Cholecystitis

Overview

Cholecystitis is an inflammatory disorder of the gallbladder that may be calculous or acalculous. Acute acalculous cholecystitis (AAC) accounts for approximately 5–10% of acute cholecystitis in adults and may occur without gallstones, including in patients who are otherwise healthy when infection or systemic disease is present.^[8]D The pathophysiology is heterogeneous and includes obstruction, impaired gallbladder emptying, biliary stasis, ischemia, microbial invasion, immune dysregulation, and, in selected patients, systemic inflammatory or drug-associated injury.^[6]D[7]D

Obstruction, stasis, and ischemia

An obstructive mechanism is central to many cases of cholecystitis, whereas nonobstructive mechanisms are particularly important in AAC.^[6]D[7]D In critically ill patients, biliary stasis and ischemia may occur without a calculus; these processes can promote gallbladder inflammation and progression to severe disease.^[6]D The available evidence supports considering obstructive and nonobstructive AAC as related but distinguishable pathophysiologic pathways rather than assuming that all acalculous disease has a single cause.^[6]D[7]D

Altered gallbladder motility may amplify stasis. Gallbladder contraction is regulated by postprandial hormonal and neural mechanisms, including bile acids and glucagon-like peptides.^[10]D GLP-1 receptor agonists have been associated clinically with cholelithiasis, while GLP-2 receptor agonists have been associated with cholecystitis; reviews of these agents have focused on their effects on gallbladder motility.^[10]D These observations support impaired emptying as a potentially modifiable contributor, although the cited review does not establish a single causal mechanism for every drug-associated event.^[10]D

Gallbladder dysmotility is also linked to injury of gallbladder interstitial Cajal-like cells. In a guinea-pig model of acute cholecystitis induced by common bile duct ligation, neutrophils were investigated as a cause of changes in the morphology, density, distribution, and function of these cells.^[181] The study supports a mechanistic relationship between neutrophilic inflammation, interstitial Cajal-like-cell injury, and impaired gallbladder contractility, but it is experimental evidence and should not be assumed to quantify the same process in humans.^[181]

Infection and the biliary microbiome

Under normal conditions, bile is considered aseptic; in cholecystitis, bacterial colonization of bile has been reported in approximately 20–70% of cases and may represent a secondary complication of biliary stasis and inflammation.^[3] Bacterial infection has been implicated in 50–85% of acute cholecystitis presentations.^[116]C In a study examining patients with acute cholecystitis, gut microbiota were enriched in Akkermansia and the Enterobacter and Escherichia/Shigella groups compared with healthy controls, supporting a possible gut–biliary relationship.^[116]C

Culture-independent and culture-based observations indicate that the gallbladder may contain diverse microbial communities during disease. Live organisms resembling Corynebacterium urinapleomorphum, Staphylococcus saprophyticus, and Helicobacter pylori were isolated from the gallbladder of a patient with cholecystitis, demonstrating that viable organisms—not only bacterial DNA—can be present in selected cases.^[15]C However, metagenomic sequencing of bile and stones from cholecystectomy patients found that bacterial diversity did not vary according to surgical pathology, cautioning against interpreting the mere presence of a microbiome as proof of causation.^[119]D

Systemic and infectious causes of acalculous disease

Specific infections can produce cholecystitis without gallstones. A systematic review identified 27 cases of Coxiella burnetii-associated cholecystitis, including 3 children, and reported that all cases occurred during acute Q fever.^[1] Gallbladder PCR was positive in 2 of 2 tested cases, whereas immunohistochemistry was negative in all cases, suggesting that molecular detection may be more informative than tissue immunostaining in this uncommon infection.^[1] Recurrent pancreatitis and chronic cholecystitis were each reported as a long-term complication in 1 patient (3.7%).^[1] The same review noted a dose-dependent association between Q fever and IgG anticardiolipin, although the clinical significance and management implications remain incompletely defined.^[1]

COVID-19 has also been reported in association with AAC. A proposed mechanism is direct or indirect gastrointestinal involvement because SARS-CoV-2 enters cells through ACE2, which is expressed in gastrointestinal epithelial tissue.^[8]D The cited narrative review supports infection as a possible trigger but does not establish that ACE2-mediated epithelial infection is sufficient to cause cholecystitis.^[8]D

Critical illness, medications, and vascular factors

Critical illness may predispose to AAC through combinations of biliary stasis, ischemia, systemic inflammation, and infection; unexplained sepsis should therefore raise consideration of AAC even when imaging shows no gallstones.^[6]D[7]D Alemtuzumab has been identified as a potential safety risk for AAC in patients with relapsing-remitting multiple sclerosis: eight pharmacovigilance and literature cases were identified, with four assessed as probable and four as possible, and seven occurring during or shortly after alemtuzumab exposure.^[11]D These reports demonstrate a temporal and pharmacovigilance signal rather than definitive proof of mechanism or causality.^[11]D

Vascular mechanisms are also relevant in portal biliopathy. In patients with extrahepatic portal-vein obstruction and portal cavernoma, biliary abnormalities may result from extrinsic compression by collateral veins and/or ischemic damage caused by altered biliary vascularization; symptomatic disease can include cholecystitis.^[2]

Immune and metabolic modifiers

Host immune status may influence susceptibility and outcome. In Wilson disease, patients had a higher incidence of cholecystitis and poorer prognosis, while single-cell analysis identified altered innate immune composition and function, with natural-killer-cell exhaustion proposed as a fundamental factor.^[20]D These findings are disease-specific and should not be generalized to all cholecystitis.^[20]D IgG4-related disease is an immune-mediated fibroinflammatory disorder that commonly involves the pancreas and bile ducts and may produce gastrointestinal and biliary manifestations resembling other inflammatory conditions.^[9]D

Chronic inflammatory states may also interact with gallbladder neoplasia. VEGF-A expression has been evaluated in advanced gallbladder carcinoma and chronic cholecystitis, while single-cell analysis has demonstrated distinct immune microenvironments across normal gallbladder tissue, cholecystitis, and gallbladder cancer.^[5][118]D These studies support biological continuity between inflammation, angiogenesis, and tissue remodeling, but they do not establish that ordinary acute cholecystitis directly causes cancer.^[5][118]D

Clinical implications

The pathophysiology is therefore best viewed as a network: impaired emptying and stasis can facilitate ischemia and bacterial colonization; infection and neutrophilic inflammation can worsen dysmotility; systemic illness, vascular abnormalities, medications, and immune or metabolic disorders can shift the balance toward AAC.^{[3][6]D[7]D[10]D[181]} Seasonal variation has also been investigated using cholecystectomy data spanning three decades, indicating that environmental influences may be relevant, although the cited study information does not provide a mechanism or definitive seasonal explanation.^[115]

