Background: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients. Methods: Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0–1, 2–3, 4–5, and 6–9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell’s concordance index (C-index), and the Kaplan–Meier method. Results: Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13). Conclusion mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

Objective:To investigate the classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy (LPD).Methods:The records of 51 consecutive patients with LPD who were treated by linear staple closure technique of pancreatic neck from February to December 2022 from Binzhou Second People′s Hospital, Shijingshan Campus, Beijing Chaoyang Hospital, Capital Medical University, Rizhao Hepatobiliary-Pancreatic-Splenic Surgery Research Institute, Chaoyang Central Hospital, Shandong Juxian People′s Hospital, Weihai Municipal Hospital, Binzhou Central Hospital, and Affiliated Hospital of Chifeng University were retrospectively reviewed. According to the visibility, position and diameter of the main pancreatic duct at the stump of the pancreas, the type of main pancreatic duct was divided into type I, type Ⅱ, type Ⅲa and type Ⅲb. The number of cases in each main pancreatic duct classification and the corresponding treatment strategies were examined.Results:A total of 51 cases of LPD were successfully completed. Of these patients, the males comprised 56.9%(29/51), and females comprised 43.1%(22/51), with age ranging from 31 to 88 years old. The type of the main pancreatic duct at the stump of the pancreas included 7 cases (13.7%) of type Ⅰ, 39 cases (76.5%) of type Ⅱ, 2 cases (3.9%) of type Ⅲa, and 3 cases (5.9%) of type Ⅲb. Corresponding treatment strategies were adopted according to different main pancreatic duct types, the main pancreatic duct was successfully found, and a support drainage tube was inserted.Conclusion:After linear stapler closure of pancreatic neck, corresponding treatment strategies should be adopted according to the classification of the main pancreatic duct, which would help to improve the success rate of finding the main pancreatic duct and placing a support drainage tube.

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

Purpose: Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions. Materials and Methods: Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients. Results: We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients. Conclusion Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Background: In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation testing of tumor tissue should be conducted at diagnosis. Alternatively, circulating tumor DNA can be used to detect EGFR mutation. We compared the cost and clinical effect of three strategies according to the application of the EGFR test. Methods: Decision models were developed to compare the cost-effectiveness of tissue-only, tissue-first, and plasma-first diagnostic strategies as first- and second-line treatments for NSCLC from the perspective of the Korean national healthcare payer. Progression-free survival (PFS), overall survival (OS), and direct medical costs were assessed. A one-way sensitivity analysis was performed. Results: The plasma-first strategy correctly identified numerous patients in the first- and second-line treatments. This strategy also decreased the cost of biopsy procedures and complications. Compared with that when using the other two strategies, the plasma-first strategy increased PFS by 0.5 months. The plasma-first strategy increased OS by 0.9 and 1 month compared with that when using the tissue-only and tissue-first strategies, respectively. The plasma-first strategy was the least expensive first-line treatment but the most expensive second-line treatment. First-generation tyrosine kinase inhibitor and the detection rate of the T790M mutation in tissues were the most cost-influential factors. Conclusions The plasma-first strategy improved PFS and OS, allowing for a more accurate identification of candidates for targeted therapy for NSCLC and decreased biopsy- and complication-related costs.

Background: Not so many reports about the association between head and neck cancer (HNC) and oral health status related to periodontitis (OHS-P) has been published in different countries with different methods. So, there is a need for an extensive meta-analysis with the total articles published until 2020. Hence, this study aimed to estimate the association between HNC and OHS-P through a meta-analysis. Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines, 22 studies were selected through PubMed and Cochrane Library databases. Metaanalysis using them was performed to evaluate the association. The risk of bias assessment using the Newcastle-Ottawa Scale (NOS) was applied to evaluate the quality of nonrandomized studies. Publication bias was evaluated by funnel plot and Egger's regression test. Results: Since heterogeneity was significant (I2 = 88%, P < 0.001), we adopted the random effect model for 22 studies. Those with bad OHS-P, compared to those with good OHS-P, were more likely to have the risk of HNC by 2.4 times (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.88–3.13) for random effect model. The association included publication bias (Egger's regression, P value < 0.001). The association among five studies (I2 = 39%, P = 0.16) using alveolar bone loss (ABL) or clinical attachment level (CAL) for assessing periodontitis increased to OR of 3.85 (CI, 3.04–4.88) in the fixed effect model without publication bias (Egger's regression, P = 0.66). Moreover, the association was higher in 10 fair or good NOS studies (OR, 3.08) and in 7 Asian studies (OR, 2.68), which were from the fixed model without publication bias. Conclusion Our meta-analysis showed that bad OHS-P was associated with the risk of HNC.The association was stronger in studies using ABL or CAL for assessing periodontitis.

Background: Not so many reports about the association between head and neck cancer (HNC) and oral health status related to periodontitis (OHS-P) has been published in different countries with different methods. So, there is a need for an extensive meta-analysis with the total articles published until 2020. Hence, this study aimed to estimate the association between HNC and OHS-P through a meta-analysis. Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines, 22 studies were selected through PubMed and Cochrane Library databases. Metaanalysis using them was performed to evaluate the association. The risk of bias assessment using the Newcastle-Ottawa Scale (NOS) was applied to evaluate the quality of nonrandomized studies. Publication bias was evaluated by funnel plot and Egger's regression test. Results: Since heterogeneity was significant (I2 = 88%, P < 0.001), we adopted the random effect model for 22 studies. Those with bad OHS-P, compared to those with good OHS-P, were more likely to have the risk of HNC by 2.4 times (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.88–3.13) for random effect model. The association included publication bias (Egger's regression, P value < 0.001). The association among five studies (I2 = 39%, P = 0.16) using alveolar bone loss (ABL) or clinical attachment level (CAL) for assessing periodontitis increased to OR of 3.85 (CI, 3.04–4.88) in the fixed effect model without publication bias (Egger's regression, P = 0.66). Moreover, the association was higher in 10 fair or good NOS studies (OR, 3.08) and in 7 Asian studies (OR, 2.68), which were from the fixed model without publication bias. Conclusion Our meta-analysis showed that bad OHS-P was associated with the risk of HNC.The association was stronger in studies using ABL or CAL for assessing periodontitis.

