Abstract
Background
Hyperkinetic and hypokinetic biliary dyskinesia commonly present with right upper quadrant pain, mimicking biliary colic or cholecystitis. Only gallbladder hypokinesia is a well-accepted indication for cholecystectomy. While there is less literature on the topic, patients with gallbladder hyperkinesia may also benefit from cholecystectomy.
Methods
This single-center cross-sectional study looked at patients 18 years or older, with EF >80% on HIDA scan who underwent cholecystectomy and at least one postoperative visit from January 1, 2018, to February 28, 2023. The primary outcome was symptomatic resolution or improvement.
Results
In total, 67 patients were identified, with a median age of 46 years, 75% female sex, and a median 30-day follow-up period. All patients presented with abdominal pain, 64% presented with nausea and vomiting, and 31% presented with chronic diarrhea. Partial symptomatic improvement was noted in 94% of patients, while 85% had complete resolution. There was a statistically significant difference in gallbladder ejection fraction between 2 groups: 94% (IQR 90-98%) for those with complete symptom resolution vs 88% (IQR 83-97%) for those who did not have symptom resolution (P = 0.033). Chronic cholecystitis was demonstrated in 73% of specimens.
Conclusions
This data adds to a body of evidence supporting laparoscopic cholecystectomy for gallbladder hyperkinesia. The study further establishes a higher degree of gallbladder ejection fraction to have an association with complete symptomatic improvement after cholecystectomy. A patient’s presenting symptoms do not appear to have an association with complete symptom resolution.
Introduction
Gallbladder hyperkinesia (GBH) is a diagnosis which has received less attention than its counterpart, biliary dyskinesia, which can also be termed “biliary hypokinesia.” Biliary dyskinesia can present in a few ways, most commonly with right upper quadrant or epigastric abdominal pain, particularly in association with food ingestion, and mimicking cholecystitis or biliary colic. Other symptoms may include abdominal cramping, chronic nausea/vomiting, diarrhea, or early satiety. The diagnosis is made in patients who have biliary symptoms with the absence of cholelithiasis or ultrasonographic evidence of mechanical obstruction of gallbladder bile outflow. 1 Biliary dyskinesia has a well-established set of diagnostic criteria, the Rome IV criteria, which notably includes a gallbladder ejection fraction (EF) < 35% after cholecystokinin (CCK) administration during a hepatobiliary iminodiacetic acid (HIDA) scan. The Rome IV criteria also include a set of criteria for diagnosing “biliary pain.” Cholecystokinin is given intravenously during HIDA scans to cause gallbladder contraction, simulating the response that occurs upon ingestion of a food bolus. Cholecystectomy is a well-established surgical treatment of this disorder.1-3
Conversely, gallbladder hyperkinesia (GBH) has less published literature on its diagnosis and management. It is a clinical entity thought to occur secondary to either increased serum levels of CCK, or potentially increased expression of CCK receptors, and lacks well-defined criteria for surgical intervention. The literature that is available has established a gallbladder EF >80% as a marker of a hyperkinetic gallbladder. Several small-scale studies have noted that a significant portion of patients who underwent cholecystectomy specifically for biliary hyperkinesia had partial or complete resolution of their symptoms.3,4 Even though these studies were compiled into a meta-analysis, patient-level studies with larger sample sizes have not yet been performed. 5
A cross-sectional retrospective study was conducted at a single institution, looking at patients who underwent laparoscopic cholecystectomy for gallbladder hyperkinesia over 5 years. This study sought to describe the common presenting symptoms, imaging findings, and postoperative outcomes for GBH patients undergoing cholecystectomy, including the rate of symptomatic improvement or resolution to further establish cholecystectomy as a viable treatment option for these patients.
Methods
This was a cross-sectional retrospective study of patients who underwent laparoscopic cholecystectomy for GBH between January 1, 2018, and February 28, 2023. Surgeries were performed at a single suburban community hospital. The institutional review board (IRB) reviewed the protocol and determined that it met the requirements for exemption under 45 CFR 46.104(d) for secondary research. Results have been reported in this article per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. 6
Record Identification and Inclusion/Exclusion Criteria
Patients were identified from the operating room scheduler over the study period by Current Procedural Terminology (CPT) codes: 47562 and 47563. Patients were included if they were 18 years or older, had a HIDA with CCK performed prior to surgery, had a gallbladder EF greater than 80% on HIDA after administration of CCK, underwent laparoscopic cholecystectomy, and presented to at least one postoperative appointment. Patients were excluded if they had cholelithiasis present on preoperative imaging, active hepatopancreatobiliary pathology separate from their gallbladder hyperkinesia, a history of chronic pancreatitis, conversion to an open cholecystectomy, conversion to a partial cholecystectomy, or adenomyomatosis/gallbladder cancer present on final pathology.
Data Extraction
After initial identification, patient records were reviewed and variables were extracted from the inpatient and outpatient electronic medical records (EMRs) by several authors (GH, RP, RN, JA, and CH) according to previously determined criteria and definitions. The extracted data was reviewed by the study coordinator (GH) to ensure that variables were being interpreted from charts and recorded uniformly. Data was stored in a secured spreadsheet.
Definitions
Patient preoperative symptoms were defined as “pain,” “nausea/vomiting,” “diarrhea,” and “early satiety.” These symptoms had to be documented in the patient’s office note to be considered present. Patient comorbidities likewise required documented presence in their chart. “Complete resolution of symptoms” was defined as the documented complete absence of initial presenting symptoms in a patient’s postoperative office note. If a patient was noted to have “improvement” of symptoms, this was recorded as an improvement in our data set, but not a complete resolution. Thirty-day readmission was defined as inpatient admission to the hospital for any reason within 30 days of surgery; it did not include emergency department visits in the 30-day postoperative window. Follow-up duration was established as the time from cholecystectomy until the last surgery or gastroenterology office visit, as most of these patients were referred for surgical evaluation from the gastroenterology clinic after appropriate workup.
