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Breast lymphomas are rare, malignant breast neoplasms with a heterogeneous pattern of clinical symptoms. Burkitt’s lymphoma is a rare, highly aggressive, and rapidly growing B-cell non-Hodgkin lymphoma. We report about a 27-year-old woman diagnosed as having secondary breast Burkitt’s lymphoma, probably originating from the stomach, with multiple distant metastases. Breast ultrasonography revealed multiple, variable sized, heterogeneous masses with posterior acoustic enhancement and echogenic rims. These imaging findings may sometimes overlap with those of other breast malignancies. However, unlike other breast malignancies, lymphoma can be diagnosed by biopsy and does not require surgical excision. To avoid unnecessary treatment, radiologists and clinicians should be aware of the characteristic imaging features of breast lymphomas.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL-NT) is the most common subtype of Epstein-Barr virus-associated NK/T-cell lymphomas. ENKTCL-NT occurs infrequently in the gastrointestinal tract. In particular, reports of ENKTCL-on NT arising from the stomach are extremely rare. Several clusters of differentiation (CDs) have been useful in recognizing NK-cells, T-cells, and tumor cells of NK/T-cell lymphomas. Among them, the CD56 antigen is considered the most sensitive marker for ENKTCL-NT and is expressed in almost all cases of ENKTCL-NT. Thus, the development of CD56-negative ENKTCL-NT is highly atypical. This paper reports a case of a young Asian female who presented with gastric ulcer bleeding. The patient was histologically diagnosed with ENKTCL-NT. No tumor cells for CD56 were observed, whereas no monoclonality of the T-cell receptor gamma gene rearrangement was detected in the tumor cells. The patient was scheduled for systemic chemotherapy six times and achieved complete remission. Peripheral blood-hematopoietic stem cell transplantation was performed later.

Background The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education. Methods The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education. Results The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated. Conclusions Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

Myocardial infarction (MI) is a common cardiovascular disease, the early diagnosis of which is essential for effective treatment and reduced mortality. Therefore, novel methods are required for automatic screening or early diagnosis of MI, and many studies have proposed diverse conventional methods for its detection. In this study, we aimed to develop a sleep-myocardial infarction (sleepMI) algorithm for automatic screening of MI based on nocturnal electrocardiography (ECG) findings from diagnostic polysomnography (PSG) data using artificial intelligence (AI) models. The proposed sleepMI algorithm was designed using representation and ensemble learning methods and optimized via dropout and batch normalization. In the sleepMI algorithm, a deep convolutional neural network and light gradient boost machine (LightGBM) models were mixed to obtain robust and stable performance for screening MI from nocturnal ECG findings. The nocturnal ECG signal was extracted from 2,691 participants (2,331 healthy individuals and 360 patients with MI) from the PSG data of the second follow-up stage of the Sleep Heart Health Study. The nocturnal ECG signal was extracted 3 h after sleep onset and segmented at 30-s intervals for each participant. All ECG datasets were divided into training, validation, and test sets consisting of 574,729, 143,683, and 718,412 segments, respectively. The proposed sleepMI model exhibited very high performance with precision, recall, and F1-score of 99.38%, 99.38%, and 99.38%, respectively. The total mean accuracy for automatic screening of MI using a nocturnal single-lead ECG was 99.387%. MI events can be detected using conventional 12-lead ECG signals and polysomnographic ECG recordings using our model.

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002–2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups.

Recent research suggests a potential relevance between chronic periodontitis (CP) and Parkinson’s disease (PD), raising concerns about comorbid PD among elderly CP patients. However, the epidemiologic basis for this association remains unclear. Employing a nested case-control design, this study explored the association between CP and subsequent PD occurrences in Korean adults, leveraging a validated national population-based dataset covering the period from 2002 to 2019. It included 8794 PD patients and 35,176 matched control individuals, established through propensity score matching for age, sex, residential area, and income. Baseline characteristics were compared using standardized differences, and logistic regression was employed to assess the impact of CP histories on PD likelihood while controlling for covariates. We performed a thorough examination of CP events within both 1-year and 2-year intervals preceding the index date, incorporating subgroup analyses. Our analysis revealed no statistically significant association between CP history and PD development overall. However, subgroup analysis revealed a slightly increased likelihood of PD development among CP individuals with a high disease burden (Charlson Comorbidity Index score ≥ 2). In conclusion, although our study did not find a significant overall association between CP history and PD development, the elevated likelihood of PD in subgroups with high disease burden may suggest that comorbidities influence PD probability among certain CP patients. Considering comorbid conditions in PD screening for some individuals with CP may be also important.

ObjectiveAccumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database.MethodsWe selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002–2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates.ResultsThe incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04–1.19), 28% (95% CI = 1.19–1.37), or 64% (95% CI = 1.41–1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group.ConclusionThe present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300–1000 μm from HL), and distal stalk region (1500–2000 μm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 μm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings.

Abstract Background Safety concerns against the use of proton pump inhibitors (PPIs) based on the risk of dementia, especially Alzheimer’s disease (AD), remain controversial. Here, we investigated the likelihood of AD depending on previous PPI exposure, use duration, and PPI generation. Methods This nested case–control study comprised 17,225 AD patients who were 1:4 matched with 68,900 controls for age, sex, income, and region of residence from Korean National Health Insurance Service-Health Screening Cohort data between 2002 and 2015 using propensity-score matching method. Conditional and unconditional logistic regression analyses were used to evaluate the effects of previous PPI use on AD adjusting for multiple covariates. Results Prior PPI use increased likelihood for AD in current and past PPI users (adjusted odds ratio 1.36 [95% confidence interval (CI) = 1.26–1.46] and 1.11 [95% CI = 1.04–1.18], respectively). Participants with either 90 days of PPI prescription showed higher odds for AD (1.13 [95% CI = 1.07–1.19]; 1.18 [95% CI = 1.10–1.27]; 1.26 [95% CI = 1.16–1.36], respectively). Participants with either 1st-generation or 2nd-generation PPIs demonstrated higher incidences of AD in those with 90 days (1.18 [95% CI = 1.07–1.30] and 1.27 [95% CI = 1.14–1.43], respectively) of prescription. Conclusions Prior PPI use, regardless of current or past exposure, duration of use, or use of 1st- or 2nd-generation PPIs, may increase likelihood of AD, providing supportive evidence of previous pharmacoepidemiologic studies.

