Gallstone Pain: What Trials Found on Surgery Versus Watchful Waiting

Table of Contents

1. Silent Stones and Painful Stones
2. How Often the Pain Returns Without Surgery
3. The C-GALL Trial
4. The 14-Year Randomized Trials
5. The SECURE Trial
6. What the Pooled Analyses Report
7. Pain After Gallbladder Removal
8. Features Linked With Relief After Surgery
9. Complication Rates on Each Path
10. Treating an Attack: The Pain-Relief Trials
11. What the Trials Report on Costs
12. What the Guidelines State
13. Stones Found by Chance
14. Limits of the Evidence
15. Who the Trials Left Out, and Signs Hospitals Treat as Urgent
16. Key Research Papers
17. Connections
18. Featured Videos

Silent Stones and Painful Stones

The word "gallstones" covers two quite different situations, and the research treats them separately.

• Silent stones show up on a scan done for some other reason and cause no symptoms. The 2024 report of the C-GALL trial estimates that about 10 to 15% of adults have gallstones and that around 80% of those stones remain without symptoms (Innes 2024). The Japanese guideline gives a similar figure of about 70% (Fujita 2023).
• Painful stones cause attacks of biliary colic, a severe pain under the ribs on the upper right or in the upper middle of the abdomen. A Cochrane review describes biliary colic as the most common effect of gallstones, seen in over one-third of people with stones over 10 or more years (Fraquelli 2016).

Trials of surgery against waiting study a narrower group within the second category: people with "uncomplicated" symptomatic stones. That means pain, without a stone blocking the bile duct, without jaundice and without pancreatitis. The trials draw the line a little differently: C-GALL counted people electively referred after biliary colic or acute cholecystitis, while SECURE treated cholecystitis as a complication and left it out. Whether people with these complications benefit from surgery is a separate question, and the trials on this page do not answer it.

The operation itself is called a cholecystectomy, the removal of the gallbladder. It is normally done laparoscopically, through small keyhole cuts. "Conservative management" or "observation" in these trials means no planned operation. In the C-GALL trial it was care by the patient and their general practitioner, which might include dietary advice and pain management, with surgery if needed (Innes 2024). Participants also received a leaflet on what to do if symptoms flared up (Ahmed 2023).

How Often the Pain Returns Without Surgery

A person who has had one gallstone attack is more likely to have another than a person with silent stones, but many have no further attacks for long stretches. Several studies have followed people who were not operated on.

• The National Cooperative Gallstone Study. This trial of a stone-dissolving drug had 305 people on placebo. Over 24 months, biliary pain occurred in 69% of those who had pain in the 12 months before entry, against 31% of those who had not. Despite this, only 4% needed a non-elective cholecystectomy during the 24 months (Thistle 1984).
• An Italian population study. It screened 11,229 people with ultrasound and followed those with stones for a mean of 8.7 years. Among people with severe symptoms at the start, the symptoms disappeared in 52.1%, became mild in 16.8% and stayed the same in 31.1%. Among people with mild symptoms, they disappeared in 58.5%, became severe in 24.5% and stayed stable in 17% (Festi 2010).
• The Japanese guideline's summary. Within one year, 1 to 3% of people with mild symptoms develop severe symptoms or complications such as acute cholecystitis, cholangitis, jaundice or pancreatitis. For people with moderate symptoms, 6 to 8% a year develop severe symptoms and have surgery (Fujita 2023).
• A 2018 review describes symptomatic disease differently, as carrying "a persistent high risk of symptom recurrence and need of cholecystectomy" (Shabanzadeh 2018).

These sources do not fully agree, and part of the reason is design. Population screening can find people with milder disease than a surgical clinic sees. The Italian study relied on questionnaires, and the placebo group was made up of people who had chosen a non-surgical route.

