European Journal of Cardiovascular Medicine

Gallstone disease, or cholelithiasis, is one of the most common and economically important benign disorders of the digestive system, affecting nearly 10-15% of the adult population worldwide.[1] It represents a significant health-care burden owing to its high prevalence, potential for serious complications such as acute cholecystitis, choledocholithiasis, cholangitis, and gallstone pancreatitis, and the large number of cholecystectomies performed annually for symptomatic disease.[2] The prevalence of gallstone disease shows marked geographical, ethnic and gender-based variation, being highest in Native Americans and Northern Europeans, intermediate in Western populations, and comparatively lower but steadily rising in Asian countries, including India, largely attributable to changing dietary habits, increasing obesity and sedentary lifestyles.[3]

In the Indian subcontinent, several hospital-based studies have documented an increasing incidence of gallstone disease, with a distinct female preponderance and a north-south gradient, the disease being more common in northern and eastern India than in the southern states.[4] Tandon et al, in an early Indian epidemiological study, highlighted the classical risk profile for gallstone disease summarized by the mnemonic of the "four F's" - Female, Forty, Fertile and Fat - though obesity, multiparity, rapid weight loss, prolonged fasting, total parenteral nutrition, certain haemolytic disorders and a positive family history are now also well recognised contributory factors.[5]

Clinically, gallbladder calculi may remain entirely asymptomatic and be discovered incidentally, or may present with a spectrum of symptoms ranging from vague dyspepsia and fatty food intolerance to classical biliary colic, right hypochondriac pain radiating to the back or right scapula, nausea, vomiting and, in complicated cases, fever and jaundice.[6] Because clinical examination and biochemical parameters alone are often non-specific and insufficiently sensitive for confident diagnosis, imaging plays a pivotal and indispensable role in the work-up of suspected gallbladder disease.[7]

A variety of imaging modalities have been employed over the years for evaluation of the gallbladder, including plain radiography, oral cholecystography, intravenous cholangiography, computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), hepatobiliary scintigraphy (HIDA scan) and endoscopic ultrasound. Of these, transabdominal ultrasonography has, since its introduction into routine clinical practice in the 1970s, evolved into the investigation of first choice for suspected gallbladder pathology.[8] Its popularity is attributable to several distinct advantages: it is a rapid, widely available, relatively inexpensive, non-invasive, real-time modality that does not employ ionising radiation, requires no intravenous contrast, can be performed at the bedside in critically ill patients, and allows simultaneous evaluation of the liver, biliary tree, pancreas and adjacent viscera.[9]

On grey-scale ultrasonography, a gallbladder calculus is classically identified as an echogenic focus within the gallbladder lumen that casts a well-defined posterior acoustic shadow and demonstrates gravity-dependent mobility on change of patient position - features that, when present together, are considered virtually pathognomonic for cholelithiasis.[10] Sharma and colleagues, in a hospital-based Indian study conducted at a tertiary care centre, reported a sensitivity exceeding 95% for ultrasonography in the detection of gallbladder calculi and emphasised its role as a reliable screening tool in Indian patients presenting with upper abdominal pain.[11] Similarly, Verma et al, in a prospective Indian study correlating sonographic and per-operative findings, concluded that ultrasonography was an excellent, reproducible and operator-independent-enough tool for pre-operative assessment of gallstone number, size and associated gallbladder wall changes.[12]

Despite its widespread acceptance, the diagnostic accuracy of ultrasonography can be influenced by several technical and patient-related factors, including operator experience, equipment resolution, patient body habitus, bowel gas interposition, a contracted or non-visualised gallbladder, and the presence of very small (<3 mm) calculi or a gallbladder packed with stones (WES sign).[13] It is therefore important for individual institutions, especially teaching hospitals responsible for training resident doctors, to periodically audit and validate the diagnostic performance of ultrasonography against a definitive gold standard such as per-operative findings and histopathological examination.[14]

Given the substantial burden of gallstone disease in the Indian population and the pivotal, almost universal, reliance on ultrasonography as the initial and often sole pre-operative imaging investigation, the present prospective study was undertaken at our tertiary care teaching hospital to systematically evaluate the diagnostic accuracy of transabdominal ultrasonography in the detection of gallbladder calculi, with correlation to per-operative and histopathological findings in operated cases.

