FDG-PET in the diagnosis of primary progressive aphasia: a systematic review.

Primary progressive aphasia (PPA) is a disease known to affect the frontal and temporal regions of the left hemisphere. PPA is often an indication of future development of dementia, specifically semantic dementia (SD) for frontotemporal dementia (FTD) and logopenic progressive aphasia (LPA) as an atypical presentation of Alzheimer's disease (AD). The purpose of this review is to clarify the value of 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-positron emission tomography (PET) in the detection and diagnosis of PPA. A comprehensive review of literature was conducted using Web of Science, PubMed, and Google Scholar. The three PPA subtypes show distinct regions of hypometabolism in FDG-PET imaging with SD in the anterior temporal lobes, LPA in the left temporo-parietal junction, and nonfluent/agrammatic Variant PPA (nfvPPA) in the left inferior frontal gyrus and insula. Despite the distinct patterns, overlapping hypometabolic areas can complicate differential diagnosis, especially in patients with SD who are frequently diagnosed with AD. Integration with other diagnostic tools could refine the diagnostic process and lead to improved patient outcomes. Future research should focus on validating these findings in larger populations and exploring the therapeutic implications of early, accurate PPA diagnosis with more targeted therapeutic interventions.

Drinking contexts, coping motive, simultaneous cannabis use, and high-intensity drinking among adults in the United States.

AIMS: High-intensity drinking (HID), extreme drinking considerably above the level of heavy episodic drinking (HED), is associated with long-term health and social consequences. There is limited understanding of HID beyond young adulthood. This study aims to identify concurrent risk factors for HID, comparing age differences among all adults. METHODS: Multinomial logistic and linear regression modeling was performed using a nationally-representative sample of adults (analytic n = 7956) from the 2015 and 2020 National Alcohol Surveys. The outcomes were any HID of 8-11 drinks and 12+ drinks for men, and 8+ drinks for women, and corresponding frequencies. Concurrent risk factors included coping motive, sensation seeking, simultaneous use of alcohol and cannabis (SAC), and drinking at a bar or party. Analyses were stratified by age (18-29 vs. older) and sex. RESULTS: For younger men, sensation-seeking was significantly associated with HID (vs. no HED) at both levels and frequency of HID 8-11 drinks, while drinking to cope was only significant for 12+ drinks. For older men, drinking to cope was a consistent predictor for both HID level and its frequency, but sensation-seeking was not significant. Both coping and sensation-seeking were significantly associated with any HID for all women, while coping was significant for HID frequency for younger women. Frequent drinking at bars and parties were associated with greater odds of HID for all adults. With HED as referent, similar patterns of (though fewer significant) associations were observed. CONCLUSIONS: Younger and older adults share similar risk factors for HID, with coping more consistent for older men.

Drinking patterns among US men and women: Racial and ethnic differences from adolescence to early midlife.

BACKGROUND: Drinking patterns among young adult men and women in the United States have been understudied, especially among racial and ethnic groups such as Asian Americans and Hispanics. Because alcohol-related racial and ethnic health disparities persist or increase in midlife, identifying peak ages of hazardous drinking could help to reduce disparities. METHODS: We used the National Longitudinal Study of Adolescent to Adult Health to examine: (1) past 12-month heavy episodic drinking (HED) and total alcohol volume consumption among non-Hispanic White (NHW), Black, Hispanic, and Asian men and women from ages 12 through 41, and (2) age-varying associations of race and ethnicity with drinking. Hispanic and Asian ethnic groups were disaggregated by historical drinking patterns. Time-varying effect models accounted for major demographic confounders. RESULTS: NHW men and women experienced elevated drinking rates in their early 20s, with a second elevation in their 30s. Black men and women did not have elevated drinking until their 30s. Among Hispanic men and women, peak drinking periods varied by gender and subgroup drinking pattern. Peak HED and total consumption emerged in the early 30s for Asian men, while peak HED occurred in the early 20s for Asian women. Drinking at certain ages for some racial and ethnic minoritized men and women did not differ from that in their NHW counterparts. CONCLUSIONS: Age periods during which subgroups in the U.S. population experience elevated alcohol consumption vary by ethnicity and gender. Recognition of these group differences could enhance our understanding of intervention timing.