The C-GALL Trial

C-GALL is a direct test of surgery against conservative management in uncomplicated symptomatic gallstones. It took place at 20 hospitals in the United Kingdom. Of 2,667 people assessed, 434 were randomized between 2016 and 2019, half to each group (Ahmed 2023). Their mean age was 50 to 51 years and 79% were women.

The main measure was bodily pain over 18 months, scored on a standard 36-question health survey (Short Form-36), on a scale where the general population averages 50.

• Pain over 18 months: no difference. The area-under-the-curve score was 46.8 in both groups (mean difference 0.0, 95% confidence interval -1.7 to 1.7).
• Pain at 18 months: 49.4 with conservative management and 50.4 in the surgery group.
• Timing: at three months the conservative group scored better on pain, and after three months the surgery group scored better.
• Overall quality of life: no evidence of a difference up to 24 months.
• Gallstone-specific symptoms: these favored surgery. On a gallstone questionnaire the difference at 24 months was 9.0 points (95% confidence interval 4.1 to 14.0), with a similar pattern for persistent symptoms (Innes 2024).

That last point matters when reading the headline result. A general pain score did not separate the groups, while a questionnaire built for gallstone problems did. The plain-language summary of the trial says that participants in the surgery group reported fewer ongoing problems related to their gallstone disease or after surgery.

How many people actually had each treatment

Random assignment did not fix what happened next. By 24 months, 64 people (29.5%) in the conservative group and 153 (70.5%) in the surgery group had been operated on (Innes 2024). Among the 153 conservative-group participants with no operation by 24 months, 131 were not on a waiting list and 15 were. Of the 64 people assigned to surgery who had not had it, 33 had declined (Ahmed 2023). Among those operated on, median time to surgery was 4.7 months in the surgery group and 9.0 months in the conservative group (Innes 2024). The trial's sensitivity analyses suggested the waiting list was unlikely to bias the result, but the authors note that it may limit how well the findings apply in countries with shorter waits.

The authors conclude that in the short term, up to 18 months, laparoscopic surgery was no more effective than conservative management. They call for longer follow-up and for work to identify which people benefit most from an operation.

The 14-Year Randomized Trials

Before C-GALL, two small trials from one research group in Norway were the main randomized evidence. They have the longest follow-up of any trial on this page.

Uncomplicated symptomatic stones

Of 338 people considered, 137 were randomized to cholecystectomy (68) or observation (69). After a median of 67 months, 35 of the 69 in the observation group had had their gallbladders removed, and 8 of those assigned to surgery had not. Gallstone complications occurred in 3 people in the observation group and 1 in the operation group. The authors concluded at that point that watchful waiting carried a low risk of complications (Vetrhus 2002).

At 14 years the same trial reported no difference between groups in symptomatic events or major complications (p = 0.298). By then 50.7% of the observation group and 88.2% of the surgery group had been operated on. Virtually no operations took place after 5 years, and no clear escalation in disease severity was seen. The surgery group completed its assigned treatment significantly more often (p < 0.001). The authors' conclusion had shifted: they described cholecystectomy as the preferred treatment, with conservative management an alternative in the elderly (Schmidt 2011, Digestive Surgery).

Acute cholecystitis

The companion trial randomized 64 people who had already had an episode of acute cholecystitis, a gallbladder infection or inflammation. After a median of 67 months, gallstone complications or emergency admissions for pain occurred in 36% of the observation group and 19% of the operation group (Vetrhus 2003). At 14 years, 11 of the 33 people in the observation group (33%) had a new gallstone event, 8 (24.2%) had recurrent cholecystitis, and 11 (33%) had been operated on. The groups did not differ significantly in recurrent disease or complications, and long-term mortality was equal (Schmidt 2011, acute cholecystitis follow-up).

The SECURE Trial

SECURE, in 24 Dutch hospitals, asked a different question: does applying strict criteria for who gets surgery change results? It enrolled 1,067 people with abdominal pain and stones or sludge on ultrasound. One group had usual care, where the surgeon decided. In the other, surgery was advised only if a person met all five criteria: severe attacks, pain lasting 15 to 30 minutes or longer, pain in the upper middle or upper right abdomen, pain radiating to the back, and a positive response to simple painkillers (van Dijk 2019).

