Waldenström macroglobulinemia (WM) is a B-cell lymphoproliferative disease characterized by IgM monoclonal gammopathy and bone marrow (BM) infiltration caused by lymphoplasmacytic lymphoma. The MYD88 L265P variant is present in > 90% of WM cases.We used droplet digital PCR (ddPCR) to detect MYD88 L265P in initial BM samples from 15 patients with WM and assessed the implication of variant burden as a tumor load and prognostic marker. MYD88 L265P burden correlated with clinical indicators, including peripheral blood and BM lymphocyte percentages (P < 0.001 and P = 0.003, respectively), serum lactate dehydrogenase level (P = 0.045), and platelet count (P = 0.003). Patients classified into intermediate and high groups according to the Revised International Prognostic Score System for WM had higher MYD88 L265P copies/μL than patients in very low and low groups (P = 0.017), as had patients with minor response or stable disease after primary treatment than those with complete, partial, or very good partial response (P = 0.034).MYD88 L265P burden correlates well with multiple clinical indicators and has prognostic relevance, making it a potential marker for assessing tumor burden and predicting prognosis in WM.

Purpose: Although Korea’s medical care uses advanced technology, there are not enough doctors working in rural areas, and fewer doctors are working in challenging fields such as surgery. Medical care in Türkiye is very cost-effective for patients, but doctors have too many patients and too much work. This study compared the healthcare systems of the 2 countries and the gaps felt by surgeons. Methods: A comparative analysis was conducted using a comprehensive literature review and a questionnaire involving medical professionals from various working positions in both countries. Results: Doctors in both countries felt that there was a large medical gap between regions and reported that the number of doctors was small. Turkish doctors experience excessive patient overload, contributing to high stress and feelings of overwork. They also showed lower job satisfaction than in Korea. The common reasons for the low preference for general surgery residencies include intense training, excessive workload, and high risk in both countries. Conclusion This study identified the key challenges in medical and surgical training in Korea and Türkiye. In Korea, shortages can be addressed by reforms in general surgery residency, the development of a balanced residency selection system, and the provision of work opportunities for non-Korean professionals. In Türkiye, improving remuneration and alleviating unsafe work environments is urgent. Both countries should incentivize rural services to ensure balanced doctor distribution. Collaborative initiatives informed by these findings can enhance medical education and healthcare delivery in both countries.

Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM.In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treat‑ ment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These recommendations include current and emerging diagnostic tools, thera‑ peutic agents, and treatment strategies. By prioritizing a patient-centered approach and rigorous data analysis, these guidelines were developed to enhance MM management, both in Korea and globally.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Background: High B-type natriuretic peptide (BNP) levels within the first 3 postoperative days (postBNPPOD3) after liver transplantation (LT) are greatly predictive of the 30-day mortality. We evaluated clinical impact of transient decrease in postBNPPOD3 compared to pretransplant BNP (preBNP) level on mortality and major adverse cardiac event (MACE) within 30 days after LT. Methods: We retrospectively evaluated 3,811 LT patients who measured delta BNP (deltaBNP), defined by serial postBNPPOD3 minus preBNP. Thirty-day all-cause mortality and MACE were estimated in patients with deltaBNP < 0 (n = 594, 15.6%) and > 0 (n = 3,217, 84.4%), respectively. Kaplan-Meier survival and multivariable Cox regression analysis were used. Results: Within 30 days, 100 (2.6%) of all patients died. Unexpectedly, 30-day mortality rate (6.1% [95% CI: 4.2–8.4%] vs. 2.0% [95% CI: 1.5–2.5%], P < 0.001) and MACE (24.2% [95% CI: 20.4–28.5%] vs. 15.3% [95% CI: 14.0–16.7%], P < 0.001) were higher in patients with deltaBNP < 0 compared to those with deltaBNP > 0, respectively. Patients with deltaBNP < 0 had higher preBNP level (median [interquartile range], 251 [118, 586] vs. 43 [21, 92] pg/ml, P < 0.001) and model for end-stage liver disease score (26 [14, 37] vs. 14 [9, 23], P < 0.001) and more transfused intraoperatively. DeltaBNP < 0 remained significant after adjustments for potential confounders in multivariable analysis of 30-day mortality and MACE. Conclusions DeltaBNP < 0 within the first 3 postoperative days is mainly attributed to pre-LT severe liver and cardiac disease status, therefore, transient decrease in BNP level after LT does not ensure favorable post-LT 30-day outcomes.

Purpose: Tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism. Materials and Methods: To determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib. Results: Among differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway. Conclusion These results showed that PD-L1 expression may be increased in a subset of VEGFR-TKI–resistant mCCRCC patients via the mTOR pathway.

Acute-on-chronic liver failure (ACLF) is a life-threatening disease that requires urgent liver transplantation (LT). Accurate identification of high-risk patients is essential for predicting post-LT survival. The chronic liver failure consortium ACLF score is a widely accepted risk-stratification score that includes total white blood cell (WBC) counts as a component. This study aimed to evaluate the predictive value of total and differential WBC counts for short-term mortality following LT in patients with ACLF. Methods: A total of 685 patients with ACLF who underwent LT between January 2008 and February 2019 were analyzed. Total and differential WBC counts were examined as a function of the model for end-stage liver disease for sodium (MELD-Na) score. The association between total and differential WBC counts and 90-day post-LT mortality was assessed using multivariable Cox proportional hazards regression analysis. Results: The total WBC counts and neutrophil ratio were higher in patients with ACLF than in those without ACLF. The neutrophil ratio was significantly associated with 90-day post-LT mortality after adjustment (hazard ratio [HR], 1.04; P = 0.001), whereas total WBC counts were not significantly associated with 90-day post-LT mortality in either univariate or multivariate Cox analyses. The neutrophil ratio demonstrated a relatively linear trend with an increasing MELD-Na score and HR for 90-day post-LT mortality, whereas the total WBC counts exhibited a plateaued pattern. Conclusions: Neutrophilia, rather than total WBC counts, is a better prognostic indicator for short-term post-LT mortality in patients with ACLF.

