Ahmad Hormati 1,2, Saeede Jafari 3, Amir Jabbari 4, Mahdi Pezeshki Modares 1, Mahboubeh Afifian 5,
Ahmad Abasi 4, Sajjad Ahmadpour 1, Ali Reza Sharifi 6,*

BACKGROUND

Cholangiocarcinoma is the second most common malignant liver cancer. Its early diagnosis plays an important role in the success of treatment. The aim of this study was to compare the use of cold forceps biopsy without cholangioscopy with brush cytology in the diagnosis of cholangiocarcinoma.

METHODS

In this prospective study, we enrolled 19 patients. Endoscopic retrograde cholangiopancreatography (ERCP) was performed for all individuals. Sampling was performed from the narrowing site using the brush method. Then, a cold forceps biopsy was performed under fluoroscopy.

RESULTS

The mean age of the patients was 63.31 ± 11.12 years and most of them were men
(63.16 %). The brush cytology and the cold forceps biopsy diagnosed 31.85% and
68.42% of the samples as cholangiocarcinoma, respectively.

According to the McNemar test, there was a statistically significant difference between the diagnostic results of the brush cytology and cold forceps biopsy. So that more cholangiocarcinoma cases were
diagnosed using forceps biopsy (p = 0.016). No complications such as perforation, bleeding,
cholangitis, and leakage were reported during the cold forceps procedure.

CONCLUSION

Cold forceps biopsy under fluoroscopy is better than cytology brush in the diagnosis
of proximal cholangiocarcinoma. It is recommended to be used as a low-cost alternative
in cases where cholangioscopy is not available.

KEYWORDS:

Cholangiocarcinoma, Cytology, Biopsy, Diagnosis

INTRODUCTION

Cholangiocarcinoma is the most common malignancy of biliary epithelial cell origin and is the second most common malignant liver cancer in recent decades. Early diagnosis plays an important role in the success of treatment and prognosis. There are a variety of diagnostic methods, such as tumor marker measurement, imaging modalities, and histopathological examination by sampling.

There are several methods for sampling, such as brush cytology, forceps biopsy, and endoscopic ultrasound fine needle aspiration (EUS-FNA), which require a guided procedure. The most common guidelines include cholangioscopy, endoscopic ultrasound (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) plus fluoroscopy

Cholangioscopy is known as the preferred detection method for cholangiocarcinoma. EUS-FNA is a suitable method for examining proximal bile duct lesions, which is similar to forceps biopsy.6 Over the past three decades, biopsy and brush cytology under ERCP guidance have been the main methods of tissue examination.

Brush cytology is a common technique due to its simplicity and short duration of performing, but its diagnostic sensitivity is low (about 30-70%).6 Only a few cellular samples are taken in this procedure for histopathological examination, and it provides low study possibly. Forceps biopsy is another method whose diagnostic sensitivity is reported to be about 36-81%. In this method, forceps can easily enter the stenotic duct and give a complete tissue sample from the occlusion,10 which also makes it possible to study the subepithelial level to assess the extent of cancer.

To make a diagnostic comparison between the two methods of brush cytology and forceps biopsy, the study of Hasan Kulaksiz and colleagues showed that the combined use of both methods was more sensitive than the use of each method alone (specificity of both methods is 100%, the sensitivity of brush and forceps alone are 49% and 69%, respectively, and 80% in combination use).

A study by Hartman and others also showed that fluoroscopyguided sampling was better than cholangioscopy-guided. Although cholangioscopy is a preferred method in the diagnosis of cholangiocarcinoma,7 the lack of access to it in all medical centers and its high costs does not make it possible for all patients to use it, and physicians have to choose the other alternative methods. In this regard, as mentioned earlier, the two methods of brush cytology and forceps biopsy are more popular in all medical centers due to their low cost and availability.

Unfortunately, in the field of comparing the diagnostic power of these two methods, limited studies have been done, and enough resources are not available. Our aim in this study was to compare the use of cold-forceps biopsy without cholangioscopy with brush cytology in the detection of cholangiocarcinoma.

MATERIALS AND METHODS

Study design and participants

This was a prospective study. All patients with a diagnosis of proximal cholangiocarcinoma who had been referred to the gastroenterology clinic of Shahid Beheshti Hospital were entered in the study using census sampling. In this study, cholangiocarcinoma was diagnosed based on a set of clinical and laboratory findings, and Magnetic resonance cholangiopancreatography (MRCP) results.

Accordingly, the patients with no history of background disease including; surgery (iatrogenic bile duct injurie), trauma, bile duct injury, primary sclerosing cholangitis (PSC) such as underlying inflammatory bowel disease (IBD) included in the study. Cholangiocarcinoma considered when the patients presented high tumor markers and liver enzymes, clinical evidence of cholestasis such as icterus, pruritus, weight loss, and stenosis in MRCP.

Data collecting

Study data were collected from the clinical records of eligible patients. These data were included in a researchermade checklist that included two sections: demographic variables (sex and age) and laboratory variables (the result of liver enzymes, CA19_9 tumor markers, and pathology report).

Sampling protocol

For all 19 participants in the study, ERCP, with the use of Olympus cv-160 (Olympus Duodenoscope, Tokyo, Japan) was performed by a gastroenterologist, was done. First, the guidewire was passed through the narrowing site, and then the contrast agent was injected.

This determined the length, intensity, and location of the stenosis. Then, from the inside of the stenosis, sampling was performed by the brush method (Cytology Brush SU- Diameter 2.6 mm, Length 180 cm ENDO FLEX, Germany).

In the next step, cold forceps (Biopsy forceps–Diameter 1.8 mm, Length 160 cm, ENDO FLEX, Germany) sampling was performed directly using fluoroscopy-guided without cholangioscopy using small biopsy pans (Figure 1), and finally, the remaining of the contrast material in the ducts and branches was suctioned, and for establishing bile drainage, a plastic stent was placed in the involved branches and was crossed from the stenosis area.

In order to obtain suitable tissue samples, the samples were taken from the three initial, middle, and terminal parts of the stenosis, which were more likely to have cholangiocarcinoma without mucosal necrosis

Follow up

The follow-up program was designed to find the complications of the intervention: After ERCP, all patients, often with jaundice, were admitted to the hospital and monitored for at least 48 hours and were discharged if no complications occurred.

Contact numbers were provided to patients that, in cases of abdominal pain, exacerbation of jaundice, fever, and chills, they could contact to receive the necessary advice. Besides, they were followed up after 1 week, 1 month, and 3 months after ERCP. During the evaluation, in the case of jaundice exacerbation, the plastic stents were replaced with another plastic stent, and in people with a definite diagnosis, metal stents were replaced