• At 12 months: 56% were pain-free with the restrictive strategy and 60% with usual care. The trial could not show that the strict approach was as good (non-inferiority not shown).
• Operations at 12 months: 68% with the restrictive strategy against 75% with usual care.
• At 5 years: 61.2% were pain-free with the restrictive strategy and 62.8% with usual care, and non-inferiority again was not shown. Operations stood at 73.2% against 81.5% (Comes 2024).
• Among those who had surgery, at 5 years: 63.0% and 63.6% were pain-free. So more than one person in three who had the operation and answered at five years was not pain-free.
• Complications: no differences in gallstone or surgical complications between strategies at either time point.

SECURE did not include a true no-surgery group, so it cannot compare an operation with waiting. Its results describe pain after surgery and show that strict symptom criteria produced a significant but small drop in operations. The authors called for better selection criteria and for "rethinking laparoscopic cholecystectomy as treatment" to improve what patients report.

What the Pooled Analyses Report

Several reviews combine the trials, and they include different trials under the same heading. Their results favor surgery on gallstone events. On surgical harms, some favor waiting and some find no significant difference.

• 2015 review (two trials, 201 people, the same total as the two trials above). Over 14 years, 88% of those randomized to surgery and 45% of those randomized to observation had a cholecystectomy. People in the observation group were more likely to have gallstone complications (relative risk 6.69, 95% confidence interval 1.57 to 28.51), especially acute cholecystitis, and less likely to have surgical complications (relative risk 0.36, 0.16 to 0.81). The authors named surgery as the preferred treatment, and noted that about half of the observation group did not need surgery (Brazzelli 2015).
• 2021 review (39 trials, 4,483 people). Pain was less common with early cholecystectomy (relative risk 0.38, 0.20 to 0.74), as were cholangitis (0.52) and total biliary complications (0.33, 0.20 to 0.55). The comparison group mixed conservative management with delayed surgery, so this does not isolate waiting alone (Bagepally 2021).
• 2025 review (11 trials). Conservative management carried more total biliary complications (relative risk 3.63, 2.07 to 6.37), more biliary colic (2.75) and more bile duct stones (3.96). There was no significant difference in surgical complications, mortality, pancreatitis or cholangitis (Ghose 2025).
• 2026 review (four trials, 677 people). Cholecystectomy lowered biliary colic (relative risk 0.43, 0.24 to 0.78) and overall gallstone complications (0.40, 0.23 to 0.69). Conservative management was linked with fewer surgical complications and fewer operations. Mortality, acute cholecystitis, pancreatitis and bile duct stones did not differ significantly (Gad 2026).

A relative risk of 0.40 means 40% of the rate in the comparison group; 3.63 means about 3.6 times the rate. Those figures can sound large for events that are uncommon, and the reviews' abstracts mostly give relative rather than absolute numbers. The two most recent reviews also disagree on bile duct stones, which shows how much depends on which trials are counted.

Pain After Gallbladder Removal

Surgery removes the stones and the organ where they form. It does not always remove the pain, and several prospective studies have tried to measure how often this happens.

• Colic versus any abdominal pain. In 820 people from two Dutch trials, the operation resolved biliary colic in 94.8% of those followed for it, yet 36.5% reported some persistent abdominal pain at 6 months (Thunnissen 2023).
• A 12-month figure. In a 12-month prospective evaluation of 189 people at one hospital, 29% had persistent pain, and 36% had poorly controlled pain in the first 48 hours (Lee 2024).
• A 5-year figure. In two randomized trials, 27% of 124 people interviewed five years after the operation had pain: 18% a diffuse steady pain and 9% attacks resembling those before surgery. Diffuse pain occurred mainly in women, especially those under 60. Among 139 others who answered a questionnaire, 88% were satisfied with the operation, and 18% had pain (Vetrhus 2005).
• A systematic review. Across 38 studies, upper abdominal pain mostly disappeared, but persisted in up to 33% and arose new in up to 14% (Lamberts 2013).
• A 2023 review of prospective studies. Biliary pain resolved in 66 to 100%. When a randomized trial selected people with biliary pain only, 30 to 40% still had persisting pain. New diarrhea appeared in 14 to 17% (Shabanzadeh 2023).
• A 2025 narrative review reports post-cholecystectomy syndrome, meaning persistent or new symptoms after removal, in up to 47% of patients, and says there is still no consensus on its cause, diagnosis or treatment (Nam 2025).

