The Role of Endoscopic Ultrasound in Detecting Common Bile Duct  Stones Missed Post-Endoscopic Retrograde Cholangiopancreatography in Patients with Calculous Obstructive Jaundice

doi:10.21203/rs.3.rs-4888689/v1

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The Role of Endoscopic Ultrasound in Detecting Common Bile Duct Stones Missed Post-Endoscopic Retrograde Cholangiopancreatography in Patients with Calculous Obstructive Jaundice

https://doi.org/10.21203/rs.3.rs-4888689/v1

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Background

Choledocholithiasis occurs in up to 20% of patients with gallstones. Diagnosing choledocholithiasis can be challenging. Previously, the gold standard for diagnosis was endoscopic retrograde cholangiopancreatography (ERCP). However, small stones often evade detection through ERCP and magnetic resonance cholangiopancreatography (MRCP). Endoscopic ultrasound (EUS) has proven effective in identifying common bile duct (CBD) stones that MRCP and ERCP might miss, particularly small stones or those lodged in the distal CBD or papillary region. The study aimed to evaluate the accuracy of EUS in detecting CBD stones missed by MRCP and ERCP.

Methods

A case-control study was conducted; we enrolled 30 patients who were presented with calculous obstructive jaundice and had undergone both ERCP and MRCP. A stent was inserted in these patients. Prior to stent removal, these patients underwent EUS to evaluate its effectiveness in detecting any remaining CBD stones post-ERCP. The sensitivity and specificity of EUS, ERCP, and MRCP were compared based on the presence, size, and number of detected stones.

Results

The mean age of involved patients was 50.3 ± 10.2 years. ERCP demonstrated a sensitivity of 44.4%, specificity of 100%, positive predictive value (PPV) of 100%, negative predictive value (NPV) of 16.6%, and an accuracy of 50%. MRCP showed a sensitivity of 81.5%, specificity of 100%, PPV of 100%, NPV of 37.5%, and an accuracy of 83.3% when compared to EUS results. The complication rate for EUS was significantly lower than that for diagnostic ERCP. Additionally, an EUS-based strategy was more cost-effective than diagnostic ERCP for patients with low, moderate, or intermediate risk.

Conclusion

Endoscopic ultrasound (EUS) is a promising, non-invasive, non-contrast technique that may serve as a superior diagnostic tool compared to MRCP and ERCP, particularly for detecting small stones or those impacted in the distal CBD or papillary region.

Choledocholithiasis

Endoscopic retrograde cholangiopancreatography (ERCP)

Magnetic resonance cholangiopancreatography (MRCP)

Endoscopic ultrasound (EUS)

missed CBD stones

Gallstones are a common condition among the general population, with a prevalence ranging from 10–15% in adult Caucasian populations and up to 70% in American Indians. The common risk factors for the formation of cholesterol stones include being female, age over 40 years, obesity, and rapid weight loss. In most of cases and up to more than 80% of patients having gallstones, remain asymptomatic and do not cause complications, with low risk of developing symptoms or complications that ranges between 1% and 2.3% per year, and surgery is required for these patients.^{1, 2}

Historically, Endoscopic Retrograde Cholangiopancreatography (ERCP) was considered the gold standard for diagnosing choledocholithiasis due to its advantage of allowing therapeutic intervention, such as drainage. However, ERCP is invasive, may miss small stones, and carries risks such as pancreatitis. Therefore, confirming the presence of choledocholithiasis with less invasive methods before performing ERCP is often preferred. Nowadays, Endoscopic Ultrasound (EUS) considers a minimally invasive technique with low morbidity that has demonstrated effectiveness in diagnosing pancreatic diseases, particularly those affecting the head of the pancreas.^{3, 4}

In the emerging era of advanced endoscopy, particularly Endoscopic Ultrasound (EUS), there is significant value in diagnosing pancreatic and biliary diseases. EUS is approaching the diagnostic accuracy of Endoscopic Retrograde Cholangiopancreatography (ERCP) in identifying the precise etiology of obstructive jaundice.⁵

As it is well established that the main goal of any diagnostic technique is to verify the presence of biliary obstruction by detecting biliary dilatation and pinpointing its precise location. This can be done either by invasive or non-invasive tools, the noninvasive methods include using liver function tests and imaging techniques such as Ultrasound (US), Magnetic Resonance Imaging (MRI), and Computed Tomography (CT) cholangiography. Additionally, endoscopic methods such as Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Ultrasound (EUS) are valuable tools in diagnosing biliary obstruction.^{6, 7}

