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- Copyright © 2021 Jinyun Tan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract
Hindawi Journal of Healthcare Engineering Volume 2021, Article ID 8666498, 9 pages https://doi.org/10.1155/2021/8666498 Research Article Evaluation of Angiogenesis and Pathological Classification of Extrahepatic Cholangiocarcinoma by Dynamic MR Imaging for E-Healthcare 1 2 3 2 2 1 Jinyun Tan, Xijun Sun, Shaoyu Wang, Baoqin Ma, Zhaohui Chen, Yaowei Shi, 2 4 Li Zhang , and Mohd Asif Shah Department of Hepatobiliary and Pancreatic Surgery, Lanzhou Second People’s Hospital, Lanzhou, Gansu Province, China Department of Medical Imaging, %e Second People’s Hospital of Lanzhou, Lanzhou, Gansu Province, China MR Scientific Marketing,Siemens Healthineers, Shanghai, China Bakhtar University, Kabul, Afghanistan Correspondence should be addressed to Li Zhang; lizhang198@outlook.com and Mohd Asif Shah; ohaasif@bakhtar.edu.af Received 10 July 2021; Revised 7 August 2021; Accepted 1 September 2021; Published 11 October 2021 Academic Editor: Malik Alazzam Copyright © 2021 Jinyun Tan et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. For staging cholangiocarcinoma and determining respectability, MR is an accurate noninvasive method which provides size of tumor and vascular patency information. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive inspection method for evaluating the vascular structure and functional characteristics of tumor tissue. However, some limitations should be noted about the technology. At present, the technology cannot be used alone, which is just an assisted method during the conventional MRI examination. 50 ECC patients, admitted to Indira Gandhi Medical College and Hospital between 2016 and 2019, were selected as research subjects. ,ey were classified pathologically according to the Steiner classification system. After image processing, regions of interest (ROIs) were selected from the image to measure the rate constant (Kep), extravascular space volume fraction (Ve), and tissue volume transfer constant (Ktrans). ,ere were 15 cases with highly differentiated carcinoma, 23 cases with moderately differentiated carcinoma, and 12 cases with lowly differentiated carcinoma. Non-VEGF expression was noted in 21 cases, with low expression noted in 15 cases, moderate expression noted in 14 cases, and no high expression case noted. ,e relevant parameters in the dynamic MRI image can quantitatively reflect the angiogenesis and pathological classification of ECC, which is suggested in the clinical treatment of ECC. ,e Ktrans, Kep, and Ve values of the ECC patients were all not associated with the pathological classification, with no significant difference (P< 0.05). Besides, due to the fact that the patient cannot completely hold his breath, the air leak reduces the image quality. chemotherapy effect monitoring. ,e detection effect is 1. Introduction especially obvious for tumor tissues with better ,e conventional MRI results lack objective evaluation in- differentiation. ECC is the malignant tumor that originates from the dexes, making it difficult to observe the subtle changes in the disease tissue. Dynamic contrast-enhanced magnetic reso- confluence of the left and right hepatic ducts to the common nance imaging (DCE-MRI) is a noninvasive inspection bile duct lower end, usually with cancers located in the method for evaluating the vascular structure and functional ampulla and papilla excluded [2], but hilar chol- characteristics of tumor tissue. ,rough intravenous injec- angiocarcinoma accounts for more than 50%, with malig- tion of small molecule contrast agent, the circulation in the nant obstructive jaundice as the main clinical symptom. ,e blood vessel and its pharmacokinetic characteristics are disease is characterized by slow tumor growth and advanced recorded [1]. It is mainly used in the diagnosis of benign and metastasis, mainly local lymphatic metastasis. Most patients malignant lesions and tumor radiotherapy and die of various complications caused by biliary obstruction 2 Journal of Healthcare Engineering ,erefore, in this study, DCE-MRI was adopted to instead of tumor metastasis, and surgical resection is the main treatment method [3]. evaluate angiogenesis and pathological classification of ECC patients. ,e incidence of ECC has gradually increased. Patho- logical studies have found that most patients with ECC have Contribution: attention given to the application of dy- better pancreatic cancer tissues differentiation, and the namic MR imaging in the evaluation of angiogenesis and the differentiation of pancreatic cancer cells is nearly normal. pathological classification of extrahepatic chol- ,erefore, no obvious tumor markers can be detected in the angiocarcinoma (ECC) patients. ,erefore, in