Aims and Objectives

To study the clinical and demographic profile of patients presenting with suspected gallbladder disease at a tertiary care teaching hospital. To determine the sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy of ultrasonography in detection of gallbladder calculi, taking per-operative/histopathological findings as the gold standard

Study Design: Hospital-based prospective observational study.

Study Setting: Department of Radiodiagnosis, in collaboration with the Department of General Surgery, Geetanjali Medical College & Hospital, Udaipur.

Study Period: 18 months (January 2023 to June 2024), after obtaining clearance from the Institutional Ethics Committee.

Sample Size: A total of 200 patients were enrolled in the study. The sample size was calculated using the formula n = Z²pq/d², taking the expected prevalence of gallbladder calculi in symptomatic patients (p) from previous Indian studies, with a 95% confidence interval and 5% allowable error, and rounded off to 200 for logistic feasibility and adequate statistical power.

Inclusion Criteria

• Patients of either sex, aged 18 years and above, presenting with clinical features suggestive of gallbladder disease (right hypochondriac/epigastric pain, dyspepsia, fatty food intolerance, nausea/vomiting).
• Patients referred for ultrasonography of the abdomen for suspected hepatobiliary pathology.
• Patients willing to give written informed consent for participation in the study and, where applicable, for correlation with surgical/histopathological findings.

Exclusion Criteria

• Patients with a history of previous cholecystectomy.
• Pregnant patients.
• Patients unwilling to give informed consent.
• Patients in whom adequate sonological visualisation of the gallbladder could not be achieved due to technical limitations, and who were lost to surgical/clinical follow-up.

Equipment and Technique

All patients underwent transabdominal ultrasonography after a minimum of 6-8 hours of fasting, using a high-resolution ultrasound machine fitted with a 3.5-5 MHz curvilinear transducer, supplemented by a 5-7.5 MHz linear probe where required for superficial detail. Patients were examined in the supine, left posterior oblique and, where necessary, erect positions to elicit gravity-dependent mobility of intraluminal echogenic foci. The gallbladder was assessed for size, wall thickness, presence, number and size of calculi, posterior acoustic shadowing, mobility of calculi with change in position, and presence of pericholecystic fluid or other associated findings. The common bile duct, liver and pancreas were also evaluated in each patient. All examinations were performed and/or supervised by radiologists with a minimum of three years of post-graduate experience in abdominal sonography, and representative images were recorded and archived.

Gold Standard for Comparison

In patients who subsequently underwent cholecystectomy (open or laparoscopic), sonographic findings were correlated with per-operative findings noted by the operating surgeon and with histopathological examination of the resected gallbladder specimen. This combined per-operative and histopathological correlation was considered the gold standard for the purposes of calculating diagnostic accuracy. Patients who did not undergo surgery during the study period were followed up clinically and, where feasible, with repeat imaging to confirm the sonographic diagnosis.

Statistical Analysis

Data were entered into Microsoft Excel and analysed using SPSS software, version 26.0 (IBM Corp.). Categorical data were expressed as frequencies and percentages, and continuous data as mean ± standard deviation. Diagnostic accuracy of ultrasonography was assessed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall diagnostic accuracy, using a 2×2 contingency table with per-operative/histopathological findings as the reference standard. The Chi-square test was used to assess association between categorical variables, and a p-value of less than 0.05 was considered statistically significant.

A total of 200 patients with clinically suspected gallbladder disease were evaluated by transabdominal ultrasonography during the study period. The demographic, clinical and sonographic findings are summarised below.

