Purpose: The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). Materials and Methods: In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. Results: Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. Conclusion Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Background: There are inconsistent reports regarding the association between general anesthesia and adverse neurodevelopmental and behavioral disorders in children. Methods: This nationwide administrative cohort study included children born in Korea between 2008 and 2009, and followed until December 31, 2017. The cohort included 93,717 participants who received general anesthesia with endotracheal intubation (ETI) who were matched to unexposed subjects in a 1:1 ratio. General anesthesia was defined by National Health Insurance Service treatment codes with intratracheal anesthesia, and the index date was the first event of general anesthesia. The primary outcome was attention deficit hyperactive disorder (ADHD), which was defined as at least a principal diagnosis of 10th revision of the International Classification of Diseases code F90.X after the age of 72 months.Neurodevelopment, which was assessed using a developmental screening test (Korean-Ages and Stages Questionnaire [K-ASQ]), was a secondary outcome. The K-ASQ is performed annually from 1 to 6 years of age and consists of 5 domains. The association between general anesthesia and ADHD was estimated using a Cox hazard model, and its association with neurodevelopment was estimated using a generalized estimation equation, with control for multiple risk factors beyond 1 year after the index date. Results: The median age at the index date was 3.8 (95% confidence interval [CI], 1.7–5.8) years, and there were 57,625 (61.5%) men. During a mean follow-up period of 5 years, the incidence rate of ADHD was 42.6 and 27.7 per 10,000 person-years (PY) in the exposed and unexposed groups, respectively (absolute rate difference 14.9 [95% CI, 12.5–17.3] per 10,000 PY). Compared to the unexposed group, the exposed group had an increased risk of ADHD (adjusted hazard ratio, 1.41 [95% CI, 1.30–1.52]). In addition, a longer duration of anesthesia with ETI and more general anesthesia procedures with ETI were associated with greater risk of ADHD. General anesthesia with ETI was also associated with poorer results in the K-ASQ. Conclusion Administration of general anesthesia with ETI to children is associated with an increased risk of ADHD and poor results in a neurodevelopmental screening test.

Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

PURPOSE: We compared biopsy results and surgical outcomes of magnetic resonance imaging (MRI)-guided biopsy with transrectal ultrasonography (TRUS)-guided biopsy to demonstrate efficacy of MRI-guided biopsy on previous biopsy negative patients. MATERIALS AND METHODS: We retrospectively reviewed data of 120 patients who were categorized into MRI-guided biopsy groups (n=20) and TRUS-guided biopsy groups (n=100). All patients were diagnosed with prostate cancer (PCa) and had undergone radical prostatectomy (RP) after MRI-guided or TRUS-guided repeat biopsy between January 2010 and March 2016. Detection rate of significant cancer and Gleason score upgrading and downgrading were examined, in addition to biopsy results and subsequent RP outcomes. RESULTS: Median values for prostate-specific antigen level of the TRUS-guided biopsy group and the MRI-guided biopsy group were 6.67 and 5.86 ng/mL (p=0.303), respectively. Median prostate volume of each group (34.1 mL vs. 23.5 mL, p=0.007), number of positive cores (2.0 vs. 3.0, p=0.001) and maximum cancer/core rate (30.0% vs. 60.0%, p<0.001) were statistically different. Positive core rates of each group were 21.9% and 87.1%, respectively. Pathologic T stage was the only variable that showed difference in surgical outcomes (p=0.002). Most of PCa was confirmed as clinically significant PCa after RP in MRI-guided biopsy group (95%). CONCLUSIONS: MRI-guided biopsy showed higher positive core rate and detection rate of clinically significant PCa than TRUS-guided biopsy in repeat biopsy setting. Prospective multicenter large-scale study and accumulation of data is expected to further define superiority of the MRI-guided biopsy.
Biopsy* ; Humans ; Magnetic Resonance Imaging ; Neoplasm Grading ; Passive Cutaneous Anaphylaxis ; Prospective Studies ; Prostate ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms ; Retrospective Studies ; Ultrasonography