this study, serum, which inhibits the accurate diagnosis of the disease DCE-MRI was adopted to evaluate angiogenesis and [2]. pathological classification of ECC patients. Between the decades of 6th and 7th, cholangiocarcinoma (1) 50 ECC patients, admitted to Indira Gandhi Medical is common in men as compared to women. ,ere is a tumor College and Hospital between 2016 and 2019, were development at a younger age led by the presence of the selected and classified pathologically according to the choledochal cyst Caroli disease hepatolithiasis [4–6]. ,e Steiner classification system. mortality from hepatic failure and cholangiocarcinoma is (2) To observe the expression of VEGF determined reduced resulted by the liver transplantation [7–10]. ,e through immunohistochemical staining, and the cholangiocarcinoma and the histologic stage of PSC may be MVD is determined by CD34 staining. All patients simultaneously diagnosed. ,e cholangiocarcinoma is underwent the dynamic MR imaging examination. higher associated with ulcerative colitis UC as suggested by the experts [11, 12]. (3) After image processing, three regions of interest ,e cholangiocarcinomas are anatomically classified into (ROIs) were selected from the image to measure the three groups. ,e anatomic distribution of the tumor is rate constant (Kep), extravascular extracellular space correlated by these categories and preferred treatment is volume fraction (Ve), and tissue volume transfer implied. ,e classification of cholangiocarcinoma is shown constant (Ktrans). in Figure 1. ,e organization of the paper is as follows. An overview ,e cholangiocarcinoma growth has been described of the exhaustive literature survey is provided in Section 2. macroscopically; first is that mass-forming results in the liver ,e methodology adopted is detailed in Section 3, followed parenchyma definite mass, as shown in Figure 2. by the detailed discussion of obtained results in Section 4. Second infiltrating type results in peripheral ducts di- Finally, Section 5 concludes the paper. latation which is either diffusely infiltrating or nodular, as shown in Figure 3. ,e last one is the polypoidal growth type in which the 2. Literature Survey lumen of the bile duct is proliferated, as shown in Figure 4. More than one growth type encompassed by the combined ,e resectability assessment is the best accomplished by cholangiocarcinoma encompasses is more commonly seen utilizing the imaging, but the emission tomography positron with intrahepatic tumors. is unclear [20]. ,e resectability is the ability of the disease ,e squamous cell carcinoma, small cell carcinoma, and removal while leaving an adequate liver remnant. ,e undifferentiated types are included in tumor types [13–15]. routine use of diagnostic laparoscopy is recommended in the ,ere is variation of tumor grades from well-differentiated patients with high-risk features. ,e high-risk features of to undifferentiated. ,e clusters of cells are consisted in the patients should be encouraged and adjuvant therapy is most of the tumors which are surrounded by the desmo- considered. ,e development of targeted therapeutic in- plastic stroma [16]. ,e reactive tissue and well-differenti- terventions is supported by the biliary cancers genomic ated cholangiocarcinoma are difficult to distinguish. As a analyses. ,e author in this paper details the staging chol- source for metastases, a primary adenocarcinoma should be angiocarcinoma and determining respectability, for that an omitted when intrahepatic cholangiocarcinoma is consid- accurate noninvasive method which is MRI/MRA/MRCP is ered [17, 18]. detailed [21]. In this paper, the author discussed about the Tumor blood vessels not only provide oxygen and nu- routine lymphadenectomy and defined the positive lymph trients for cell metabolism during tumor growth but are also nodes and predictive indicators of survival in patients. By responsible for removing waste generated by cell meta- utilizing the uni- and multivariate analyses, assessment of bolism, serving tumor infiltration and metastasis. ,e new clinical and pathologic data was done [22]. ,e patient’s age blood vessels are continuously generated during metastasis, less than 45 having lymph node positive had a 27-month and the increasing number of blood vessels generated in- survival. Although prospective data are required, lymph dicates faster tumor growth. VEGF exerts strong effect on node positive patients have longer survival associated with inducing tumor angiogenesis, and MVD is usually used to the adjuvant therapy. For adjuvant therapy, the prognostic evaluate tumor angiogenesis. ,e VEGF and MVD values information and guidance are provided by the routine are both determined by invasive examination, and the de- lymphadenectomy. In this paper, the author aims to evaluate tection is