Neuropathic pain markedly impairs quality of life and imposes a substantial socioeconomic burden, while available treatments often provide only partial relief and are limited by safety concerns. The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG-IASP) first published pharmacologic recommendations in 2007, followed by a major update in 2015 and a new guideline in 2025. This narrative review specifically compares the 2015 and 2025 NeuPSIG-IASP guidelines, outlining key methodological changes and therapeutic shifts. The 2025 guideline is based on a larger, more rigorous meta-analysis, maintains α2δ-ligands (adds mirogabalin), serotonin-noradrenaline reuptake inhibitors, and tricyclic antidepressants as first-line drugs, downgrades tramadol into the opioid third-line group. It also introduces high-frequency motor-cortex repetitive transcranial magnetic stimulation as a weakly recommended third-line option and discusses implications for Korean clinical practice.

Background: We compared the immunoglobulin (IG) heavy chain (IGH) leader and FR1 primer sets to measure clone sizes and detect immunoglobulin heavy chain variable (IGHV) region somatic hypermutations (SHMs) in Korean patients with chronic lymphocytic leukemia (CLL). We also analyzed IGH and immunoglobulin kappa (IGK) to identify Korean-specific IGs in CLL. Methods: Next-generation sequencing (NGS)–based gene rearrangements and IGHV SHMs were assessed in 40 patients using IGH leader, IGH FR1, and IGK primers. Flow cytometry, karyotyping, interphase FISH, and NGS-based variant analyses were performed for 165 genes. Results: Clonal IGH and IGK rearrangements were detected in 100.0% and 97.5% of patients, respectively. Clonal size was generally smaller per NGS than per flow cytometry, particularly when using the IGH leader (median: 52.5%) versus the IGH FR1 primer set (73.2%). IGHV SHMs occurred in approximately 70% of patients; 10% showed primer set discrepancies. The incidence of IGHV SHMs was low in patients at high risk (i.e., with TP53 abnormalities; complex karyotypes; and ATM, NOTCH1, SF3B1, or BIRC3 variants). IGHV3 was the most common IGHV (58.3%), and IGHV4-34 was most frequently identified (14.6%). IGHV1 and IGHV1-69 usage differed significantly between Koreans and westerners. IGHJ4 was the most common IGHJ (56.3%). A single IGKV–IGKJ gene rearrangement was most frequently observed (18.9%), whereas intron-KDE was the most common rearrangement (30.6%). Conclusions NGS may underestimate CLL clonal size, particularly when using the IGH leader primer set. IGHV SHMs were inversely associated with negative prognostic factors.Our data suggest ethnic differences in CLL pathogenesis.

Purpose: This study aimed to evaluate surgical outcomes, identify complications, and analyze recurrence in patients undergoing surgery for primary retroperitoneal tumors (RPTs), which pose significant therapeutic challenges. Methods: We retrospectively reviewed the medical records of 59 patients who underwent surgery for primary RPTs at Ajou University Hospital between January 2015 and December 2024. Patients were divided into a multivisceral resection (MVR) group (n = 25) and a non-MVR group (n = 34) to compare demographics, clinical characteristics, pathological findings, and postoperative outcomes. Results: Compared to the non-MVR group, the MVR group had a significantly higher rate of open surgery (96.0% vs.73.5%, P = 0.034), longer operative times (237.6 minutes vs. 188.8 minutes, P = 0.032), more frequent R2 resections (32.0% vs. 8.8%, P = 0.018), and longer hospital stays (13.1 days vs. 7.0 days, P = 0.007). Malignant tumors comprised 67.7% of cases, with sarcoma being the most common. Recurrence rates were highest in well-differentiated liposarcoma (50.0%) and dedifferentiated liposarcoma (22.2%). While univariate analysis showed MVR was associated with severe morbidity (Clavien-Dindo grade ≥III; odds ratio, 6.200; P = 0.029), this was not sustained as an independent predictor in multivariable analysis. Conclusion Although MVR was associated with severe complications in univariate analysis, it was not an independent predictor in multivariable analysis. This suggests the increased risk reflects overall surgical complexity. Therefore, MVR should be pursued when oncologically necessary, as it presents an acceptable morbidity profile.