PURPOSE: To determine the negative predictive value (NPV) of multiparametric magnetic resonance imaging (mp-MRI) for clinically significant cancer (CSC) based on the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in very low-risk or low-risk prostate cancer patients. MATERIALS AND METHODS: We retrospectively analyzed 380 patients with low risk of prostate cancer who underwent mp-MRI before radical prostatectomy (RP) from 2011 to 2013. Of the 380 patients, 142 patients were in the very low risk group. CSC at RP was defined as follows: any T3−4, G3+4 with tumor volume>15%, G4+3 or higher. In the very low risk and low risk groups, we analyzed the rate of CSC according to PI-RADS score and calculated the NPV of mp-MRI for detection of CSC. RESULTS: In the low risk group, 20.8% (n=79) of patients had PI-RADS version 2 score 1–2 and 17.4% (n=66) of patients had PI-RADS version 2 score 3. In the very low risk group, 26.8% (n=38) of patients had PI-RADS version 2 score 1–2 and 17.6% (n=25) of patients had PI-RADS version 2 score 3 in the very low risk group. Rates of CSC were 33.7% (n=128) and 16.9% (n=24) in the low risk and very low risk groups, respectively. The NPV of MRI was 93.7% in the very low risk group and 78.6% in the low risk group. CONCLUSIONS: The NPV of PI-RADS for CSC is high in the very low risk group, but not in the low risk group. Further multicenter studies are needed to investigate the utility of PI-RADS version 2 for NPV.
Humans ; Information Systems* ; Magnetic Resonance Imaging* ; Prostate* ; Prostatectomy* ; Prostatic Neoplasms* ; Retrospective Studies

PURPOSE: The aims of this study were to compare the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manuals on tumor, node, and metastasis (TNM) staging systems and to evaluate whether the 8th edition represents a better refinement of the 7th staging system, when applied for the classification of gastric cancers. MATERIALS AND METHODS: A total of 5,507 gastric cancer patients, who underwent treatment from January 1989 to December 2013 at a single institute, were included. We compared patient survival rates across the disease groups classified according to the 7th and 8th editions of the AJCC TNM staging systems. RESULTS: Stage migration was observed in 6.4% (n=355) of the patients. Of these, 3.5% (n=192) and 2.9% (n=158) of patients showed a higher stage and lower stage, respectively. According to the 8th edition of the AJCC TNM staging criteria, the 5-year overall survival rates of the patients with stage IIIB and IIIC showed a significant difference (40.8% vs. 20.2%, P<0.001) whereas no significant differences in the 5-year overall survival rates were observed according to the 7th edition criteria (37.6% vs. 33.2%, P=0.381). CONCLUSIONS: Restaging stage III cancers according to the 8th edition of the AJCC TNM classification criteria improved survival rate discrimination, particularly, in institutes where the stage III patients were not distinctly categorized.
Academies and Institutes ; Adenocarcinoma* ; Classification ; Discrimination (Psychology) ; Humans ; Joints ; Korea* ; Neoplasm Metastasis ; Neoplasm Staging* ; Prognosis ; Stomach Neoplasms ; Survival Rate*

BACKGROUND: This study are to identify the symptomatic changes and condylar stability after 2 jaw surgery without preceding treatments for Temporomandibular joints(TMJ) in class III patients with the TMJ symptoms; and to assess therapeutic effect of 2 jaw surgery and the necessity of preceding treatment for alleviation of TMJ symptoms. METHODS: 30 prognathic patients with preexisting TMJ symptoms were divided into 2 groups according to presence or absence of preceding treatments before the surgery. We evaluated symptomatic changes on both TMJ by questionnaires and clinical examinations. And we reconstructed 3D cone beam computed tomography images before 2 jaw surgery, immediately after the surgery, and 6 months or more after the surgery with SimPlant software, and analyzed the stability of condylar position on 3D reconstruction model. Significances were assessed by the Wilcoxon signed rank test on SPSS ver. 20.0. RESULTS: Both groups had favorable changes of TMJ symptoms after orthognathic surgery. And postoperative position of condyle had good stability during follow-up period. CONCLUSION: 2 jaw surgery without preceding treatments for TMD can have therapeutic effect for TMD patients with class III malocclusion.
Cone-Beam Computed Tomography ; Follow-Up Studies ; Humans ; Malocclusion ; Orthognathic Surgery* ; Surveys and Questionnaires ; Temporomandibular Joint

