Hepatobiliary Pancreat Dis Int

	2021 Vol. 20 No. 3
	Published: 2021-06-15


	Pages 205-306
	EDITORIAL REVIEW ARTICLES ORIGINAL ARTICLES/Transplantation ORIGINAL ARTICLES/Liver ORIGINAL ARTICLES/Biliary ORIGINAL ARTICLES/Pancreas NEW TECHNIQUES CLINICAL IMAGE LETTERS TO THE EDITOR

EDITORIAL

	205	Chierici A, Ofosu A, Cincione I, Sacco R, Cotsoglou C, Facciorusso A
		Transarterial chemoembolization as adjuvant treatment after surgery: The cure of huge hepatocellular carcinoma?
		Hepatocellular carcinoma (HCC) represents the sixth common cancer and the second leading cause of cancer-related death. Its incidence is higher in Eastern countries. HCC is frequently detected at advanced stage of disease, and therefore, the mortality is high [1].
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 205-206 . [Abstract] ( 55 ) [HTML 1KB] [PDF 0KB] ( 95 )

REVIEW ARTICLES

	207	Li H, Ding P, Peng B, Ming YZ
		Cross-talk between hepatic stellate cells and T lymphocytes in liver fibrosis ^Hot!
		Background: Fibrosis results from inflammation and healing following injury. The imbalance between extracellular matrix (ECM) secretion and degradation leads to the ECM accumulation and liver fibrosis. This process is regulated by immune cells. T lymphocytes, including alpha beta (αβ) T cells, which have adaptive immune functions, and gamma delta (γδ) T cells, which have innate immune functions, are considered regulators of liver fibrosis. This review aimed to present the current understanding of the cross-talk between T lymphocytes and hepatic stellate cells (HSCs), which are the key cells in liver fibrosis. Data sources: The keywords “liver fibrosis”, “immune”, and “T cells” were used to retrieve articles published in PubMed database before January 31, 2020. Results: The ratio of CD8 + (suppressor) T cells to CD4 + (helper) T cells is significantly higher in the liver than in the peripheral blood. T cells secrete a series of cytokines and chemokines to regulate the inflammation in the liver and the activation of HSCs to influence the course of liver fibrosis. In addition, HSCs also regulate the differentiation and proliferation of T cells. Conclusions: The cross-talk between T cells and HSCs regulates liver fibrosis progression. The elucidation of this communication process will help us to understand the pathological process of liver fibrosis.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 207-214 . [Abstract] ( 64 ) [HTML 1KB] [PDF 0KB] ( 71 )

ORIGINAL ARTICLES/Transplantation

	215	Wang YJ, Li JH, Guan Y, Xie QH, Hao CM, Wang ZX
		Diabetes mellitus is a risk factor of acute kidney injury in liver transplantation patients
		Background: Diabetes mellitus has become an increasing global health burden with rapid growing preva- lence. Patients with diabetes have higher susceptibility to acute kidney injury (AKI). Liver transplantation (LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate (eGFR), the model for end-stage liver disease (MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients (35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of eGFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of eGFR within the first year after surgery.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 215-221 . [Abstract] ( 59 ) [HTML 1KB] [PDF 0KB] ( 112 )

	222	He ZL, Zhou JB, Liu ZK, Dong SY, Zhang YT, Shen T, Zheng SS, Xu X
		Application of machine learning models for predicting acute kidney injury following donation after cardiac death liver transplantation ^Hot!
		Background: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. Methods: A total of 493 patients with donation after cardiac death LT (DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes (KDIGO). The clinical data of patients with AKI (AKI group) and without AKI (non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve (AUC). Results: The incidence of AKI was 35.7% (176/493) during the follow-up period. Compared with the non-AKI group, the AKI group showed a remarkably lower survival rate ( P < 0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval (CI): 0.794–0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models ( P < 0.001). Conclusions: The random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 222-231 . [Abstract] ( 62 ) [HTML 1KB] [PDF 0KB] ( 95 )