Evaluating Debio 1347 in Patients with FGFR Fusion-Positive Advanced Solid Tumors from the FUZE Multicenter, Open-Label, Phase II Basket Trial.

PURPOSE: This multicenter phase II basket trial investigated the efficacy, safety and pharmacokinetics of Debio 1347, an investigational, oral, highly selective, ATP-competitive, small molecule inhibitor of FGFR1-3, in patients with solid tumors harboring a functional FGFR1-3 fusion. PATIENTS AND METHODS: Eligible adults had a previously treated locally advanced (unresectable) or metastatic biliary tract (cohort 1), urothelial (cohort 2) or other histologic cancer type (cohort 3). Debio 1347 was administered at 80 mg once daily, continuously, in 28-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included duration of response, progression-free survival, overall survival, pharmacokinetics, and incidence of adverse events. RESULTS: Between March 22, 2019 and January 8, 2020, 63 patients were enrolled and treated, 30 in cohort 1, four in cohort 2, and 29 in cohort 3. An unplanned preliminary statistical review showed that the efficacy of Debio 1347 was lower than predicted and the trial was terminated. Three of 58 evaluable patients had partial responses, representing an ORR of 5%, with a further 26 (45%) having stable disease (≥6 weeks duration). Grade ≥3 treatment-related adverse events occurred in 22 (35%) of 63 patients, with the most common being hyperphosphatemia (13%) and stomatitis (5%). Two patients (3%) discontinued treatment due to adverse events. CONCLUSIONS: Debio 1347 had manageable toxicity; however, the efficacy in patients with tumors harboring FGFR fusions did not support further clinical evaluation in this setting. Our transcriptomic-based analysis characterized in detail the incidence and nature of FGFR fusions across solid tumors.

Safety and efficacy of large-bore uncovered stents for treating malignant superior vena cava syndrome.

PURPOSE: To investigate the safety and efficacy of large-bore uncovered stents for treating malignant superior vena cava syndrome. METHODS: This retrospective study included 115 patients (89 men, 26 women; mean age 63.2 years; range 21-83 years) who underwent endovascular large-bore (≥18 mm in diameter) uncovered stent placement between August 2015 and July 2022. One patient was lost to follow-up. Therefore, 114 patients were available for follow-up. RESULTS: Stent placement was technically successful in all 115 patients. Minor procedure-related complications occurred in nine (7.8 %) patients. One hundred eight (93.9 %) patients experienced complete or marked symptomatic relief (Kishi score ≤ 2) at a mean of 3 days after procedure. The cumulative stent patency rates were 98.2 %, 95 %, 93.7 %, 91.5 %, 83.5 %, and 83.5 % at 1, 3, 6, 12, 18, and 24 months, respectively. Stent occlusion occurred in ten (8.8 %) of 114 patients at a mean of 215 days (range 1-732 days) due to thrombosis (n = 7) and tumor ingrowth (n = 3). Stent occlusion did not occur in 21 patients who underwent subsequent central venous catheter insertion. The median patient survival time was 159 days (95 % confidence interval 102-216 days). Univariate and multivariate Cox regression analysis revealed adjuvant anticancer treatment (p = 0.001) and tumor response (p < 0.001) as independent predictors of patient survival. CONCLUSIONS: Endovascular placement of large-bore uncovered stents was a safe and effective treatment for malignant superior vena cava syndrome. Large-bore stent placement can effectively prevent stent occlusion by tumor ingrowth in most cases, and it can provide a sufficient diameter for subsequent insertion of central venous catheters.

Alcoholic beverage types consumed by population subgroups in the United States: Implications for alcohol policy to address health disparities.

