Jin Hong Lim

Liver cancer remains a major global health burden with high mortality and limited treatment response prediction tools. Patient-derived cancer organoids have emerged as promising preclinical models that recapitulate tumor heterogeneity; however, the biological significance of morphological diversity within established organoids remains poorly characterized in hepatocellular carcinoma (HCC). In this exploratory study, we investigated whether distinct organoid growth phenotypes reflect underlying tumor biology and correlate with clinical outcomes. We established liver cancer organoids from resected tumor tissues of 27 patients and analyzed their clinical, histological, and genomic characteristics. Organoids were classified morphologically into cystic and solid types. Whole exome sequencing (WES) was conducted on six matched tumor–organoid pairs to assess genomic fidelity. Associations between organoid establishment, growth characteristics, and clinical parameters were statistically evaluated. Progression-free survival (PFS) was analyzed using the Kaplan–Meier method and univariate Cox proportional hazards regression. Organoids were successfully established in 13 of 27 cases (48.1%). Solid-type organoids were significantly associated with shorter PFS compared to cystic types (HR = 13.91; p = 0.0039, log-rank test). Organoid establishment was more frequent in older patients (>70 years), those with HBV infection, and tumors with positive β-catenin expression. WES analysis demonstrated high concordance in somatic mutation profiles and variant allele frequency distributions between tissues and corresponding organoids. In univariate Cox regression, organoid growth pattern (solid vs. cystic) showed a significant association with PFS within this exploratory cohort (p = 0.0207). Patient-derived liver cancer organoids preserved the genomic and histopathological features of the original tumors. Notably, solid morphology was associated with shorter PFS, suggesting that organoid growth phenotype may serve as a supplementary indicator of tumor biological behavior in HCC. Given the modest cohort size and the absence of multivariate analysis, these preliminary findings should be interpreted with caution and warrant further large-scale validation.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, mainly due to its high recurrence rate after curative treatments. The macrotrabecular-massive (MTM) subtype has recently been recognized as an aggressive histologic variant associated with vascular invasion and poor differentiation. This study aimed to investigate the prognostic impact of the MTM subtype on recurrence after surgical resection of HCC. Methods: We retrospectively reviewed 171 patients who underwent curative hepatic resection for HCC between January 2007 and December 2017 at Gangnam Severance Hospital, Seoul, Korea. Clinicopathologic parameters, including immune-related features such as lymphoid infiltration and tertiary lymphoid structures (TLSs), were evaluated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression analyses. Results: During a median follow-up of 4.4 ± 3.4 years, 74 patients (43.3%) experienced recurrence. The MTM subtype was significantly more frequent in the recurrence group than in the non-recurrence group (47.3% vs. 21.6%, p < 0.001). Multivariate analysis identified MTM subtype as an independent predictor of recurrence (hazard ratio, 1.88; 95% CI, 1.14–3.10; p = 0.013). Lymphoid infiltration and TLSs were not associated with prognosis. Kaplan–Meier analysis showed higher recurrence in MTM-positive cases (p = 0.001), whereas OS did not differ significantly (p = 0.094). Conclusions: The macrotrabecular-massive subtype is an independent histopathologic predictor of recurrence after curative resection in HCC. Incorporating MTM subtype recognition into postoperative risk assessment may enhance patient stratification and inform future adjuvant therapy strategies.

Background/Objectives: Accurate determination of malignancy in pancreatic masses through endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is crucial for appropriate clinical management and prognostic assessment. However, the diagnostic sensitivity of conventional cytology using Papanicolaou (Pap) staining remains limited, often leading to inconclusive results. In this study, we investigated the diagnostic utility of methionyl-tRNA synthetase 1 (MARS1) through immunohistochemical (IHC) and immunofluorescence (IF) staining as a potential biomarker for pancreatic cancer. IHC analysis was conducted on resected tissue samples from 10 patients, including both pancreatic ductal adenocarcinoma and corresponding non-neoplastic pancreatic tissue. Additionally, cytologic samples were obtained from 198 patients with pancreatic masses who underwent EUS-FNA for diagnostic evaluation. Pap staining and MARS1 IF staining were performed on liquid-based cytology slides derived from EUS-FNA specimens. Results: MARS1 was detected by IHC staining in the 10 surgical specimens diagnosed with pancreatic adenocarcinomas. After Pap staining, 37 patients were excluded because of unsuitable specimens, leaving 161 patients who underwent both Pap and MARS1 IF staining. EUS-FNA specimens from the 151 patients with pancreatic ductal adenocarcinoma were classified by Pap staining as atypia (n = 36), suspicious for malignancy (n = 55), or malignancy (n = 60). MARS1 IF staining was positive in 147 of these patients and negative in 4. MARS1 IF staining distinguished pancreatic cancer in specimens with atypia on Pap staining. The sensitivity for detecting pancreatic cancer was significantly higher for MARS1 IF staining than for conventional Pap staining (97.4% vs. 79.1%, p < 0.0001). Conclusions: The high sensitivity of MARS1 IF staining improved malignancy detection in pancreatic masses. Further prospective studies are required to validate our findings.

