Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out ‘inclusion criteria’ and defining ‘successful downstaging.’ Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level <500 ng/mL after LRT. Reports indicate that successful downstaging rates following LRT are about 50%, with post- LT recurrence rates comparable to those of patients within the Milan criteria. A comprehensive multicenter US study on 10-year outcomes post-LT after downstaging showed 10-year post-LT survival and recurrence rates of 52.1% and 20.6%, respectively, for patients whose disease was downstaged; this compares to 61.5% and 13.3% for those consistently within the Milan criteria. Recently, the development of effective systemic treatments for HCC, such as immuno-oncologic agents, has provided additional opportunities for downstaging. Numerous clinical trials are exploring a multidisciplinary approach (MDA) combining LRT and systemic therapy. Although concrete evidence of the superiority of MDA for HCC downstaging is lacking, some retrospective studies and phase I and II trials have shown promising results regarding the efficacy and safety of MDA for this purpose. In this review, we will also discuss the future of MDA protocols in downstaging for improved clinical outcomes.

Objective: Several lines of evidence indicate verbal abuse (VA) critically impacts the developing brain; however, whether VA results in changes in brain neurochemistry has not been established. Here, we hypothesized that exposure to recurrent parental VA elicits heightened glutamate (Glu) responses during the presentation of swear words, which can be measured with functional magnetic resonance spectroscopy (fMRS). Methods: During an emotional Stroop task consisting of blocks of color and swear words, metabolite concentration changes were measured in the ventromedial prefrontal cortex (vmPFC) and the left amygdalohippocampal region (AMHC) of healthy adults (14 F/27 M, 23 ± 4 years old) using fMRS. The dynamic changes in Glu and their associations with the emotional state of the participants were finally evaluated based on 36 datasets from the vmPFC and 30 from the AMHC. Results: A repeated-measures analysis of covariance revealed a modest effect of parental VA severity on Glu changes in the vmPFC. The total score on the Verbal Abuse Questionnaire by parents (pVAQ) was associated with the Glu response to swear words (ΔGluSwe ). The interaction term of ΔGluSwe and baseline N-acetyl aspartate (NAA) level in the vmPFC could be used to predict state-trait anxiety level and depressive mood. We could not find any significant associations between ΔGluSwe in the AMHC and either pVAQ or emotional states. Conclusion Parental VA exposure in individuals is associated with a greater Glu response towards VA-related stimuli in the vmPFC and that the accompanying low NAA level may be associated with anxiety level or depressive mood.

Purpose: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. Materials and Methods: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period. Results: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. Conclusions During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

Background and Objectives: Natural and synthetic speech signals effectively stimulate cortical auditory evoked potential (CAEP). This study aimed to select the speech materials for CAEP and identify CAEP waveforms according to gender of speaker (GS) and gender of listener (GL). Subjects and Methods: Two experiments including a comparison of natural and synthetic stimuli and CAEP measurement were performed of 21 young announcers and 40 young adults. Plosive /g/ and /b/ and aspirated plosive /k/ and /p/ were combined to /a/. Six bisyllables–/ga/-/ka/, /ga/-/ba/, /ga/-/pa/, /ka/-/ba/, /ka/-/pa/, and /ba/-/pa/–were formulated as tentative forwarding and backwarding orders. In the natural and synthetic stimulation mode (SM) according to GS, /ka/ and /pa/ were selected through the first experiment used for CAEP measurement. Results: The correction rate differences were largest (74%) at /ka/-/ pa/ and /pa/-/ka/; thus, they were selected as stimulation materals for CAEP measurement. The SM showed shorter latency with P2 and N1-P2 with natural stimulation and N2 with synthetic stimulation. The P2 amplitude was larger with natural stimulation. The SD showed significantly larger amplitude for P2 and N1-P2 with /pa/. The GS showed shorter latency for P2, N2, and N1-P2 and larger amplitude for N2 with female speakers. The GL showed shorter latency for N2 and N1-P2 and larger amplitude for N2 with female listeners. Conclusions Although several variables showed significance for N2, P2, and N1-P2, P1 and N1 did not show any significance for any variables. N2 and P2 of CAEP seemed affected by endogenous factors.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

It is challenging to diagnose metastatic tumors whose cellular morphology is different from the primary. We characterized canine primary pulmonary adenocarcinoma (PAC) and its xenografted tumors by histological and immunohistochemical analyses for critical diagnostic and cancer stem cell (CSC) markers. To generate a tumor xenograft model, we subsequently transplanted the tissue pieces from the PAC into athymic nude mice. Immunohistochemical examination was performed for diagnostic (TTF-1, Napsin A, and SP-A) and CSC markers (CD44 and CD133). The use of CSC markers together with diagnostic markers can improve the detection and diagnosis of canine primary and metastatic adenocarcinomas.

