Keratin 19 Expression in Hepatocellular Carcinoma Is Regulated by Fibroblast-Derived HGF via a MET-ERK1/2-AP1 and SP1 Axis

Rhee, Hyungjin,Kim, Hye-Young,Choi, Ji-Hye,Woo, Hyun Goo,Yoo, Jeong Eun,Nahm, Ji Hae,Choi, Jin-Sub,Park, Young Nyun American Association for Cancer Research 2018 Cancer Research Vol.78 No.7

The Role of Imaging in Current Treatment Strategies for Pancreatic Adenocarcinoma

Rhee Hyungjin,Park Mi-Suk 대한영상의학회 2021 Korean Journal of Radiology Vol.22 No.1

In pancreatic cancer, imaging plays an essential role in surveillance, diagnosis, resectability evaluation, and treatment response evaluation. Pancreatic cancer surveillance in high-risk individuals has been attempted using endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI). Imaging diagnosis and resectability evaluation are the most important factors influencing treatment decisions, where computed tomography (CT) is the preferred modality. EUS, MRI, and positron emission tomography play a complementary role to CT. Treatment response evaluation is of increasing clinical importance, especially in patients undergoing neoadjuvant therapy. This review aimed to comprehensively review the role of imaging in relation to the current treatment strategy for pancreatic cancer, including surveillance, diagnosis, evaluation of resectability and treatment response, and prediction of prognosis.

Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Rhee, Hyungjin,An, Chansik,Kim, Hye-Young,Yoo, Jeong Eun,Park, Young Nyun,Kim, Myeong-Jin S. Karger AG 2019 Liver cancer Vol.8 No.1

<P><B><I>Background and Aims:</I></B> The purpose of our study was to examine the histopathologic characteristics of hepatocellular carcinoma (HCC) with irregular rim-like arterial phase enhancement (IRE), which has been reported to be associated with more aggressive tumor behavior. <B><I>Methods:</I></B> We investigated 84 pathologically confirmed HCCs in 84 patients who underwent curative hepatic resection after gadoxetate-enhanced magnetic resonance imaging between January 2008 and February 2013. Two abdominal radiologists independently reviewed these images and classified HCCs into two categories: HCC showing IRE (IRE-HCC) and HCC showing hypoenhancement or diffuse arterial enhancement (non-IRE-HCC). Twenty-two HCCs were classified as IRE-HCCs, and 51 were classified as non-IRE-HCCs concordantly by both reviewers. The remaining 11 HCCs, on whose radiologic classifications the reviewers disagreed, were classified as HCCs with intermediate enhancement patterns. The HCC clinicopathologic characteristics and patient outcomes were then compared. <B><I>Results:</I></B> IRE-HCCs showed more frequent microvascular invasion (91 vs. 35%), lower microvascular density (246.5 vs. 426.5/mm<SUP>2</SUP>), higher proportions of sinusoid-like microvascular pattern (55 vs. 0%) and macrotrabecular pattern (45 vs. 0%), and larger areas of tumor necrosis (15 vs. 0%) and fibrous stroma (8.3 vs. 2.1%) than non-IRE-HCCs. IRE-HCCs also expressed higher levels of immunomarkers of hypoxia (carbonic anhydrase IX, 64 vs. 8%) and stemness (EpCAM, 50 vs. 20%). <I>p</I> values were < 0.001 for all comparisons except for EpCAM (<I>p</I> = 0.026). HCCs with intermediate enhancement patterns showed mixed/intermediate pathologic features from both IRE- and non-IRE-HCCs. IRE-HCC patients showed poorer 5-year disease-free survival after curative resection than non-IRE-HCC patients (<I>p</I> = 0.005). <B><I>Conclusions:</I></B> IRE-HCCs demonstrate aggressive histopathologic features, including more hypoxic and fibrotic tumor microenvironments and increased stemness, compared to non-IRE-HCCs. IRE might therefore serve as a noninvasive imaging biomarker for aggressive HCC.</P>

Update on Pathologic and Radiologic Diagnosis of Combined Hepatocel-lular-Cholangiocarcinoma

( Hyungjin Rhee ),( Jae Hyon Park ),( Young Nyun Park ) 대한간암학회 2021 대한간암학회지 Vol.21 No.1