History

The history should establish the time course, character, and severity of pain; associated gastrointestinal symptoms; systemic features; previous biliary episodes; relevant comorbidity; medication exposure; and prior biliary or hepatic procedures. Acute cholecystitis commonly presents with right-upper-quadrant pain or tenderness, but no single historical or physical finding reliably confirms or excludes the diagnosis. ^[134][135] Record symptom onset and progression because early sonographic abnormalities may precede gallbladder-wall changes, which can develop later during the clinical course. ^[139]

Ask specifically about fever, vomiting, jaundice, rigors, anorexia, and inability to tolerate oral intake, while documenting whether pain is persistent or recurrent. These features help distinguish an acute episode from chronic or recurrent disease, although the available validation study found that diagnosis is best supported by combining symptoms, examination findings, and point-of-care ultrasonography rather than relying on one feature alone. ^[135]

Assess for previous episodes managed non-operatively. Recurrence after conservative treatment is clinically important, and low skeletal-muscle mass together with high visceral adiposity was associated with recurrent acute cholecystitis in a propensity-score-matched cohort. ^[23] Document body habitus and functional reserve, particularly when considering delayed or nonoperative management. ^[23] In patients with suspected difficult laparoscopic cholecystectomy, a body-mass index greater than 30 kg/m² was an identified preoperative clinical risk factor; CT findings were also evaluated as predictors of operative difficulty. ^[140]C

Medication and procedural history should include anticoagulants, antiplatelet agents, recent surgery, biliary instrumentation, endoscopic stenting, and hepatic arterial therapies. Hemorrhagic cholecystitis is uncommon, may be difficult to recognize before operation, and has been associated with anticoagulation. ^[141]C Cholecystitis may also occur after yttrium-90 radioembolization, particularly when the gallbladder is at risk of embolization through the cystic artery; the relevant history should therefore include recent radioembolization and its timing. ^[144]C

Clarify prior imaging and interventions, including known gallstones, choledocholithiasis, Mirizzi syndrome, biliary stents, percutaneous cholecystostomy, and previous cholecystectomy attempts. Patients with choledocholithiasis, Mirizzi syndrome, or biliary stents were excluded from one randomized drain study, so its findings should not be extrapolated to these groups. ^[22] In high-risk patients undergoing percutaneous cholecystostomy, pain and procedural tolerance may be particularly relevant; an erector spinae plane block reduced procedural and post-procedural pain compared with conscious sedation in a retrospective cohort. ^[137]

Physical examination

Perform a focused general, abdominal, and systemic examination. Record temperature, heart rate, blood pressure, respiratory rate, oxygen saturation, mental status, hydration, and overall appearance because these findings help identify systemic illness and potential severe disease. Examine for right-upper-quadrant tenderness, guarding, rebound, abdominal distension, and a palpable mass, and assess for jaundice and signs of generalized peritonitis. Right-upper-quadrant tenderness was associated with a positive hepatobiliary scintigraphy result in a retrospective study, although clinical findings alone remain insufficient for diagnosis. ^[134][135]

Document a reproducible gallbladder-provocation finding, such as pain or inspiratory arrest during right-upper-quadrant palpation, but interpret it with the remainder of the examination and imaging. The validated bedside sonographic score combined historical symptoms, physical signs, and point-of-care ultrasound because no isolated finding could rule in or rule out acute cholecystitis. ^[135]

Look for features suggesting complications or alternative diagnoses: marked toxicity, persistent tachycardia or hypotension, peritoneal irritation, jaundice, gastrointestinal bleeding, or disproportionate pain. Hemorrhagic cholecystitis may have variable clinical presentation and characteristic blood products on ultrasound or CT, but the condition can be diagnosed only after integrating clinical, laboratory, imaging, and sometimes histopathological findings. ^[141]C[143]C

Bedside imaging adjuncts

Point-of-care ultrasound should be integrated into the bedside assessment. Early findings include gallstones and gallbladder tenderness, whereas wall thickening and pericholecystic fluid may appear later; absence of these secondary wall changes early in the presentation does not necessarily exclude acute cholecystitis. ^[139] Peak systolic cystic-artery velocity of ≥40 cm/s has been proposed as a highly specific sonographic marker, but its diagnostic performance was evaluated retrospectively and should be interpreted with other ultrasound and clinical findings. ^[28]D

If clinical assessment remains indeterminate, hepatobiliary scintigraphy may assist diagnosis, although it has limitations. In one retrospective model, male sex, increasing age, and right-upper-quadrant tenderness were associated with positive scans. ^[134]

Atypical and special presentations

Consider xanthogranulomatous cholecystitis when chronic inflammatory disease produces an unusual mass-like or severe presentation; it is benign but may be difficult to distinguish from gallbladder cancer before surgery and frequently requires operative management. ^[132] In children, eosinophilic or lymphoeosinophilic cholecystitis is a rare histopathological diagnosis; one pediatric series defined eosinophilic cholecystitis as more than 90% eosinophils among inflammatory cells and lymphoeosinophilic cholecystitis as 50–90%. ^[26]C

Emphysematous cholecystitis data in the supplied literature concern dogs rather than humans and should not be used to define human history or examination findings. In that veterinary series, vomiting was reported in 23/35 (66%) dogs. ^[133] Social context may also matter: a retrospective study explored associations between food-desert residence and severity or outcomes among emergency general-surgery patients with acute biliary disease, but this does not establish an individual diagnostic sign. ^[29]D

Pain should be quantified at baseline and on reassessment using a consistent numerical or visual scale. In patients undergoing laparoscopic cholecystectomy for chronic calculous cholecystitis, ultrasound-guided intercostal nerve block and subcostal transversus abdominis plane block were directly compared for postoperative analgesia, supporting structured perioperative pain assessment rather than reliance on narrative description alone. ^[21] Drain placement after laparoscopic cholecystectomy was studied in mild and moderate acute calculous cholecystitis, but patients with complications, partial cholecystectomy, malignancy, choledocholithiasis, Mirizzi syndrome, or biliary stents were excluded. ^[22]

Overview

Acute cholecystitis encompasses a spectrum from uncomplicated gallbladder inflammation to necrotizing, infectious, ischemic, and chronic inflammatory variants. The most clinically consequential progression is gangrenous cholecystitis (GC), which is associated with gallbladder-wall necrosis, perforation, sepsis, and increased mortality. ^[182][183] GC is defined histopathologically by focal or diffuse necrosis of the gallbladder wall, and its clinical manifestations may be heterogeneous and nonspecific before surgery. ^[37][183]