"Pain-free" and "better" are different results. In one Dutch cohort, 59.2% reported no pain at 24 weeks while about 90% reported general improvement and a positive result of surgery (Wennmacker 2017). In another study, pain was cured or improved in about 90% and two-thirds had complete symptom relief (Schmidt 2012).

New symptoms

In the 820-person analysis, the most common new symptoms at 6 months were frequent bowel movements (9.6%), bowel urgency (8.5%) and diarrhea (8.4%). Flatulence (17.8%) and restricted eating (14.5%) were the symptoms that most often persisted (Thunnissen 2023).

Features Linked With Relief After Surgery

Researchers have looked for features that separate people likely to gain from those who are not. These are links found in groups, and they do not predict the result for any one person.

• A 1,008-person follow-up in two United States centers. 59% reported relief from upper abdominal pain at 12 months. Relief was linked with pain attacks no more than once a month, onset within a year before surgery, and waking at night with the pain. It was less likely with lower abdominal pain, an abnormal bowel pattern, or frequently feeling bloated or burpy. Reflux, irritable bowel syndrome and somatization, where emotional distress is felt as body symptoms, also lowered the odds (Thistle 2011).
• A prediction tool from 1,561 Dutch patients. Clinically relevant pain reduction at 6 months was predicted by older age, no earlier abdominal surgery, a higher baseline pain score, pain radiating to the back, pain eased by simple painkillers, nausea, and no heartburn (Latenstein 2021).
• The same teams' 5-year model. Predictors were male sex, higher baseline pain, pain radiating to the back and nausea, with absence of constipation, diarrhea and bloating after meals (Comes 2025).
• Functional gut disorders. In 153 people, these disorders were present in 88% before and 57% after surgery (p = 0.244), and having none before surgery meant almost complete cure. The authors concluded that they were a dominant cause of symptoms after the operation (Schmidt 2012).

A 2023 review concluded that strategies for selecting people for surgery based on symptoms alone "are exhausted" and called for studies of objective markers (Shabanzadeh 2023).

Complication Rates on Each Path

The risks of the operation

• Bile duct injury. Among 152,776 cholecystectomies in Sweden from 1987 to 2001, 613 (0.40%) led to a reconstructive bile duct operation within a year. Older age and male sex raised the risk (Waage 2006).
• Death within 30 days. Among 47,912 cholecystectomies for gallstone disease in Sweden from 2007 to 2010, 72 people died (0.15%), about 2.58 times the rate expected in the general population of the same age and sex. This count includes emergency surgery. Predictors were age over 70, other illnesses, acute surgery, open surgery and complications during the operation (Sandblom 2015).
• Any complication at 30 days. The C-GALL report cites a United Kingdom study of 8,909 people in which 10.8% had complications within 30 days (Ahmed 2023).

The risks inside the trials

By 18 months in C-GALL, 32 people (15%) in the conservative group and 44 (20%) in the surgery group had a complication (relative risk 0.72, 95% confidence interval 0.46 to 1.14), not a statistically significant difference. The kinds differed. Complications before surgery, mostly cholecystitis or biliary colic, affected 25 people (12%) in the conservative group and 11 (5%) in the surgery group. Complications during surgery, mostly bile or stone spillage, affected 9 (4%) and 24 (11%). One cardiovascular death occurred in the surgery group. Further treatment was needed by 5% and 6% (Ahmed 2023).

