【Lancet】Auxiliary diagnosis of new models! Chinese Academy of Medical Sciences detects gene mutations and methylation changes in bile to diagnose pancreatobiliary cancer!

Patients with pancreatobiliary tract cancer generally have a poor clinical prognosis, with a 5-year overall survival rate of less than 20%.

This is mainly related to
late diagnosis.
Accurate preoperative diagnosis, including differentiation from benign disease, is essential
to avoid unnecessary treatment.
Here, a staff from the Chinese Academy of Medical Sciences developed BileScreen, a sensitive test for diagnosing pancreatobiliary cancer based on massively parallel sequencing mutations and methylation changes in bile samples
.

This article is the original of Translational Medicine Network, please indicate the source for reprinting

Author: kope

The team of Zhao Hong/Jiao Yuchen/Cai Jianqiang/Wang Guiqi of the Chinese Academy of Medical Sciences established an auxiliary diagnostic model for biliary system malignant tumors based on parallel analysis of mutations and methylation in bile DNA, which can interrogate mutations and methylation changes in bile samples in parallel, thus making it a potentially sensitive detection method that helps to diagnose pancreatobiliary cancer
in a safe, convenient and less invasive way.

Diagnosis is challenging

 01 

The incidence of biliary tract cancer (BTC) has increased
rapidly worldwide in recent years.
At the same time, pancreatic cancer is one of
the most common and deadliest cancers in humans.
It is the seventh leading cause
of cancer death worldwide.
Strategies for the detection and treatment of pancreatobiliary tract cancer can improve the quality of life and survival of affected individuals
.

However, the diagnosis of pancreatobiliary cancer is challenging
.
Most patients are diagnosed at an advanced stage and have no symptoms even in the early stages due to non-specific symptoms
.
Patients with bile duct stenosis and jaundice may have CCA, GBC, or pancreatic cancer, but it is difficult to distinguish malignancy from benign strictures such as iatrogenic bile duct injury, primary sclerosing cholangitis (PSC), and common bile duct stones
.

In general, late diagnosis results in a poor prognosis for BTC patients, with a 5-year overall survival rate of less than 20%.

Pancreatobiliary carcinoma is usually diagnosed by a combination of clinical examination, radiographic studies (computed tomography, magnetic resonance imaging, magnetic resonance cholangiopancreatography [MRCP]), endoscopic procedures (endoscopic ultrasonography [EUS], fine-needle aspiration [FNA], and endoscopic retrograde cholangiopancreatography [ERCP]), pathological evaluation (histopathology and cytology), and biochemistry (carbohydrate antigens 19-9 [CA19-9]).

The method has limitations

 02 

Existing methods have some limitations, in particular unsatisfactory
sensitivity and specificity.
For example, ERCP is the gold standard for diagnosing pancreatobiliary cancer, as the procedure is used both to detect malignant bile duct stenosis and to obtain biliary brushing and forceps biopsy for further pathological evaluation
.
However, the sensitivity of pathologic evaluation of brush cytology and forceps biopsy to detect malignancy may be quite low (45-48%), and even less
in patients with PSC.

ERCP's inevitable inability to detect many malignancies, especially those in its early stages, leads to more aggressive treatment but lower
survival rates.
The sensitivity of conventional brush cytology has been shown to be improved by auxiliary methods, including PCR mutation analysis and fluorescence in situ hybridization, but remains below 70%
overall.
Conversely, serum CA19-9 has a relatively high sensitivity of ∼80%, but its specificity varies widely, ranging from 63% to 98%.

At this level of sensitivity and specificity, some patients may be overtreated, such as surgery
.

In fact, it has been reported that 15-24% of patients undergoing malignant biliary stenosis surgery are eventually diagnosed with benign disease
.
In addition, CA19-9 is not indicated in Lewis antigen-negative patients (7% of the general population) and finally, EUS-FNA carries a high risk of
tumor dissemination.
Therefore, there is an urgent need to develop a safe diagnostic test for pancreatobiliary cancer with high sensitivity and
specificity.

The new model is widely applicable

 03 

This NGS-based approach uses mutation capsule technology to analyze 23 gene mutations and 44 genes
with methylation changes in parallel from bile samples.
BileScreen was applied to detect malignant tumors in the pancreatobiliary system and compare their performance with traditional methods, especially ERCP-based pathological assessment
.

The primary objective of the study was to investigate whether the combination of mutations and methylation changes specific to pancreatobiliary tract cancer could improve clinical diagnostic capabilities, particularly for undetected cases, for pathological evaluation
of ERCP-obtained samples relative to current standards of care.
The analysis showed that this combination actually showed higher sensitivity than mutations or methylation changes alone, although both were equally specific.

Bile screening is also better than serum CA19-9
.

The BileScreen assay shows high sensitivity and specificity
.
In addition, the availability of routinely drawn decompression bile samples in patients receiving ERCP makes this assay widely applicable
.
Finally, this assay may help improve the diagnosis and management of patients with pancreatobiliary disease, preventing unnecessary resection in benign cases and early initiation of treatment
in malignant cases.

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Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.

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