Table 1: Age-wise Distribution of Study Population (n=200)

The mean age of patients in the study was 43.6 ± 12.4 years, with the maximum number of patients (34%) in the 31-45 year age group, followed by the 46-60 year age group (31%), consistent with the classical age predilection of gallstone disease described in earlier Indian series.[15]

Table 2: Gender-wise Distribution of Study Population (n=200)

Females (66%) outnumbered males (34%), giving a female to male ratio of 1.9:1, in agreement with the well-established female preponderance of gallstone disease reported in both Indian and Western literature.[16]

Table 3: Distribution According to Presenting Clinical Symptoms (n=200)

*Multiple responses possible; percentages do not add up to 100. Right hypochondriac/epigastric pain was the most common presenting complaint, seen in 88% of patients, followed by nausea/vomiting (59%) and fatty food intolerance (52%).

Table 4: Distribution of Associated Risk Factors (n=200)

*Percentage calculated out of the 132 female patients for the multiparity variable. Obesity and sedentary lifestyle emerged as the most frequent associated risk factors, consistent with the described 'four F' risk profile for gallstone disease.[17]

Table 5: Sonographic Findings - Number of Gallbladder Calculi (n=152 USG-positive cases)

Table 6: Sonographic Findings - Size of Gallbladder Calculi (n=152)

Calculi measuring 6-10 mm were most frequently observed (42.1%), and multiple calculi (61.2%) were more common than solitary calculi (38.8%), a pattern comparable to that reported by Bansal et al in a north Indian tertiary care series.[18]

Table 7: Gallbladder Wall Thickness in USG-Positive Cases (n=152)

Table 8: Comparison of Ultrasonography Findings with Per-operative/Histopathological Findings (n=200)

TP = True Positive, FP = False Positive, FN = False Negative, TN = True Negative. Of the 200 patients, 155 were confirmed to have gallbladder calculi on the basis of per-operative and/or histopathological examination. Ultrasonography correctly identified 150 of these (true positives), missed 5 cases (false negatives, largely attributable to small calculi < 3 mm or a contracted, gas-obscured gallbladder), and correctly excluded calculi in 43 of 45 true-negative cases, with 2 false-positive results (chi-square = 128.4, p < 0.001).

Table 9: Diagnostic Accuracy of Ultrasonography for Detection of Gallbladder Calculi

Ultrasonography demonstrated a high sensitivity of 96.8%, specificity of 95.6%, positive predictive value of 98.7%, negative predictive value of 89.6% and overall diagnostic accuracy of 96.5% for the detection of gallbladder calculi, when compared with the combined.

Gallstone disease continues to be one of the most frequently encountered hepatobiliary disorders in surgical and radiological practice, and ultrasonography remains the cornerstone imaging investigation for its diagnosis. The present prospective study, conducted on 200 patients at a tertiary care teaching hospital, demonstrated a sensitivity of 96.8%, specificity of 95.6%, and an overall diagnostic accuracy of 96.5% for ultrasonography in the detection of gallbladder calculi, findings that are in close agreement with previously published Indian and international literature.[19]

In terms of demographic profile, the mean age of patients in our study was 43.6 ± 12.4 years, with maximum involvement in the 31-45 year age group, comparable to the age distribution reported by Khan et al in an Indian tertiary care hospital study, who observed peak incidence in the fourth and fifth decades of life.[20] The female preponderance observed in our study (female to male ratio of 1.9:1) is well supported by earlier Indian work; Unisa et al, in a large community-based Indian study on gallstone disease, similarly reported a higher prevalence among females, attributed to the influence of oestrogen on hepatic cholesterol secretion and biliary stasis during pregnancy.[21] Agrawal and colleagues, in a hospital-based north Indian study, also documented a comparable female predominance and highlighted multiparity and obesity as major contributory risk factors, findings that closely mirror our own risk factor analysis in which sedentary lifestyle (54%) and obesity (46%) emerged as the leading associated factors.[22]

Right hypochondriac and epigastric pain was the predominant presenting symptom in our series (88%), consistent with the classical clinical presentation of biliary colic described in standard surgical and radiological texts, and similar to the symptom profile reported by Chawla et al in their prospective Indian study correlating clinical presentation with sonographic findings of cholelithiasis.[23]

