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Indigenous stewardship of lands and waters has been suppressed around the world for centuries by colonization, but it has nonetheless persisted. Specific places that are cared for through such stewardship are known as Indigenous and community conserved areas (ICCAs). Some ICCAs are formally recognized in bureaucratic government systems, whereas others are not. In Hawaiʻi, communities have been reviving various aspects of Indigenous stewardship, which is Place-based and holistic in nature, extending from the mountains to the sea. However, these attempts to engage in Indigenous stewardship have confronted countless obstacles and hurdles within the American form of centralized governance in the process. Some communities have found novel ways to engage in Indigenous stewardship via formal recognition of ICCAs through collaborative management agreements with various governmental authorities, both state and federal, as well as with large landowners. As scholars and knowledge keepers of Place, we have synthesized our intergenerational knowledge of the communities we have lived and/or worked in within the context of other studies that we have led or otherwise collaborated on spanning the past 30+ years. We focus on exploring how three Hawaiʻi communities (Hāʻena, Kauaʻi; Heʻeia, Oʻahu; and Kaʻūpūlehu, Hawaiʻi Island) have navigated bureaucracy to get formal recognition of their ICCAs in ways that have garnered governmental support for community-based revival of Indigenous stewardship practices. These three communities have all achieved biocultural resource management successes using a compartmented approach to stitch together various ICCAs as a means to holistically work across contemporary land-ownership boundaries, with one of these communities forming a “collaboratively managed meta-ICCA” to increase synergistic effects. These communities are the first in Hawaiʻi in the modern era to be engaging in Indigenous stewardship via a patchwork of ICCAs from the mountains to the sea, and, therefore, demonstrate that this is a viable, albeit arduous, avenue for communities to holistically engage in Indigenous stewardship within an American system of governance.

PurposeThe Liver Imaging Reporting and Data System (LI-RADS) was created to standardize the diagnostic criteria for hepatocellular carcinoma (HCC) and has undergone multiple revisions including a recent update in 2018 (v2018). The primary aim of this study was to determine the diagnostic performance and interrater reliability (IRR) of LI-RADS v2018 for distinguishing HCC from non-HCC primary hepatic malignancy in patients ‘at-risk’ for HCC. A secondary aim was to assess the impact of changes introduced in the v2018 diagnostic algorithm.MethodsThis retrospective study combined a 10-year experience of pathologically proven primary liver malignancies from two large liver transplant centers. Two blinded readers independently evaluated each lesion and assigned a LI-RADS diagnostic category, additionally scoring all relevant imaging features. Changes in category based on the reader-provided features and the new v2018 criteria were assessed by a study coordinator.ResultsThe final study cohort comprised 105 HCCs and 73 non-HCC primarily liver malignancies. LI-RADS had a high specificity for distinguishing HCC from non-HCC (89% and 90% for reader 1 and reader 2, respectively), and IRR was moderate to substantial for final LI-RADS category and most features. Revision of the LI-RADS v2018 diagnostic algorithm resulted in very few changes [5 (2.8%) and 3 (1.7%) for reader 1 and reader 2, respectively] in overall lesion classification.ConclusionLI-RADS diagnostic categories and features had moderate to substantial IRR and high specificity for distinguishing HCC from non-HCC primary liver malignancy. Revision of LI-RADS v2018 diagnostic algorithm resulted in reclassification of very few lesions.

Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10–20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.

Background Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer that is challenging to diagnose at an early stage. Despite recent advances in combination chemotherapy, drug resistance limits the therapeutic value of this regimen. iCCA reportedly harbors high HMGA1 expression and pathway alterations, especially hyperactivation of the CCND1/CDK4/CDK6 and PI3K signaling pathway. In this study, we explored the potential of targeting CDK4/6 and PI3K inhibition to treat iCCA. Methods The significance of HMGA1 in iCCA was investigated with in vitro/vivo experiments. Western blot, qPCR, dual-luciferase reporter and immunofluorescence assays were performed to examine the mechanism of HMGA1 induced CCND1 expression. CCK-8, western blot, transwell, 3D sphere formation and colony formation assays were conducted to predict the potential role of CDK4/6 inhibitors PI3K/mTOR inhibitors in iCCA treatment. Xenograft mouse models were also used to determine the efficacy of combination treatment strategies related to HMGA1 in iCCA. Results HMGA1 promoted the proliferation, epithelial-mesenchymaltransition (EMT), metastasis and stemness of iCCA. In vitro studies showed that HMGA1 induced CCND1 expression via promoting CCND1 transcription and activating the PI3K signaling pathway. Palbociclib(CDK4/6 inhibitor) could suppress iCCA proliferation, migration and invasion, especially during the first 3 days. Although there was more stable attenuation of growth in the HIBEpic model, we observed substantial outgrowth in each hepatobiliary cancer cell model. PF-04691502(PI3K/mTOR inhibitor) exhibited similar effects to palbociclib. Compared with monotherapy, the combination retained effective inhibition for iCCA through the more potent and steady inhibition of CCND1, CDK4/6 and PI3K pathway. Furthermore, more significant inhibition of the common downstream signaling pathways is observed with the combination compared to monotherapy. Conclusions Our study reveals the potential therapeutic role of dual inhibition of CDK4/6 and PI3K/mTOR pathways in iCCA, and proposes a new paradigm for the clinical treatment of iCCA.