ORIGINAL ARTICLES/Liver

	232	Wang H, Yu H, Qian YW, Cao ZY, Wu MC, Cong WM
		Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma ^Hot!
		Background: Surgical resection of huge hepatocellular carcinoma (HCC, ≥ 10 cm) is potentially curative. More adjuvant treatments are needed to reduce relapses in these patients. We evaluated the influence of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on the prognosis of huge HCC. Methods: Data from consecutive patients who underwent curative resection for huge HCC in our center were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients who did and did not undergo PA-TACE. Propensity score matching (PSM) was used. Results: Among the 255 enrolled patients, 93 underwent PA-TACE. The clinical outcomes were significantly better in the PA-TACE group than those in the non PA-TACE group (5-year RFS rate: 33.5% vs. 18.0%; 5-year OS rate: 47.0% vs. 28.0%, all P < 0.001). After PSM, similar results were obtained (5-year RFS rate: 28.8% vs. 17.6%, P < 0.001; 5-year OS rate: 42.5% vs. 25.0%, P = 0.004). PA-TACE decreased the possibility of early recurrence ( < 2 years, crude cohort: P < 0.001, PSM cohort: P < 0.001) but not late recurrence ( ≥ 2 years, crude cohort: P = 0.692, PSM cohort: P = 0.325). Multivariable Cox regression analysis suggested that PA-TACE was an independent protective factor prolonging early RFS, RFS and OS. Conclusions: PA-TACE is a safe intervention for huge HCC patients after liver resection and improves outcomes.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 232-239 . [Abstract] ( 75 ) [HTML 1KB] [PDF 0KB] ( 108 )

	240	Li TT, Sun J, Wang Q, Li WG, He WP, Yang RC, Duan XZ
		The effects of stereotactic body radiotherapy on peripheral natural killer and CD3+ CD56+ NKT-like cells in patients with hepatocellular carcinoma
		Background: Both natural killer (NK) and CD3+ CD56+ natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis. Methods: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. Results: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+ NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3 + CD56 + NKT-like cells was associated with a higher overall survival rate in HCC patients. Conclusions: SBRT has an apparent effect on both peripheral NK and CD3 + CD56 + NKT-like cells. Lower percentage of NKp30 + NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT are correlated with poor patients’ PFS. Higher percentage of CD3 + CD56 + NKT-like cells is associated with higher OS in HCC patients.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 240-250 . [Abstract] ( 64 ) [HTML 1KB] [PDF 0KB] ( 101 )

	251	Han Q, Chen CA, Yang W, Liang D, Lv HW, Lv GS, Zong QN, Wang HY
		ATP-citrate lyase regulates stemness and metastasis in hepatocellular carcinoma via the Wnt/beta-catenin signaling pathway ^Hot!
		Background: Hepatocellular carcinoma (HCC) is one of the most highly malignant tumors. Liver tumor-initiating cells (LTICs) have been considered to contribute to HCC progression and metastasis. ATP-citrate lyase (ACLY), as a key enzyme for de novo lipogenesis, has been reported to be upregulated in various tumors. However, its expression and role in HCC and LTICs remain unknown. Methods: The expressions of ACLY in HCC tissues were detected by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. Kaplan-Meier curves and Chi-square test were used to determine the clinical significance of ACLY expression in HCC patients. A series of assays were performed to determine the function of ACLY on stemness, migration and invasion of HCC cells. Luciferase reporter assay, Western blotting and immunoprecipitation were used to study the regulation of the Wnt/β-catenin signaling by ACLY. Rescue experiments were performed to investigate whether β-catenin was the mediator of ACLY-regulated stemness and migration in HCC cells. Results: ACLY was highly expressed in HCC tissues and LTICs. Overexpression of ACLY was significantly correlated with poor prognosis, progression and metastasis of HCC patients. Knockdown of ACLY remarkably suppressed stemness properties, migration and invasion in HCC cells. Mechanistically, ACLY could regulate the canonical Wnt pathway by affecting the stability of β-catenin, and Lys49 acetylation of β-catenin might mediate ACLY-regulated β-catenin level in HCC cells. Conclusions: ACLY is a potent regulator of Wnt/ β-catenin signaling in modulating LTICs stemness and metastasis in HCC. ACLY may serve as a new target for the diagnosis and treatment of HCC.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 251-261 . [Abstract] ( 90 ) [HTML 1KB] [PDF 0KB] ( 99 )