INTRODUCTION: We aimed to identify alcoholic beverage types more likely to be consumed by demographic subgroups with greater alcohol-related health risk than others, mainly individuals with low socio-economic status, racial/ethnic minority status and high drinking levels. METHODS: Fractional logit modelling was performed using a nationally representative sample of US adult drinkers (analytic N = 37,657) from the National Epidemiologic Survey on Alcohol and Related Conditions Waves 2 (2004-2005) and 3 (2012-2013). The outcomes were the proportions of pure alcohol consumed as beer, wine, liquor and coolers (defined as wine-/malt-/liquor-based coolers, hard lemonade, hard cider and any prepackaged cocktails of alcohol and mixer). RESULTS: Adults with lower education and low or medium income were more likely to drink beer, liquor and coolers, while those with a 4-year college/advanced degree and those with high income preferred wine. Excepting Asian adults, racial/ethnic minority adults were more likely to drink beer (Hispanics) and liquor (Blacks), compared with White adults. High- or very-high-level drinkers were more likely to consume liquor and beer and less likely to consume wine (and coolers), compared with low-level drinkers. High-level and very-high-level drinkers, who were less than 10% of all drinkers, consumed over half of the total volume of beer, liquor and coolers consumed by all adults. DISCUSSION AND CONCLUSIONS: Individuals with low socio-economic status, racial/ethnic minority status or high drinking level prefer liquor and beer. As alcohol taxes, sales and marketing practices all are beverage-specific, targeted approaches to reduce consumption of these beverages, particularly among individuals with these profiles, are warranted.

Comparing the efficacy of combined versus single immune cell adaptive therapy targeting colorectal cancer

Purpose@#Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC. @*Methods@#CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells. @*Results@#The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing no therapy-related death or general toxicity symptoms. @*Conclusion@#The results suggested that combined immune cell adaptive therapy could overcome the limited efficacy of cell immunotherapy.

Intracorporeal versus extracorporeal anastomosis in minimally invasive right hemicolectomy: systematic review and meta-analysis of randomized controlled trials

Purpose@#Compared with extracorporeal anastomosis (ECA), intracorporeal anastomosis (ICA) is expected to provide some benefits, including a shorter operation time and less intraoperative bleeding. Nevertheless, the benefits of ICA have mainly been evaluated in nonrandomized studies. Owing to the recent update of randomized controlled trials (RCTs) for minimally invasive surgery (MIS) of right hemicolectomy (RHC), the need to measure the actual effect by synthesizing the outcomes of these studies has emerged. @*Methods@#We performed a comprehensive search of the PubMed, Embase, and Cochrane databases (from inception to January 30, 2023) for studies that applied ICA and ECA for RHC with MIS. We included 7 RCTs. The operation time, intraoperative blood loss, conversion rate, length of incision, and postoperative outcomes such as ileus, anastomosis leakage, length of hospitalization, and postoperative pain were compared between ICA and ECA. @*Results@#A total of 740 patients were included in the study. Among them, 377 and 373 underwent ICA and ECA, respectively.There were significant differences in age (P = 0.003) and incision type (P < 0.001) between ICA and ECA. ICA was associated with a significantly longer operation time (P = 0.033). Although the postoperative pain associated with ICA was significantly lower than that associated with ECA on postoperative day 2 (POD 2) (P = 0.003), it was not different on POD 3 between the groups. Other perioperative outcomes were similar between the 2 groups. @*Conclusion@#In this meta-analysis, ICA did not significantly improve short-term outcomes compared to ECA; other advantages to overcome ICA’s longer operation time are not clear.