susceptible to the sample site, resulting in inac- the patient’s outcome, who had delayed staging at 3 months curate measurement results [19]. after a cholecystectomy [23]. ,e preoperative staging using Journal of Healthcare Engineering 3 Cholangiocarcinomas Distal Intrahepatic Perihilar extrahepatic Hepatic Peripheral Hilar Intraductal duct Figure 1: ,e classification of cholangiocarcinoma. (a) (b) Figure 2: Intrahepatic cholangiocarcinoma (a) axial T1-weighted and (b) axial T2-weighted. multidetector computed tomography is delayed by the 49 histologic type, the radiologic manifestations of chol- patients who underwent using multidetector computed angiocarcinomas are extremely diverse [7]. For accurate detection and characterization of these tumors and assess- tomography (MDCT) followed selectively by laparoscopy after a cholecystectomy. ,e analysis of patient’s long-term ment of respectability, the imaging manifestations of cholangiocarcinomas are important. ,e imaging tech- and perioperative outcomes is performed. ,e statistical analysis is done by the SPSS tool. A favorable prognosis niques are advanced and have led to the availability of an associated with the intraductal growth (IG) type of intra- array of modalities that is utilized independently. For correct hepatic cholangiocarcinoma (ICC) is compared with the diagnosis and appropriate management of these tumors, the mass-forming (MF) and periductal-infiltrating (PI) ICC emerging imaging applications are required [26]. ,e black [24]. After controlling for competing risk factors, IG patients race was associated with worse survival is demonstrated by had a similar prognosis as MF patients on multivariable the Cox proportional hazard ratio model with worse survival analysis. ,e IG patients’ prognosis was comparable with while surgical resection was not independently associated MF patients and the IG patients are frequently presented with survival. As compared to chemotherapy alone, the surgical resection for patients with LN-positive ICC may not with adverse pathological characteristics. ,e author details the lymph node (LN) status which is a survival for resected improve pathologic survival. IHCC [25]. ,e evaluation of number of LNs resected is done at the time of surgery. ,e maximal chi-square testing 3. Materials and Methods and five-year overall survival were utilized for LN thresholds evaluation. ,e 3 LNs as the threshold are identified as a ,e 50 ECC patients (28 males, 22 females; age 45–68), maximal chi-square testing. ,e 39% of resections reached admitted to Indira Gandhi Medical College and Hospital this threshold. ,e prognostic yield is carefully considered between 2016 and 2019, were selected as research subjects. by the surgeons to determine the extended lymphadenec- Inclusion criteria: patients diagnosed with ECC pathologi- tomy at the time of curative-intent resection. Since these cally; patients diagnosed with ECC by imaging examination tumors vary greatly in location, growth pattern, and or tumor markers; patients with abdominal pain, jaundice, 4 Journal of Healthcare Engineering (a) (b) Figure 3: Perihilar cholangiocarcinoma. (a) An MRCP image as a focal stricture and (b) T1W in-phase SGRE; the mass is hypointense relative to liver parenchyma. (a) (b) Figure 4: Intraductal cholangiocarcinoma (a) axial gadolinium-enhanced T1 SGRE image and (b) coronal T2W SSFSE MRCP images. or poor appetite or being emaciated; patients with the tumor Each scan lasted for 9.3 seconds and there were 35 scans in a row. originating from extrahepatic biliary system. ,e principle of DCE-MRI technology: continuous and All images were reviewed by two doctors with at least 5 rapid imaging sequence was used to scan the disease tissue in years of experience in MRI diagnosis. ,ose with poor multiple phases to obtain a series of images at different quality and enhancement were excluded. ,e processed periods of before, during, and after intravenous injection of images were analyzed by the o.k software. ,ree ROIs were contrast agent. ,e scanning process is shown in Figure 5. selected from the image (away from the vessel and necrotic ,e image contains information of tissue perfusion and areas) to measure the Kep, Ve, and Ktrans values, with an vascular permeability, and the physiological characteristics average taken from the three. of the disease tissue were quantitatively and accurately Pathological classification: according to the Steiner grading system, ECC patients were divided into 3 grades of analyzed based on these parameters [27]. ,e patients were in the supine position with an empty high differentiation, moderate differentiation, and poor stomach. ,e contrast agent gadolinium-diethylene- differentiation. If the same pathological tissue had different triaminepentaacetate (Gd-DTPA) was injected intrave- degrees