Objective: To evaluate the impact of adding CT to ultrasound (US) for nodal assessment in patients with papillary thyroid microcarcinoma (PTMC), particularly in those with US-node-negative disease. Materials and Methods: This single-center retrospective study included consecutive patients with PTMC (≤1 cm on US) who underwent both US and CT for PTMC staging between August 2016 and January 2020, and subsequently underwent surgery including neck dissection. The number of patients with clinical N1 and pathological N1 disease was assessed. The diagnostic performance of US, CT, and combined US + CT (positive if either was positive) for macroscopic lymph node metastasis (LNM) (i.e., metastatic tumor foci >2 mm) was evaluated. Cases with discordant nodal staging between US and CT were identified.The diagnostic utility of CT was also assessed in a subgroup of patients with node-negative findings on US. Results: Among 982 patients (mean age ± standard deviation, 47.3 ± 11.5 years; 774 female), pathological analysis confirmed cervical LNM in 377 patients, including macroscopic, microscopic, and size-unknown LNM in 187, 175, and 15 patients, respectively. The addition of CT to US improved sensitivity for detecting macroscopic LNM compared to US alone (68.4% [128/187] vs. 26.7% [50/187]; P < 0.001), while maintaining high specificity despite a significant decrease (90.9% [709/780] vs. 97.2% [758/780]; P < 0.001). Discordant nodal staging between US and CT regarding macroscopic LNM was observed in 149 cases (15.2% [149/982]), with 131 patients (87.9% [131/149]) being upstaged by CT. In patients with node-negative US findings, CT detected US-undetected macroscopic LNM in 78 patients (8.7% [78/895]) and exhibited a sensitivity of 56.9% (78/137) and specificity of 93.5% (709/758) for macroscopic LNM. Conclusion The integration of CT with US improved sensitivity for detecting macroscopic LNM in patients with PTMC, identifying those who would otherwise be inappropriately considered candidates for active surveillance based solely on US findings. This may assist in refining patient management.

Purpose: Enhanced Recovery After Surgery (ERAS) protocols have demonstrated significant benefits, but their safety and effectiveness in high-risk patients remain unclear. This study evaluated clinical postoperative outcomes in elderly patients and those with comorbidities undergoing colon cancer surgery. Methods: This retrospective cohort study included 1,035 patients who underwent elective colon cancer surgery from 2017 to 2022. A standardized 25-element ERAS protocol was implemented across all groups. Patients were categorized into a control group (aged <70 years without comorbidities, n = 534) and high-risk groups including elderly patients (≥70 years, n = 312) and those with cardiac (n = 60), pulmonary (n = 81), renal (n = 24), or hepatic disease (n = 24). Results: ERAS compliance rates were significantly lower in all high-risk groups compared to controls (79.39% ± 10.9%), with renal disease patients showing the most pronounced reduction (69.69% ± 17.0%). Post-hoc analysis revealed that only renal disease patients demonstrated significantly higher complication rates (45.8% vs. 18.9%, P < 0.01). Despite lower compliance, multivariate analysis revealed ERAS compliance ≥70% as the strongest independent predictor of both length of stay (odds ratio [OR], 0.139; P < 0.001) and complications (OR, 0.298; P < 0.001), substantially outweighing patient risk factors. After adjusting for treatment factors, patient comorbidity groups showed no independent association with clinical outcomes. Conclusion ERAS protocols can be successfully implemented in high-risk patients with appropriate attention to compliance optimization. Treatment factors, particularly ERAS adherence, consistently outweigh patient risk factors in determining outcomes, and well-tailored ERAS implementation should be considered with high-risk patients for perioperative care.

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.

Limited data exist regarding the real-world practices and clinical outcomes in patients with ischemic heart failure with reduced left ventricular ejection fractions (LVEFs).Using nationwide registry data from South Korea, we aimed to investigate long-term outcomes and clinical practices, especially implantable cardioverter defibrillators (ICDs) implantation, in patients with reduced LVEFs at least 40 days after acute myocardial infarction (AMI). Of 13,056 patients with AMI between 2011 and 2015, we analyzed 350 (median age, 66 years [interquartile range, 56-75]) who had LVEFs <40% on follow-up transthoracic echocardiogram 40 days after the index event. The primary outcome was cardiac-cause mortality at 3 years. Secondary outcomes comprised major cardiovascular events as well as outcomes defined by the use of ICDs, cardiac resynchronization therapy defibrillators (CRT-Ds), and electrophysiology studies. Among 350 patients, 39 (11.1%) died from cardiac causes during 3 years of follow-up. Eleven (3.1%) were hospitalized for ventricular tachycardia. The rate of ICD or CRT-D implantation up to 3 years was 5.7% (20/350). Cox time-to-event analysis revealed older age, LVEF <30%, diabetes mellitus, and previous MI or revascularization as positively associated with cardiac death, whereas the use of statins and body weight <67 kg were negatively associated. This nationwide Korean registry demonstrated that only 5.7% of patients who had reduced LVEFs after 40 days of AMI underwent ICD implantations over 3 years. Considering the high mortality, concerted efforts are needed to improve clinical outcomes for patients who may have been candidates for ICD implantation.

