Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers.However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumorinfiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269–0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019–2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT– showed a significantly better prognosis than those who were TIL–/EMT+ (P = 0.049). Conclusion This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti–PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. RESULTS: Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. CONCLUSION: Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.
Aged ; Biomarkers/metabolism ; Carcinoma, Transitional Cell/genetics/*metabolism/pathology ; Carnitine/*analogs & derivatives/genetics/metabolism ; Case-Control Studies ; Female ; Humans ; Male ; Metabolic Networks and Pathways/*physiology ; Middle Aged ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Urinary Bladder Neoplasms/genetics/*metabolism/pathology

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.
Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics/*urine ; Calgranulin B/*genetics ; Cohort Studies ; Humans ; Male ; Middle Aged ; Nucleic Acids/*genetics/*urine ; Oligonucleotide Array Sequence Analysis ; Prostate/metabolism ; Prostatic Hyperplasia/diagnosis/genetics/urine ; Prostatic Neoplasms/diagnosis/*genetics/*urine ; RNA, Messenger/genetics/metabolism ; RNA, Neoplasm/genetics/metabolism ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Tetraspanins/*genetics

BACKGROUND: Infants with deformational plagiocephaly (DP) usually present with cranial vault deformities as well as facial asymmetry. The purpose of this study was to use three-dimensional anthropometric data to evaluate the influence of cranial deformities on facial asymmetry. METHODS: We analyzed three-dimensional computed tomography data for infants with DP (n=48) and without DP (n=30, control). Using 16 landmarks and 3 reference planes, 22 distance parameters and 2 angular parameters were compared. This cephalometric assessment focused on asymmetry of the orbits, nose, ears, maxilla, and mandible. We then assessed the correlation between 23 of the measurements and cranial vault asymmetry (CVA) for statistical significance using relative differences and correlation analysis. RESULTS: With the exception of few orbital asymmetry variables, most measurements indicated that the facial asymmetry was greater in infants with DP. Mandibular and nasal asymmetry was correlated highly with severity of CVA. Shortening of the ipsilateral mandibular body was particularly significant. There was no significant deformity in the maxilla or ear. CONCLUSION: This study demonstrated that the cranial vault deformity in DP is associated with facial asymmetry. Compared with the control group, the infants with DP were found to have prominent asymmetry of the nose and mandible.
Congenital Abnormalities ; Ear ; Facial Asymmetry* ; Humans ; Infant ; Mandible ; Maxilla ; Nose ; Orbit ; Plagiocephaly, Nonsynostotic*

No abstract available.

PURPOSE: The deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC. MATERIALS AND METHODS: The expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. RESULTS: DBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05). CONCLUSIONS: The expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC.
Chromosomes, Human, Pair 9 ; Genes, Tumor Suppressor ; Humans ; Kaplan-Meier Estimate ; Loss of Heterozygosity ; Mucous Membrane ; Prognosis ; Real-Time Polymerase Chain Reaction ; Recurrence ; Urinary Bladder ; Urinary Bladder Neoplasms

Pneumocystis carinii pneumonia (PCP), now known as Pneumocystis jirovecii, is a fungal pathogen that causes opportunistic disease, especially pneumonia, in immunocompromised patients. The patients can have a spectrum of illnesses ranging from asymptomatic to fulminant respiratory failure. Here we report two cases with pneumocystis pneumonia after liver transplantation who presented with different clinical features. One patient developed acute respiratory failure requiring mechanical ventilation and expired due to PCP and a superimposed bacterial infection. The other patient was asymptomatic and discovered by regular X-ray check-up. He was successfully treated with trimethoprim/sulfamethoxazole. As shown by our cases, PCP presents with broad clinical manifestations and leads to various clinical courses in liver transplant recipients. Thus, Pneumocystis jirovecii has to be considered a potential pathogen of pneumonia in liver transplant recipients regardless of severity, especially one who is not on prophylactic medications. We consider prophylaxis of PCP in liver transplant recipients in our center.
Bacterial Infections ; Humans ; Immunocompromised Host ; Liver ; Liver Transplantation ; Pneumocystis ; Pneumocystis jirovecii ; Pneumonia ; Pneumonia, Pneumocystis ; Respiration, Artificial ; Respiratory Insufficiency