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a malignant primary liver carcinoma characterized by the unequivocal presence of both hepatocytic and cholangiocytic differentiation within the same tumor. Recent research has highlighted that cHCC-CCAs are more heterogeneous than previously expected. In the updated consensus terminology and WHO 2019 classification, “classical type” and “subtypes with stem-cell features” of the WHO 2010 classification are no longer recommended. Instead, it is recommended that the presence and percentages of various histopathologic components and stem-cell features be mentioned in the pathologic report. The new terminology and classification enable the exchange of clearer and more objective information about cHCC-CCAs, facilitating multi-center and multinational research. However, there are limitations to the diagnosis of cHCC-CCA by imaging and biopsy. cHCC-CCAs showing typical imaging findings of HCC could be misdiagnosed as HCC and subjected to inappropriate treatment, if other clinical findings are not sufficiently considered. cHCC-CCAs showing at least one of the CCA-like imaging features or unusual clinical features should be subjected to biopsy. There may be a sampling error for the biopsy diagnosis of cHCC-CCA. An optimized diagnostic algorithm integrating clinical, radiological, and histopathologic information of biopsy is required to resolve these diagnostic pitfalls. (J Liver Cancer 2021;21:12-24)

간암의 영상학적 소견

이형진 ( Hyungjin Rhee ) 대한간학회 2022 간질환 연수강좌 Vol.2022 No.1

Genetic, Clinicopathological, and Radiological Features of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern

Chung Taek,Rhee Hyungjin,Shim Hyo Sup,Yoo Jeong Eun,Choi Gi Hong,Kim Haeryoung,Park Young Nyun 거트앤리버 소화기연관학회협의회 2022 Gut and Liver Vol.16 No.4

Background/Aims: Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated. Methods: Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancerrelated genes. Results: From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR2 and PTPRT were most frequently mutated (three cases each) including an FGFR2-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found. Conclusions: iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR2 and ARID1A variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.

Tumor Marker Response and Radiologic Response Can Predict Survival Following Radioembolization: A Landmark Analysis

( Tae Seop Lim ),( Hyungjin Rhee ),( Beom Kyung Kim ),( Seung Up Kim ),( Jun Yong Park ),( Sang Hoon Ahn ),( Kwang-hyub Han ),( Jin-young Choi ),( Do Young Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: It remains unclear whether alpha-fetoprotein (AFP), Des-gamma-carboxy protein (DCP), and modified Response Evaluation Criteria in Solid Tumor (mRECIST) can be used as predictors for overall survival (OS) after radioembolization. Methods: Between 2009 and 2016, 63 patients with AFP >20 ng/mL, DCP >20 mAU/mL, and Child-Pugh A were analyzed. AFP or DCP responders were defined as decrease > 50% from baseline at 1, 3, 6 month landmark after radioembolization. mRECIST responders were defined as complete response or partial response. Results: At 1month landmark, OS was not statistically different between AFP, DCP, and mRECIST responder and nonresponders. From 3month landmark, AFP (75.8 vs 7.6 months, P=0.001), DCP (75.8 vs 7.1 months, P<0.001), and mRECIST responders (75.8 vs 10.0 months, P=0.001) live longer than nonresponders. From 6month landmark, AFP (72.8 vs 9.4 months, P<0.001), DCP (72.8 vs 3.9 months, P<0.001), and mRECIST responders (not reached vs 12.1 months; P=0.012) also showed better OS than nonresponders. At 6 month risk of death from each landmark, there was statistical difference only between DCP responders and nonresponders (9.5% versus 36.8%, P=0.010 at 1month landmark, 2.9% versus 33.3%, P=0.002 at 3month landmark, and 4.3% versus 40.0%, P=0.009 at 6month landmark). In multivariate Cox proportional hazard analysis, at 3month landmark, DCP responder (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.072-0.593, P=0.003) and mRECIST responder (HR 0.19, 95% CI 0.065-0.571, P=0.003) were independent predictors for OS. At 6month landmark, only DCP responder (HR 0.02, 95% CI 0.001-0.392, P=0.010) was an independent predictor for OS. Conclusions: AFP, DCP, and mRECIST responder showed better OS than nonresponder at 3month and 6month landmark after radioembolization, and DCP responder was the most potent predictor among them.