ORIGINAL ARTICLES/Biliary

	262	Bartsch F, Hahn F, Muller L, Baumgart J, Hoppe-Lotichius M, Kloeckner R, Lang H
		Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging
		Background: Intrahepatic cholangiocarcinoma (ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. Methods: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. Results: Out of 184 patients, 135 (73.4%) underwent curative intended resection. Median overall survival (OS) was 22.2 months with a consecutive 1-, 3- and 5-year OS of 73%, 29%, and 17%. Median recurrence-free survival (RFS) was 9.3 months with a consecutive 1-, 3- and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction (POP) score was created showing significance for OS and RFS (all P < 0.001). In multivariate analysis, POP score (HR = 1.779; 95% CI: 1.26 8-2.4 95; P = 0.001), T stage (HR = 1.255; 95% CI: 1.040-1.514; P = 0.018) and N stage (HR = 1.334; 95% CI: 1.081-1.645; P = 0.007) were the independent predictors for OS. For RFS, POP score (HR = 1.733; 95% CI: 1.30 0-2.311; P < 0.0 01) and M stage (HR = 3.036; 95% CI: 1.376-6.697; P = 0.006) were the independent predictors. Conclusions: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 262-270 . [Abstract] ( 68 ) [HTML 1KB] [PDF 0KB] ( 83 )

ORIGINAL ARTICLES/Pancreas

	271	Luu AM, Braumann C, Belyaev O, Janot-Matuschek M, Rudolf H, Praktiknjo M, Uhl W
		Long-term survival after pancreaticoduodenectomy in patients with ductal adenocarcinoma of the pancreatic head
		Background: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignant tumors due to unavailable screening methods, late diagnosis with a low proportion of resectable tumors and resistance to systemic treatment. Complete tumor resection remains the cornerstone of modern multi-modal strategies aiming at long-term survival. This study was performed to investigate the overall rate of long-term survival (LTS) and its contributing factors. Methods: This was a retrospective single-center analysis of consecutive patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2007 and 2014 at the St. Josef Hospital, Ruhr University Bochum, Germany. Clinical and laboratory parameters were assessed and evaluated for prediction of LTS with Cox regression analysis. Results: The overall rate of LTS after PD for PDAC was 20.4% (34/167). Median survival was 24 months regardless of adjuvant treatment. Carbohydrate antigen 19-9 levels, tumor grade, lymph vessel invasion, perineural invasion and reduced general condition were significantly associated with LTS in univariate analysis ( P < 0.05). Serum levels of carbohydrate antigen 19-9, American Joint Committee on Cancer stage, tumor grade, abdominal pain, male, exocrine pancreatic insufficiency and duration of postoperative hospital stay were independent predictors of cancer survival in multivariable analysis. Conclusions: Cancer related characteristics are associated with LTS in multimodally treated patients after curative PDAC surgery.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 271-278 . [Abstract] ( 62 ) [HTML 1KB] [PDF 0KB] ( 88 )

	279	Kettler B, Trauzold A, Roder C, Egberts JH, Kalthoff H
		Topology impacts TRAIL therapy: Differences in primary cancer growth and liver metastasis between orthotopic and subcutaneous xenotransplants of pancreatic ductal adenocarcinoma cells ^Hot!
		Background: To study novel treatment modalities for pancreatic ductal adenocarcinoma (PDAC), we need to transfer the knowledge from in vitro to in vivo . It is important to mirror the clinical characteristics of the typically local invasive growth of pancreatic cancer and the distant spread resulting in liver metastasis. Notably, for xenotransplant studies using human specimen, two models, i.e. subcutaneous (s.c.) and orthotopic (o.t.) transplantation are widely used. Methods: The subcutaneously and orthotopically inoculated Colo357 Bcl-x L cell-derived tumors were di- rectly compared with and without TNF-related apoptosis inducing ligand (TRAIL) treatment. The size of primary tumors, number of liver metastasis and the histologic markers Ki67, M30, TNF-α and CD31 were assessed. Results: Upon TRAIL treatment, the primary tumors did not change their size, neither in the s.c. nor in the o.t. approaches. But when s.c. was compared to o.t., the size of the s.c. tumors was more than two- fold bigger than that of the o.t. tumors ( P < 0.01). However, mice with orthotopically inoculated PDAC cells developed liver metastasis upon TRAIL treatment much more frequently ( n = 13/17) than mice with subcutaneously inoculated PDAC cells ( n = 1/11) ( P < 0.01). As a likely driving force for this increased metastasis, a higher TNF-α staining intensity in the o.t. tumors was observed by immunohistochemistry. Conclusions: These data from a direct side-by-side comparison underline the importance of the proper inoculation site of the PDAC cells. Local invasion and liver metastases are a hallmark of PDAC in the clinic; the o.t. model is clearly superior in reflecting this setting. Moreover, a serious side-effect of a possible new therapeutic compound became obvious only in the o.t. model.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 279-284 . [Abstract] ( 89 ) [HTML 1KB] [PDF 0KB] ( 83 )

