|Year : 2020 | Volume
| Issue : 3 | Page : 981-986
Role of diffusion-weighted imaging as a new technique in diagnosis of cholangiocarcinoma
Mohamed R Elkholy1, Tarek F abdellah1, Mohamed S Abdelgawad2, Heba S Ellaban2
1 Department of Radiology, Faculty of Medicine, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt
2 Department of Radiology, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt
|Date of Submission||12-Jan-2019|
|Date of Acceptance||26-Jan-2019|
|Date of Web Publication||30-Sep-2020|
Heba S Ellaban
Shobra Bokhom, Quesna, Menoufia Governorate
Source of Support: None, Conflict of Interest: None
To study the role of diffusion-weighted (DW) imaging in the evaluation of cholangiocarcinoma (CC).
In analyzing the presentation of different types of CC, DW-MRI as a noninvasive, safe technique had great importance.
Patients and methods
The patients were referred from Hepatobiliary Surgery and Hepatology Departments of the National Liver Institute, Menoufia University, during the period from October 2016 to November 2018. The study included 50 cases, comprising 34 males and 16 females, with age ranging from 34 to 77 years. Patients who were diagnosed with CC by pathology underwent dynamic MRI.
The study included 50 cases, comprising 34 (68%) men and 16 (32%) women. The sensitivity of dynamic study and DW imaging is 100% in detection of mass-forming and intraductal CCs. We found that apparent diffusion coefficient value of CC is lower than that of the liver and higher than that of the spleen. Relation between the apparent diffusion coefficient and CC pathological grading is evident.
DW imaging is a new effective technique in the detection and improvement of the diagnosis of CC.
Keywords: cholangiocarcinoma, diffusion, dynamic, magnetic resonance, mass forming
|How to cite this article:|
Elkholy MR, abdellah TF, Abdelgawad MS, Ellaban HS. Role of diffusion-weighted imaging as a new technique in diagnosis of cholangiocarcinoma. Menoufia Med J 2020;33:981-6
|How to cite this URL:|
Elkholy MR, abdellah TF, Abdelgawad MS, Ellaban HS. Role of diffusion-weighted imaging as a new technique in diagnosis of cholangiocarcinoma. Menoufia Med J [serial online] 2020 [cited 2021 May 17];33:981-6. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/981/296695
| Introduction|| |
A variety of malignant hepatic neoplasms have been studied with diffusion-weighted (DW) MRI. However, a few studies have focused special attention on the appearance of intrahepatic and hilar cholangiocarcinomas (CCs) on DW-MRI ,.
CC is the most common primary malignant tumor of the liver after hepatocellular carcinoma, representing 5–30% of all prime hepatic malignant tumors .
In this view, intrahepatic CC arises from an intrahepatic biliary duct. Extrahepatic CC is further classified into hilar CC (Klatskin's tumor), which arises from the main (right or left) hepatic duct, the divergence of the common hepatic duct and below the divergence ,.
Many researchers have recommended that DW-MRI increases the sensitivity of MRI for CC diagnosis and in addition differentiates between intrahepatic and hilar CCs and other malignant neoplasm ,.
DW-MR can be analyzed quantitatively with apparent diffusion coefficient (ADC) measurement and qualitatively by analysis of the lesion by image .
The aim of this study was to assess the role of DW imaging in diagnosis and evaluation of different types of CC.
| Patients and Methods|| |
This study was conducted on 50 patients, comprising 34 males and 16 females. Their age ranged between 34 and 77 years.
The patients were referred from Hepatobiliary Surgery and Hepatology Departments of the National Liver Institute, Menoufia University, during the period from October 2016 to November 2018.
Regarding ethical consideration, consent was taken from patients or their relatives before making computed tomography, and they had the right to refuse at any time. The study was approved by the Research Ethics Committee of National Liver Institute and the Research Ethics Committee of the Faculty of Medicine, Menoufia University.
Clinical assessment, laboratory investigation, ultrasound, pathological data, and then detailed MRI was done.
The patients recruited for the study were reviewed against inclusion and exclusion criteria.