In the older trial, 16 of 222 people who had a cholecystectomy had a major complication and 10 a minor one (Vetrhus 2002). In SECURE, gallstone complications affected about 7 to 8% of each arm and surgical complications about 21 to 22% of those operated, at 12 months (van Dijk 2019).

The risks of waiting

• Waiting lists. A Cochrane review found one trial of 75 people comparing surgery within 24 hours of diagnosis with a mean wait of 4.2 months. Serious adverse events occurred in 0 of 28 and 9 of 40, and they included pancreatitis, gallbladder perforation and cholangitis, while 14 people on the wait needed hospital admission. One person in the delayed group died, a difference that was not statistically significant. The trial was at high risk of bias (Gurusamy 2013).
• Older adults. Among 92,436 United States Medicare patients over 65 with symptomatic stones who did not have prompt surgery, 11.1% had an emergency gallstone hospitalization within 2 years. Those admissions carried 56.5% morbidity and 6.5% in-hospital mortality. Risk varied widely: 51% of the group had under 10% risk at 2 years and 5.4% had over 40%. Men, older people and those whose first episode was complicated or came through the emergency department were at higher risk (Parmar 2015).
• After treating acute cholecystitis without surgery. In a Swedish study of 909 people, 348 had a new gallstone complication, with a median time to recurrence of 82 days (Helenius 2025).

Treating an Attack: The Pain-Relief Trials

Choosing not to operate means some people will face further attacks, so the trials of pain relief bear on the question. A 2016 Cochrane review collected 12 randomized trials with 828 people, all admitted to emergency departments with acute biliary pain (Fraquelli 2016).

• Non-steroidal anti-inflammatory drugs compared with placebo: far fewer people were left without complete pain relief (relative risk 0.27, 95% confidence interval 0.19 to 0.40, moderate-quality evidence).
• Compared with spasm-relieving drugs: better pain control and fewer complications, on low-quality evidence that a further statistical check did not confirm.
• Compared with opioids: no difference in complete pain relief (relative risk 0.98, 0.47 to 2.07), on very low-quality evidence.
• Safety: there were no deaths and none of the trials reported severe adverse events. The review's background notes that this drug class may increase gastrointestinal bleeding, kidney impairment and cardiovascular events. Most trials did not include elderly people or people with other illnesses, who are more prone to complications.

Only one of the 12 trials was at low risk of bias, and none measured quality of life.

What the Trials Report on Costs

• C-GALL, United Kingdom National Health Service, 24 months. Mean costs were £2,510 per person in the surgery group and £1,477 in the conservative group, a difference of £1,033. The quality-adjusted life year difference was small and not significant, at 0.019 in favor of surgery (Ahmed 2023). That works out at £55,235 per quality-adjusted life year, well above the usual £20,000 threshold used for United Kingdom decisions.
• C-GALL, 10-year model. The figure was £78,063, which still favored conservative management, but a scenario using longer-term quality-of-life scores cut it to £14,698, below the threshold. The authors state that later operations and quality of life beyond 24 months could reverse the short-term result (Hernández 2024).
• SECURE, the Netherlands, 12 months. The restrictive strategy saved €162 per person from a societal perspective, and led to fewer pain-free patients: €4,563 saved per pain-free patient lost (Latenstein 2022).
• A 2015 model, costed in pounds. Surgery cost on average £1,236 more per person and was more effective (Brazzelli 2015).
• An Indian model. Early laparoscopic cholecystectomy cost less than conservative management and gained more quality-adjusted life years in an Indian health-system analysis (Haridoss 2023). The direction differs from the C-GALL result, in a different health system with different prices.

These figures describe costs to health systems and societies, not what an individual pays.

What the Guidelines State

Guideline wording is reported here as a fact about the guideline. All three below were published before the C-GALL results appeared in December 2023.