NEW TECHNIQUES

	285	Llado L, Iborra E, Ramos E, Sabe N, Cachero A, Fabregat J
		Extra-anatomic aortic bypass for the treatment of a mycotic pseudoaneurysm after liver transplantation for hilar cholangiocarcinoma
		Liver transplantation (LT) after neoadjuvant chemoradiotherapy in patients with unresectable hilar cholangiocarcinoma (HC) is an accepted treatment strategy [1]. Neoadjuvant therapy is associated with an increased risk of arterial and portal complications after LT [1,2]. In most cases, radiation therapy makes the use of the native hepatic artery inadvisable, and an aortic anastomosis is needed, either with or without a graft [2].
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 285-287 . [Abstract] ( 66 ) [HTML 1KB] [PDF 0KB] ( 119 )

CLINICAL IMAGE

	288	Chu XH, Zhao YK, Shan XD, Sun YY, Shi YZ, Sun XT
		Arantius’ ligament approach for the laparoscopic left hemihepatectomy
		In recent years, the technique of laparoscopic hepatectomy has been developed rapidly, and its indications are approximately equal to open surgery [1,2]. Laparoscopic left hemihepatectomy (LLH) has become a mature and standardized operation [3,4], and there are many reports on the relevant surgical paths and norms [5-7]. Herein, the Arantius’ ligament approach for the LLH is proposed, which provides a reference for the standardized path of LLH.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 288-292 . [Abstract] ( 73 ) [HTML 1KB] [PDF 0KB] ( 91 )

	293	D’Ovidio V, Bruno G, Sodani G, Lucidi C, Bazuro ME
		Intraparenchymal hepatic hematoma following endoscopic retrograde cholangiopancreatography: Risk factors and conservative approach in acute management
		Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure with a complication rate ranging from 4% to 10% [1]. While post-procedure pancreatitis is the most common risk, bleeding also deserves attention. The most common symptoms of post-procedure bleeding were abdominal pain (91.7%), anemia (43.8%), hypotension (29.2%) and fever (20.8%) [2,3].
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 293-295 . [Abstract] ( 69 ) [HTML 1KB] [PDF 0KB] ( 109 )

	296	Guerra F, Petrelli F, Patriti A
		Robotic choledochoduodenostomy for complicated common bile duct stones - a video vignette
		Despite that endoscopic retrograde cholangiopancreatography (ERCP) has become the gold standard in the treatment of benign biliary obstruction, bilioenteric anastomosis still represents a valid option to treat the increasing number of patients with recalcitrant obstruction, and/or altered anatomy after digestive surgery [1,2]. Minimally invasive techniques have become the standard of care for the surgery of the biliary tract in specialized centers [2,3]. In recent years robotic platforms have shown promising results overcoming some of the technical difficulties of conventional laparoscopy, especially in the case of demanding procedures requiring complex dissection and bilioenteric reconstruction [3].
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 296-297 . [Abstract] ( 73 ) [HTML 1KB] [PDF 0KB] ( 121 )