Gangrenous cholecystitis

GC is a severe pathological subtype of acute cholecystitis requiring rapid recognition because necrosis may progress to perforation, localized or diffuse peritonitis, and postoperative morbidity or mortality. ^{[182][183][184]D} Retrospective cohorts have evaluated demographic, clinical, laboratory, and imaging predictors of GC, while newer studies have assessed inflammatory indices—including AISI, SII, and SIRI—as potential predictors of gangrenous evolution in acute calculous cholecystitis. ^[37][152]

Computed tomography (CT) is used to assess complicated cholecystitis and identify features associated with histopathologically confirmed GC; however, the diagnostic value of individual CT signs remains variable and is the subject of systematic review and meta-analysis. ^[182] Multicenter retrospective studies have also investigated artificial-intelligence approaches using plain and contrast-enhanced CT, including a self-supervised model trained on 7,368 CT images from 1,228 patients, to improve preoperative identification of GC. ^[34] Explainable machine-learning models using routine clinical and laboratory variables have been developed and externally or temporally validated, including studies with training, internal-testing, and external-validation cohorts. ^{[36][183][184]D} These models are intended for risk stratification and decision support, but their retrospective design means that they do not replace clinical assessment, radiological interpretation, or operative and pathological confirmation. ^{[34][36][183][184]D}

Emphysematous cholecystitis

Emphysematous cholecystitis (EC) is a rare, severe variant characterized in the veterinary literature as an acute cholecystitis subtype diagnosed by ultrasonography or CT. ^[133] In a retrospective series of 35 dogs, common presenting signs included vomiting in 23/35 (66%); the study also evaluated laboratory findings, ultrasonographic features, bile cytology, bacterial culture and susceptibility, histopathology, treatment, and outcomes. ^[133] Human EC management has been examined in a 10-year single-center retrospective study comparing percutaneous cholecystostomy, cholecystectomy, and medical management, with outcomes including hospital stay, complications, conversion after drainage, and overall mortality. ^[147]C In medically vulnerable patients, percutaneous cholecystostomy is also used for acute cholecystitis when early cholecystectomy is considered unsuitable; predictors of in-hospital mortality and radiological disease burden after the procedure have been investigated. ^[148] Diabetes is a clinically relevant background condition because hyperglycemia impairs neutrophil chemotaxis, oxidative burst, complement activation, tissue perfusion, and barrier integrity, increasing susceptibility to severe infection generally. ^[35]D

Xanthogranulomatous and plasma-cell-rich variants

Xanthogranulomatous cholecystitis (XGC) is an uncommon chronic inflammatory variant characterized by marked fibrosis and infiltration by macrophages and foamy histiocytes. ^[49]D[151]C It can produce gallbladder-wall thickening and inflammatory adhesions that mimic gallbladder carcinoma, making preoperative differentiation difficult. ^{[38][49]D[50]D} In a multicenter study of 1,246 patients—554 with XGC and 692 with gallbladder cancer—the LIDGAX machine-learning model used clinical, imaging, and laboratory variables and achieved an AUC of 0.94 internally and 0.88 on external testing. ^[50]D CT, MRI, and 18F-FDG PET/CT may all show overlapping abnormalities; a five-patient report specifically examined PET/CT in patients with XGC and elevated CA19-9. ^[49]D Dense inflammation and adhesions increase operative difficulty and the likelihood of conversion from laparoscopic to open surgery in XGC. ^[38]

Lymphoplasmacytic cholecystitis and IgG4-related cholecystitis are plasma-cell-rich inflammatory patterns that may overlap histologically. ^[151]C Lymphoplasmacytic cholecystitis has historically been associated with primary sclerosing cholangitis and autoimmune pancreatitis, whereas IgG4-related cholecystitis represents gallbladder involvement in IgG4-related disease; approximately 25–32% of patients with autoimmune pancreatitis demonstrate concomitant IgG4-related cholecystitis. ^[151]C

Gallbladder torsion

Gallbladder torsion is a rare, life-threatening ischemic emergency that disproportionately affects older adults and may be obscured by multimorbidity or age-related anatomical changes. ^[154]D Its presentation can mimic acute cholecystitis; a reported 84-year-old man developed sudden severe right-upper-quadrant pain, nausea, and vomiting, with CT showing a markedly distended gallbladder, gallstones, and pericholecystic fluid. ^[154]D Torsion may remain uncertain preoperatively and be confirmed only during laparoscopic exploration. ^[154]D

Operative severity and evolving assessment

Clinical severity may also be reflected by operative grading: a study of symptomatic cholelithiasis used a Parkland Grading Scale of ≥3 to define increased surgical severity and examined patient-related and health-system factors, including the 48-hour interval to surgery. ^[48]D Conversion from laparoscopic to open cholecystectomy remains an important marker of technical difficulty; a large cohort developed a predictive nomogram, while another study evaluated conversion risk specifically in XGC. ^[149][38] Contemporary acute-care studies have compared robotic and laparoscopic cholecystectomy, and newer observational work has assessed single-incision techniques and their learning curves, but these approaches do not alter the pathological definitions of the clinical variants described above. ^[128]C[150]

Scope of the updated evidence

The available evidence emphasizes imaging-based characterization, severity assessment, and selection of drainage strategies rather than establishing a new diagnostic definition for acute cholecystitis. The cited studies do not provide a validated replacement for clinical assessment, laboratory testing, and targeted biliary imaging; therefore, diagnosis should be documented together with disease severity, complications, surgical fitness, and suspected biliary obstruction. ^[156][160]

Initial assessment and severity stratification

The workup should identify whether acute cholecystitis is uncomplicated or associated with perforation, emphysematous change, systemic deterioration, cirrhosis, malignancy, or high operative risk. The Tokyo classification was evaluated as a prognostic framework, but one retrospective study noted that it primarily identifies risk in Tokyo grade 3 disease, whereas mortality also occurs among patients with lower grades. ^[160] Hypoglycemia was investigated as an additional prognostic marker in acute calculous cholecystitis, because it may identify patients at increased risk even when the Tokyo grade is not the highest. ^[160]

Clinical and laboratory documentation should therefore include comorbidity burden, physiological deterioration, operative-risk assessment, and glucose concentration. Hypoglycemia should not be treated as a diagnostic criterion for cholecystitis, but it may be a warning sign requiring escalation of monitoring and management. ^[160]

