Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

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: 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.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

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.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Objective: This study aimed to investigate the closure rate and adverse effects of combination therapy with acetaminophen and ibuprofen for hemodynamically significant patent ductus arteriosus (hsPDA) compared with monotherapy with ibuprofen in extremely preterm infants (EPTs). Methods: This was a single-center, retrospective, and historical control study of infants with hsPDA born at <28 weeks of gestation and a birth weight <1,000 g. Based on the first-line therapeutic policy for hsPDA, the cohort was classified into a monotherapy group (period I: January 2019-July 2021) and a combination therapy group (period II: September 2021-August 2023). Baseline characteristics, treatment outcomes, adverse effects, and morbidities were compared between the groups. Results: Of the 43 EPTs with hsPDA, 26 received monotherapy with ibuprofen during period I, and 17 received combination therapy with acetaminophen and ibuprofen during period II. The successful closure rates after the first medical therapy were 42.3% in the monotherapy group vs. 76.5% in the combination therapy group (P=0.027). No significant difference in adverse effects during medication use was observed between the groups. Conclusion Combination therapy with acetaminophen and ibuprofen improved the closure rate for hsPDA without detectable adverse effects. Combination therapy could be considered the first therapeutic option for hsPDA in EPTs. Further well-designed studies are needed to define the safety and effectiveness of combination therapy.

Objective: This study aimed to investigate the closure rate and adverse effects of combination therapy with acetaminophen and ibuprofen for hemodynamically significant patent ductus arteriosus (hsPDA) compared with monotherapy with ibuprofen in extremely preterm infants (EPTs). Methods: This was a single-center, retrospective, and historical control study of infants with hsPDA born at <28 weeks of gestation and a birth weight <1,000 g. Based on the first-line therapeutic policy for hsPDA, the cohort was classified into a monotherapy group (period I: January 2019-July 2021) and a combination therapy group (period II: September 2021-August 2023). Baseline characteristics, treatment outcomes, adverse effects, and morbidities were compared between the groups. Results: Of the 43 EPTs with hsPDA, 26 received monotherapy with ibuprofen during period I, and 17 received combination therapy with acetaminophen and ibuprofen during period II. The successful closure rates after the first medical therapy were 42.3% in the monotherapy group vs. 76.5% in the combination therapy group (P=0.027). No significant difference in adverse effects during medication use was observed between the groups. Conclusion Combination therapy with acetaminophen and ibuprofen improved the closure rate for hsPDA without detectable adverse effects. Combination therapy could be considered the first therapeutic option for hsPDA in EPTs. Further well-designed studies are needed to define the safety and effectiveness of combination therapy.

Objective: This study aimed to investigate the closure rate and adverse effects of combination therapy with acetaminophen and ibuprofen for hemodynamically significant patent ductus arteriosus (hsPDA) compared with monotherapy with ibuprofen in extremely preterm infants (EPTs). Methods: This was a single-center, retrospective, and historical control study of infants with hsPDA born at <28 weeks of gestation and a birth weight <1,000 g. Based on the first-line therapeutic policy for hsPDA, the cohort was classified into a monotherapy group (period I: January 2019-July 2021) and a combination therapy group (period II: September 2021-August 2023). Baseline characteristics, treatment outcomes, adverse effects, and morbidities were compared between the groups. Results: Of the 43 EPTs with hsPDA, 26 received monotherapy with ibuprofen during period I, and 17 received combination therapy with acetaminophen and ibuprofen during period II. The successful closure rates after the first medical therapy were 42.3% in the monotherapy group vs. 76.5% in the combination therapy group (P=0.027). No significant difference in adverse effects during medication use was observed between the groups. Conclusion Combination therapy with acetaminophen and ibuprofen improved the closure rate for hsPDA without detectable adverse effects. Combination therapy could be considered the first therapeutic option for hsPDA in EPTs. Further well-designed studies are needed to define the safety and effectiveness of combination therapy.

Objective: This study aimed to investigate the closure rate and adverse effects of combination therapy with acetaminophen and ibuprofen for hemodynamically significant patent ductus arteriosus (hsPDA) compared with monotherapy with ibuprofen in extremely preterm infants (EPTs). Methods: This was a single-center, retrospective, and historical control study of infants with hsPDA born at <28 weeks of gestation and a birth weight <1,000 g. Based on the first-line therapeutic policy for hsPDA, the cohort was classified into a monotherapy group (period I: January 2019-July 2021) and a combination therapy group (period II: September 2021-August 2023). Baseline characteristics, treatment outcomes, adverse effects, and morbidities were compared between the groups. Results: Of the 43 EPTs with hsPDA, 26 received monotherapy with ibuprofen during period I, and 17 received combination therapy with acetaminophen and ibuprofen during period II. The successful closure rates after the first medical therapy were 42.3% in the monotherapy group vs. 76.5% in the combination therapy group (P=0.027). No significant difference in adverse effects during medication use was observed between the groups. Conclusion Combination therapy with acetaminophen and ibuprofen improved the closure rate for hsPDA without detectable adverse effects. Combination therapy could be considered the first therapeutic option for hsPDA in EPTs. Further well-designed studies are needed to define the safety and effectiveness of combination therapy.