There are few studies on the prognosis of elderly intrahepatic cholangiocarcinoma (iCCA) patients after liver resection. The aims of this study were to assess the cumulative incidences of cancer-specific mortality in elderly iCCA patients and to construct a corresponding competing risk nomogram for elderly iCCA patients. We performed a retrospective analysis of elderly patients with iCCA who underwent liver resection between January 2006 and December 2019. Eligible elderly iCCA patients were randomly divided into training and validation sets at a ratio of 7:3. Based on the results of multivariate analysis using the Fine-Gray competing risk model, we developed a competing risk nomogram using data from the training set to predict the cumulative probabilities of iCCA-specific mortality. The performance of the nomogram was measured by the concordance index (C-index) and calibration curves. To evaluate the clinical usefulness of the nomogram, the clinical benefit was measured by using decision curve analysis (DCA). Furthermore, the patients were categorized into two groups according to the dichotomy values of the nomogram-based scores, and their survival differences were assessed using Kaplan-Meier and cumulative incidence function (CIF) curves. The 1-year, 3-year and 5-year cumulative iCCA-specific mortalities were 19.7%, 48.3% and 56.1%, respectively, for elderly iCCA patients. The multivariate Fine-Gray analysis indicated that microvascular invasion, macroscopic vascular invasion and lymph node metastasis were related to a significantly higher likelihood of iCCA specific mortality. The established nomogram was well calibrated and had a good discriminative ability, with a concordance index (C-index) of 0.742 (95% CI, 0.708-0.748). Furthermore, the DCA indicated that the nomogram had positive net benefits compared with the conventional staging systems. In the training set and validation sets, the high-risk group had the higher probabilities of iCCA cancer-specific mortality than the low-risk group; meanwhile, the patients in the high-risk the group had significantly poorer overall survival (OS) than those in the low-risk group. Elderly iCCA patients had comparable long-term outcomes with non-elderly iCCA patients. In addition, we constructed a prognostic nomogram for predicting survival in elderly iCCA patients based on the competing risk analysis. The competing risk nomogram displayed excellent discrimination and calibration.

Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53–79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.

There are limited treatment options available to improve the prognosis of patients with advanced or metastatic cholangiocarcinoma particularly intrahepatic cholangiocarcinoma (iCCA). This study aimed to evaluate the efficacy and safety of combining chemotherapy plus anti-PD-1/L1 drugs compared to chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma patients. Patients with advanced, unresectable, or recurrent iCCA who received chemotherapy combined with PD-1/PD-L1 inhibitors or chemotherapy alone were retrospectively screened and analyzed. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety. 81 eligible patients were included in the study (chemotherapy plus anti-PD-1/L1 group n=51, and chemotherapy-alone group n=30). The median OS was 11 months for the chemotherapy plus anti-PD-1/L1 group, significantly longer than the 8 months in the chemotherapy-alone group, with a hazard ratio (HR) of 0.53 (95% CI 0.30-0.94, = 0.008). The median PFS of 7 months in the chemotherapy plus anti-PD-1/L1 group was significantly longer than the 4 months in the chemotherapy-alone group, with HR of 0.48 (95% CI 0.27-0.87); = 0.002). Similarly, the combined therapy group showed a higher ORR (29.4%) and DCR (78.4%) compared to 13.3% and 73.3% in the chemotherapy-alone group, respectively. More grade 3-4 treatment-related adverse effects were recorded in the chemotherapy plus anti-PD-1/L1 group (66.7%) compared to the chemotherapy-alone group (23.3%), however, they were manageable and tolerable. Chemotherapy plus anti-PD-1/L1 represents a more effective and tolerable treatment option for advanced, unresectable, and recurrent iCCA patients compared to chemotherapy alone.