Purpose: While progesterone receptor (PR) negativity in luminal-type breast cancer is generally associated with worse oncologic outcomes, its prognostic role in estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains underexplored. This study aimed to evaluate the prognostic significance of PR expression in ER-positive, HER2-positive breast cancer. Methods: A retrospective analysis was conducted on patients diagnosed with ER-positive, HER2-positive breast cancer who underwent primary surgery at Korea University Guro Hospital between January 2009 and December 2019. Patients were grouped by PR expression as negative/low (Allred score, 0–6) or strongly positive (Allred score,7 or 8). Prognostic outcomes, including disease-free survival (DFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) were analyzed. Results: A total of 223 patients were included. Patients in the negative/low PR group were older compared to the strongly positive PR group. The negative/low PR group showed significantly worse DFS (P = 0.005) and DRFS (P = 0.014) but showed no significant difference in BCSS (P = 0.153). On multivariate analysis, negative or low PR expressions were linked to inferior DFS (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.34–7.16; P = 0.008) and DRFS (HR, 9.55; 95% CI, 1.22– 74.77; P = 0.032). Conclusion In ER-positive, HER2-positive breast cancer, negative or weak PR expression was associated with inferior DFS and DRFS compared to strong PR expression. These findings highlight the potential prognostic value of PR status in this group, underscoring its relevance in guiding treatment and follow-up strategies for more individualized patient care.

Purpose: Postoperative complications following gastric cancer surgery significantly impact patient outcomes, yet standardized definitions for these events have not been consistently applied across institutions in Korea. This study aimed to develop a consensus-based, standardized complication classification system specific to gastrectomy for gastric cancer as part of the Korean Quality Improvement Platform in Surgery (K-QIPS) initiative. Methods: As part of K-QIPS, a dedicated task force team (TFT) was formed with surgical experts from fourteen high-volume hospitals across Korea. The TFT conducted ten formal meetings to review existing literature and international guidelines, and incorporated findings from randomized controlled trials. The final complication list was developed through expert consensus and structured into a standardized framework. A Data Entry Manual was created to support consistent data collection by surgical clinical reviewers. Results: The TFT defined specific postoperative complications following gastrectomy for gastric cancer, including anastomotic leakage, duodenal stump leakage, pancreatic fistula, intra-abdominal and luminal bleeding, delayed gastric emptying, and internal hernia. Notably, internal hernia was described in standardized form for the first time. General complications were developed first and overlapped in part with the gastric cancer-specific list. The task force also produced a Data Entry Manual that provides practical instructions to ensure consistency and accuracy in complication reporting. Conclusion This nationwide consensus initiative established the first standardized complication classification system for gastric cancer surgery in Korea. The proposed definitions and data entry system are expected to improve complication reporting, enable multicenter research, support surgical quality benchmarking, and ultimately enhance patient outcomes.

Background: When positioning the acetabular component for total hip arthroplasty (THA) in patients with sequelae of LeggCalvé-Perthes disease (LCPD), elevating the center of rotation (COR) of the hip is often unavoidable. We aimed to compare the outcomes between the preserved and elevated COR groups in patients with sequelae of LCPD. Methods: We enrolled 53 patients who underwent primary THA for sequelae of LCPD between 2006 and 2019. Patients were divided into 2 groups based on the postoperative COR position: 19 in the preserved COR group and 34 in the elevated COR group.The mean elevation of COR was 2.7 mm (range, 0–5.0 mm) in the preserved COR group and 8.1 mm (range, 6.0–12.0 mm) in the elevated COR group. Radiological outcomes, such as osteolysis and implant loosening, were evaluated. Additionally, reoperation, perioperative complications, limping gait, pelvic obliquity, and the modified Harris hip score (mHHS) were assessed. Results: There were no significant differences in radiological or clinical outcomes between the 2 groups. Neither osteolysis nor implant loosening was observed, and no reoperations were required. Intraoperative periprosthetic femoral fractures occurred in 3 cases (6%), but no cases of sciatic nerve palsy were observed. Residual limping gait was noted in 10 patients (19%), and pelvic obliquity persisted in 8 patients (15%). At the last follow-up, the mean mHHS was 89.2. Conclusions The 5–17-year follow-up results of primary cementless THA in patients with sequelae of LCPD were satisfactory.Furthermore, a moderate elevation of the COR, with a mean of 8.1 mm (range, 6.0–12.0 mm), did not significantly affect the outcomes of THA in these patients. Therefore, a moderate elevation of the COR can be considered an acceptable option for patients undergoing THA with sequelae of LCPD.

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.

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.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.