Imaging workup

Imaging should establish gallbladder inflammation and evaluate for complications that alter treatment. The cited artificial-intelligence meta-analysis included diagnostic-accuracy studies of AI-assisted imaging for abdominal infections, including cholecystitis, appendicitis, and pneumoperitoneum. ^[156] Its inclusion supports AI as an investigational or adjunctive imaging tool, but the available evidence summary does not establish a specific algorithm, modality, threshold, or sufficiently validated performance standard for routine diagnosis. ^[156]

Cross-sectional imaging is particularly relevant when perforation, emphysematous disease, sarcopenia, or alternative intra-abdominal pathology is suspected. Studies of perforated cholecystitis specifically classified contained perforation as Niemeier type 2 and examined whether endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) could be performed in this setting. ^[158] Retrospective and prospective cohorts also evaluated EUS-GBD in patients with gallbladder perforation, a condition traditionally considered a contraindication to endoscopic treatment. ^[129]C[158] These reports suggest that imaging should define whether the perforation is contained and whether a safe apposition window exists, but they do not establish EUS-GBD as standard diagnostic management for all perforations. ^[129]C[158]

Computed tomography can also provide prognostic information beyond anatomic diagnosis. In a radiological study of gallbladder perforation, skeletal muscle index, intramuscular adipose tissue content, and the visceral-to-subcutaneous fat ratio were measured at the L3 vertebral level to investigate associations with perforation subtype, treatment selection, and mortality. ^[164] These body-composition measurements remain risk-stratification variables rather than diagnostic criteria. ^[164]

Emphysematous cholecystitis requires recognition of intraluminal or mural gas and prompt assessment of disease severity. A human retrospective study compared percutaneous cholecystostomy, cholecystectomy, and medical management over 10 years, while a veterinary case series described ultrasonographic and computed-tomographic diagnosis, bile cytology, culture, susceptibility testing, and histopathology. ^[147]C[133] The veterinary findings should not be extrapolated directly to humans, but they illustrate the diagnostic value of imaging combined with microbiological and pathological evaluation when emphysematous disease is suspected. ^[133]

Evaluation for associated biliary disease

The diagnostic workup should assess for common bile duct or residual biliary stones when clinically indicated. A cohort evaluating cystic-duct exploration during laparoscopic cholecystectomy was designed around the problem of residual cystic-duct and common bile duct stones after conventional surgery, although it does not establish a preoperative diagnostic test. ^[179]C The presence of suspected ductal stones should be recorded separately from gallbladder inflammation because it may alter endoscopic, operative, or drainage planning. ^[179]C

Potential contributing or modifying factors should also be documented. A large retrospective cohort examined gallstone disease, cholecystitis, pancreatitis, ERCP, and cholecystectomy among patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists; this evidence concerns risk associations rather than diagnostic criteria. ^[161]

Workup when surgery is high risk

For patients considered unfit for immediate surgery, diagnostic workup should define gallbladder accessibility, perforation status, cirrhosis, malignancy, and the feasibility of drainage. Comparative evidence includes EUS-GBD with lumen-apposing metal stents (LAMS), percutaneous transhepatic gallbladder drainage (PTGBD), and endoscopic transpapillary drainage. ^[186][66] A 2026 systematic review included 712 patients across six comparative studies of EUS-GBD and PTGBD, while a multicenter cohort specifically compared EUS-GBD and percutaneous drainage in high-risk patients with cirrhosis. ^[186][159]C

EUS-GBD practice is heterogeneous across Western centers, and outcomes have been evaluated according to LAMS-related adverse events, recurrent biliary disease, recurrent acute cholecystitis, and mortality. ^[157]C Contained or other perforation should be reported explicitly because available cohorts were selected for this difficult subgroup and do not justify assuming that EUS-GBD is safe in every perforation. ^[129]C[158]

Finally, the workup should document whether drainage is intended as a bridge to interval cholecystectomy or definitive treatment. Studies of early versus delayed cholecystectomy after percutaneous drainage, operative outcomes after different drainage routes, and long-term PTGBD without cholecystectomy show that timing, recurrence risk, catheter/device complications, and later surgery are clinically relevant downstream considerations. ^{[123][66][187]} These studies inform planning after diagnosis but do not replace the initial diagnostic assessment.

Initial supportive management

Management should combine resuscitation, analgesia, antiemetics, correction of fluid and electrolyte abnormalities, and early assessment of operative risk and disease severity. Definitive treatment for most adults with acute cholecystitis remains laparoscopic cholecystectomy (LC), and randomised-trial evidence compares index-admission surgery with delayed surgery after conservative treatment of at least 4 weeks. ^[122] A 2026 randomised-trial meta-analysis specifically separated timing according to symptom onset from timing according to hospital admission, addressing the limitations created by inconsistent definitions of “early” surgery. ^[122]

For mild-to-moderate acute cholecystitis treated by acute cholecystectomy, routine perioperative antibiotics have not demonstrated a statistically significant reduction in infectious complications: infection occurred in 9% versus 12% without antibiotics, with pooled OR 0.78 (95% CI 0.58–1.07; eight studies; I²=0%). ^[124] Surgical-site infection likewise showed no significant antibiotic effect, occurring in 5% versus 8% in the reported analysis. ^[124] These findings support avoiding indiscriminate prolonged antibiotic therapy after source control, while antibiotic decisions should remain individualised according to severity, systemic infection, perforation, immunosuppression, bacteremia, and adequacy of source control. ^[124]

Timing of cholecystectomy

Early LC during the index admission is supported by contemporary randomised evidence as the principal comparator to delayed LC after conservative management. ^[122] In a 100-patient randomised trial, early LC performed within 72 hours had a longer mean operative time than interval LC performed after 6–8 weeks of conservative management (95.47 versus 73.69 minutes; P=0.001), but a shorter total hospital stay (6.50 versus 10.80 days; P=0.009). ^[126]C A multicentre international retrospective study evaluated whether symptom duration beyond 7 days should itself preclude early LC, because the traditional seven-day threshold is not supported by definitive evidence. ^[127] Early LC has also been evaluated in high-risk patients classified using Tokyo Guidelines 2018 criteria; in 126 patients, there was no in-hospital mortality, and major complications occurred in 5.6%, without a significant difference between high- and low-risk groups (6.0% versus 5.1%; P=0.467). ^[130]C