Objectives: . Differentiated thyroid cancer (DTC) has a favorable prognosis. However, indeterminate lymph nodes (LNs) are common, making it challenging to distinguish recurrent from persistent DTC. Previous studies have not specifically compared the prognosis between recurrent and persistent DTC. Therefore, we aimed to compare prognosis and oncologic characteristics between these two groups. Methods: . This retrospective cohort study was conducted at a single tertiary care institution and included 265 patients with DTC (recurrent, 109; persistent, 156) who underwent reoperation between November 1, 1999, and August 31, 2018, for structural disease. Patients with distant metastasis at the time of initial diagnosis were excluded. Clinical and oncological characteristics, patterns of LN metastasis, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. For DFS, time zero was defined as the date of the second operation. Results: . Recurrent DTC had a higher incidence of central LN metastasis (P=0.003), infield recurrence (P<0.001), and distant metastasis (P<0.001). In contrast, persistent DTC more frequently exhibited lateral LN metastasis (P=0.003) and outfield recurrence (P<0.001). The most common site of neck LN metastasis was ipsilateral level VI/VII (51.4%) in recurrent DTC and ipsilateral level IV (43.0%) in persistent DTC. Ten-year DFS was significantly lower in recurrent DTC than in persistent DTC (41.0% vs. 67.9%; P<0.001). Recurrent DTC, older age, a higher number of metastatic LNs at the second operation (first reoperation), and R1/R2 resection at the second operation were associated with decreased DFS. OS did not significantly differ between recurrent and persistent DTC (P=0.160). Conclusion . Recurrent DTC is associated with poorer DFS than persistent DTC, although OS does not significantly differ between the two groups.

Objective: To examine the risk of cardiovascular disease (CVD) associated with use of tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS). Methods: This study used data from the Korean National Health Insurance database. Patients aged ≥18 years who were newly diagnosed with AS between 2010 and 2018 and did not suffer prior CVD were included. The primary outcome was a composite endpoint of myocardial infarction (MI) or stroke. The secondary outcomes were specific endpoints of MI, stroke, or congestive heart failure. TNFi use was evaluated as a time-dependent variable. Cox proportional hazard regression was used to examine the association between TNFi use and risk of incident CVD. Results: Of 19,775 patients (mean age, 36.1 years; 75% male), 5,978 (30.2%) were exposed to TNFi treatment during the study period. During a follow-up of 4.8 (interquartile range, 2.9~7.2) years, 522 events of MI or stroke occurred. TNFi use was associated with a lower risk of MI or stroke than no TNFi use after adjusting for traditional CV risk factors and medications (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.55~0.94). The lower risk of MI or stroke associated with TNFi use was consistently observed across subgroups. Risk of congestive heart failure did not differ between users and non-users of TNFi (aHR, 0.94; 95% CI, 0.75~1.18). Conclusion In a real-world AS cohort, TNFi treatment was associated with a reduced risk of atherosclerotic CVD. However, TNFi use was not associated with risk of congestive heart failure.

Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks clinical biomarkers. Exosomes are extracellular vesicles that facilitate cell–cell communication by distributing macromolecules, such as small RNAs (smRNAs). We assessed the potential of exosome-derived small RNAs (Ex-smRNAs) as PDAC biomarkers. Methods: Peripheral blood was collected from 51 patients with PDAC and 15 control individuals. Exosomes were isolated using an aqueous two-phase system. Ex-smRNAs were analyzed using smRNA sequencing. smRNA-mediated target gene regulation was verified via The Cancer Genome Atlas analysis and in vitro transfection and wound-healing assays using PDAC organoids. Results: The total Ex-smRNA count was substantially reduced in patients with PDAC compared with that in control individuals. The levels of microRNAs (miRNAs) miR-125a-5p, miR-30e-5p, miR-16-2-3p, miR-98-5p, and the let-7 family were significantly suppressed, whereas that of miR-6731-5p was significantly elevated. Let-7c-5p and miR-98-5p were found to interact with the long non-coding RNA OLMALINC to regulate their common target genes, BACH1 and CCND1, thus controlling PDAC proliferation and migration. The expressions of CARS1-AS1 and miR-142-5p were upregulated in treatment-responsive patients.Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15–0.73; P = 0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61–1.01; P = 0.0581) were associated with improved overall survival. Conclusions We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.

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.