Hyperparathyroidism is common in patients with chronic kidney disease with reduced renal function and has been observed after kidney transplantation. The optimal treatment for cases in which hyperparathyroidism persists after kidney transplantation has not been determined. Methods: This retrospective study included 83 patients with tertiary hyperparathyroidism who underwent kidney transplantation between 2000 and 2018 at a single tertiary center in Korea. Sixty-four patients underwent parathyroidectomy and 19 patients were treated with cinacalcet following renal transplantation. Biochemical parameters and clinical outcomes were compared between the two groups. Results: Serum calcium and parathyroid hormone (PTH) levels improved in both the parathyroidectomy and cinacalcet groups. One year after treatment, parathyroidectomy resulted in a lower mean serum calcium level than cinacalcet (9.7 ± 0.7 mg/dL vs. 10.5 ± 0.7 mg/dL, p = 0.001). Regarding serum PTH, the parathyroidectomy group showed a significantly lower PTH level than the cinacalcet group at 6 months (129.1 ± 80.3 pg/mL vs. 219.2 ± 92.5 pg/mL, p = 0.002) and 1 year (118.8 ± 75.5 pg/mL vs. 250.6 ± 94.5 pg/ mL, p < 0.001). There was no statistically significant difference in the incidence of kidney transplant rejection, graft failure, cardiovascular events, fracture risk, or bone mineral density changes between the two groups. Conclusion: Parathyroidectomy appears to reduce PTH and calcium levels effectively in tertiary hyperparathyroidism. However, creatinine level and allograft rejection should be monitored closely.

Purpose: There are increased therapeutic usages of rituximab in kidney transplantation (KT). However, few studies have evaluated the effect of rituximab on cancer development following KT. This study aimed to evaluate the effect of rituximab on the cancer occurrence and mortality rate according to each type of cancer. Methods: Five thousand consecutive recipients who underwent KT at our center were divided into era1 (1990–2007) and era2-rit– (2008–2018), and era2-rit+ (2008–2018) groups. The era2-rit+ group included patients who received single-dose rituximab (200–500 mg) as a desensitization treatment 1–2 weeks before KT. Results: The 5-year incidence rates of malignant tumors after KT were 3.1%, 4.3%, and 3.5% in the era1, era2-rit–, and era2-rit+ group, respectively. The overall incidence rate of cancer after transplantation among the 3 study groups showed no significant difference (P = 0.340). The overall cancer-related mortality rate was 17.1% (53 of 310). Hepatocellular carcinoma (HCC) had the highest mortality rate (61.5%) and relative risk of cancer-related death (hazard ratio, 8.29; 95% confidence interval, 2.40–28.69; P = 0.001). However, we found no significant association between rituximab and the incidence of any malignancy. Conclusion Our results suggest that single-dose rituximab for desensitization may not increase the risk of malignant disease or cancer-related mortality in KT recipients. HCC was associated with the highest risk of cancer-related mortality in an endemic area of HBV infection.

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels and enhance the function of pancreatic βcells. Yet, it is unknown whether posttransplant administration of DPP4 inhibitors is beneficial for pancreas transplant recipients. Methods: We thus retrospectively analyzed the records of 312 patients who underwent pancreas transplantation between 2000 and 2018 at Asan Medical Center (Seoul, Korea) and compared the metabolic and survival outcomes according to DPP-4 inhibitor treatment. Results: The patients were divided into the no DPP-4 inhibitor group (n = 165; no treatment with DPP-4 inhibitors or treated for <1 month) and the DPP-4 inhibitor group (n = 147; treated with DPP-4 inhibitors for ≥1 month). There were no significant differences in levels of glucose, hemoglobin A1c, and insulin between the 2 groups during 36 months of follow-up. However, the level of C-peptide was significantly higher in the DPP-4 inhibitor group at 1, 6, and 24 months posttransplant (all P < 0.05). Moreover, the DPP-4 inhibitor group had significantly higher rates of overall (log-rank test, P = 0.009) and death-censored (log-rank test, P = 0.036) graft survival during a 15-year follow-up. Conclusion Posttransplant DPP-4 inhibitor administration may help improve the clinical outcomes including β cell function after pancreas transplantation.

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels and enhance the function of pancreatic βcells. Yet, it is unknown whether posttransplant administration of DPP4 inhibitors is beneficial for pancreas transplant recipients. Methods: We thus retrospectively analyzed the records of 312 patients who underwent pancreas transplantation between 2000 and 2018 at Asan Medical Center (Seoul, Korea) and compared the metabolic and survival outcomes according to DPP-4 inhibitor treatment. Results: The patients were divided into the no DPP-4 inhibitor group (n = 165; no treatment with DPP-4 inhibitors or treated for <1 month) and the DPP-4 inhibitor group (n = 147; treated with DPP-4 inhibitors for ≥1 month). There were no significant differences in levels of glucose, hemoglobin A1c, and insulin between the 2 groups during 36 months of follow-up. However, the level of C-peptide was significantly higher in the DPP-4 inhibitor group at 1, 6, and 24 months posttransplant (all P < 0.05). Moreover, the DPP-4 inhibitor group had significantly higher rates of overall (log-rank test, P = 0.009) and death-censored (log-rank test, P = 0.036) graft survival during a 15-year follow-up. Conclusion Posttransplant DPP-4 inhibitor administration may help improve the clinical outcomes including β cell function after pancreas transplantation.