Patients with obstructive jaundice, having diagnoses indeterminate by the other diagnostic modalities (namely US), underwent diagnostic MRI for better characterization of these lesions. Patients who underwent upper endoscopy to detect the cause of the obstruction but could not reach the diagnosis were included. Patient who undergo with obstructive jaundice that entered the intervention partition for percutaneous external drainage application. Another selected group included was the patients undergoing regular follow-up of cirrhosis, and had hepatic focal lesion on diagnosis. Moreover, a group of patient that will undergo surgery for the removal of the tumor was included.
Patients with adverse general condition (e.g., tense ascites) and/or unable to hold breath, patients with general contraindications to MRI such as ferromagnetic prosthesis (aneurysmal clip and surgical clips) or foreign bodies (gunshot bullets), patients with cardiac pacemaker or electronic neurostimulant, those having claustrophobia or with unstable clinical status, patients having contraindications to contrast media administration, i.e. history of prior allergic-type reaction to gadolinium chelates, or those having severe renal insufficiency were excluded.
Procedure: all the patients included in this study fasted for 8 h before the procedure. A venous catheter was placed in a peripheral vein (antecubital vein in most cases), being through a long connecting tube to automatic injector to allow easy injection. The patients were trained on how to hold breath, and MRI was performed on high field system (1.5 Tesla – General Electric Optima 450w, 32 channels, New York- Chicago) using a phased array coil to cover the whole liver, manufactured in the USA since 2009.
MR protocol used was as follows: coronal survey BFFE, axial T1-weighted (T1W) images (FRFSE/PROP): axial in-phase and out-phase gradient echo sequence (dual-FFE-BHSENSE) axial images: axial T2-weighted (ax T2 RTr prop), coronal T2W-(FRFSE/prosp), axial T2 fat suppression sequence, and axial heavy T2-weighted images. Regarding diffusion study (DW), respiratory-triggered fat-suppressed single-shot echoplanar DW imaging was performed in the transverse plane with tridirectional diffusion gradients by using b values 0, 500, and 1200 s/mm 2 to increase sensitivity to cellular packing. The dynamic study was performed after bolus injection of 0.1 mmol/kg body weight of Gd-DTPA at a rate of 2 ml/s and flushed with 20 ml of sterile 0.9% saline solution from the antecubital vein. The patient was asked to hold breath at the end of expiration.
Imaging evaluation: data analysis was done at the workstation started with the morphological features of the CC (stricture, intraductal, or mass forming). Measurement of the ADC value of mass-forming, intraductal CC, as well as of the liver at a fixed site such as segment IV and spleen was done to compare the ADC of CC with ADC of the liver and spleen.
Statistical analysis of the data
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 (IBM Corp., Armonk, New York, USA). It included descriptive, for example, percentage and mean ± SD, and analytical statistics, such as χ2-test, Fisher's exact or Monte Carlo correction, and F-test (analysis of variance).
| Results|| |
MRI was carried out for 50 adult patients. The technique was successfully performed in 34 (68%) men and 16 (32%) women, with a mean age of 61.52 ± 10.45 years [Table 1].
|Table 1: Distribution of the studied cases according to demographic data (n=50)|
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According to CC types and their distribution, CC is classified according their distribution into intrahepatic (30 cases) and extrahepatic (20 cases). According to the morphology pattern, the intrahepatic type is subclassified into mass-forming type (28 cases, 93.3%) and intraductal type (2 cases, 6.6%). The extrahepatic type is subclassified into mass forming (10 cases, 50%), stricture type (8 cases, 40%), and intraductal type (2 cases, 10%) [Table 2].
|Table 2: Distribution of the studied cases according to the different types of cholangiocarcinoma (n=50)|
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According to CC morphological features and effect, we found that lobar atrophy owing to fibrosis is seen in 14 (28%) of cases. According to wall definition (mass-forming and intraductal types 42 cases), we found that 22 (52.4%) are well-defined lesions and 20 (47.6%) cases are ill-defined lesions. Portal vein invasion is seen in 10 (20%) cases, and hepatic artery invasion is seen in two (4%) cases. Intrahepatic biliary dilation is not seen in 10 (20%) cases, mild Intra-hepatic biliary radicle dilatation (IHBRD) is seen in 12 (24%) cases, moderate IHBRD is seen in 26 (52%), and marked IHBRD is seen in two (4%) cases [Table 3].