Intrahepatic cholangiocarcinoma (ICCA), the second most prevalent primary liver malignancy, remains poorly understood at the molecular level. Research into the function of N6-methyladenosine (m6A) modification in the formation of ICCA and its potential as a therapeutic approach is being spurred by mounting evidence that it plays a crucial role in tumor biology. Immunohistochemical examination of patient samples in this investigation revealed a significant decrease in m6A methyltransferase METTL3 expression, accompanied by lower levels, which were associated with a lower overall survival rate. Functional assays demonstrated that the enforced expression of METTL3 inhibited ICCA cell proliferation and migration, while concurrently increasing the levels of the long non-coding RNA H19. Mechanistic experiments using RNA-binding protein immunoprecipitation and methylated RNA immunoprecipitation confirmed that METTL3 directly interacted with H19 and enhanced its m6A modification. Importantly, silencing of H19 reversed the growth- and migration-suppressive effects of METTL3, whereas H19 overexpression counteracted the phenotype induced by METTL3 downregulation. Further analysis revealed that the METTL3-H19 regulatory axis suppressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, an oncolytic adenovirus engineered to overexpress H19, in combination with the PPARγ inhibitor BAY-4931, elicited potent antitumor effects both and . Collectively, these findings identify METTL3-mediated m6A modification of H19 as a critical suppressor of ICCA progression through modulation of PPARγ signaling. One interesting treatment option for ICCA may be the use of H19-armed oncolytic adenoviruses, especially when combined with PPARγ suppression.

This special section is dedicated to the papers selected from the 22nd International Conference on Control, Automation, and Systems (ICCAS 2022), held in Busan BEXCO, Korea, from November 27 to December 1, 2022. The selectionprocess was overseen by the award committee chair, Prof. Chul-Goo Kang, who recommended a total of ten papers: five finalist papers for the Best Paper Award and five finalist papers for the Best Student Paper Award. Following Prof. Kang’s recommendations, the authors of these selected papers were invited to submit an extended version of their conference papers for review at the International Journal of Control, Automation, and Systems (IJCAS). The guidelines required the authors to augment their papers by at least 35% from the original conference version and include additional results. Moreover, authors were asked to cite their respective ICCAS papers in the journal version while addressingany notable differences between the two versions. The submitted papers underwent an expedited review process conducted by a panel of distinguished reviewers. Despite the fast-track handling, the reviews were conducted with utmost rigor to ensure the quality and excellence of the selected papers. Subsequently, the following four papers were chosen for publication:1. “Koopman Operator-based Model Identification and Control for Automated Driving Vehicle” by Jin Sung Kim, Ying Shuai Quan, and Chung Choo Chung. 2. “Adaptive Online Steering Efficiency Coefficient Estimation for Enhanced Terrain Motion Control in Four-wheeled Skid-steering Mobile Robots” by Le Bao, Kai Li, Changsoo Han, Kyoosik Shin, and Wansoo Kim. 3. “A Model Predictive Voltage Control for Dual-active-bridge DC-DC Converter Using Generalized Averaging Model” by Ngoc-Duc Nguyen and Young Il Lee. 4. “ASAD: Autonomous Seismic Acquisition Device” by Grigoriy Yashin, Valerii Serpiva, Artem Timoshenko, Nikita Mikhailovskiy, Anton Egorov, and Pavel Golikov. Moving forward, the editorial board of IJCAS plans to continue its efforts in identifying exceptional papers from future editions of The International Conference on Control, Automation, and Systems for potential publication at IJCAS. KCI Citation Count: 0

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with a poor prognosis. Recently, an immunotherapy strategy represented by programmed cell death 1 (PD-1) inhibitors has been applied to the systemic treatment of advanced iCCA. However, immunotherapy combined with chemotherapy as first-line maintenance therapy was rarely reported. Our report presented an advanced iCCA patient who had a dramatic response to the PD-1 inhibitor sintilimab combined with gemcitabine plus cisplatin as the first-line therapy and sintilimab combined with capecitabine as maintenance therapy, yielding an ongoing progression-free survival of 16 months.