Drainage when surgery is unsuitable

Percutaneous cholecystostomy (PC) or percutaneous transhepatic gallbladder drainage may be used as temporising treatment in high-risk patients who do not respond to conservative management. ^[123] The optimal interval before definitive cholecystectomy remains uncertain. A systematic review of 12 retrospective studies evaluated early versus late interval cholecystectomy after PC, using one-month and eight-week cut-offs and assessing perioperative, operative, length-of-stay, and catheter-related outcomes. ^[123] A multicentre cohort likewise assessed major complications, defined as Clavien–Dindo grade ≥III, after cholecystectomy following PC. ^[91] After PTGBD, a 2026 restricted-cubic-spline study analysed the interval continuously rather than relying solely on arbitrary timing categories and focused on its relationship with operative technical difficulty and bailout surgery. ^[131]

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is described as a drainage option for high-surgical-risk patients with acute cholecystitis. ^[129]C A retrospective series specifically evaluated EUS-GBD using electrocautery-enhanced lumen-apposing metal stents in patients with gallbladder perforation, a condition often regarded as a contraindication to endoscopic treatment, and assessed technical success, clinical success, and adverse events. ^[129]C

Preventing and managing operative complications

When inflammation or distorted anatomy prevents safe achievement of the critical view of safety, subtotal cholecystectomy is a guideline-supported bailout rather than unsafe dissection toward the common bile duct. ^[58] A contemporary systematic review and meta-analysis evaluated subtotal versus total cholecystectomy and compared fenestrating with reconstituting subtotal techniques, examining their safety–effectiveness trade-offs and patient factors associated with risk. ^[58] Bailout procedures include deviations from standard LC such as subtotal cholecystectomy; the multicentre BOLAC study evaluated their incidence, risk factors, and postoperative outcomes in acute calculous cholecystitis. ^[185]

Indocyanine-green fluorescence cholangiography may improve visualisation of biliary anatomy and was evaluated against conventional white-light LC in a propensity-score-matched acute-cholecystitis cohort, with particular attention to failed critical view of safety and the need for bailout procedures. ^[125] Ultrasonic and electrocautery dissection were compared in an updated systematic review of acute cholecystitis LC, including operative time, hospital stay, blood loss, and intraoperative and postoperative complications; the available evidence does not establish a universal replacement of one energy modality by the other. ^[62]

If a residual gallbladder remnant causes recurrent symptoms after subtotal cholecystectomy, completion cholecystectomy may be considered. A meta-analysis of 48 studies involving 1,225 patients found symptomatic cholelithiasis and acute cholecystitis among the common indications; the median interval to completion surgery was 47 months, laparoscopy was used in 75.6%, open surgery in 15.6%, and symptom resolution was achieved in 92.5%. ^[60]

Analgesia and approach selection

Postoperative pain should be treated with multimodal analgesia, combining non-opioid agents with rescue opioids when required. In a randomised trial of LC, ultrasound-guided T7–11 intercostal nerve block and subcostal transversus abdominis plane block, each using 40 mL of 0.3% ropivacaine, were compared for 24-hour tramadol use, pain scores, time to rescue analgesia, and satisfaction. ^[21]

Robotic LC may offer improved visualisation and instrument dexterity, but comparative evidence in emergency cholecystitis remains observational and heterogeneous, with no randomised trials. ^[59] A 2026 acute-care cohort compared 107 robotic with 215 laparoscopic procedures, while another study reported equivalent outcomes across acute-cholecystitis severity grades; these data do not establish robotic surgery as superior. ^[128]C[162] Evidence concerning a 5-mm umbilical port derives from 240 obese patients with chronic, not acute, calculous cholecystitis and therefore should not be directly extrapolated to acute disease. ^[65]

Overall prognosis

Acute cholecystitis is usually treatable, but prognosis depends on disease severity, physiological reserve, comorbidity, and whether definitive source control is achieved. Reported mortality in acute calculous cholecystitis is approximately 0.6–6.0%, although risk is concentrated among patients with severe disease and major comorbidity.^[160] In a contemporary cohort of high-risk patients undergoing early laparoscopic cholecystectomy, there was no in-hospital mortality and major complications (Clavien–Dindo grade ≥IIIa) occurred in 5.6%; grade 3 cholecystitis independently predicted overall complications.^[130]C These findings support individualized early surgery in selected high-risk patients rather than assuming that high-risk classification alone precludes operative treatment.^[130]C

Hypoglycaemia may identify patients at increased risk even when conventional severity categories are less advanced. A retrospective study specifically evaluated hypoglycaemia as a predictor of mortality in acute calculous cholecystitis because existing Tokyo classification-based prediction is most informative in grade 3 disease; the study’s reported objective was to assess whether hypoglycaemia independently predicts death.^[160] The finding should be interpreted as prognostic association rather than proof that correcting hypoglycaemia alone changes outcomes.^[160]

Early versus interval cholecystectomy

Early laparoscopic cholecystectomy generally reduces the total treatment pathway by avoiding a second admission and prolonged conservative management. In a randomized trial of 100 patients, surgery within 72 hours produced a shorter total hospital stay than interval surgery after 6–8 weeks of conservative treatment (6.50 versus 10.80 days), but the early-operation group had a longer mean operative time (95.47 versus 73.69 minutes).^[126]C The trial was small, and its findings should be integrated with anatomical difficulty, anaesthetic risk, local expertise, and the feasibility of safe dissection.^[126]C

For patients initially managed with percutaneous cholecystostomy, the optimal interval before cholecystectomy remains uncertain. A 2026 systematic review and meta-analysis identified 12 retrospective studies evaluating early versus late interval cholecystectomy after drainage, with perioperative complications as the primary outcome and operative time, blood loss, postoperative length of stay, and catheter-related complications as secondary outcomes.^[123] Because this evidence is retrospective, timing should be individualized rather than determined by a universally established interval threshold.^[123] A separate meta-analysis compared interval surgery after percutaneous, EUS-guided, and endoscopic transpapillary drainage, recognizing that each drainage route may alter subsequent operative anatomy and outcomes.^[66]

Subtotal and completion cholecystectomy

When inflammation or distorted anatomy prevents achievement of the critical view of safety, subtotal cholecystectomy is a guideline-supported bailout intended to reduce major bile duct injury.^[58] The contemporary systematic review by the Society for Surgery of the Alimentary Tract assessed single-arm subtotal outcomes, subtotal versus total cholecystectomy, and fenestrating versus reconstituting techniques; the evidence base should therefore be used to balance immediate safety against the possibility of later biliary or remnant-related problems.^[58] In a multicentre study, bailout procedures—including subtotal cholecystectomy—were evaluated for incidence, determinants, and postoperative consequences in acute calculous cholecystitis.^[185]