With regard to sonographic characteristics, multiple calculi were more frequently observed than solitary calculi in our study (61.2% versus 38.8%), and stones in the 6-10 mm range constituted the largest proportion (42.1%). This distribution pattern parallels the findings of an earlier Indian ultrasonographic correlative study by Mishra et al, who similarly reported a preponderance of multiple, medium-sized calculi in their study population, and is also broadly consistent with the international literature on gallstone morphology.[24]

The diagnostic accuracy of ultrasonography documented in the present study (96.5%) closely corroborates the results of several previous validation studies. Shea et al, in a widely cited meta-analysis pooling data from multiple international studies, reported a pooled sensitivity of 97% and specificity of 95% for ultrasonography in the detection of gallstones, figures almost identical to those obtained in our study.[25] Similarly, an earlier Indian prospective study by Rathi et al, correlating pre-operative sonographic findings with per-operative findings in patients undergoing cholecystectomy, reported a sensitivity of 94.7% and specificity of 96.3%, further reinforcing the excellent diagnostic performance of ultrasonography in the Indian clinical setting.[26] Gupta and Sood, in another Indian tertiary care hospital-based study evaluating the accuracy of USG against operative findings, reported comparably high concordance and emphasised the cost-effectiveness of ultrasonography as a first-line investigation, particularly relevant in resource-limited government teaching hospital settings such as ours.[27]

The five false-negative cases in our study were retrospectively attributable to very small calculi (< 3 mm), a markedly contracted gallbladder at the time of scanning, and, in one case, overlying bowel gas obscuring adequate visualisation - limitations that have been similarly described by Bree in an analysis of the causes of missed gallstones on ultrasonography, underscoring the importance of adequate patient preparation, technique and operator experience.[28] The two false-positive results in our series were later attributed to gallbladder sludge mimicking small calculi, a recognised pitfall also highlighted by Kaur et al in an Indian study on sonographic mimics of gallbladder calculi.[29]

Taken together, the findings of the present study reaffirm the position of transabdominal ultrasonography as an extremely reliable, safe, cost-effective, radiation-free and widely accessible investigation for the diagnosis of gallbladder calculi, well suited for use as a frontline screening and pre-operative planning tool in busy tertiary care teaching hospitals, particularly in the Indian setting where patient load is high and access to cross-sectional imaging such as CT or MRCP may be comparatively limited or reserved for complicated or diagnostically equivocal cases.[30]

Limitations of the Study

The study was conducted at a single tertiary care centre with a relatively modest sample size of 200 patients, which may limit generalisability. Ultrasonography is inherently operator-dependent, and inter-observer variability was not separately assessed in this study. Not all USG-negative patients underwent surgical correlation, and a small proportion were followed up only clinically, which may have introduced a degree of verification/work-up bias. Patients with extreme obesity or excessive bowel gas, in whom sonographic visualisation is technically limited, may have been under-represented among those willing to complete the full study protocol.

The present prospective study reaffirms that transabdominal ultrasonography is a highly sensitive (96.8%), specific (95.6%) and accurate (96.5%) imaging modality for the detection of gallbladder calculi when correlated against per-operative and histopathological gold-standard findings. Given its additional advantages of being non-invasive, free of ionising radiation, inexpensive, widely available and capable of simultaneously evaluating the liver, biliary tree and pancreas, ultrasonography should continue to be recommended as the first-line and, in the majority of cases, the only imaging investigation required in patients with clinically suspected gallbladder disease. Cross-sectional modalities such as CT or MRCP may be reserved for diagnostically equivocal cases, evaluation of complications, or pre-operative delineation of the biliary anatomy in complex cases. Continued departmental training, standardisation of scanning technique, and periodic diagnostic audit, as undertaken in the present study, are recommended to further improve and sustain the excellent diagnostic performance of ultrasonography in tertiary care teaching hospital settings.

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