Purpose: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. Materials and Methods: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. Results: The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS. Conclusion The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

PURPOSE: An enhanced recovery after surgery (ERAS) protocol incorporates up-to-date perioperative care principles; the primary aim in using an ERAS protocol is to reduce issues that delay the recovery and cause the complications. The aim of this study was to compare outcomes associated with head and neck cancer surgery with free-flap reconstruction before and after implementation of an ERAS protocol. METHODS: Outcomes were analyzed by dividing patients into 2 groups: 29 patients in the non-ERAS group and 60 patients in the ERAS group. The ERAS group performed a prospective observational cohort study of patients who underwent a head and neck cancer surgery with free-flap reconstruction in Ajou University Hospital from August 2015 to December 2017. The non-ERAS group retrospectively reviewed the medical records of patients who had undergone the same surgery from August 2012 to July 2015. RESULTS: Demographics, comorbidities, hospital length of stay (LOS), postoperative complications, starting time of rehabilitation, and postoperative periods before radiotherapy for the non-ERAS and ERAS groups were compared. Hospital LOS was significantly lower for patients whose care followed the ERAS protocol than for patients in the non-ERAS group (30.87 ± 20.72 days vs. 59.66 ± 40.43 days, P < 0.0001). CONCLUSION: In this study, hospital LOS was reduced through fast recovery after the implementation of the ERAS protocol. Therefore, the ERAS protocol appeared feasible and safe in head and neck cancer surgery with free-flap reconstruction.
Cohort Studies ; Comorbidity ; Demography ; Free Tissue Flaps ; Head and Neck Neoplasms ; Head ; Humans ; Length of Stay ; Medical Records ; Perioperative Care ; Postoperative Care ; Postoperative Complications ; Postoperative Period ; Prospective Studies ; Radiotherapy ; Radiotherapy, Adjuvant ; Rehabilitation ; Retrospective Studies

PURPOSE: The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. METHODS: A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. RESULTS: The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. CONCLUSION: The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women.
Advanced Glycosylation End Product-Specific Receptor ; Apoptosis ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease* ; Genetic Variation ; HMGB1 Protein ; Humans ; Matrix Metalloproteinase 2 ; Myeloid Cells ; Neoplasm Metastasis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prognosis* ; Proportional Hazards Models ; Seoul ; Toll-Like Receptors

OBJECTIVES: The purpose of this study was to examine the associations of childbirth, breastfeeding, and their interaction with breast cancer (BC) risk reduction, and to evaluate the heterogeneity in the BC risk reduction effects of these factors by menopause, hormone receptor (HR) status, and pathological subtype. METHODS: BC patients aged 40+ from the Korean Breast Cancer Registry in 2004-2012 and controls from the Health Examinee cohort participants were included in this study after 1:1 matching (12 889 pairs) by age and enrollment year. BC risk according to childbirth, breastfeeding, and their interaction was calculated in logistic regression models using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: BC risk decreased with childbirth (3+ childbirths relative to 1 childbirth: OR, 0.66; 95% CI, 0.56 to 0.78 and OR, 0.80; 95% CI, 0.68 to 0.95 in postmenopausal and premenopausal women, respectively); and the degree of risk reduction by the number of children was heterogeneous according to menopausal status (p-heterogeneity=0.04), HR status (p-heterogeneity < 0.001), and pathological subtype (p-heterogeneity < 0.001); whereas breastfeeding for 1-12 months showed a heterogeneous association with BC risk according to menopausal status, with risk reduction only in premenopausal women (p-heterogeneity < 0.05). The combination of 2 more childbirths and breastfeeding for ≥13 months had a much stronger BC risk reduction of 49% (OR, 0.51; 95% CI, 0.45 to 0.58). CONCLUSIONS: This study suggests that the combination of longer breastfeeding and more childbirths reduces BC risk more strongly, and that women who experience both 2 or more childbirths and breastfeed for ≥13 months can reduce their BC risk by about 50%.
Breast Feeding* ; Breast Neoplasms* ; Breast* ; Child ; Cohort Studies ; Female ; Humans ; Logistic Models ; Menopause ; Odds Ratio ; Parturition* ; Population Characteristics ; Risk Reduction Behavior*

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with ascites caused by advanced liver disease. While gram negative bacteria, such as Escherichia coli and Klebsiella pneumonia are the common pathogens, Listeria monocytogenes has been recognized as a very rare pathogen. Empirical treatment with third generation cephalosporins does not provide adequate antibiotics coverage against L. monocytogenes. Diagnosis is often delayed as it requires confirmation from ascitic fluid culture. Herein, we describe the first case of SBP caused by L. monocytogenes in a patient with advanced alcoholic liver cirrhosis in Korea. Clinicians should be aware of the atypical pathogens, especially in patients with inadequate response to empirical antibiotics.
Ampicillin/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Ascites/microbiology ; Humans ; Listeria monocytogenes/*physiology ; Listeriosis/*diagnosis/drug therapy ; Liver Cirrhosis, Alcoholic/*diagnosis ; Male ; Middle Aged ; Peritonitis/*diagnosis/*microbiology