Increased Expression of the Matrix-Modifying Enzyme Lysyl Oxidase-Like 2 in Aggressive Hepatocellular Carcinoma with Poor Prognosis

Jiwoon Choi,Taek Chung,Hyungjin Rhee,Young-Joo Kim,Youngsic Jeon,Jeong Eun Yoo,Songmi Noh,Dai Hoon Han,Young Nyun Park 거트앤리버 소화기연관학회협의회 2019 Gut and Liver Vol.13 No.1

Background/Aims: Lysyl oxidase-like 2 (LOXL2), a collagenmodifying enzyme, has been implicated in cancer invasiveness and metastasis. Methods: We evaluated the expression of LOXL2 protein, in addition to carbonic anhydrase IX (CAIX), keratin 19, epithelial cell adhesion molecule, and interleukin 6, in 105 resected hepatocellular carcinomas (HCCs) by immunohistochemistry. Results: LOXL2 positivity was found in 14.3% (15/105) of HCCs, and it was significantly associated with high serum α-fetoprotein levels, poor differentiation, fibrous stroma, portal vein invasion, and advanced TNM stage (p<0.05 for all). Additionally, LOXL2 positivity was significantly associated with CAIX (p=0.005) and stromal interleukin 6 expression (p=0.001). Survival analysis of 99 HCC patients revealed LOXL2 positivity to be a poor prognostic factor; its prognostic impact appeared in progressed HCCs. Furthermore, LOXL2 positivity was shown to be an independent predictor of overall survival and disease-specific survival (p<0.05 for all). Interestingly, co-expression of LOXL2 and CAIX was also an independent predictor for overall survival, disease-specific survival, disease-free survival, and extrahepatic recurrence-free survival (p<0.05 for all). Conclusions: LOXL2 expression represents a subgroup of HCCs with more aggressive behavior and is suggested to be a poor prognostic marker in HCC patients.

Door-Opening Control of a Service Robot Using the Multifingered Robot Hand

Woojin Chung,Changju Rhee,Youngbo Shim,Hyungjin Lee,Shinsuk Park IEEE 2009 IEEE transactions on industrial electronics Vol.56 No.10

<P>Service robots are spreading their application areas to human coexisting real environments. However, it is still difficult to find an autonomous robot that is capable of manipulation services in a real environment. The three major difficulties of manipulation service can be summarized as follows: 1) unstructured human-centered environment; 2) limited resources in a robot; and 3) uncertainties in real environments. This paper deals with the autonomous manipulation task by a service robot in human coexisting environment. We focus on a door-opening problem. In this paper, we concentrate on three issues from the viewpoint of service-robot applications. The first issue is to estimate kinematic parameters by using an active-sensing strategy to overcome uncertainties in a real environment. The second issue is to provide an integrated strategy of motion coordination for door-opening control. This paper discusses the role assignment of each subsystem that depends on the physical characteristics. The third issue is to use the fingertip-contact forces to estimate the external force from a doorknob, instead of using an additional high-cost force sensor at the wrist. The proposed scheme is shown to be useful through experimental results.</P>

Preoperative cephalhematoma size measured with computed tomography predicts intraoperative bleeding in pediatric patients undergoing cranioplasty

김승현,민경태,Park Eun Kyung,Rhee Hyungjin,Yang Hyukjin,최승호 대한마취통증의학회 2021 Anesthesia and pain medicine Vol.16 No.2

Background: Cranioplasty for the treatment of cephalhematomas in small infants with limited blood volume is challenging because of massive bleeding. This study aimed to elucidate the correlation between cephalhematoma size and intraoperative blood loss and identify criteria that can predict large intraoperative blood loss.Methods: We reviewed the medical records of 120 pediatric patients aged less than 24 months who underwent cranioplasty for treatment of a cephalhematoma. The cephalhematoma sizes in preoperative brain computed tomography (CT) were measured using ImageJ. Results: Pearson correlation showed that the cephalhematoma size in the pre-operative brain CT was weakly correlated with intraoperative blood loss (Pearson coefficient = 0.192, P = 0.037). In a multivariable logistic regression analysis, a cephalhematoma size greater than 113.5 cm3 was found to be a risk factor for large blood loss. The area under the curve in the receiver operating characteristic plot of the multivariable model was 0.714 (0.619–0.809).Conclusions: A cephalhematoma size cutoff value of 113.5 cm3, as measured in the preoperative CT imaging, can predict intraoperative blood loss exceeding 30% of the total body blood volume. The establishment of a transfusion strategy prior to surgery based on cephalhematoma size could be useful in pediatric cranioplasty.