Acute necrotizing pancreatitis after kidney transplantation is a rare, but serious complication. We report a case of patient who was developed acute pancreatitis after cadaveric kidney transplantation with several causative factors: viral infection (Cytomegalovirus, Varicella zoster virus), usage of immunosuppressant, gallbladder stones, and previous peritoneal dialysis history. Cytomegalovirus infection was suspected as major etiologic factor of this case, but other factors would have a complex effect on development of acute pancreatitis.
Cadaver ; Chickenpox ; Cytomegalovirus Infections ; Gallbladder ; Herpes Zoster ; Humans ; Immunosuppressive Agents ; Kidney ; Kidney Transplantation ; Pancreatitis ; Pancreatitis, Acute Necrotizing ; Peritoneal Dialysis

PURPOSE: The purpose of this study was to evaluate the possibility of expanding the indication for living donor liver transplantation (LDLT) for treatment of hepatocellular carcinoma (HCC), beyond the Milan criteria without compromising patient survival. METHODS: This was a retrospective study of 5patients (36.4%) that had undergone LDLT, beyond the Milan criteria, among 143 patients with HCC. The study was conducted in patients treated by the Department of Surgery, Catholic University of Korea from Oct 2000 to May 2008. We evaluated the survival curve, prognostic factors for survival and compared survival between our new criteria and Milan criteria. RESULTS: The 5 year patient survival and disease free survival rate in patients treated with LDLT beyond the Milan criteria were 50.2% and 61.9%, respectively. The prognostic factors affecting disease free survival and patient survival included serum AFP level, tumor size, vascular invasion, and tumor cell differentiation on univariate analysis. In multivariate analysis, AFP (200 ng/mL), tumor size (7 cm) and vascular invasion had significant influence on survival and disease free survival. According to our new criteria (size <7 cm, AFP <200 ng/ mL), 88.1% of our patients were included compare to the 63.6% that would have been if limited to the Milan criteria. With both factors met, the survival was comparable to the survival of Milan criteria (63.7% on our criteria and 78.2% on Milan criteria at 5 years) (P =0.103). CONCLUSION: A tumor size <7 cm and an AFP < 200 ng/mL appear to be useful cut-off values, beyond that criteria required by Milan. An analysis according to our criteria showed an acceptable survival outcome. Further verification of these findings by a large volume or prospective study is required for widespread adoption of our new criteria.
Adoption ; Carcinoma, Hepatocellular ; Cell Differentiation ; Disease-Free Survival ; Humans ; Korea ; Liver ; Liver Transplantation ; Living Donors ; Multivariate Analysis ; Retrospective Studies

BACKGROUND/AIMS: Our study aimed to evaluate the efficacy of MMF as compared with intravenous cyclophosphamide as induction therapy for proliferative lupus nephritis in Koreans. METHODS: Forty-three patients who were diagnosed with proliferative lupus nephritis (WHO Class III and IV) between Jan 2000 and Dec 2006 were included in this study. Nineteen patients were treated with oral MMF (initial dose: 1.0 g/day and then it was increased to 2.0 g/day) and 24 patients were treated with 0.75-1.0 g/m2 of monthly intravenous cyclophosphamide (CP) followed by subsequent treatment with oral corticosteroid (initial dose 1 mg/kg/day and then it was slowly tapered down) for 6 months. The demographic and laboratory findings, the response rate and the adverse events were reviewed retrospectively and these were compared between the two groups. RESULTS: A complete response occurred in 7 out of the 19 patients (36.8%) treated with MMF and in 8 out of the 24 patients (33.3%) treated with CP, and the difference was not significantly different between the two groups (p=0.66). A partial response was achieved in 52.6% and 45.8%, respectively. There were no significant differences of the laboratory findings such as serum albumin, C3, C4, the urine protein/creatinine ratio and serum creatinine after treatment for 6 months. In addition, both groups had similar rates of adverse events. CONCLUSIONS: Our study showed that for the treatment of lupus nephritis, MMF was as effective as IV cyclophosphamide with similar adverse events. This finding suggests that MMF could be an alternative treatment for active lupus nephritis as induction therapy.
Creatinine ; Cyclophosphamide ; Humans ; Lupus Nephritis ; Mycophenolic Acid ; Retrospective Studies ; Serum Albumin