Statistical Analysis
Examination of data began with calculation of summary statistics [median (IQR) for non-normally distributed data; n(%) for nominal data]. The Wilcoxon rank sum test with exact option was used to assess differences in continuous demographic and clinical variables by symptom improvement status. The Fisher’s exact test was used to assess associations of demographic and clinical characteristics with symptom improvement status. All testing was conducted using STATA/BE v17.0 with results interpreted at a type I error rate of alpha = 0.05 level of statistical significance.
Results
Frequency Distributions of Comorbidities and Presenting Symptoms for All Patients With Gallbladder Hyperkinesia.
Frequency Distributions of Postoperative Outcomes for All Patients With Gallbladder Hyperkinesia.
Summary Statistics by Symptom Improvement Status, Along With Results of Wilcoxon Rank Sum Tests With Exact Option and Fisher’s Exact Tests.
aWilcoxon rank sum test.
bFisher’s exact test.
Discussion
This study sought to add to a growing body of evidence that gallbladder hyperkinesia can cause a symptom pattern similar to biliary colic or cholecystitis, which is improved after cholecystectomy. Our research identifies commonalities in patients experiencing biliary symptoms, who have a gallbladder EF >80% on HIDA scan with CCK. All 67 patients included in this study presented with abdominal pain. Two-thirds of the patients presented with chronic nausea or vomiting, and another third presented with chronic diarrhea, although there was significant overlap between these two groups. The data suggests that cholecystectomy is a viable treatment option for patients with hyperkinetic gallbladders, as 85% of patients reported complete resolution of their symptoms, and 94% of patients reported at least symptomatic improvement during their follow-up period. The rates of symptom resolution in this study are consistent with other cross-sectional retrospective studies in the literature, which range from 61% to 96% of patients.1,3,4,7,8 Likewise, a meta-analysis on gallbladder hyperkinesia patients by Eltyeb et al 5 found an aggregate rate of symptom resolution of 91% across 332 included patients. 5 An interesting retrospective study by Williford et al identified patients with hyperkinetic gallbladders from HIDA scan orders and separated them into two groups: those who underwent cholecystectomy and those who did not. The authors found that those who did not undergo a cholecystectomy for gallbladder hyperkinesia presented for more emergency room visits, were given more prescriptions, and had a worsened quality of life score, when compared to those who received a cholecystectomy. 9 The study in this article adds to a growing body of evidence that patients with gallbladder hyperkinesia benefit from cholecystectomy, and these patients should be offered the procedure as treatment for their symptoms.
While this data suggests improvement of symptoms with cholecystectomy, the mechanism behind the symptoms is unconfirmed. When stratifying our patients on a number of variables, those who experienced complete symptom resolution after cholecystectomy had an increased gallbladder ejection fraction compared to those who did not have complete resolution (94% vs 88%, P = 0.033). This may suggest that the severity of gallbladder hyperkinesia correlates with the intensity of gallbladder contraction. The theory here is that intense gallbladder contractions produce intense pain, and patients with more intense gallbladder contractions are more likely to experience complete symptom resolution or improvement after cholecystectomy than those with less intense gallbladder contractions. Previously in the literature, the hypothesis has been proposed that intense gallbladder contractions cause an increased luminal pressure, and eventual resultant chronic inflammation.10,11 Of the patients in this study, 73% of pathology specimens noted chronic cholecystitis.
Morris-Stiff et al demonstrated that symptom reproduction with CCK may be superior to gallbladder ejection fraction in predicting outcomes after cholecystectomy; however, their study focused specifically on patients with hypokinetic gallbladders (EF <35%). 12 Other prior studies have reported that only 53-74% of GBH patients have symptom reproduction with CCK infusion.3,4,7 This calls into question the role of symptom reproduction on CCK infusion as a predictive variable for symptom resolution, but it may serve a purpose as a variable that suggests the diagnosis of gallbladder hyperkinesia.
In our medical records, symptom reproduction with CCK administration was not reliably recorded, and this is a significant limitation. Our study was further limited by its small sample size and the retrospective nature of the study design, which limit the generalizability of the findings.
Future studies should be directed toward questioning if gallbladder hyperkinesia should be considered higher in the differential diagnosis for patients with chronic, vague, “biliary-type” symptoms of abdominal pain, nausea/vomiting, diarrhea, and early satiety. These patients frequently undergo an exhaustive workup, requiring multiple referrals to different specialities, and undergoing a multitude of tests and procedures to rule out other diagnoses. Two-thirds of the patients in this study had an EGD performed as part of their workup, in addition to other testing. Patients with gallbladder hyperkinesia will also commonly present several times to the emergency department over the lifetime of their symptoms before their eventual cholecystectomy.
Conclusions
Gallbladder hyperkinesia is a diagnosis which has gained recognition over the past decade as a clinical entity which can be effectively treated with cholecystectomy. This article presented a single institution’s experience with 67 patients with GBH and outlined their presenting symptoms, rates of symptomatic resolution or improvement, and postoperative courses. We have highlighted that patients with higher gallbladder ejection fractions on HIDA with CCK may see improved rates of symptom resolution after cholecystectomy, and discussed where our data fits into the broader discussion on GBH in the literature.
Footnotes
Author Contributions
GH: conception, design, data collection, data analysis, and manuscript writing; RP: conception, data collection, and manuscript writing; RN: conception, data collection, and manuscript writing; NM: conception, design, and data analysis; JA: data collection; CH: data collection; SC: conception, design, and manuscript editing; and RG: conception, design, and manuscript editing.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