Background: Given the severe shortage of donor liver grafts, coupled with growing proportion of cardiovascular death after liver transplantation (LT), precise cardiovascular risk assessment is pivotal for selecting recipients who gain the greatest survival benefit from LT surgery. We aimed to determine the prognostic value of pre-LT combined measurement of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI) in predicting early post-LT mortality. Methods: We retrospectively evaluated 2,490 consecutive adult LT patients between 2010 and 2018. Cut-off values of BNP and hsTnI for predicting post-LT 90-day mortality were calculated. According to the derived cut-off values of two cardiac biomarkers, alone and in combination, adjusted hazard ratios (aHR) of post-LT 90-day mortality were determined using multivariate Cox regression analysis. Results: Mortality rate after 90 days was 2.9% (72/2,490). Rounded cut-off values for post-LT 90-day mortality were 400 pg/ml for BNP (aHR 2.02 [1.15, 3.52], P = 0.014) and 60 ng/L for hsTnI (aHR 2.65 [1.48, 4.74], P = 0.001), respectively. Among 273 patients with BNP ≥ 400 pg/ml, 50.9% of patients were further stratified into having hsTnI ≥ 60 ng/L. Combined use of pre-LT cardiac biomarkers predicted post-LT 90-day mortality rate; both non-elevated: 1.0% (21/2,084), either one is elevated: 9.0% (24/267), and both elevated: 19.4% (27/139, log-rank P < 0.001; aHR vs non-elevated 4.23 [1.98, 9.03], P < 0.001). Conclusions Concomitant elevation of both cardiac biomarkers posed significantly higher risk of 90-day mortality after LT. Pre-LT assessment cardiac strain and myocardial injury, represented by BNP and hsTnI values, would contribute to prioritization of LT candidates and help administer target therapies that could modify early mortality.

Background: Given the severe shortage of donor liver grafts, coupled with growing proportion of cardiovascular death after liver transplantation (LT), precise cardiovascular risk assessment is pivotal for selecting recipients who gain the greatest survival benefit from LT surgery. We aimed to determine the prognostic value of pre-LT combined measurement of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI) in predicting early post-LT mortality. Methods: We retrospectively evaluated 2,490 consecutive adult LT patients between 2010 and 2018. Cut-off values of BNP and hsTnI for predicting post-LT 90-day mortality were calculated. According to the derived cut-off values of two cardiac biomarkers, alone and in combination, adjusted hazard ratios (aHR) of post-LT 90-day mortality were determined using multivariate Cox regression analysis. Results: Mortality rate after 90 days was 2.9% (72/2,490). Rounded cut-off values for post-LT 90-day mortality were 400 pg/ml for BNP (aHR 2.02 [1.15, 3.52], P = 0.014) and 60 ng/L for hsTnI (aHR 2.65 [1.48, 4.74], P = 0.001), respectively. Among 273 patients with BNP ≥ 400 pg/ml, 50.9% of patients were further stratified into having hsTnI ≥ 60 ng/L. Combined use of pre-LT cardiac biomarkers predicted post-LT 90-day mortality rate; both non-elevated: 1.0% (21/2,084), either one is elevated: 9.0% (24/267), and both elevated: 19.4% (27/139, log-rank P < 0.001; aHR vs non-elevated 4.23 [1.98, 9.03], P < 0.001). Conclusions Concomitant elevation of both cardiac biomarkers posed significantly higher risk of 90-day mortality after LT. Pre-LT assessment cardiac strain and myocardial injury, represented by BNP and hsTnI values, would contribute to prioritization of LT candidates and help administer target therapies that could modify early mortality.

Purpose: We aimed to investigate whether adjuvant oxaliplatin-based chemotherapy after treatment for hepatic metastasis affects recurrence or survival and to determine the risk factors for recurrence or survival. Methods: Forty-six patients who underwent curative treatment for hepatic metastasis from colorectal cancer between July 2009 and December 2017 were included from a retrospectively collected patient database. Curative resection included hepatic resection, radiofrequency ablation (RFA), or a combination of both, followed by adjuvant chemotherapy with oxaliplatin-based chemotherapy. Results: Thirty-seven patients (80.4%) had colon cancer and 9 (19.6%) had rectal cancer. Twenty-six patients (56.5%) underwent hepatic resection, 7 (15.2%) RFA, and 13 (28.3%) hepatic resection and RFA. Thirty-two patients (69.6%) underwent chemotherapy after hepatic treatment. The recurrence incidence was 50% in the non-chemotherapy group and 46.9% in the chemotherapy group (P > 0.999). The incidence of death was 7.1% in the non-chemotherapy group and 18.8% in the chemotherapy group (P = 0.657). The recurrence risk factors were N stage (N0 vs. N2; P = 0.013, P = 0.005) and bilobed hepatic metastasis (P = 0.027, P = 0.009) in the univariate and multivariate analyses, respectively. However, chemotherapy after hepatic treatment was not a risk factor for disease-free survival (DFS) or overall survival (OS) in the univariate and multivariate analyses (P = 0.656 and P = 0.414, respectively; P = 0.510 and P = 0.459, respectively). Conclusion Oxaliplatin-based adjuvant chemotherapy after colorectal hepatic metastasis treatment did not affect the DFS or OS. The N stage of the primary tumor and bilobed hepatic metastasis are risk factors for recurrence and death.