Endoscopic Ultrasound (EUS) is a minimally invasive technique that offers detailed imaging of the biliary system and pancreas. It enables fine-needle aspiration for diagnostic biopsies and has up to 98% accuracy in detecting causes of obstructive jaundice. EUS can visualize both internal and adjacent structures of the gastrointestinal tract, with the advantage of imaging the biliary tree from within the duodenum, avoiding interference from abdominal gas or fat.^8–10

The primary aim of our study was to evaluate the role of EUS in diagnosis of missed common bile duct stones that is not detected by routine imaging studies

This study was a cross-sectional study conducted on 30 patients that were recruited from Internal medicine department, Gastroenterology and Hepatology unit, faculty of medicine, Cairo university.

EUS and ERCP were done by expert hands at endoscopy and also MRCP was examined by professional radiologists who are experts at diagnostic MRI. We recruited patients diagnosed with residual clinical picture of obstruction post ERCP, both genders were involved, all participants aged between 18 to 70 years old. Patients who had an altered or postsurgical upper gastrointestinal anatomy, or whom presented with gastrointestinal hemorrhage, pregnant women, patients with severe acute cholangitis, patients otherwise deemed unfit by the investigators, malignant masses detected by EUS, or patient' s refusal to participate in this study all were excluded from the study. The study was approved by our institution’s Research Ethical Committee with the reference number: MS-255-2023, and all patients or their illegal caregiver gave their informed written consent before inclusion in the study, according to the ethical guidelines of the 1975 Declaration of Helsinki.

All the patients, after thorough full history taking and clinical examination, were subjected to: Biochemical profile including alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin total and direct, Alkaline phosphatase, gamma-glutamyl transferase (GGT), serum amylase and lipase. Complete blood count (CBC) and C-reactive protein (CRP) for excluding patients with cholangitis. Noninvasive radiological evidence of biliary obstruction in abdominal ultrasound and MRCP by assessment of gall bladder, CBD size and dilated intrahepatic biliary radicals (IHBRDs). ERCP done and stent was inserted.

An EUS examination was conducted on all participants using a Pentax EG3870UTK linear echoendoscope (HOYA Corporation, PENTAX Life Care Division, Showanomori Technology Center, Tokyo, Japan) connected to a Hitachi AVIUS ultrasound unit (Hitachi Medical Systems, Tokyo, Japan). The procedures were performed under deep sedation with intravenous propofol. For EUS-FNA, we utilized Cook 19G and 22G needles (Echotip; Wilson-Cook, Winston-Salem, NC). EUS assessment of biliary tree regarding CBD size, size and number of CBD stones and the pancreas was done.

ERCP examination was done to all involved participants. It was done using a side view scope Pentax ED-3490TK (HOYA Corporation, 2-7-5 Naka-Ochiai, Shinjuku-ku, Tokyo 161–8525, Japan). All examinations were performed under deep sedation with IV propofol. ERCP findings regarding CBD findings (dilatation, stones, stricture) were assessed.

The CBD was considered dilated if its diameter exceeded 6 mm and 10 mm in patients with and without gall bladder (cholecystectomy) respectively. ERCP is considered till now the gold standard for biliary imaging, so data from EUS and MRCP were compared to the findings in ERCP to assess the sensitivity and specificity of EUS and MRCP in

o Detecting stones.

o Number of stones detected.

o Size of stones

This study assessed the accuracy of EUS in detecting common bile duct (CBD) stones, particularly those missed by MRCP and ERCP, in patients with an intermediate probability of CBD stones and recurrent unexplained pancreatitis.

Statistical methods:

Data were analyzed using Statistical Program for Social Science (SPSS) version 24. Qualitative data were expressed as frequency and percentage. Quantitative data were expressed as mean ± SD. Mean (average): the central value of a discrete set of numbers, specifically the sum of values divided by the number of values. Standard deviation (SD): is the measure of dispersion of a set of values. A low SD indicates that the values tend to be close to the mean of the set, while a high SD indicate that the values are spread out over a wider range. Kappa test (k) was done for measurement of agreement between IHP and Deauville score.