Long-term durability is not guaranteed after subtotal surgery. A population-based cohort of 2,682 patients who underwent subtotal cholecystectomy for acute cholecystitis examined cumulative remnant cholecystitis, subsequent cholecystectomy, and completion surgery over longitudinal follow-up.^[163] Patients with persistent or recurrent biliary symptoms may require completion cholecystectomy, which is technically challenging because of altered anatomy and adhesions.^[60] In a meta-analysis of 1,225 patients, the common indications for completion surgery were symptomatic cholelithiasis (55.8%) and acute cholecystitis (19.8%); the median interval from the initial operation to completion surgery was 47 months, laparoscopy was used in 75.6%, and symptom resolution was reported in 92.5%.^[60]

Drainage without definitive surgery

For patients who remain unsuitable for cholecystectomy, drainage may provide source control but does not eliminate the risk of recurrent biliary disease. A network meta-analysis of 2,254 patients from 17 trials compared percutaneous, EUS-guided, and endoscopic transpapillary gallbladder drainage in high-surgical-risk patients, evaluating technical success, clinical success, and adverse events.^[67] The analysis found that percutaneous and EUS-guided drainage had higher technical success than endoscopic transpapillary drainage.^[67] Western multicentre data on EUS-guided drainage with lumen-apposing metal stents evaluated stent-related adverse events, recurrent biliary disease, recurrent acute cholecystitis, and all-cause mortality, while also demonstrating heterogeneity in practice between centres.^[157]C

In cirrhotic patients unfit for surgery, a comparative multicentre study assessed EUS-guided drainage versus percutaneous drainage, including long-term biliary, catheter-related, and device-related adverse events.^[159]C EUS-guided drainage has also been studied in selected high-risk patients with gallbladder perforation, a condition traditionally considered a contraindication to endoscopic treatment.^[129]C These data are observational and specialized; perforation requires multidisciplinary assessment and cannot be generalized to routine acute cholecystitis.^[129]C

Long-term nonoperative management after percutaneous drainage remains an option for selected patients, but recurrence is clinically important. A retrospective cohort of 161 patients treated with percutaneous transhepatic drainage, catheter removal, and no subsequent cholecystectomy assessed recurrence-free survival over a median follow-up of 40.3 months and examined comorbidity and stone removal as potential determinants.^[187] In emphysematous cholecystitis, a rare severe form, a 10-year single-centre study compared percutaneous drainage, cholecystectomy, and medical management, including length of stay, complications, later conversion to surgery, and overall survival.^[147]C These findings should not be extrapolated to uncomplicated disease.

Robotic surgery and residual stones

Robotic emergency cholecystectomy may improve visualization and instrument dexterity, but comparative evidence remains observational and heterogeneous; a systematic review found no randomized emergency-setting trials comparing robotic with laparoscopic surgery.^[59] Retrospective acute-care cohorts have reported comparative outcomes across robotic and laparoscopic approaches, including outcomes across different severity grades, but equivalence or superiority should not be assumed because of selection and centre effects.^[128]C[162] Finally, a retrospective cohort evaluating cystic-duct exploration during laparoscopic cholecystectomy examined whether the technique reduces mid- to long-term residual biliary stones; its findings are procedure-specific and do not establish routine exploration for all patients.^[179]C

Early versus delayed laparoscopic cholecystectomy

Yadav and colleagues conducted a prospective randomized clinical trial comparing early and delayed laparoscopic cholecystectomy in patients with acute calculous cholecystitis. ^[99] The study was performed in the Department of Surgery at BP Koirala Institute of Health Sciences between February 2003 and June 2004. ^[99] Its prespecified aims were to compare intraoperative and postoperative complications between treatment strategies and to determine the frequency and reasons for conversion to open surgery. ^[99]

The report states that 145 cases were assessed and that 50 patients were included in the study. ^[99] Among the included patients, 12 (24%) were male and 38 (76%) were female, giving a male-to-female ratio of 1:3.16. ^[99] The mean age was 42.68 years (standard deviation [SD], 14.18) in the early-treatment group and 40.26 years (SD, 11.62) in the delayed-treatment group. ^[99] The abstract also distinguishes an early successful group from an early converted group when describing symptom duration, although the supplied abstract does not provide the full corresponding results. ^[99]

This trial is classified as evidence level 1b in the cited evidence set. ^[99] Its design directly addressed whether laparoscopic surgery should be undertaken early during the acute episode or deferred, while also evaluating conversion and perioperative complications. ^[99] However, the supplied abstract excerpt does not report the complete comparative complication rates, conversion rates, reasons for conversion, length of stay, or other numerical outcome data; these endpoints therefore cannot be quantified from the available reference information. ^[99]

High-risk patients: surgery versus percutaneous drainage

The CHOCOLATE study was designed to address management of acute calculous cholecystitis in patients considered high risk for surgery. ^[100]D The study protocol states that laparoscopic cholecystectomy in this population may be associated with substantial morbidity and mortality, whereas percutaneous cholecystostomy may provide an alternative treatment approach. ^[100]D The protocol also identifies a lack of adequate evidence-based guidance as the rationale for undertaking the trial. ^[100]D

CHOCOLATE was planned as a randomized, parallel-group, superiority, multicenter trial comparing laparoscopic cholecystectomy with percutaneous cholecystostomy. ^[100]D High-risk eligibility was defined by an APACHE-II score of 7–14 in patients with acute calculous cholecystitis. ^[100]D The protocol planned enrollment of 284 patients over 2 years from 30 high-volume teaching hospitals. ^[100]D

The primary endpoint was a composite measure of major complications occurring within 3 months after randomization. ^[100]D The protocol therefore framed the clinical question around comparative short-term safety and effectiveness rather than treating percutaneous cholecystostomy as an automatically equivalent substitute for cholecystectomy. ^[100]D Because the cited publication is a study protocol, it does not provide the trial’s eventual comparative results, complication frequencies, mortality findings, recurrence outcomes, or subsequent need for definitive gallbladder treatment. ^[100]D

Evidence synthesis

Together, these references identify two important decision points in acute calculous cholecystitis: the timing of laparoscopic cholecystectomy in the general surgical population and the choice between laparoscopic cholecystectomy and percutaneous cholecystostomy in selected high-risk patients. ^[99][100]D The randomized trial by Yadav et al. provides direct comparative evidence for early versus delayed laparoscopic treatment, whereas the CHOCOLATE publication supplied here establishes the design and clinical rationale of a randomized comparison in patients with APACHE-II 7–14, but not its outcome results. ^[99][100]D Accordingly, the available evidence supports recognizing early-versus-delayed surgery and high-risk source-control strategy as separate clinical questions, with the numerical conclusions limited to the data explicitly reported in these references. ^[99][100]D