An 82-year-old woman presented with a 5-year history of erythematous to brown patches and plaques on both legs, arms and trunk. Histopathological findings of biopsy specimens were consistent with mycosis fungoides, and the tumor cells were positive for CD3 and negative for CD20 in immunohistochemical stain. Imaging studies proposed the suspicion of ureter cancer, and the result of cystoscopic biopsy showed papillary urothelial carcinoma. Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, characterized by variable cutaneous manifestations, including patches, plaques, tumors, and erythroderma. There were several studies concerning the evaluation of the second malignancy risk after cutaneous T-cell lymphoma, however the relationship between mycosis fungoides and ureter cancer is not revealed. This patient is considered a case of mycosis fungoides with coincidental ureter cancer.
Aged, 80 and over ; Arm ; Biopsy ; Dermatitis, Exfoliative ; Female ; Humans ; Leg ; Lymphoma, T-Cell, Cutaneous ; Mycosis Fungoides ; Neoplasms, Second Primary ; Ureter ; Ureteral Neoplasms

PURPOSE: The purpose of this in vitro study was to compare the marginal adaptation of a ceramic-pressed-to-metal restoration with traditional metal-ceramic restoration. MATERIALS AND METHODS: Duplicating the prepared resin tooth, 20 metal dies were fabricated. Twenty metal copings of 2 groups which were metal ceramic restoration and pressed to metal restoration were fabricated. The marginal opening of each coping was measured with Microscope (BX 60M-36E 41D(R): Olympus, Japan). After porcelain build-up, the marginal opening of metal ceramic restoration and pressed to metal restoration (PoM(R): Ivoclar vivadent., Liechtenstein) were also evaluated in the same method. The measurements were analyzed using Wilcoxon Signed Ranks test and Mann-Whitney U test. RESULTS: Within the limits of this study, the results were as follows. 1. Metal-ceramic restorations in coping state (64.93 +/- 12.48 microm) in compared with Metal ceramic restorations after porcelain build-up (63.43 +/- 12.86 microm) had no significant difference in marginal adaptation. 2. Pressed-metal-ceramic restorations in coping state (50.00 +/- 12.28 microm) in compared with Pressed metal ceramic restorations after porcelain build-up (56.72 +/- 13.80 microm) had no significant difference in marginal adaptation. 3. Metal-ceramic restorations in compared Pressed-metal-ceramic restorations had no significant difference in marginal adaptation. CONCLUSION: Pressed-metal-ceramic restorations have the advantage of being technically less change through using of the lost-wax technique and this allows for the convenience of a full-contour ceramic wax-up as opposed to the more technique-sensitive layering method. Pressed-metal-ceramic restorations may be considered in clinic on the basis of the result of this study and the advantage of this system.
Acrylic Resins ; Ceramics ; Composite Resins ; Dental Porcelain ; Imidazoles ; Metal Ceramic Alloys ; Nitro Compounds ; Polyurethanes ; Tooth ; Waxes

BACKGROUND/AIMS: The apoptosis of chondrocytes is assumed to be involved in the pathogenesis of osteoarthritis (OA), and the TNF related apoptosis inducing ligand (TRAIL) is thought to have a pivotal role in the apoptosis of chondrocytes. We investigated the expression of TRAIL and its receptors in human osteoarthritic cartilages. METHODS: Human OA cartilage tissues were obtained from the medial side of the cartilage in the knee joints of 25 patients who underwent total knee replacement surgery, and the normal human cartilages of the knee joint were obtained at autopsy from seven young adults who had no history of joint diseases. The expressions of TRAIL and the death receptor were analyzed by immunohistochemistry or immunofluorscent staining. The concentration of TRAIL in the synovial fluid was measured by enzyme linked immunosorbent assay. RESULTS: TRAIL and its receptors were expressed in the OA cartilage, but not in the normal cartilage. TUNEL staining and immunohistochemistry for TRAIL on the serial sections showed that most TRAIL positive cells were TUNEL positive. The OA joint fluid contained concentrations of TRAIL that were readily detectable (80 and 120 microgram/ppm in the synovial fluid of each, respectively). However, the synovial fluid of the knee joint obtained at autopsy from the seven young adults contained low concentrations of detectable TRAIL (0~2 microgram/ppm). CONCLUSIONS: These results support the notion that TRAIL and its receptors are involved in the pathogenesis of human OA. A better understanding of TRAIL induced apoptosis in chondrocytes might lead to the development of a new therapeutic strategy for OA.
Apoptosis ; Arthroplasty, Replacement, Knee ; Autopsy ; Cartilage ; Chondrocytes ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Joint Diseases ; Joints ; Knee Joint ; Osteoarthritis ; Synovial Fluid ; TNF-Related Apoptosis-Inducing Ligand ; Young Adult