According to evaluation of different types of CC [mass forming (38 cases), stricture (eight cases), and intraductal type (four cases)], the stricture type of CC is diagnosed by morphological appearance in Magentic Resonance Cholangiography (MRCP) and elevated tumor markers (CA 19-9), which is highly suggestive of CC.
We found that the sensitivity of dynamic MRI was similar to DW imaging in detecting the mass-forming and intraductal types of CC; however, the stricture type of CC shows no enhancement pattern and is not restricted at DWI [Table 4].
|Table 4: Diffusion-weighted imaging and postcontrast enhancement patterns for the three types of cholangiocarcinoma in (n=50) and apparent diffusion coefficient value of cholangiocarcinoma (intraductal and mass-forming cholangiocarcinoma, hepatic parenchyma, and splenic parenchyma on diffusion-weighted MRI)|
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We found that ADC value of CC (0.80–1.50) was lower than that of the ADC of the liver (0.90–2.0) and higher than that of the spleen (0.50–1.10) [Table 2].
According to relation between ADC value of mass-forming CC and it is grading by pathology, poorly differentiated CC is associated with lower ADC value (mean: 0.98 ± 0.12), whereas well-differentiated CC is associated with higher ADC value (mean: 1.23 ± 0.16) [Table 5].
|Table 5: Relation between grading of mass-forming cholangiocarcinoma with pathological correlation and apparent diffusion coefficient value (n=38)|
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A 35-year-old male patient presented with right hepatic lobe mass-forming CC, measuring 8 × 5.5 cm. There was no IHBRD, and the mass shows T1 hypointense signal, T2 hyperintense signal, delayed filling in pattern of enhancement, and DWI restriction. The ADC of the lesion was 1.2, ADC of the liver was 1.7, and ADC of the spleen was 0.9 [Figure 1].
|Figure 1: (a) Axial T1 shows hypointense intrahepatic mass lesion. (b) Axial T2 shows hyperintense mass. (c) DWI shows mass restriction. (d) ADC the lesion is hypointense with ADC value 1.2. (e) Arterial phase shows peripheral arterial enhancement. (f) Delayed phase shows filling in pattern. ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging.|
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Another 67-year-old male patient showed cirrhotic liver, and had mild ascites with intraductal hilar CC measuring 2 × 2.5 cm. The mas shows T1 hypointense signal DWI restriction, and MRCP shows intraductal lesion and moderate IHBRD. ADC of the lesion is 1.09, ADC of the liver is 1.6, ADC of the spleen is 0.8 [Figure 2].
|Figure 2: (a) Coronal T2 shows hypointense hilar intraductal CC. (b) Coronal MRCP shows intraductal mass with moderate IHBRD. (d) Axial MRCP shows intraductal mass with moderate IHBRD. (e) ADC. The lesion is hypointense with ADC value of 1.09. ADC, apparent diffusion coefficient.|
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| Discussion|| |
A variety of imaging modalities, invasive and noninvasive, are employed in diagnosis and staging of cholangiocarcinoma . More new research studies have been done for testing new imaging techniques . In this view, several researchers have recommended that DW-MRI helps increase MRI sensitivity for CC diagnosis .
DW-MRI provides distinctive close visuals into tissue organization, cellularity, integrity of cells, and membranes, as well as the tortuosity of the extracellular space, which can be helpful for diagnosis of neoplastic diseases, and for differentiating neoplastic tissues from non-neoplastic tissues .
The current study was conducted on 50 patients, with age ranging from 34 to 77 years and mean age of 61.52 years. This means that CCs are more predominant after age of 60 years, which was in line with other studies such as Park et al. , which included 52 patients with mean age of 63.4 years. Sex distribution showed a male predominance (36 cases, 68%) than female (16 cases, 32%). This is owing to both studies had even similar number of cases.
In our study, we found that the mass-forming CC and the intraductal CC which were pathologically diagnosed were enhanced at the dynamic phase. Moreover, the mass-forming CC and the intraductal CC were restricted at DWI. This means that the dynamic study and DWI had the same sensitivity in detection of both types of CC; however, the periductal stricture type is diagnosed by morphological features at MRCP, and elevated tumor marker shows no enhancement pattern and is not restricted in DWI. This is in line with Doshi et al. , who found that all 12 masses of the mixed mass-forming lesions showed restricted diffusion in either most or some part of the lesion; however, most of the perihilar infiltrating types of lesions (28 out of 35 patients) did not show any restriction of the diffusion. This is may be because restricted diffusion was prevalent in that region of the lesions which was hyperintense on DWI suggesting the active (cellular) area; however, in stricture type of CC, there is no mass lesion with no restriction.