of differentiation, the dominant differentiation nously at 0.2 mmoL/kg, with the dynamic enhancement scan degree was selected as the representative. starting 15 seconds later. Determination of VEGF expression level: immuno- ,e patients should hold breath during the whole histochemical staining method was used to detect the process. After the contrast agent is injected with a speed of VEGF expression level in ECC patients. To have brown 3 mL/s, another 20 mL normal saline is injected at the same particles in the cytoplasm was considered positive for speed to flush the residual contrast agent. VEGF expression. ,en, the count started, high-power ,en, a cross-sectional DCE-MRI examination was fields were selected to count the number of positive cells and the total number of cells. According to the proportion performed, with liver acquisition with volume acceleration (LA-VA) scan sequence adopted: repetition time 3.9 ms/ of positive cells in the tissue, they were divided into 4 echo time 1.9 ms; slice thickness 4.4 mm. levels, as shown in Table 1. Differentiation Grade Journal of Healthcare Engineering 5 Empty stomach Patient Apply Gadolinium- diethylenetriaminepentaacetate 20mL normal saline injected Flush residual contrast agent. Repetition time 3.9 ms/echo time 1.9 ms, DCE-MRI examination slice thickness 4.4 mm performed Each scan lasted for 9.3 seconds Figure 5: DCE-MRI technology. Table 1: ,e proportion of positive cells in the tissue. Positive cells in the tissue No positive cell Positive cell <25% Positive cell 25%–50% Positive cell >50% Unexpressed Lowly expressed Moderately expressed Highly expressed 0.6 0.48 0.475 0.5 0.47 0.4 0.465 0.3 0.46 0.2 0.455 0.1 0.45 High Medium Low Differentiation Grade High Medium Figure 7: ,e Ve value of different differentiation grades. Low Figure 6: ,e Ktrans value of different differentiation grades. high-power microscope. ,e average of the three areas was taken as the final result. ,e data were processed by SPSS 21.0. ,e CD34 was adopted to observe the number of ,e measurement data were calculated as mean ± deviation microvessels in the diseased tissue. It was considered positive, if (‾x± s). ,e correlation between ECC perfusion parameters there were brown particles in the vascular endothelial cyto- with ECC pathological classification, as well as with VEGF plasm. At first, three areas with the highest vessel density were expression, was analyzed by the Spearman test. ,e Pearson selected under a low power microscope. ,en, the number of test was for the correlation analysis between ECC and MVD. stained microvessels in these three areas was counted under a P< 0.05 was set as the threshold for significance. Ktrans (min-1) Ve 6 Journal of Healthcare Engineering 1.8 1.6 1.4 1.2 0.8 0.6 0.4 0.2 High Medium Low Differentiation Grade Figure 8: ,e Kep value of different differentiation grades. Table 2: ,e correlation between the DCE-MRI perfusion parameters with pathological classification. ,e ECC perfusion High differentiation Moderate differentiation Low differentiation r value P value parameter (n � 15) (n � 23) (n � 12) −1 Ktrans (min ) 0.431± 0.034 0.541± 0.161 0.472± 0.136 0.124 0.267 −1 Kep (min ) 1.159± 0.561 1.521± 0.543 1.178± 0.965 0.068 0.583 Ve 0.472± 0.139 0.463± 0.128 0.474± 0.232 0.125 0.421 4. Results and Discussion Table 3: ,e correlation between the DCE-MRI perfusion pa- rameters with VEGF expression. 4.1. %e DCE-MRI Examination Results. ,e data used in this VEGF work are open access and available publically. ,ere were 15 ,e ECC perfusion parameter cases with differentiated carcinoma, 23 cases with moder- r value P value −1 ately differentiated carcinoma, and 12 cases with lowly Ktrans (min ) 0.024 0.843 −1 differentiated carcinoma. Non-VEGF expression was noted Kep (min ) 0.014 0.926 in 21 cases, with low expression noted in 15 cases, moderate Ve 0.072 0.635 expression noted in 14 cases, and no high expression case noted. ,e MVD range was between 40 and 70 among the 50 patients, observed at high power. 0.9 0.8 0.7 4.2. %e Correlation between the DCE-MRI Perfusion Pa- 0.6 rameters with Pathological Classification. ,e Ktrans, Kep, 0.5 and Ve values of the ECC patients were all not associated 0.4 with the pathological classification (P> 0.05), as shown in 0.3 Figures 6–8. ,e correlation between the DCE-MRI per- 0.2 fusion parameters with pathological classification is also 0.1 given in Table 2. Ktrans (min-1) Kep (min-1) Ve ECC Perfusion Parameter 4.3. %e Correlation between the DCE-MRI Perfusion Pa- VEGF r value rameters with VEGF Expression. ,e Ktrans, Kep, and Ve VEGF P values of the ECC patients were all not associated with the Figure 9: Perfusion parameter with VEGF. VEGF expression (P> 0.05). ,e correlation between the DCE-MRI perfusion parameters with VEGF expression is shown in Table 3 and graphically presented in Figure 9. Table 4: ,e correlation between the DCE-MRI perfusion pa- rameters with MVD. 4.4. %e Correlation between the DCE-MRI Perfusion Pa- MVD rameters with MVD. ,e MVD of the ECC patients was ,e ECC perfusion parameter found to be positively correlated with Ktrans value r value P value −1 (r � 0.524, P< 0.001) and was not associated with the Kep Ktrans (min ) 0.524 <0.001 −1 and Ve values, as given in Table 4, and the values are Kep (min ) 0.223 0.135 graphically presented in Figure 10. Ve 0.127 0.289 Kep (min-1) VEGF Journal of Healthcare Engineering 7 0.6 Table 5: Comparison of the presented technique with existing technique. 