Orbital floor defect caused by invasive aspergillosis: a case report and literature review

Fungal sinusitis is relatively rare, but it has become more common in recent years. When fungal sinusitis invades the orbit, it can cause proptosis, chemosis, ophthalmoplegia, retroorbital pain, and vision impairment. We present a case of an extensive orbital floor defect due to invasive fungal sinusitis. A 62-year-old man with hypertension and a history of lung adenocarcinoma, presented with right-side facial pain and swelling. On admission, the serum glucose level was 347 mg/dL, and hemoglobin A1c was 11.4%. A computed tomography scan and a Waters’ view X-ray showed right maxillary sinusitis with an orbital floor defect. On hospital day 3, functional endoscopic sinus surgery was performed by the otorhinolaryngology team, and an aspergilloma in necrotic inflammatory exudate obtained during exploration. On hospital day 7, orbital floor reconstruction with a Medpor Titan surgical implant was done. In principle, the management of invasive sino- orbital fungal infection often begins with surgical debridement and local irrigation with an antifungal agent. Exceptionally, in this case, debridement and immediate orbital floor reconstruction were performed to prevent enophthalmos caused by the extensive orbital floor defect. The patient underwent orbital floor reconstruction and received intravenous and oral voriconazole. Despite orbital invasion, there were no ophthalmic symptoms or sequelae.

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). @*Materials and Methods@#Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. @*Results@#RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). @*Conclusion@#GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT). @*Materials and Methods@#Patients (aged 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively. @*Conclusion@#The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex. @*Materials and Methods@#This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea. @*Results@#A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits. @*Conclusion@#Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. @*Materials and Methods@#Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. @*Results@#The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. @*Conclusion@#In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM. @*Materials and Methods@#Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed. @*Results@#Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05). @*Conclusion@#GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. @*Materials and Methods@#In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer. @*Results@#A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%. @*Conclusion@#The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP / Journal of the Korean Cancer Association, 대한암학회지

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Combined High-Dose Radiotherapy with Sequential Gemcitabine-Cisplatin Based Chemotherapy Increase the Resectability and Survival in Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma: A Multi-institutional Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC. @*Materials and Methods@#Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model. @*Results@#The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05). @*Conclusion@#Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

COVID-19 (SARS-CoV-2) mRNA vaccination does not affect basal sex hormone levels (follicle-stimulating hormone, luteinizing hormone, estradiol) in reproductive-age women / 대한생식의학회지

Objective@#People vaccinated with the coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) mRNA vaccine have reported experiencing various adverse effects. For instance, reproductive-age women have presented with complaints of abnormal uterine bleeding or menstrual cycle changes. We speculated that differences in basal sex hormone levels before and after vaccination may be present in women who experienced irregular bleeding or menstrual cycle changes; thus, this study aimed to investigate the differences in basal sex hormone levels of women before and after two doses of SARS-CoV-2 mRNA vaccination. @*Methods@#This retrospective study included patients who received SARS-CoV-2 mRNA vaccines between January 2021 and February 2022 at a single center. In an outpatient setting, patients were queried regarding their menstrual cycle, the date of SARS-CoV-2 mRNA vaccination, vaccination type, and vaccination side effects. Differences in basal hormone levels (menstrual cycle days 2–3, follicle-stimulating hormone [FSH], luteinizing hormone [LH], and estradiol) before and after vaccination were compared. @*Results@#Among the 326 patients, patients with no laboratory records of the hormones were excluded. The median time interval between SARS-CoV-2 mRNA vaccination and the laboratory test day was 79 days (interquartile range, 44 to 127). A comparative analysis of these hormones before and after vaccination revealed no significant differences. Subgroup analyses based on age and reported adverse events also found no statistically significant differences. @*Conclusion@#This study showed no significant differences in basal hormone levels (FSH, LH, and estradiol) before and after SARS-CoV-2 mRNA vaccination.

Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression

Background/Aims@#Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. @*Methods@#Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. @*Results@#After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. @*Conclusions@#We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study

Background/Aims@#To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. @*Methods@#Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression. @*Results@#Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68–3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63–2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18–1.50; P<0.001) had an increased risk of HCC compared to persistent non-MASLD. @*Conclusions@#The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.