Prebiotics are substrates selectively utilized by microorganisms to confer health benefits to their hosts. Various prebiotics have been supplemented in standard milk formulas for infants who cannot be exclusively breastfed, aiming to provide benefits similar to those of breast milk. One of the most commonly used prebiotics is a mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]). Systematic review and metaanalysis were conducted to determine the effectiveness of scGOS:lcFOS (9:1) supplementation in standard milk formula for improving gastrointestinal health and immunity among healthy infants and toddlers, using parameters such as stool pH and intestinal colonization with beneficial bacteria. This systematic review was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Randomized clinical trials comparing scGOS/lcFOS (9:1)-supplemented formula versus placebo- or nonsupplemented formula milk were eligible for inclusion. Related studies on gastrointestinal health and immunity among healthy infants up to five years old were searched from the earliest available date until February 29, 2024. Eighteen publications (number of participants=1,675) were selected for the systematic review, of which 11 were subsequently subjected to a metaanalysis. Results showed that the standard formula supplemented with scGOS/lcFOS (9:1) was well tolerated and conferred various gastrointestinal health and immunity to healthy infants and toddlers. These findings support the supplementation of standard milk formula with scGOS/lcFOS (9:1) for healthy infants and toddlers.

Background: Core needle biopsy (CNB) improves diagnostic accuracy by providing precise tissue sampling for histopathological evaluation, overcoming the limitation of inconclusive fine-needle aspiration results. This study evaluated the diagnostic performance of CNB in assessing thyroid nodules, with additional analysis of the benefits of BRAF V600E and RAS Q61R immunohistochemical (IHC) markers. Methods: This retrospective study enrolled patients with thyroid nodules who underwent CNB at Dr. Cipto Mangunkusumo Hospital, Jakarta, from July 2022 to July 2024. CNB diagnoses were classified using the Korean Thyroid Association Criteria. Diagnostic efficacy was evaluated for neoplastic and malignant lesions, both independently and with BRAF V600E and RAS Q61R IHC. The correlation between nodule size and postoperative diagnosis was also analyzed. Results: A total of 338 thyroid nodule samples was included, and 52.7% were classified as CNB category II. In the 104 samples with postoperative diagnoses, category IV was the most prevalent (39.4%). CNB demonstrated a sensitivity of 74% and a specificity of 100% for neoplastic lesions and 23.8% sensitivity and 100% specificity for malignant lesions. Combining CNB with BRAF V600E and RAS Q1R IHC increased the sensitivity to 77% for neoplastic lesions and 28.8% for malignant lesions. Larger nodules (>3 cm) were significantly associated with neoplastic (p = .005) and malignant lesions (p = .004). Conclusions CNB performs well in identifying neoplastic lesions, with or without BRAF V600E and RAS Q61R IHC, but its low sensitivity for malignant lesions warrants caution. While CNB categories V–VI indicate malignancy, the possibility of malignancy in categories I–IV should not be overlooked.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Prebiotics are substrates selectively utilized by microorganisms to confer health benefits to their hosts. Various prebiotics have been supplemented in standard milk formulas for infants who cannot be exclusively breastfed, aiming to provide benefits similar to those of breast milk. One of the most commonly used prebiotics is a mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]). Systematic review and metaanalysis were conducted to determine the effectiveness of scGOS:lcFOS (9:1) supplementation in standard milk formula for improving gastrointestinal health and immunity among healthy infants and toddlers, using parameters such as stool pH and intestinal colonization with beneficial bacteria. This systematic review was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Randomized clinical trials comparing scGOS/lcFOS (9:1)-supplemented formula versus placebo- or nonsupplemented formula milk were eligible for inclusion. Related studies on gastrointestinal health and immunity among healthy infants up to five years old were searched from the earliest available date until February 29, 2024. Eighteen publications (number of participants=1,675) were selected for the systematic review, of which 11 were subsequently subjected to a metaanalysis. Results showed that the standard formula supplemented with scGOS/lcFOS (9:1) was well tolerated and conferred various gastrointestinal health and immunity to healthy infants and toddlers. These findings support the supplementation of standard milk formula with scGOS/lcFOS (9:1) for healthy infants and toddlers.

Prebiotics are substrates selectively utilized by microorganisms to confer health benefits to their hosts. Various prebiotics have been supplemented in standard milk formulas for infants who cannot be exclusively breastfed, aiming to provide benefits similar to those of breast milk. One of the most commonly used prebiotics is a mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]). Systematic review and metaanalysis were conducted to determine the effectiveness of scGOS:lcFOS (9:1) supplementation in standard milk formula for improving gastrointestinal health and immunity among healthy infants and toddlers, using parameters such as stool pH and intestinal colonization with beneficial bacteria. This systematic review was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Randomized clinical trials comparing scGOS/lcFOS (9:1)-supplemented formula versus placebo- or nonsupplemented formula milk were eligible for inclusion. Related studies on gastrointestinal health and immunity among healthy infants up to five years old were searched from the earliest available date until February 29, 2024. Eighteen publications (number of participants=1,675) were selected for the systematic review, of which 11 were subsequently subjected to a metaanalysis. Results showed that the standard formula supplemented with scGOS/lcFOS (9:1) was well tolerated and conferred various gastrointestinal health and immunity to healthy infants and toddlers. These findings support the supplementation of standard milk formula with scGOS/lcFOS (9:1) for healthy infants and toddlers.

This article outlines the systematic radiological approach preoperative evaluation of perihilar cholangiocarcinoma (pCCA) using CT and MRI to provide key information regarding the suitability for curative surgical resection. It discusses older classification systems (BismuthCorlette, Memorial Sloan Kettering Cancer Center T staging) and follows the Korean Society of Abdomi­nal Radiology 2019 consensus recommendations for step-by-step assessment.The correlation between radiological, surgical, and pathological findings is illustrated through a pictorial review of pathologically proven cases. Benign and malignant mimics of pCCA are included to provide a comprehensive overview.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.