LETTERS TO THE EDITOR

	298	Yan D, Huang YD, Chen YB, Lv T, Zhu CX, Huang JR, Li LJ
		Prediction of Clostridium difficile infection based on gut microbial traits in patients with Clostridium difficile colonization
		Cirrhotic patients usually require multiple hospitalizations due to upper gastrointestinal hemorrhage, abdominal infection, and hepatic encephalopathy. These patients need long-term hospital stay, and long-term application of proton pump inhibitors and antibiotics, which may result in Clostridium difficile infection (CDI) [1]. To our best knowledge, Clostridium difficile colonization (CDC) is the major risk factor for the pathogenesis of CDI. Our previous study demonstrated that 19.8% patients with hepatic cirrhosis have CDC, and about 26% of the CDC patients may develop CDI during hospitalization [2]. In cirrhotic patients, gut microbial structure and diversity may lead to overgrowth of intestinal bacteria, which may trigger the overgrowth of conditioned pathogens and opportunistic infection [3]. The antibiotics could further destroy the gut microbiota which makes the intestinal tract vulnerable to the growth of pathogenic bacteria [4]. A previous study showed that decline of gut microbial diversity and structural changes were the main etiology of CDI [5]. In this study, we aimed to analyze the roles of gut microbial traits in the pathogenesis of CDI among patients carrying Clostridium (C.) difficile .
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 298-300 . [Abstract] ( 75 ) [HTML 1KB] [PDF 0KB] ( 97 )

	301	Li Y, Zhang W, Sun H, Liu XM, Lv Y
		Variations of the hilar biliary confluence from postoperative cholangiography in Chinese population
		Treatment of the bile ducts at the porta hepatis is a critical step for avoiding post-surgical bile leakage and atrophy of the residual liver and/or the graft during hepatobiliary surgeries, such as hemihepatectomy, surgeries for cholangiocarcinoma or procurement of graft. Precise knowledge of the bile duct anatomy in individual cases has great importance in avoiding these kinds of complications. According to the Couinaud nomenclature, the intrahepatic biliary system can be divided into eight segments: the right anterior hepatic lobe (S5, S8), the right posterior lobe (S6,S7), the left liver (S2-4), and the caudate lobe (S1). The incidence of this normal anatomy was reported in 40%–80% cases [1]. Numerous intrahepatic biliary variations have been reported [2–4]. However, the data for the Chinese population are paucity.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 301-303 . [Abstract] ( 67 ) [HTML 1KB] [PDF 0KB] ( 106 )

	304	Pitcairn CFM, Kawka M
		Contrast-enhanced ultrasonography for intrahepatic cholangiocarcinoma: A cost-effective alternative for low-resource settings
		We would like to congratulate Tian and colleagues on their recent article: Diagnostic value of contrast-enhanced ultrasonography for intrahepatic cholangiocarcinoma with tumor diameter larger than 5 cm [1]. They argued that, despite not being included in the American Association for the Study of Liver Diseases (AASLD) guidelines for the diagnosis of liver diseases, contrast-enhanced ultrasonography (CEUS) can be of use for diagnosis of large ( > 5 cm), mass-forming intrahepatic cholangiocarcinoma (ICC). We would like to highlight the added value that CEUS can present in low-resource settings, where other diagnostic modalities may be neither cost-effective nor readily available.
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 304-305 . [Abstract] ( 65 ) [HTML 1KB] [PDF 0KB] ( 96 )

	306	Tian SY, Tian G, Jiang TA
		Reply to: Contrast-enhanced ultrasonography for intrahepatic cholangiocarcinoma: A cost-effective alternative for low-resource settings
		We thank Pitcairn et al. [1] for their discussion of our study recently published in Hepatobiliary & Pancreatic Diseases International [2]. They highlighted the added value that contrast-enhanced ultrasonography (CEUS) can present in low-resource settings, where other diagnostic modalities may be neither cost-effective nor readily available. We agree with their point. In addition, we also would like to highlight that CEUS is safer for human body than computed tomography (CT) and magnetic resonance imaging (MRI).
		Hepatobiliary Pancreat Dis Int. 2021; 20(3): 306-306 . [Abstract] ( 67 ) [HTML 1KB] [PDF 0KB] ( 96 )

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