0.5 ,e ECC perfusion Existing technique Presented technique 0.4 parameter (r value) (r value) 0.3 −1 Ktrans (min ) 0.510 0.524 −1 0.2 Kep (min ) 0.190 0.223 Ve 0.105 0.127 0.1 Ktrans (min-1) Kep (min-1) Ve ECC Perfusion Parameter 0.6 MVD r value 0.5 MVD P 0.4 Figure 10: Perfusion parameter with MSD. 0.3 New vessels are formed mainly based on the existing 0.2 capillaries in the tissue and venules adjacent to the capil- 0.1 laries. According to the different distribution characteristics of angiogenesis, it can be divided into physiological an- Ktrans (min-1) Kep (min-1) Ve giogenesis and pathological angiogenesis [28–31]. ,e physiological angiogenesis is distributed orderly, and the Parameters branches on the main trunk are mostly regular, while the Existing Technique pathological angiogenesis is distributed disorderly and is Presented technique (r value) prone to arteriovenous short circuits. In tumor blood vessels, Figure 11: Comparative analysis of the proposed and existing immature blood vessels with partially missing histological technique. structures account for a large proportion. Due to the lack of a complete basement membrane tightly connected to the cells and a single thin blood vessel wall, the permeability of the 25.00 tumor blood vessels is greatly improved, resulting in the 20.95% leakage of substances in the blood vessels. Studies have 20.00 17.37% shown that an increasing number of new blood vessels and the opening of arteriovenous short circuit indicate the 15.00 further enhancement of tumor tissue invasion and metas- tasis ability, accompanied by higher malignant degree and 10.00 pathological classification [32–34]. 5.00 2.75% 0.00 4.5. Comparative Analysis of the Proposed Technique with the Ktrans (min-1) Kep (min-1) Ve Existing Techniques. ,e proposed technique is compared Parameters with the existing technique [10] in terms of r value and the ECC perfusion parameters. ,e comparison is tabulated in Figure 12: ,e improvement of the presented technique over existing technique. Table 5 and also presented graphically in Figure 11 for better analysis and visualization. It is analyzed and observed from the presented figure that the presented technique is highly correlated than the polypeptide factor that can specifically induce the new blood existing technique. ,ese both techniques are positively vessels formation in tumor tissues and usually acts on tumor correlated with Ktrans value as compared to the Kep and Ve vascular endothelial cell membranes. Studies have found values. ,e proposed technique performance is evaluated that there is no correlation between MVD and VEGF. It is and the improvement in terms of percentage is shown in because before promoting angiogenesis in pathological Figure 12 over the existing technique. tissues, VEGF often needs to go through some complicated ,e proposed technique outperforms the existing processes to act on specific receptors on the vascular en- technique in terms of Ktrans, Kep, and Ve values by 2.75%, dothelial cell membrane [36–38]. 17.37%, and 20.95%, respectively. In this study, the CD34 MRI is widely used in the current medical imaging by was used to label ECC blood vessels to count MVD, because virtue of its multiparameter, multisequence, and multidi- its specificity for vascular endothelium is much higher than rectional imaging function. It is a more objective and ac- other markers. ,e number of tumor neovascularization can curate inspection method. With the continuous development of science and technology, many new magnetic be intuitively determined by counting MVD, so as to de- termine the tumor tissue malignant degree [35]. VEGF is a resonance technologies have been developed, such as arterial MVD e ECC perfusion parameter Percentage Improvement (%) 8 Journal of Healthcare Engineering [4] J. Szklaruk, E. Tamm, and C. Charnsangavej, “Preoperative spin labeling (ASL), diffusion-weighted imaging (DWI), and imaging of biliary tract cancers,” Surgical Oncology Clinics of Perfusion-weighted imaging (PWI). 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Journal
Journal of Healthcare Engineering – Hindawi Publishing Corporation
Published: Oct 11, 2021