This case describes a male with a history of type 1 autoimmune pancreatitis (AIP) who had a concomitant branch-duct intraductal papillary mucinous neoplasm under long-term surveillance. During follow-up, new high-risk radiologic features developed within the pancreatic cyst, raising concern for malignant transformation and ultimately leading to surgical resection. However, final histopathologic examination revealed recurrent type 1 AIP rather than malignant progression of branch-duct intraductal papillary mucinous neoplasm, a finding that represents an uncommon and diagnostically challenging manifestation. This case suggests that when new imaging changes are observed during surveillance of pancreatic cystic lesions, clinicians should consider not only malignant transformation but also the possibility of recurrence or coexistence of underlying diseases such as AIP.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers. Methods: A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals. Results: The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence. Conclusion The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.

Background: The pulse wave transit time (PWTT) increases with decreased vascular tone resulting from sympathetic blockade caused by regional anesthesia. It oscillates, exhibiting variability due to the interaction between the autonomic nervous and cardiovascular systems. We hypothesized that interscalene brachial plexus block (ISBPB) placement increases the PWTT and reduces the low-frequency power of PWTT variability (LF). Methods: Fifty-six patients receiving an ISBPB were analyzed. The PWTT was defined as the difference in milliseconds (ms) between the R peak of the electrocardiogram and the peak of the second-derivative photoplethysmographic waveform. The LF was calculated by integrating from 0.04 to 0.15 Hz on the power spectrum obtained from fast Fourier transform. The two variables were collected during the 5 min before the end of acclimatization (baseline), between 5 and 10 min after block needle insertion, and between 15 and 20 min after block needle insertion. Results: The PWTT increased significantly (P < 0.001) from baseline (mean [SD]: 155.3 [16.7] ms) to 5–10 min post-needle insertion (166.9 [15.4] ms) (mean difference [MD]: 11.6, 95% CI [9.2–14.0], P < 0.001) and 15–20 min post-needle insertion (165.6 [16.1] ms) (MD: 10.3, 95% CI [7.3–13.2], P < 0.001). The natural log-transformed LF (lnLF) decreased significantly (P < 0.01) from baseline (1.539 [0.560] ln[ms2/Hz]) to 5–10 min post-needle insertion (1.341 [0.617] ln[ms2/Hz]) (MD: –0.198, 95% CI [–0.356 to –0.040], P < 0.01) and 15–20 min post-needle insertion (1.396 [0.548] ln[ms2/Hz]) (MD: –0.144, 95% CI [–0.274 to –0.013], P = 0.03). Conclusions The post-ISBPB decrease in lnLF and increase in PWTT may be attributable to ISBPB-induced sympathectomy.

Background/Aims: Early detection and removal of colon polyps are critical for preventing colorectal cancer. Computer-aided detection (CADe) systems have been introduced to increase the polyp detection rate (PDR) during colonoscopy, potentially enhancing its effectiveness. This study aimed to evaluate the efficacy of a CADe system in colorectal neoplasm detection. Methods: This prospective, randomized controlled trial was conducted at two tertiary centers (May 2023 to April 2025). Patients were randomly assigned to CADe or conventional colonoscopy and underwent screening, surveillance, or diagnostic colonoscopy. The primary endpoint was the adenoma detection rate (ADR), while the secondary endpoints were the PDR, relative risk (RR) of polyp detection, adenomas per colonoscopy (APC), and factors influencing adenoma detection. Results: Of 1,004 enrolled patients, 998 were randomly allocated into CADe and conventional colonoscopy groups (497 CADe system and 501 conventional colonoscopy). The CADe group had greater polyp counts (2.2 per colonoscopy vs 1.4 per colonoscopy; p<0.001) and APC values (1.2 vs 0.8; p<0.001). The CADe group showed significantly higher PDRs (72.2% vs 54.5%;p<0.001; RR, 2.173; 95% confidence interval [CI], 1.669 to 2.828) and ADRs (52.3% vs 36.1%;p<0.001; RR, 1.940; 95% CI, 1.505 to 2.499). CADe also significantly increased the detection rate of hyperplastic polyps (p=0.007; RR, 1.474; 95% CI, 1.113 to 1.952) and increased the detection rates across all sizes and locations. In multivariable analysis, CADe use was the strongest independent predictor of adenoma detection (odds ratio, 1.914; 95% CI, 1.467 to 2.496), outweighing male sex, older age, diagnostic indication, and withdrawal time. Conclusions Real-time CADe-assisted colonoscopy significantly increased PDR and ADR and proved to be a strong independent predictor of adenoma detection (cris.nih.go.kr, KCT0009664).

Background/Aims: Accurate diagnosis of and timely eradication therapy for Helicobacter pylori are crucial for managing and preventing adverse clinical outcomes associated with H. pylori infection. H. pylori infection is typically diagnosed using endoscopic biopsy-based tests such as the rapid urease test (RUT). In this study, we investigated the usefulness of mucosal brush sampling for H. pylori detection using the RUT and culture. Methods: Twenty patients with H. pylori infection underwent endoscopy, and specimens were collected from the greater curvature of the gastric corpus via both mucosal brush and biopsy sampling methods. Brushing was performed using a disposable cytology brush, and the brush specimen was used for the RUT (brush-RUT) and then for culture. Two biopsies were obtained for the RUT (biopsy-RUT) and culture. H. pylori detection rates using RUT and culture yields from brush and biopsy samples were compared. Results: The H. pyloridetection rate was 100% with the brush-RUT, whereas it was 75% with the biopsy-RUT. Notably, among patients taking acid-suppressive agents, the sensitivity of the biopsy-RUT decreased to 66.7%, whereas that of the brush-RUT remained at 100%. The biopsy-RUT yield was also associated with the delta over baseline value determined by the urea breath test.H. pylori was successfully isolated from all the biopsy specimens and 95% of the brush samples, and all H. pylori isolates were tested for antimicrobial susceptibility. No significant procedurerelated adverse events occurred with either sampling method. Conclusions Mucosal brushing is a simple, effective, and highly sensitive diagnostic method for H. pylori infection. The mucosal brush method is a practical alternative to biopsy, expanding the diagnostic capabilities while minimizing invasiveness.