• United Kingdom, National Institute for Health and Care Excellence (guideline CG188, 2014). It recommends offering laparoscopic cholecystectomy to people diagnosed with symptomatic gallbladder stones. It also states that people with stones without symptoms, in a normal gallbladder and normal biliary tree, do not need treatment unless they develop symptoms.
• Japan, Japanese Society of Gastroenterology (2021 edition). It recommends laparoscopic cholecystectomy for symptomatic gallbladder stones (strong recommendation, 91% agreement, evidence level C). For silent stones, its commentary says prophylactic surgery is generally not recommended, with a weak recommendation for cholecystectomy in people at high risk of gallbladder cancer (Fujita 2023).
• Denmark, Danish Surgical Society (2021). For uncomplicated symptomatic gallstone disease, it suggests observation as an alternative to laparoscopic cholecystectomy (2 randomized trials, weak recommendation). For acute cholecystitis, it recommends acute laparoscopic cholecystectomy (16 randomized trials, strong recommendation) (Shabanzadeh 2022).

Of these three, the Danish society lists observation as an option, while the other two keep surgery as the standard for symptomatic stones. The 2019 SECURE paper describes international guidelines as advising surgery for symptomatic, uncomplicated stones, and the C-GALL authors write that a discussion of conservative management belongs in the decision and consent process.

Stones Found by Chance

A Cochrane search through 2006 found no randomized trial of surgery against no surgery for silent stones (Gurusamy 2007). What is known comes from following people over time.

• The largest cohort. Among 22,257 people with silent stones from a general medical population, 10.1% developed symptoms by 5 years, 21.5% by 10 years and 32.6% by 15 years, about 2% per year. The strongest predictors were female sex, younger age, multiple stones, gallbladder polyps, large stones and chronic hemolytic anemia (Morris-Stiff 2023).
• A 2026 pooled analysis. Eight cohort studies with 25,924 participants gave 10% at 5 years, 19% at 10 years and 26% at 15 years (Alzoubi 2026).
• The Italian population study. Of 580 people without symptoms, 78.1% remained without symptoms over a mean of 8.7 years, 10.5% developed mild symptoms and 11.4% severe symptoms. Even so, 41.3% of all cholecystectomies in the study were done on people without symptoms (Festi 2010).
• A 24-year follow-up. The cholecystectomy rate was 6.2% and no adverse events could be ascertained. Unexpectedly, ultrasound found stones in only 28.1% of those re-examined (Schmidt 2011, silent stones).

The Japanese guideline's commentary gives rates for silent stones of 0.3% for acute cholecystitis, 0.2% for obstructive jaundice and 0.04 to 1.5% for pancreatitis (Fujita 2023).

Preventive surgery

A 1983 decision analysis, using the operation death rates of that time, calculated that preventive surgery slightly shortened survival: on average 4 days of life lost for a 30-year-old man and 18 days for a 50-year-old man (Ransohoff 1983). A 2023 systematic review concluded that most evidence points to the safety and feasibility of follow-up for silent stones, while the authors favored preventive surgery after heart transplantation and in people with very small stones (microlithiasis) and low surgical risk, on limited evidence (Alves 2023).

Gallbladder cancer

Cancer risk is part of the discussion about silent stones. Cohort data link the two: in 396,720 South Koreans, people with gallstones had a higher rate of gallbladder cancer death than people without them (hazard ratio 7.35, 95% confidence interval 2.60 to 20.8). This rested on only 20 such deaths among all participants, and cholecystectomy was not significantly linked with cancer death from the liver and bile ducts (Ryu 2016). The Japanese guideline reports the incidence of gallbladder cancer from silent stones as rare, at 0 to 0.5%. It names stones larger than 3 cm, polyps larger than 10 mm, porcelain gallbladder, thickened gallbladder walls and stone-filled gallbladders as high-risk groups (Fujita 2023). There is more on the Gallbladder Cancer page.