Kappa interpretation:
K < 0.2 means poor agreement.
K = 0.2–0.4 means fair agreement.
K = 0.4–0.6 means moderate agreement.
K = 0.6–0.8 means good agreement.
K = 0.8–1.0 means very good agreement.
Probability (P-value)
P-value < 0.05 was considered significant.
P-value < 0.001 was considered as highly significant.
P-value > 0.05 was considered insignificant.

The mean age of all studied patients was 50.3 ± 10.2 years with minimum age of 30 years and maximum age of 67 years. 14 were males (46.7%) and 16 were females (53.3%) in the studied patients (Table 1).

Table 1

Description of demographic data in all studied patients.
		Studied patients (N = 30)
Sex	Male	14	46.7%
Sex	Female	16	53.3%
Age (years)	Mean ± SD	50.3 ± 10.2
Age (years)	Min - Max	30–67
SD: Standard deviation.

ERCP showed CBD stone in 12 patients (40%), distal CBD stricture in 17 patients (56.7%) and papillary swelling in 1 patient (3.3%) (Fig. 1), meanwhile, MRCP showed CBD stone in 22 patients (73.3%) and distal CBD stricture in 4 patients (13.3%) while it was normal in 4 patients (13.3%) (Fig. 2).

EUS revealed CBD stone in 27 patients (90%), and it was normal in 3 patients (10%). CBD stone was single in 19 patients (70.4%) and multiple in 8 patients (29.6%) (Fig. 3).

Comparing the clinical agreement between (ERCP & MRCP) and EUS in diagnosis of CBD stones revealed that there was no statistically significant difference (p-value = 0.136), poor agreement (k = 0.13) between ERCP and EUS results in diagnosis of CBD stone, while there was a statistically significant difference (p-value = 0.002), moderate agreement (k = 0.46) between MRCP and EUS results in diagnosis of CBD stone (Table 2).

Table 2

The Clinical agreement between (ERCP & MRCP) and EUS in diagnosis of CBD stones.
(n = 30)		EUS				Stat. test	P-value
		-ve stone		+ve stone
ERCP	-ve stone	3	10%	15	50%	k = 0.13	0.136 NS
	+ve stone	0	0%	12	40%
MRCP	-ve stone	3	10%	5	16.7%	k = 0.46	0.002 S
	+ve stone	0	0%	22	73.3%
S: p-value < 0.05 is considered non-significant.
k: kappa test (test of agreement). NS: p-value > 0.05 is considered non-significant.

As regards ERCP results, of total studied 30 patients, there were 12 true positive results (40%), 3 true negative results (10%) and 15 false negative results (50%) while there were no false positive results. Thus, ERCP had the sensitivity of 44.4%, specificity of 100%, PPV of 100%, NPV of 16.6% and accuracy of 50% in relation to EUS results, while MRCP results, revealed that there were 22 true positive results (73.3%), 3 true negative results (10%) and 5 false negative results (16.7%) while there were no false positive results. Thus, MRCP had the sensitivity of 81.5%, specificity of 100%, PPV of 100%, NPV of 37.5% and accuracy of 83.3% in relation to EUS results (Table 3), (Fig. 4, 5).

Table 3

Diagnostic performance of (ERCP & MRCP) in diagnosis of CBD stones in relation to EUS results.
	ERCP		MRCP
True positive	12	40%	22	73.3%
False positive	0	0%	0	0%
False negative	15	50%	5	16.7%
True Negative	3	10%	3	10%
Sensitivity	44.4%		81.5%
Specificity	100%		100%
PPV	100%		100%
NPV	16.6%		37.5%
Accuracy	50%		83.3%
PPV: Positive predictive value, NPV: Negative predictive value.

As it is well known and documented that EUS examination provide a highly and accurate tool for diagnosing pancreatic diseases and tissue sampling, its effectiveness in diagnosing choledocholithiasis is less established. Many studies have been conducted to evaluate its role in detecting the causes of biliary obstruction.^{11, 12}

It is also documented in the latest ASGE and ESGE guidelines that MRCP or EUS are useful tools for evaluating patients with an intermediate probability of choledocholithiasis, without favoring one method over the other.^{13, 14}

In our study, we evaluated the accuracy of EUS in detecting CBD stones, especially that missed by MRCP and ERCP in patients with an intermediate probability of CBD stones and recurrent unexplained pancreatitis.

