Purpose: Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood. Materials and Methods: We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared. Results: A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes. Conclusions GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: Non-operative management (NOM) has emerged as a promising organ-preserving strategy for patients with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (CRT). However, no standardized treatment protocol has been established for watch-and-wait strategies. Materials and Methods: This prospective study evaluated oncological outcomes of NOM combined with 4 months of adjuvant capecitabine. Patients with resectable rectal cancer (≤ 8 cm from the anal verge, cT2-4 or N+) underwent CRT (50-54 Gy in 25-27 fractions with capecitabine). Eight weeks post-CRT, a multidisciplinary team assessed cCR. Patients achieving cCR received six cycles of capecitabine (2 weeks on/1 week off) and were actively monitored. Results: Among 89 patients receiving CRT (2018-2023), 17 (19.1%) achieved cCR and were included. The median age was 65 years, and 64.7% were male. Eleven (64.7%) completed all six cycles of adjuvant therapy. After a median follow-up of 31.4 months, 11 patients (64.7%) remained disease-free. Local regrowth occurred in six patients (35.3%) with 2- and 4-year rates of 34.5% and 47.6%, respectively. Five underwent radical surgery, and one received transanal excision with systemic chemotherapy. At the time of assessment, 15 patients (88.2%) showed no evidence of disease, while two (11.8%) received palliative chemotherapy. All patients were alive. Conclusion NOM with adjuvant capecitabine showed promising oncological outcomes, offering an alternative to passive watch-and-wait approaches. Further refinement through multidisciplinary strategies is warranted.

Purpose: Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. Materials and Methods: This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. Results: We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. Conclusion Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

Purpose: Adjuvant treatment for craniopharyngioma after surgery is controversial. Adjuvant external beam radiation therapy (EBRT) can increase the risk of long-term sequelae. Stereotactic radiosurgery (SRS) is used to reduce treatment-related toxicity.In this study, we compared the treatment outcomes and toxicities of adjuvant therapies for craniopharyngioma. Materials and Methods: We analyzed patients who underwent craniopharyngioma tumor removal between 2000 and 2017. Of the 153 patients, 27 and 20 received adjuvant fractionated EBRT and SRS, respectively. We compared the local control (LC), progression-free survival (PFS), and overall survival between groups that received adjuvant fractionated EBRT, SRS, and surveillance. Results: The median follow-up period was 77.7 months. For SRS and surveillance, the 10-year LC was 57.2% and 57.4%, respectively. No local progression was observed after adjuvant fractionated EBRT. One patient in the adjuvant fractionated EBRT group died owing to glioma 94 months after receiving radiotherapy (10-year PFS: 80%). The 10-year PFS was 43.6% and 50.7% in the SRS and surveillance groups, respectively. The treatment outcomes significantly differed according to adjuvant treatment in nongross total resection (GTR) patients. Additional treatment-related toxicity was comparable in the adjuvant fractionated EBRT and other groups. Conclusion Adjuvant fractionated EBRT could be effective in controlling local failure, especially in patients with non-GTR, while maintaining acceptable treatment-related toxicity.

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.

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.

Purpose: Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. Materials and Methods: This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. Results: We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. Conclusion Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

Purpose: Adjuvant treatment for craniopharyngioma after surgery is controversial. Adjuvant external beam radiation therapy (EBRT) can increase the risk of long-term sequelae. Stereotactic radiosurgery (SRS) is used to reduce treatment-related toxicity.In this study, we compared the treatment outcomes and toxicities of adjuvant therapies for craniopharyngioma. Materials and Methods: We analyzed patients who underwent craniopharyngioma tumor removal between 2000 and 2017. Of the 153 patients, 27 and 20 received adjuvant fractionated EBRT and SRS, respectively. We compared the local control (LC), progression-free survival (PFS), and overall survival between groups that received adjuvant fractionated EBRT, SRS, and surveillance. Results: The median follow-up period was 77.7 months. For SRS and surveillance, the 10-year LC was 57.2% and 57.4%, respectively. No local progression was observed after adjuvant fractionated EBRT. One patient in the adjuvant fractionated EBRT group died owing to glioma 94 months after receiving radiotherapy (10-year PFS: 80%). The 10-year PFS was 43.6% and 50.7% in the SRS and surveillance groups, respectively. The treatment outcomes significantly differed according to adjuvant treatment in nongross total resection (GTR) patients. Additional treatment-related toxicity was comparable in the adjuvant fractionated EBRT and other groups. Conclusion Adjuvant fractionated EBRT could be effective in controlling local failure, especially in patients with non-GTR, while maintaining acceptable treatment-related toxicity.

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.