Limits of the Evidence

• Short follow-up in the largest trial. C-GALL's main result covers 18 months, with data to 24 months. Its authors state that costs, complications and benefits continue beyond this, and call for longer follow-up.
• Crossover in both directions. Roughly 3 in 10 people in the conservative arm and 7 in 10 in the surgery arm had surgery by 24 months, so the trial compares strategies rather than "operated" against "not operated".
• Long waits. Waiting times in C-GALL ran longer than planned because of limited health-service capacity and later the COVID-19 restrictions. The trial's economic report notes this might have favored conservative management in both groups (Hernández 2024).
• No blinding. Participants and surgeons knew the assignment, and pain is self-reported. A placebo effect from an operation cannot be separated in these designs.
• Selected participants. Only about one person in six assessed for C-GALL (434 of 2,667) and about 4 in 10 assessed for the first long trial (137 of 338) were randomized. Those willing to be randomized may differ from those with a firm preference.
• Small old trials. The long-term evidence rests on 201 people. The operations in them date from an earlier period.
• Choice of measure. C-GALL's general pain score and gallstone-specific questionnaire pointed in different directions, and SECURE's measure, pain-free or not, is a higher bar than "improved".
• Few data on subgroups. C-GALL found no difference in treatment effect by sex, age or ethnicity. Its participants were 79% women and 86% white, so it says less about other groups. The authors name identifying who benefits most from surgery as work still to be done.
• Different definitions. C-GALL's "uncomplicated" group included people referred after acute cholecystitis, and SECURE's did not, so the two trials studied overlapping but different people.

Who the Trials Left Out, and Signs Hospitals Treat as Urgent

None of the waiting data above applies to everyone with stones. C-GALL excluded people with stones in the common bile duct or evidence of past ones, a history of acute pancreatitis, obstructive jaundice, a gallbladder full of pus with sepsis, a perforated gallbladder, suspected gallbladder cancer or hemolytic disease, as well as people who were pregnant or medically unfit for surgery (Ahmed 2023).

These complications behave differently from uncomplicated colic. The signs hospitals treat as urgent are severe abdominal pain lasting several hours, abdominal pain with fever or chills, yellowing of the skin or eyes, dark urine or pale stools, and persistent vomiting. They can signal a blocked duct, infection or pancreatitis, and they are described on the main Gallstones page and the pages for acute cholecystitis, cholangitis and pancreatitis.