The aim of this study was to investigate the usefulness of a clinical screening test [the Korean Infant and Child Developmental Test (KICDT)] compared to language specific tests: the sequenced language scale for infant (SELSI) and the Preschool Receptive-Expressive language Scale (PRES) in children with delayed language development. A retrospective chart review was conducted on 615 children who visited the Department of Pediatrics at Chonbuk National University Hospital from January 2013 to December 2016. All patients were evaluated with KICDT as a clinical screening test and SELSI or PRES as a language specific test. Language Developmental Quotients (LDQs) from the KICDT were compared with the Receptive Language Quotient (RLQ) and expressive language quotient (ELQ) from the SELSI or PRES. The sensitivity, specificity and predictive values of LDQ of KICDT were calculated by comparing with SELSI/PRES. Language DQs from the KICDT were significantly correlated with the RLQ (r=0.706), ELQ (r=0.768), and total language quotient (TLQ) (r=0.766) from the SELSI/PRES (p<0.05). In cross tabulation, the patients belonging to the retardation groups in both KICDT and SELSI/PRES were 417 (67.8%). Otherwise, patients belonging to the normal group in KICDT but not in SELSI/PRES were 151 (24.6%). Sensitivity and specificity of LDQ of KICDT relative to SELSI/PRES were 72.3% and 92.2% respectively (p<0.05). Our data suggests that clinical screening tests alone, not cumbersome language specific tests, can determine language developmental delays in children.

BACKGROUND: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. However, the number of patients who register to the Korea Hemophilia Foundation (KHF) is much lower than the expected prevalence rate and only few hospitals perform tests for diagnosis autonomously. Thus, we surveyed practical realities of VWD in Yeungnam region. METHODS: Patients with VWD (N=267) who were diagnosed at eleven university hospitals from March 1995 to March 2018 were enrolled in this study. We evaluated the medical records from each hospital retrospectively. RESULTS: Two hundred and twenty-eight children and 39 adults met the diagnostic criteria for VWD. Seventy-eight (57.4%) patients had the blood type O. Fifty-eight patients were definite type 1 (21.7%), 151 were possible type 1 (56.6%), and the others were type 2. Abnormal laboratory findings were the most common factor for the diagnosis in children. VWF mutations were detected in 17 patients. Patients with a family history showed age of diagnosis of 9 y, which is higher than in those with no family history (6 yr), and also showed a higher rate of significant bleeding (32.1% vs. 14.2%). VWF:RCo and VWF:Ag tests were performed in-hospital at only 1 of 11 hospitals. Twelve of 267 patients were enrolled at the KHF (4.5%). CONCLUSION: A high rate of out-sourcing studies may result in inaccurate diagnosis. The registration rate to the KHF is still lower than the prevalence rate. A comprehensive nationwide registration system is necessary in order to identify the actual prevalence rate and promote the diagnosis of VWD in Korea.
Adult ; Child ; Diagnosis ; Hemophilia A ; Hemorrhage ; Hospitals, University ; Humans ; Korea ; Medical Records ; Prevalence ; Retrospective Studies ; von Willebrand Diseases

BACKGROUND: JAK2 V617F is the most common mutation in myeloproliferative neoplasms (MPNs) and is a major diagnostic criterion. Mutation quantification is useful for classifying patients with MPN into subgroups and for prognostic prediction. Droplet digital PCR (ddPCR) can provide accurate and reproducible quantitative analysis of DNA. This study was designed to verify the correlation of ddPCR with pyrosequencing results in the diagnosis of MPN and to investigate clinical implications of the mutational burden. METHODS: Peripheral blood or bone marrow samples were obtained from 56 patients newly diagnosed with MPN or previously diagnosed with MPN but not yet indicated for JAK2 inhibitor treatment between 2012 and 2016. The JAK2 V617F mutation was detected by pyrosequencing as a diagnostic work-up. The same samples were used for ddPCR to determine the correlation between assays and establish a detection sensitivity cut-off. Clinical and hematologic aspects were reviewed. RESULTS: Forty-two (75%) and 46 (82.1%) patients were positive for JAK2 V617F by pyrosequencing and ddPCR, respectively. The mean mutated allele frequency at diagnosis was 37.5±30.1% and was 40.7±31.2% with ddPCR, representing a strong correlation (r=0.9712, P < 0.001). Follow-up samples were available for 12 patients, including eight that were JAK2 V617F-positive. Of these, mutational burden reduction after treatment was observed in six patients (75%), consistent with trends of hematologic improvement. CONCLUSIONS: Quantitative analysis of the JAK2 V617F mutation using ddPCR was highly correlated with pyrosequencing data and may reflect the clinical response to treatment.
Bone Marrow ; Diagnosis ; DNA ; Follow-Up Studies ; Gene Frequency ; Humans ; Polymerase Chain Reaction*