Background: Robot-assisted pylorus-preserving pancreaticoduodenectomy (RPPPD) has been increasingly adopted, leveraging the advantages of robotic technology. RPPPD is rarely performed using the da Vinci SP system. In this study, we address the technical issues encountered during the early experiences with robotic pylorus-preserving pancreaticoduodenectomy (RPPPD) using the da SP Vinci system and propose effective solutions. Method: We retrospectively analyzed the outcomes of seven patients who underwent RPPPD using the da Vinci SP system. The primary technical challenges included limited instrument maneuverability, difficulty in maintaining clear surgical views, and the need for precise anastomosis. Results: Postoperatively, all patients were discharged without significant complications, with no clinically relevant pancreatic fistulas observed. Only minimal scarring was observed postoperatively. In addition, our results showed that operative time gradually decreased. The operation time was significantly shorter in the RPPPD using the SP system group compared to the RPPPD using the multiport system group. Conclusions: Implementing enhanced preoperative planning, advanced intraoperative imaging, and specialized robotic tools can significantly improve surgical efficiency and patient outcomes.

Background: Hemostatic products are widely used to control bleeding in hepatic resections. Stopad is a pad-type hemostatic agent containing carboxymethyl chitosan and recombinant thrombin-like hemocoagulase. Methods: We conducted a prospective, multicenter, randomized, noninferiority study of Stopad vs. Tachosil in 104 patients who required open hepatic resection. The subjects were randomized 1:1 to either the investigational group (Stopad; 53) or the control group (Tachosil; 51). Results: The 3-min bleeding control success rate was 92.45% in the Stopad group and 90.20% in the Tachosil group. The lower bound of the one-sided 97.5% confidence level for the between-group difference in the success rate was −9.82%, which was within the preset noninferiority limit of −22.9%. The 5- and 10-min bleeding control success rates were both 100.00% for the Stopad group and were both 98.04% in the Tachosil group. A significantly higher incidence of adverse events was reported in the Stopad group (29/53, 54.72%) than in the Tachosil group (17/51, 33.33%; p = 0.0282). However, the higher number of adverse events in the Stopad group was likely due to a higher proportion of subjects with a past history of surgical or interventional procedure. Conclusions: The hemostatic efficacy of Stopad was noninferior to that of Tachosil in patients undergoing open hepatic resection, introducing new possibilities for more potent hemostatic products in the future. Trial registration number: KCT0004404.

Background: Minimal invasive surgery in hepatobiliary and pancreatic (HBP) surgery has been accepted worldwide in recent years. However, applications of single‐site laparoscopic surgery in complex HBP surgery have been limited due to difficulty in manoeuvring instruments and the limited range of motion resulting from clashing instruments. Methods: To overcome the limitations, we have used the Da Vinci single‐site surgical platform with one additional port in a Da Vinci Xi system to perform donor right hepatectomy, pancreaticoduodenectomy, and combined resection of the common bile duct and spleen vessels preserving distal pancreatectomy. Results: In selected patients, using a robotic single‐site plus one port system allowed the successful completion of complex HBP surgery. Discussion: Complex HBP surgery can be performed safely in a stable environment using the robotic single‐site plus one port system. Further exploration of a robotic single‐site plus one port in complex HBP surgery is necessary.

Background: Some studies have analyzed the frequency of HCV RNA testing and actual treatment among anti-HCV positive patients in Korea, which has a low prevalence of HCV infection. This study aimed to analyze the diagnosis process, treatment results, and prognosis according to care cascade in patients who are anti-HCV positive. Methods: Three thousand two hundred fifty-three anti-HCV positive patients presented to a tertiary hospital between January 2005 and December 2020. The number of patients who underwent HCV RNA testing, treatment, and proportion of sustained virologic response (SVR) according to the type of antivirals was investigated. We investigated the cumulative incidence of hepatocellular carcinoma (HCC) and liver cirrhosis. Results: Of a total of 3,253 people, 1,177 (36.2%) underwent HCV RNA testing and 858 (72.9%) were positive for HCV RNA. 494 (57.6%) of HCV RNA positive patients received antiviral treatment, and 443 (89.7%) of initiated hepatitis C treatment experienced SVR. Of the 421 treated patients, 16 (14.2%) developed HCC. The cumulative incidence of HCC at 15 years was significantly different according to the presence of liver cirrhosis (10/83, 29.5% vs. 6/338, 10.8%, p < 0.001). The cumulative incidences of HCC or liver cirrhosis did not show significant differences according to the presence of SVR₁₂ (14/388, 13.2% vs. 2/33, 52.5%, p = 0.084, 21/319, 15.0%, vs. 3/22, 28.7%, p = 0.051). Conclusions: Owing to the introduction of direct-acting antivirals, high SVR₁₂ was achieved, but the proportion of anti-HCV positive patients who received HCV RNA testing and treatment was not high. HCC surveillance after SVR₁₂ is recommended for chronic hepatitis C patients with cirrhosis.

Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.