Purpose: Common bile duct (CBD) stone recurrence after laparoscopic CBD exploration (LCBDE) is relatively common. No studies have been conducted evaluating the safety and feasibility of re-do LCBDE in the treatment of recurrent CBD stones. Methods: This single-center retrospective study reviewed 340 consecutive patients who underwent LCBDE for CBD stones between January 2004 and December 2020. Patients with pancreatobiliary malignancies and those who underwent other surgical procedures were excluded. Results: Of the 340 included patients, 45 experienced a recurrence after a mean follow-up period of 24.2 months. Of them, 18 underwent re-do LCBDE, 20 underwent endoscopic intervention, 2 underwent radiologic intervention, and 5 underwent observation. Re-do LCBDE and initial LCBDE showed similar surgical outcomes in terms of operative time (113.1 minutes vs. 107.5 minutes, P = 0.515), estimated blood loss (42.5 mL vs. 49.1 mL, P = 0.661), open conversion rate (2.9% vs. 0%, P = 0.461), postoperative complication (15.3% vs. 22.2%, P = 0.430), and postoperative hospital stay (6.5 days vs. 6.4 days, P = 0.921). Comparing re-do LCBDE and nonsurgical treatment (endoscopic or radiologic), no statistically significant differences were noted in posttreatment complication (22.2% vs. 13.6%, P = 0.477), hospital stay (6.4 days vs.7.3 days, P = 0.607), and recurrence (50.0% vs. 36.4%, P = 0.385). The clearance rate was higher in the re-do LCBDE group than in the nonsurgical group (100% vs. 81.8%, P = 0.057). Conclusion Compared to initial LCBDE and endoscopic or radiological treatments, re-do LCBDE for recurrent CBD stones is a treatment option worth considering in selected patients.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. Materials and Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment. Conclusion HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

Primary cholangiocarcinoma is a rare bile duct epithelial neoplasm that can present with atypical clinical manifestations, complicating its diagnosis. A 62-year-old male showed symptoms suggestive of a complicated hepatic cyst that was later identified as intrahepatic cholangiocarcinoma. The patient presented with abdominal discomfort without fever. Imaging revealed a large cystic lesion in the liver. Despite the initial treatment for a presumed abscess, a biopsy confirmed cholangiocarcinoma. This case highlights the diagnostic challenge of distinguishing between benign complicated hepatic cysts and malignancies, particularly when typical markers of infection are absent. Early biopsy and vigilant assessments are crucial in such presentations to avoid a delayed diagnosis and initiate appropriate treatment.

Hepatic tuberculosis, typically associated with miliary tuberculosis, can occasionally present as localized liver lesions. This case report describes a 77-year-old male presenting with persistent abdominal pain and fever, following an endoscopic retrograde cholangiopancreatography for bile duct sludge removal. Subsequent computed tomography revealed focal liver lesions. Despite initial treatment with antibiotics for a suspected inflammatory liver abscess, his condition did not improve. A liver biopsy was performed, revealing caseous granulomas, and the tuberculosis polymerase chain reaction result was positive. The patient was diagnosed with primary hepatic tuberculosis, which later disseminated. Oral anti-tuberculosis therapy was initiated and is currently being closely monitored. This case emphasizes the importance of considering hepatic tuberculosis in the differential diagnosis of liver lesions, particularly in cases involving cholestatic liver function tests, and persistent symptoms unresponsive to conventional antibiotics.

Purpose: The adjusted Global Antiphospholipid Syndrome (APS) Score (aGAPSS) was developed for assessing the probability of thrombotic events in APS patients. This study investigated whether the aGAPSS at diagnosis was associated with poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Materials and Methods: This study included 170 AAV patients who had the results of APS-related antibodies at diagnosis but were not diagnosed with APS. All-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were considered poor AAV outcomes. The aGAPSS comprises five items, with 5, 4, 4, 3, and 1 points assigned to anticardiolipin antibodies, anti-β2-glycoprotein 1 antibodies, lupus anticoagulants, hyperlipidaemia, and arterial hypertension at AAV diagnosis, respectively. Results: The median age of the 170 patients [93 microscopic polyangiitis (MPA), 44 granulomatosis with polyangiitis (GPA), and 33 eosinophilic GPA (EGPA)] was 63.0 years. The optimal cut-off of the aGAPSS at diagnosis for ESKD during follow-up was set as two using the receiver operating characteristic curve. AAV patients with an aGAPSS ≥2 at diagnosis exhibited a significantly reduced ESKD-free survival rate compared to those with an aGAPSS <2 at diagnosis (p=0.045). Additionally, MPA and GPA patients, excluding EGPA patients for whom the median aGAPSS at diagnosis was close to 0, also showed similar patterns to the results among the 170 patients with AAV (p=0.021). Conclusion This study is the first to demonstrate that the aGAPSS at diagnosis was significantly associated with ESKD during follow-up in AAV patients without APS.

Purpose: The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity. Materials and Methods: We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire. Results: We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported. Conclusion Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.