Purpose: Surgical resection is the primary curative treatment for gastrointestinal (GI) cancer; however, it is associated with high postoperative complication rates and impaired recovery. Frailty, malnutrition, and sarcopenia increase morbidity and mortality, underscoring the need for perioperative rehabilitation programs. Standardized rehabilitation protocols during the perioperative period are currently lacking in Korea. We aimed to develop an evidence-based rehabilitation protocol for GI cancer patients to enhance postoperative outcomes and facilitate clinical implementation. Methods: A multidisciplinary task force team comprising experts in surgery, clinical nutrition, and rehabilitation medicine conducted a systematic literature search and comprehensive review from 2012 to 2022 to develop a standardized pre- and re-habilitation protocol for GI cancer surgery. The protocol underwent external validation and subsequent refinements before being finalized through expert consensus. Results: The protocol development process was organized into four consecutive phases: keyword selection, literature review and case report form development, initial protocol drafting, and external validation leading to the final version of the protocol. The final version of the rehabilitation protocol is presented in the main text and included as Supplements. Conclusion This protocol provides a standardized clinical guideline based on the latest evidence-based pre- and re-habilitation strategies and is designed for seamless integration into routine clinical practice. By facilitating proactive rehabilitation interventions, it aims to improve outcomes in GI cancer patients who are at high risk of postoperative complications, functional decline, and malnutrition.

Purpose: Despite the widespread use of liquid skin adhesives (LSA), concerns persist regarding the increase in wound care costs. This study aimed to investigate the cost-effectiveness of LSA for surgical wound management. Methods: In this prospective, open-label, single-center randomized controlled trial, adults aged 19 years and older who were scheduled for elective minimally invasive colorectal surgeries were included. The participants were randomly divided into 2 groups: an n-butyl cyanoacrylate skin adhesive was used in the experimental group (LSA group), while a surgical skin stapler was employed in the control group (stapler group). The primary outcome measure was the sum of the total time required for wound management. Results: A total of 58 patients were randomly assigned to 2 groups, with 29 patients in each group. The findings revealed comparable wound complication rates in the 2 groups (8 out of 29 in the LSA group vs. 5 out of 29 in the stapler group, P = 0.530). Notably, the LSA group had a significantly shorter wound management time (median 235 seconds vs. 1,201 seconds, P < 0.001) and similar wound management cost (median US dollar [USD] 50.6 vs. USD 54.6, P = 0.529) compared to the stapler group. Subgroup analysis showed that the LSA group had a shorter management time for uncomplicated wounds and a lower cost for complicated wounds. Conclusion LSA not only provides a safe alternative but also offers a resource-efficient option for wound management compared to staplers.

Background: The advantages of using an acellular dermal matrix (ADM) for implantbased breast reconstruction in breast cancer patients are well-documented across multiple studies. However, there have been no previous instances of using multilayered ADM for reconstruction following breast-conserving surgery (BCS). This study evaluated the outcomes of breast reconstruction employing multilayered ADM for volume replacement using a local glandular flap post-BCS, and aims to underscore the advantages of this surgical approach. Methods: Breast cancer patients who underwent BCS using several layers of ADM from August 2016 to December 2019 were retrospectively reviewed. Only patients with at least 3 years of follow-up were included in this study. The anticipated postoperative complications were breast deformity, seroma, hematoma, and infection. Results: Seventy-four patients were included in this study. Most patients experienced symptoms of hard palpation at the reconstruction site, which indicated the surface of the ADM inserted into the breast. Ten patients developed breast deformities, accounting for 13.5% of the cases, and required surgical correction. Other complications were less frequent: four patients (5.3%) had a confirmed seroma for 6 months or longer, two patients (2.6%) experienced fat necrosis, and one patient (1.3%) underwent re-operation to remove the ADM. Conclusions Reconstruction with a glandular flap and ADM following BCS is generally simpler and requires less surgical time compared to using a latissimus dorsi flap or other local flaps. Additionally, it avoids complications at the donor site, presenting a feasible surgical alternative for BCS in breasts with small defects.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.

Purpose: This network meta-analysis aimed to evaluate the relative efficacy of systemic treatments in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), focusing on key genetic mutations, specifically the 17p deletion and TP53 mutations. Methods: We conducted a systematic literature review to identify all publicly available randomized controlled trials (RCTs) using PubMed, EMBASE, the Cochrane database, and meeting abstracts published through December 2023.A Bayesian network meta-analysis was performed to estimate the hazard ratios (HRs) for progression-free survival (PFS) with 95% confidence intervals (CIs) and to determine the ranking of the included regimens. Results: Twelve trials involving 4,437 patients and 13 treatment options were included in the meta-analysis. Venetoclax plus rituximab and zanubrutinib emerged as the most effective treatments for the overall R/R CLL population, showing the lowest PFS HR (HR 0.62, 95% CI 0.32–1.20 and HR 0.65, 95% CI 0.49–0.86, respectively) versus ibrutinib, and were ranked as the best agent (surface under the cumulative ranking curve [SUCRA] value of both 90%, respectively) among the included drugs. In the 17p deletion/TP53 mutation subgroup, zanubrutinib demonstrated the most favorable efficacy (HR 0.52, 95% CI 0.31–0.88 versus ibrutinib) with the highest SUCRA value (97%). In patients without these mutations, venetoclax plus rituximab was the most effective (HR 0.49, 95% CI 0.26–0.94 versus ibrutinib) with a SUCRA value of 94%. Conclusion Our findings highlight the superior efficacy of venetoclax plus rituximab and zanubrutinib for treating R/R CLL and confirm that the role of each regimen may vary depending on the clinically significant mutations.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.