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Page 6 of 16 Chandrasekar et al. Mini-invasive Surg 2021;5:33 https://dx.doi.org/10.20517/2574-1225.2021.12

[35]
margins and invasion of the tumor into surrounding tissues are some of the features of malignancy .
Presence of a sessile intra- or extra-ductal tumor and the size of the tumor more than 10 mm were also
[36]
suggested as high-risk features by Tamada et al. . Studies have also shown IDUS to demonstrate higher
sensitivity and specificity when compared to endoscopic ultrasound (EUS) while similar sensitivity and
almost similar specificity compared to ERCP guided tissue biopsies, in distinguishing benign and malignant
strictures [37,38] . IDUS can also be useful in guiding biopsies, as the presence of a sessile tumor or high-risk
features on IDUS resulted in higher rates of positive sampling. IDUS can also provide information
regarding the longitudinal spread of the tumor along the bile duct, depth of tumor invasion and vascular
invasion . Diagnostic accuracy for hepatic artery and portal vein invasion has been reported to be between
[39]
[39]
86% to 100% in studies . The drawback of IDUS despite the above advantages is that tissue sampling
cannot be obtained, availability mainly in only tertiary care centers and teaching hospitals and requires
sufficient expertise to interpret the findings.

Endoscopic ultrasound
EUS can be used in the diagnosis and staging of biliary tract cancers by being able to detect masses that can
appear hypoechoic, biliary ductal dilatation and evaluation of the vasculature and lymph nodes for
involvement with the tumor [Figure 2A]. Studies have shown high rates of sensitivity and specificity for
[40]
detection of malignant strictures up to 80% with detection of distal cancers up to 100% and lower rates for
proximal CCAs [41,42] . Linear EUS scopes provide the ability to perform fine-needle aspiration (FNA), thus
improving the diagnostic accuracy [Figure 2B]. With FNA, sensitivity ranging from 43%-90% and specificity
ranging from 80%-100% have been reported, with higher rates in distal CCA . Comparing EUS-FNA with
[43]
ERCP for diagnosis, studies have shown mixed results with some favoring EUS-FNA and others showing
ERCP with biopsies to be superior [44-46] . But EUS-FNA with ERCP and brushings during the same session
has demonstrated superiority compared to EUS-FNA alone . There are some drawbacks to remember
[46]
while performing and interpreting the results of EUS-FNA. Studies have shown low negative predictive
values ranging from 30% to 65% and hence a negative result does not rule out malignancy in the appropriate
clinical setting. An additional complication with EUS-FNA not seen with endo-biliary sampling is tumor
seeding after FNA, especially in proximal biliary tumors involving the hilum, as they can lead to peritoneal
metastasis. Peritoneal metastasis rates up to 80% have been reported after EUS-FNA sampling [47,48] . Liver
transplantation protocols usually preclude these patients from undergoing transplantation if FNA is
performed pre-operatively for hilar malignancies. The concern for tumor seeding is lower with distal biliary
strictures and hence EUS-FNA is not a contraindication in such cases.

Despite the use of the above-mentioned techniques, false-negative results are still possible. While a positive
result can confirm a diagnosis of malignancy, a negative result does not necessarily rule it out, especially if
the pre-test probability is high and these are labelled “indeterminate strictures”. They are defined as
strictures with no obvious mass on imaging and cannot be reliably differentiated as benign or malignant,
despite workup with ERCP and tissue sampling as described above. Furthermore, the diagnostic yield for
strictures due to various etiologies is different, with higher rates for CCA compared to other peri-ductal
etiologies like pancreatic cancer and gall bladder cancer, thus adding more confusion in clearly defining
these strictures. Surgical exploration can be considered in such cases but recently the use of direct
cholangioscopy guided biopsy has led to a reduction in the need for surgeries and provide the ability for
direct visualization of these strictures. Despite all the workup, if the concern for malignancy remains high,
such patients can be referred to surgery for further exploration.

Cholangioscopy
Digital single operator cholangioscope (DSOC, SpyGlass, Boston Scientific Inc. Massachusetts, USA)
consists of a single disposable 10.5 Fr scope, which can be passed through a duodenoscope. This scope can