According to the comparison between the ADC value of CC and the ADC value to liver and spleen, we found that ADC value of CC was lower than that of the liver and higher than that of the spleen. This is in line with Fattach et al.  who also found that the same results and reported that using the spleen and the liver as a reference organ is a relatively recent concept that helps improve reproducibility and reduce variability in ADC measurement at 1.5-T. This is done by calculating two normalized ADC ratios for each CC, when using the apparently normal hepatic parenchyma for normalization, measurements are facilitated when Region of Interest (ROIs) used for calculation are placed on the same level of slice.
Finally, according to the relation between pathological grading of mass-forming CC and its ADC value, we found that higher ADC value (mean: 1.23 ± 0.16) was associated with well-differentiated CC and low ADC value (mean: 0.98 ± 0.12) was associated with poorly differentiated CC. These results are in line with Lwis et al.  and Cui et al.  who reported that lower mean ADC value were associated with poorer tumor differentiation. This illustrates the value of ADC in detecting tumor degree of differentiation.
| Conclusion|| |
DWI is a noninvasive, simple, non-contrast-dependent method that helps in diagnosis of CC and evaluating its grade of differentiation. Therefore, it is a promising new technique.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chandarana H, Taouli B. Diffusion and perfusion imaging of the liver. Eur J Radiol. 2010; 76
Taouli B. Diffusion-weighted MR imaging for liver lesion characterization: acritical look. Radiology 2012; 262
Choi B, Lee J, Han J. Imaging of intrahepatic and hilar cholangiocarcinoma. Abdom Imaging. 2004; 29
Khan S, Emadossadaty S, Ladep N, LThomas H, Elliott P, Taylor-Robinson S, et al
. Rising trends in cholangiocarcinoma: is the ICD classification system misleading us. J Hepatol 2012; 56
Aljiffry M, Walsh M, Molinari M. Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009. World J Gastroenterol 2009; 15
Manfredi R, Barbaro B, Masselli G, Vecchioli A, Marano P. Magnetic resonance imaging of cholangiocarcinoma. Semin Liver Dis 2004; 24
Sainani N, Catalano O, Holalkere N, Zhu A, Hahn P, Sahani D, et al
. Cholangiocarcinoma: current and novel imaging techniques. Radiographics. 2008; 28
Ganeshan D, Moron F, Szklaruk J Extrahepatic biliary cancer: new staging classification. World J Radiol 2012; 4
Péporté A, Sommer W, Nikolaou K, Reiser M, Zech C. Imaging features of intrahepatic cholangiocarcinoma in Gd-EOB-DTPA-enhanced MRI. Eur J Radiol. 2013; 82
Thoeny H, De Keyzer F. Extracranial applications of diffusion-weighted magnetic resonance imaging. Eur Radiol 2007; 17
Park M, Kim Y, Park H, Hwang J, Lee W. Scirrhous hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging and diffusion-weighted imaging: emphasis on the differentiation of intrahepatic cholangiocarcinoma. J Comput Assist Tomogr 2013; 37
Doshi R, Reddy B, Hyderbad I. Review of MR imaging findings of cholangiocarcinoma with emphasis on diffusion weighted imaging. Eur Soc Radiol 2010; 15
Fattach H, Dohan A, Guerrache Y, Dautry R, Boudiaf M, Hoeffel C, et al
. Intrahepatic and hilar mass-forming cholangiocarcinoma: qualitative and quantitative evaluation with diffusion-weighted MR imaging. Eur J Radiol 2015; 84
Lwis S, Besa C, Wagner M, Jhaveri K, Kihira S, Zhu H, et al
. Prediction of the histopathological finding of the intrahepatic cholangiocarcinoma: qualitative and quantitave assessment of diffusion-weighted imaging. Eur Radiol 2018;28
Cui X, Chen H, Cai S, Bao J, Tang Q, Wu L, et al
. Diffusion-weighted MR imaging for detection of extrahepatic cholangiocarcinoma. Eur J Radiol 2012; 81
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]