Older adults and medically high-risk patients

Management should be individualized according to physiologic reserve, comorbidity burden, disease severity, operative risk, and local expertise. In a statewide analysis of 8,112 emergency admissions across 40 hospitals, 990 patients (12%) underwent percutaneous cholecystostomy (PCT); age and clinical severity were the strongest factors associated with PCT use, although sex and insurance status also influenced treatment selection.^[168] These findings indicate substantial variation in drainage use and suggest that institutional practice and nonclinical characteristics may affect access to a procedure generally reserved for patients considered medically high risk.^[168]

Early laparoscopic cholecystectomy (LC) may remain feasible in selected high-risk patients. In a retrospective study of 126 patients treated with early LC and classified using Tokyo Guidelines 2018 (TG18), 67 were categorized as high risk and 59 as low risk; there were no in-hospital deaths, and major complications (Clavien–Dindo grade ≥IIIa) occurred in 5.6% overall, without a significant difference between high- and low-risk groups.^[130]C Grade 3 cholecystitis was independently associated with overall complications, with an adjusted odds ratio of 3.12 (95% CI 1.03–21.47).^[130]C These results support assessment for early surgery rather than assuming that TG18 high-risk status alone mandates drainage, although the study was retrospective and selection-dependent.^[130]C

When surgery is unsuitable, drainage options include PCT and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD). A multicenter Western cohort described marked heterogeneity in EUS-GBD practice and evaluated lumen-apposing metal stent (LAMS)-related adverse events, recurrent biliary disease, recurrent acute cholecystitis, and all-cause mortality among patients considered unfit for immediate surgery.^[157]C The available study summary does not provide the corresponding numerical outcomes; therefore, EUS-GBD should be considered an expertise-dependent alternative rather than a universally interchangeable replacement for surgery.^[157]C

Cirrhosis

Patients with cirrhosis who are unfit for surgery represent a particularly high-risk subgroup. A multicenter comparative cohort evaluated EUS-guided transmural gallbladder drainage with LAMS versus percutaneous drainage in this population, assessing technical success, clinical success, and adverse events, including long-term biliary tract-, catheter-, and device-related events.^[159]C The study used both intention-to-treat and additional outcome analyses, but the supplied abstract does not report the numerical comparative results.^[159]C Treatment selection should therefore account for portal hypertension, coagulopathy, ascites, endoscopic access, and the anticipated ability to manage an indwelling catheter or stent, with multidisciplinary input.^[159]C

Gallbladder perforation and emphysematous cholecystitis

Gallbladder perforation has traditionally been considered a contraindication to EUS-GBD, but newer observational data suggest that carefully selected contained perforations may be treatable endoscopically.^[158] In a prospective cohort of 23 patients with contained perforated acute cholecystitis (Niemeier type 2), this subgroup represented 39.7% of the overall EUS-GBD cohort and had a high prevalence of underlying malignancy (87.0%); the study included comparison with patients whose gallbladder walls were intact.^[158] A separate retrospective series evaluated EUS-GBD with electrocautery-enhanced LAMS in high-surgical-risk patients with perforated cholecystitis, focusing on technical and clinical success and adverse events.^[129]C These data support referral to experienced centers for selected contained perforations, but they do not establish EUS-GBD as appropriate for free perforation, diffuse peritonitis, or uncontrolled sepsis.^[129]C[158]

Emphysematous cholecystitis is another severe presentation in which drainage may be considered when operative risk is prohibitive. A 10-year single-center study compared percutaneous cholecystostomy, cholecystectomy, and medical management, reporting treatment-specific hospital stay, complications, conversion to cholecystectomy after drainage, and overall mortality; the PCT group had a median age of 68.6 years and the cholecystectomy group a median age of 69.0 years.^[147]C Because the supplied abstract does not provide the complete comparative outcome figures, treatment should be based on physiologic stability, extent of infection, surgical candidacy, and response to antibiotics and source control.^[147]C

Timing and difficult operative disease

For acute calculous cholecystitis, a randomized trial of 100 patients compared early LC within 72 hours with interval LC after 6–8 weeks of conservative treatment. Early surgery had a longer mean operative time (95.47 versus 73.69 minutes) but a shorter total hospital stay (6.50 versus 10.80 days).^[126]C A separate international cohort examined early LC performed within versus beyond 7 days of symptom onset because evidence for a strict seven-day threshold is limited; the available abstract does not report the final comparative estimates.^[127] Symptom duration should therefore inform, but not alone determine, timing.^[127]

After PCT, the optimal interval before LC remains uncertain. Restricted cubic-spline analysis was used to evaluate the continuous relationship between the drainage-to-surgery interval and technical difficulty, including the need for bailout surgery.^[131] The supplied abstract does not provide the identified inflection point or outcome estimates, so timing should be individualized rather than based on an arbitrary cutoff.^[131]

Bailout procedures—including subtotal cholecystectomy—are used to reduce major injury when standard dissection is unsafe. The multicenter BOLAC study evaluated their incidence, risk factors, and postoperative outcomes across 22 hospitals in Northern Italy.^[185] Preoperative conversion risk may also be estimated using a dedicated score: a single-center study of 183 adults compared a point-based model with TG18 grade for predicting conversion from laparoscopic to open surgery.^[189] These tools may support consent and operative planning, but external validation is required before routine adoption.^[189]

Other clinically relevant subgroups

Gangrenous cholecystitis can cause necrosis, perforation, localized or diffuse peritonitis, and high morbidity and mortality. A retrospective cohort of 487 patients undergoing LC developed an interpretable machine-learning model using routinely available preoperative variables and SHAP-based explanations to predict gangrenous disease.^[183] Such models may assist early risk stratification but should complement, not replace, clinical assessment and imaging.^[183]

GLP-1 receptor agonists are associated with a potentially relevant gallbladder-risk question in adults with type 2 diabetes. A propensity-matched TriNetX cohort evaluated cholelithiasis or choledocholithiasis, cholecystitis, pancreatitis, ERCP, and cholecystectomy, with subgroup analyses by GLP-1 receptor agonist exposure.^[161] The supplied abstract does not provide effect estimates; medication exposure should therefore be recorded during assessment without assuming causality in an individual patient.^[161]

Robotic LC is an alternative operative approach. Comparative studies reported outcomes by operative platform in acute cholecystitis, including a 322-patient cohort (107 robotic and 215 laparoscopic procedures) and a separate study stratified by American Association for the Surgery of Trauma severity grade.^[128]C[162] The latter reported equivalent outcomes between robotic and laparoscopic surgery across grades, while the former evaluated perioperative safety and feasibility in an acute-care service.^[162][128]C Platform choice should depend on surgeon expertise, availability, disease severity, and the need for bailout surgery.^[128]C[162]