Key Research Papers

1. Innes K, Ahmed I, Hudson J, Hernández R, Gillies K, Bruce R, et al. Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones: the C-GALL RCT. Health Technology Assessment. 2024;28(26):1-151. PubMed PMID: 38943314
2. Fujita N, Yasuda I, Endo I, Isayama H, Iwashita T, Ueki T, et al. Evidence-based clinical practice guidelines for cholelithiasis 2021. Journal of Gastroenterology. 2023;58(9):801-833. PubMed PMID: 37452855
3. Fraquelli M, Casazza G, Conte D, Colli A. Non-steroid anti-inflammatory drugs for biliary colic. Cochrane Database of Systematic Reviews. 2016;9(9):CD006390. PubMed PMID: 27610712
4. Ahmed I, Hudson J, Innes K, Hernández R, Gillies K, Bruce R, et al. Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): pragmatic, multicentre randomised controlled trial. BMJ. 2023;383:e075383. PubMed PMID: 38084426
5. Thistle JL, Cleary PA, Lachin JM, Tyor MP, Hersh T. The natural history of cholelithiasis: the National Cooperative Gallstone Study. Annals of Internal Medicine. 1984;101(2):171-5. PubMed PMID: 6742647
6. Festi D, Reggiani ML, Attili AF, Loria P, Pazzi P, Scaioli E, et al. Natural history of gallstone disease: Expectant management or active treatment? Results from a population-based cohort study. Journal of Gastroenterology and Hepatology. 2010;25(4):719-24. PubMed PMID: 20492328
7. Shabanzadeh DM. Incidence of gallstone disease and complications. Current Opinion in Gastroenterology. 2018;34(2):81-89. PubMed PMID: 29256915
8. Vetrhus M, Søreide O, Solhaug JH, Nesvik I, Søndenaa K. Symptomatic, non-complicated gallbladder stone disease. Operation or observation? A randomized clinical study. Scandinavian Journal of Gastroenterology. 2002;37(7):834-9. PubMed PMID: 12190099
9. Schmidt M, Søndenaa K, Vetrhus M, Berhane T, Eide GE. A randomized controlled study of uncomplicated gallstone disease with a 14-year follow-up showed that operation was the preferred treatment. Digestive Surgery. 2011;28(4):270-6. PubMed PMID: 21757915
10. Vetrhus M, Søreide O, Nesvik I, Søndenaa K. Acute cholecystitis: delayed surgery or observation. A randomized clinical trial. Scandinavian Journal of Gastroenterology. 2003;38(9):985-90. PubMed PMID: 14531537
11. Schmidt M, Søndenaa K, Vetrhus M, Berhane T, Eide GE. Long-term follow-up of a randomized controlled trial of observation versus surgery for acute cholecystitis: non-operative management is an option in some patients. Scandinavian Journal of Gastroenterology. 2011;46(10):1257-62. PubMed PMID: 21736531
12. van Dijk AH, Wennmacker SZ, de Reuver PR, Latenstein CSS, Buyne O, Donkervoort SC, et al. Restrictive strategy versus usual care for cholecystectomy in patients with gallstones and abdominal pain (SECURE): a multicentre, randomised, parallel-arm, non-inferiority trial. Lancet. 2019;393(10188):2322-2330. PubMed PMID: 31036336
13. Comes DJ, Wennmacker SZ, Latenstein CSS, van der Bilt J, Buyne O, Donkervoort SC, et al. Restrictive Strategy vs Usual Care for Cholecystectomy in Patients With Abdominal Pain and Gallstones: 5-Year Follow-Up of the SECURE Randomized Clinical Trial. JAMA Surgery. 2024;159(11):1235-1243. PubMed PMID: 39167382
14. Brazzelli M, Cruickshank M, Kilonzo M, Ahmed I, Stewart F, McNamee P, et al. Systematic review of the clinical and cost effectiveness of cholecystectomy versus observation/conservative management for uncomplicated symptomatic gallstones or cholecystitis. Surgical Endoscopy. 2015;29(3):637-47. PubMed PMID: 25119541
15. Bagepally BS, Haridoss M, Sasidharan A, Jagadeesh KV, Oswal NK. Systematic review and meta-analysis of gallstone disease treatment outcomes in early cholecystectomy versus conservative management/delayed cholecystectomy. BMJ Open Gastroenterology. 2021;8(1):e000675. PubMed PMID: 34261757
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17. Gad MM, Ayad Q, Elgamal MM, Moubarak ES, Ziada AF, Beddor A, et al. Cholecystectomy versus conservative management for patients with uncomplicated symptomatic gallstones and cholecystitis: an updated systematic review and meta-analysis. BMC Surgery. 2026;26(1):381. PubMed PMID: 42265664
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PubMed Topic Searches

1. PubMed: gallstones, cholecystectomy versus conservative management
2. PubMed: pain and symptoms after cholecystectomy
3. PubMed: natural history of silent gallstones
4. PubMed: pain relief in biliary colic

Connections

• Gallstones — the main page on causes, symptoms and treatment
• Gallbladder Disease — the wider group of gallbladder conditions
• Acute Cholecystitis — when a stone blocks the gallbladder outlet
• Choledocholithiasis — stones in the common bile duct
• Cholangitis — infection of a blocked bile duct
• Pancreatitis — inflammation of the pancreas, which a stone can trigger
• Gallbladder Cancer — the cancer linked with long-standing stones
• Abdominal Pain — the wider list of causes

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