In the current study, we found that EUS has higher accuracy in detecting choledocholithiasis than MRCP and ERCP. ERCP had the sensitivity of 44.4%, specificity of 100%, PPV of 100%, NPV of 16.6% and accuracy of 50% in relation to EUS results. MRCP had the sensitivity of 81.5%, specificity of 100%, PPV of 100%, NPV of 37.5% and accuracy of 83.3% in relation to EUS results.

Studies on EUS for diagnosing choledocholithiasis have shown varied results. For example, EUS and MRCP sensitivities were both high in Jagtap N et al. (2021), while Wee D et al. (2020) found EUS sensitivities between 85% and 100%, and MRCP sensitivities between 73% and 99%. A meta-analysis by Meeralam Y et al. (2017) indicated that EUS had pooled sensitivities of 97% and specificities of 90%, compared to MRCP's 87% sensitivity and 92% specificity.^14–16

Meanwhile, Materne et al. (2000) found MRCP had 91% sensitivity and 94% specificity, similar to EUS. However, Scheiman et al. (2001) reported EUS had superior results with 95% sensitivity and 80% specificity, compared to MRCP's 40% sensitivity and 96% specificity.^{17, 18}

MRCP may overlook stones that EUS can detect, particularly those situated at the papillary region or distal common bile duct (CBD), which is a known limitation of MRCP interpretation. Moreover, stones smaller than 5 mm are more challenging for MRCP to identify, underscoring EUS's ability to detect smaller stones.^{19, 20}

Several studies have found that EUS provides higher diagnostic yields for idiopathic acute pancreatitis compared to MRCP, Consequently, EUS is recommended as the first choice for diagnosing idiopathic acute pancreatitis.^{21, 22}

In our study, cases with unexplained pancreatitis were evaluated by EUS and MRCP, which showed EUS was more sensitive in detecting stones than MRCP (90% vs. 81.5%, respectively MRCP, meanwhile no other causes of acute pancreatitis as cystic pancreatic lesions, pancreatic divisum or pancreatic duct stones could be detected by MRCP or EUS. This finding is consistent with several studies indicating that EUS sensitivity for evaluating acute pancreatitis can reach up to 89.65%, whereas MRCP sensitivity is around 72.4%.^{22, 23}

The main limitation of our study was the financial cost associated with performing EUS, ERCP, and MRCP on all included patients. Another limitation is our reliance on ERCP as the gold standard for detecting common bile duct (CBD) stones. While ERCP is generally accurate, false-negative results can occur. Small stones may be missed if the CBD is not optimally filled with contrast, and minute stones or gravel may be overlooked during balloon sweeping.

Our study found that EUS, MRCP, and ERCP are not equally effective for diagnosing choledocholithiasis in patients with an intermediate probability. EUS is superior in detecting stones in the papillary region, small stones, and accurately defining stone size and number. Combining EUS with MRCP enhances diagnostic accuracy for these patients.

EUS is a valuable first choice for evaluating patients with an intermediate probability of choledocholithiasis, provided it is available and performed by experienced practitioners. For a more accurate assessment, combining EUS with MRCP is recommended if both modalities are accessible.

ERCP: Endoscopic retrograde cholangiopancreatography.
MRCP: Magnetic resonance cholangiopancreatography.
EUS: Endoscopic ultrasound.
CBD: Common bile duct.
PPV: Positive predictive value.
NPV: Negative predictive value.
CT: Computed Tomography.
AST: Aspartate aminotransferase.
ALT: Alanine transaminase.
GGT: Gamma-glutamyl transferase.
CBC: Complete blood count.
CRP: C-reactive protein.
IHBRDs: Intrahepatic biliary radical dilatation.

Author Contribution

MM did the final review & editing, AM collected the data, AA wrote the manuscript, and MA designed the methodology and helped in writing.All authors read, reviewed and approved the final manuscript.

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No competing interests reported.

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You are reading this latest preprint version

The Role of Endoscopic Ultrasound in Detecting Common Bile Duct Stones Missed Post-Endoscopic Retrograde Cholangiopancreatography in Patients with Calculous Obstructive Jaundice

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Background

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Introduction

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Statistical methods:

Results

Discussion

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Abbreviations

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Author Contribution

References

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