OBJECTIVES: The purpose of this study is to analyze clinical impact factors on the survival rate, and to acquire basic clinical data for the diagnosis of oral cancer, for a determination of the treatment plan with long-term survival in oral cancer patients. MATERIALS AND METHODS: Through a retrospective review of the medical records, the factors for long-term survival rate were analyzed. Thirty-seven patients, among patient database with oral cancer treated in the Department of Oral and Maxillofacial Surgery at Pusan National University Hospital within a period from March 1998 to March 2008, were selected within the study criteria and were followed-up for more than 5 years. The analyzed factors were gender, age, drinking, smoking, primary tumor site, type of cancer, TNM stage, recurrence of affected region, and metastasis of cervical lymph node. The 5-year survival rate on the impact factors was calculated statistically using the Kaplan-Meier method. RESULTS: By classification of clinical TNM at the 1st visit, there were 11 (29.7%) cases for stage I, 11 (29.7%) cases for stage II, 3 (8.1%) cases for stage III, and 12 (32.5%) cases for stage IV. The 5-year survival rate of total oral cancer patients after the operation were 75.7%, pathological TNM stage related 5-year survival rate were as follows: stage I 90.0%, stage II 81.8%, stage III 100% and stage IV 45.5%; in which the survival rate difference by each stage was significantly observed. The recurrence of cervical lymph node was the significant impact factor for the survival rate, because only 30.0% the survival rate in recurrent cases existed. During the follow-up, there were 15 (40.5%) patients with confirmed recurrence, and the 5-year survival rate of these patients was decreased as 46.7%. CONCLUSION: The classification of clinical and pathological TNM stage, local recurrence after surgery, and metastasis of cervical lymph node after surgery were analyzed as the 3 most significant factors.
Drinking ; Follow-Up Studies ; Humans ; Lymph Nodes ; Medical Records ; Mouth Neoplasms* ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Smoke ; Smoking ; Surgery, Oral ; Survival Rate*

PURPOSE: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. MATERIALS AND METHODS: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. RESULTS: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. CONCLUSIONS: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.
Axis, Cervical Vertebra ; Blotting, Western ; Carcinogenesis ; Classification ; CpG Islands ; DNA Methylation* ; DNA* ; Epigenomics ; Gastric Mucosa* ; Gastritis* ; Helicobacter pylori ; Humans* ; Inflammation ; Methylation ; Mucous Membrane ; Phenotype ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-myc

INTRODUCTION: Fibrous-osseous lesions of the jaws are difficult to diagnose precisely until excised biopsy results are found, so they might be confused with malignant lesions. This clinical study focused on the diagnostic aids of lesions that demonstrate different clinical, radiologic, and histological findings. MATERIALS AND METHODS: A total of 16 patients with benign fibrous-osseous lesions on the jaws (6 fibrous dysplasias, 6 ossifying fibromas, 3 cemental dysplasias, and one osteoblastoma) were reviewed. Nine patients with malignant fibrous-osseous lesions (8 osteosarcomas and one Ewing's sarcoma) were also retrospectively reviewed. RESULTS: Osteosarcoma patients complained of facial swelling and tooth mobility. The radiographic findings showed the irregular resorption of cortical bone and periosteal reactions. Histological features included cellular pleomorphism and atypical mitosis. An Ewing's sarcoma patient complained of tooth mobility and facial swelling. Onion-skin appearance and irregular expansile marginal bony radiolucency were seen in the radiography. Fibrous dysplasia patients complained of facial swelling and asymmetry. The radiographic features were mostly ground-glass radiopacity. Histological findings showed a bony trabeculae pattern surrounded by fibrous ground substances. Ossifying fibroma patients complained of buccal swelling and jaw pains, showing expanded cortical radiolucent lesions with a radiopaque margin. Histological findings were revealed as cellular fibrous stroma with immature woven bones. In cemental dysplasia, most of their lesions were found in a routine dental exam. Well-circumscribed radiopaque lesions were observed in the radiography, and cementum-like ossicles with fibrous stroma were seen in the microscopy. An osteoblastoma patient complained of jaw pain and facial swelling. Radiographic findings were mottled, dense radiopacity with osteolytic margin. Trabeculae of the osteoid with a vascular network and numerous osteoblasts with woven bone were predominantly found in the microscopy. CONCLUSION: Our study showed similar results as other studies. We suggest the clinical parameters of diagnosis and treatment for malignant and benign fibrous-osseous lesions of the jaws.
Biopsy ; Fibroma, Ossifying ; Humans ; Jaw ; Microscopy ; Mitosis ; Osteoblastoma ; Osteoblasts ; Osteosarcoma ; Retrospective Studies ; Sarcoma, Ewing ; Tooth Mobility