases and controls were sent a validated questionnaire including twenty-one questions about persisting abdominal pain and inflammatory symptoms. The questions were divided into four groups: abdominal pain, consequences of pain e.g., fatigue and loss of sleep, gastrointestinal symptoms e.g., bloating and nausea, and repeated operation. Simple weighted linear regression was performed on the sum of all answers within the group and mean numerical values between cases and controls were compared.</p><p dir="ltr">PAPER IV is a matched cohort study, using data from GallRiks to identify patients who had undergone a cholecystectomy at Södersjukhuset 2008-2022 and had registered retained gallstones in the abdominal cavity. These patients were matched 1:2 with a control group without an intraoperatively perforated gallbladder. Preoperative, intraoperative, and postoperative variables were collected. The cases and controls were compared with chi-square test and data was analyzed using Cox regression with stone spillage as exposure, adjusted for ASA-classification and antibiotic treatment.</p><p dir="ltr">Results</p><p dir="ltr">PAPER I: Data from 108 714 cholecystectomies was analyzed. Intraoperative perforation was recorded in 33.8% of the cases, and in 2.4% of procedures there was a record of retained gallstones. There was a significantly increased risk for postoperative abscess in patients with gallbladder perforation (OR 1.53 [1.36- 1.71]) and stone spillage (OR 1.75 [1.35.2.27]) when adjusting for age, sex, antibiotic prophylaxis, presence of acute cholecystitis and surgical approach. Antibiotic prophylaxis yielded an OR of 0.99 [0.86-1.16] in case of gallbladder perforation and 1.07 [CI 0.92-1.24] in the case of retained stones.</p><p dir="ltr">PAPER II: No difference in incidence of all surgical complications were seen between groups. Operation time was shorter (OR 0.76 [0.69 - 0.83]), and gallbladder perforation (OR 0.61 [0.45 - 0.82]) and bleeding complications (OR 0.34 [0.14 - 0.86]) were significantly fewer in patients operated by the "Fundus first > 80%" group.</p><p dir="ltr">PAPER III: No significant differences between cases and controls were found in any of the groups of questions. We saw a tendency towards an increased re- operation rate among the patients with retained gallstones, 7.1% in the study group and 5.3 % in the control group underwent a repeated operation, but this difference was not significant (p= 0.057).</p><p dir="ltr">PAPER IV: No significant associations between retained gallstones and abdominal pain, nor abscess development, were found. There was however a significant association between retained gallstones and SSI with a hazard ratio of 6.18 [1.63 - 23.4]. There was no significant effect of antibiotics on the hazard ratio for any of the outcomes.</p><p dir="ltr">Conclusions</p><p dir="ltr">Intraoperative gallbladder perforation increases the risk for abscess and should ideally be avoided. However, if perforation does occur, antibiotic prophylaxis or treatment do not decrease the risk for abscess and should only be used in patients that have an infection. If the gallbladder perforation leads to spilled gallstones, these should be retrieved, if possible. However, since so few patients develop complications from retained stones, the surgery should not be extended for too long, and not converted to open surgery to retrieve the stones. The standard method of dissection as well as fundus first dissection are safe methods, none resulting in more post operative complications than the other. Surgeons should try to learn both methods in a controlled way, so they are able to choose the most appropriate method for each individual case.</p><h3>List of scientific papers</h3><p dir="ltr">The thesis is based on the following papers, which will be referred to in the text by their Roman numerals.</p><p dir="ltr">I. Intraoperative gallbladder perforation and risk of postoperative abscess with or without antibiotics: a national cohort study of more than 108 000 cholecystectomies<b>. </b><b>Åsa Edergren</b>, Gabriel Sandblom, Thorhallur Agustsson and Gona Jaafar. British Journal of Surgery. 2023 Jul 17;110(8):896-900. <a href="https://doi.org/10.1093/bjs/znac351" rel="noreferrer" target="_blank">https://doi.org/10.1093/bjs/znac351</a></p><p dir="ltr">II. Safety of cholecystectomy performed by surgeons who prefer fundus first versus surgeons who prefer a standard laparoscopic approach<b>. </b><b>Åsa Edergren</b>, Gabriel Sandblom, Mikael Franko, Thorhallur Agustsson, Yucel Cengiz and Gona Jaafar. Surgery Open Science. 2024 Jun; 19: 141-145. <a href="https://doi.org/10.1016/j.sopen.2024.04.004" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.sopen.2024.04.004</a></p><p dir="ltr">III. No significant persistent symptoms from gallstones left in the abdomen after cholecystectomy<b>. </b><b>Åsa Edergren</b>, Gabriel Sandblom, Henrik Renlund, Thorhallur Agustsson and Gona Jaafar. The surgeon. 2024 Aug 14; online ahead of print. <a href="https://doi.org/10.1016/j.surge.2024.08.002" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.surge.2024.08.002</a></p><p dir="ltr">IV. Don't cry over spilled gallstones. Sequalae from gallstones left in the abdominal cavity, a matched cohort study<b>. </b><b>Åsa Edergren</b>, Gabriel Sandblom, Omar Ali, Alva von Gerber, Thorhallur Agustsson and Gona Jaafar. [Manuscript]</p>