Fever should not be used as an isolated exclusionary finding in older or early-presenting patients. A 2026 retrospective cohort specifically evaluated fever prevalence according to symptom duration of ≤24 hours versus >24 hours and examined associations with medical and surgical complications.^[188]C The study’s numerical findings are not available in the supplied abstract; clinical diagnosis should therefore integrate symptoms, examination, laboratory results, and imaging rather than rely on fever alone.^[188]C

Evidence-based diagnostic resources

The 2024 Infectious Diseases Society of America (IDSA) guideline update provides recommendations for diagnostic imaging in suspected acute cholecystitis and acute cholangitis in adults, children, and pregnant people. The recommendations were developed from systematic literature reviews using the GRADE framework to assess certainty of evidence and strength of recommendations. ^[107]

The American College of Radiology (ACR) Appropriateness Criteria® for right upper-quadrant pain, updated in 2022 and published in 2023, addresses imaging for suspected biliary and nonbiliary causes of acute right-upper-quadrant pain. Although acute calculous cholecystitis is a leading diagnostic consideration, hepatic, pancreatic, gastroduodenal, and musculoskeletal disorders may produce similar symptoms; the resource also considers complications of cholecystitis, acute pancreatitis, peptic ulcer disease, ascending cholangitis, liver abscess, hepatitis, and painful liver neoplasms. ^[109]

Operative management

Laparoscopic cholecystectomy remains the standard operative treatment referenced in contemporary acute-cholecystitis studies. A prospective cohort from a national emergency center evaluated a proactive emergency laparoscopic cholecystectomy protocol in complex cases, including patients with symptom duration ≥7 days, advanced age, severe inflammation, or Tokyo Guidelines grade II/III disease. The protocol was implemented irrespective of symptom duration or inflammatory severity, with intraoperative indocyanine-green assessment incorporated into management. ^[83]D

A 2023 study evaluated early laparoscopic cholecystectomy performed within 72 hours of diagnosis in patients stratified by age as younger than 65 years, 65–79 years, and ≥80 years. The investigators reported no mortality and assessed predictors of postoperative complications across these age groups. ^[172] A 2026 retrospective study likewise evaluated early laparoscopic cholecystectomy in patients classified as high risk by Tokyo Guidelines 2018; among 126 patients, no in-hospital mortality occurred, and major complications (Clavien–Dindo grade ≥IIIa) occurred in 5.6%, without a significant difference between high- and low-risk groups. Grade 3 cholecystitis was independently associated with overall complications. ^[130]C

Timing remains an important management variable. A retrospective quality-of-life study compared early surgery within 1 week, intermediate surgery at 1–6 weeks, and delayed surgery after that interval in patients with acute cholecystitis. ^[171] A multidisciplinary protocol and surgical-audit study examined whether structured local pathways could increase the rate of early cholecystectomy and improve therapeutic indicators, while tracking both operative and nonoperative management. ^[176]

Intraoperative safety and bailout strategies

Near-infrared fluorescent cholangiography has been prospectively evaluated during emergency laparoscopic cholecystectomy. In one cohort, patients with clinically and radiologically diagnosed acute cholecystitis underwent surgery within 24–72 hours from symptom onset, and fluorescence was assessed at multiple operative stages to support identification of biliary anatomy across different severity grades. ^[111] A separate 2025 case-control study evaluated intraoperative indocyanine-green roadmap use as a safety measure in emergency laparoscopic cholecystectomy, with the rationale that improved visualization and procedural standardization may reduce biliary tract injury. ^[177]C

Tokyo Guidelines 2018-based bailout approaches have been examined in difficult disease. Fundus-first laparoscopic cholecystectomy was studied as a bailout technique for severe cholecystitis in a retrospective cohort of 772 laparoscopic procedures; the study compared periods with lower and higher use of the technique. ^[174]C Magnetic-resonance cholangiopancreatography findings were also evaluated as predictors of conversion from laparoscopic cholecystectomy to bailout procedures in a retrospective cohort of 161 patients. ^[173] A 2026 study developed a preoperative conversion-risk score and compared individualized prediction with Tokyo Guidelines grade alone in 183 patients with acute calculous cholecystitis. ^[189]

High-risk and nonoperative management

The SICUT guideline addresses acute cholecystitis in high-risk, critically ill, and unfit-for-surgery patients. Following a systematic review and multidisciplinary expert-panel process, it issued 15 statements concerning approaches intended to postpone or avoid surgery in patients who temporarily or permanently cannot undergo an operation. ^[108]

Percutaneous cholecystostomy or percutaneous transhepatic gallbladder drainage is described in the cited literature as a less invasive option for selected patients with severe comorbidity who are unsuitable for surgery or general anesthesia. A retrospective tertiary-center cohort assessed outcomes after percutaneous cholecystostomy, including patients managed with drainage alone and those later undergoing elective or emergency cholecystectomy. ^[113] Subsequent surgery after drainage remains an area of active investigation; a 2026 study analyzed the interval between percutaneous transhepatic gallbladder drainage and laparoscopic cholecystectomy as a continuous variable using restricted cubic-spline methods, with bailout surgery as an outcome. ^[131]

Patient selection after drainage may depend on baseline function and nutrition. In a cohort of 73 medically fragile patients, pre-admission Barthel Index and serum albumin were evaluated as predictors of discharge to the pre-admission residence after percutaneous transhepatic gallbladder drainage. ^[190]C

Infection, endoscopy, and special circumstances

Prior endoscopic sphincterotomy may influence microbiological risk: a retrospective study of 238 patients evaluated its association with multidrug-resistant bacteria in bile cultures from acute cholecystitis and considered its implications for empiric antibiotic selection. ^[170]

The American Society for Gastrointestinal Endoscopy guideline provides a GRADE-based framework for therapeutic endoscopic ultrasound in biliary tract disorders, including EUS-guided biliary drainage versus percutaneous transhepatic drainage after failed ERCP and comparisons among endoscopic approaches for biliary obstruction. ^[106] These recommendations primarily address biliary obstruction rather than routine gallbladder inflammation but may be relevant when acute cholecystitis coexists with complex biliary disease. ^[106]

During active COVID-19 infection, the 2025 SAGES guideline update makes conditional recommendations supporting either operative or nonoperative management for COVID-positive patients with appendicitis or cholecystitis, reflecting uncertainty and the need for individualized multidisciplinary assessment. ^[105]