Rosai–Dorfman Disease (RDD) is a rare lymphoproliferative disease, and the occurrence of isolated intracranial RDD is extremely rare. Most cases of intracranial RDDs present as dural masses showing homogenous enhancement on MRI, which makes it difficult to differentiate these masses from meningiomas before surgery unless massive cervical lymphadenopathy is observed. We herein report a rare case of isolated intracranial RDD in a 65-year-old male. Brain MRI revealed a well-defined enhancing mass-like lesion involving the right frontal convexity and subtle diffusion restriction. However, only a subtle blush was observed on the preoperative cerebral angiogram. Although instances of isolated intracranial RDD are rare, it should be considered as a potential differential diagnosis when a dural mass with hypovascularity is visualized on the cerebral angiogram.

Background: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.

Tonsillar squamous cell carcinomas (TSCCs) exhibit high rates of human papillomavirus (HPV) positivity. The expression profiles of microRNA (miRNA), which are small RNA molecules that play pivotal roles in biological processes, in TSCC in relation to the HPV status and cancer-related genetic mutations are not well investigated. Herein, we expanded our previous research, which was focused on established clinicopathological and genetic mutational data, to profile miRNA expression in TSCC, aiming to identify clinically relevant targets for early diagnosis and therapeutic intervention. The miRNA profiles were analyzed using the nCounter Nanostring miRNA Expression assay in 22 surgically resected TSCC tissues and their contralateral normal tonsil tissues. The TERT promoter (TERTp) gene was the only relevant candidate gene associated with differentially expressed miRNAs in TSCC. Hierarchical clustering analysis revealed high expression levels of hsa-miR-1285-5p, hsa-miR-1203, hsa-miR-663a, hsa-miR-1303, hsa-miR-33a-5p, and hsa-miR-3615 coupled with low expression levels of hsa-miR-3182, hsa-miR-219a-2-3p, and hsa-miR-767-3p, which were associated with HPV-positive TSCC (p = 0.009). Functional enrichment analysis revealed that these dysregulated miRNAs tended to be involved in protein binding (molecular function) and cellular components (biological processes). Therefore, hsa-miR-1285-5p and hsa-miR-663a may be associated with HPV-positive TERTp-mutated tumors and may serve as potential treatment targets and biomarkers for early detection.

Post-partum galactocele is a common benign disease among breastfeeding women, whereas retromammary and peri-implant galactocele are relatively rare conditions. Herein, a 34-yearold, 1 month-postpartum female, who had augmentation mammoplasty and a 1-month history of breast pump use, presented with left breast enlargement for 2 weeks. An initial left breast US revealed hyperechoic peri-implant fluid collection. Additional US-guided fine needle aspiration was done using a 21G-needle, draining the milk component in the process, and cytologic results revealed numerous crystals, suggestive of galactocele. Various diseases, especially breast implant-associated anaplastic large cell lymphoma, can cause peri-implant fluid collection in an augmented breast. Thus, correlating imaging features with clinical information and cytologic analysis plays an important role in appropriate management.

Hereditary spherocytosis is the most common hereditary red blood cell membrane disorder. It results from a deficiency in certain proteins that are part of the red blood cell membrane cytoskeleton. We report a case of adrenal myelolipoma in a 23-year-old patient with hereditary spherocytosis. She was diagnosed with hereditary spherocytosis at 7 months of age. As she grew older, hemoglobin level was low, so splenectomy was recommended, but continuous follow up was not possible due to the circumstances of the patient, so the splenectomy was delayed. Adrenal myelolipoma was discovered incidentally at the age of 23 with abdominal pain and cholecystitis with gallstones at the time. Myelolipoma is a benign tumor of the mesenchymal origin; its etiology remains unclear. Myelolipoma is composed of adipose and hematopoietic tissues and mainly arises from adrenal tissues. The mass is often detected during routine radiologic examinations because myelolipoma is usually asymptomatic and not generally associated with hematologic diseases. The prevalence of myelolipoma appears to be increasing due to the increased use of imaging modalities. The association of myelolipoma with hereditary spherocytosis has rarely been reported in the literature. To our best knowledge, this is the first report of adrenal myelolipoma associated with hereditary spherocytosis in the Korean population.

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Recent studies suggest that miRNA may be involved in the development of rectal neuroendocrine tumors (NETs). We explored the frequency of clinicopathologically relevant mutations and miRNA expression in rectal NETs to examine molecular profiles related to prognosis and behavior. Twenty-four eligible specimens with endoscopically excised rectal NETs were selected. Next-generation sequencing and an miRNA expression assay were used to evaluate the expression profile relevant to common genetic mutations in rectal NETs. Kyoto Encyclopedia of Genes and Genomes analysis predicted that the possible target signaling pathways were correlated with dysregulated miRNAs. Nineteen rectal NETs harbored more than one mutation in the 24 cancer-related genes. Seven miRNAs (hsa-miR-769-5p, hsa-miR-221-3p, hsa-miR-34a-5p, hsa-miR-181c-5p, hsa-miR-1246, hsa-miR-324-5p, and hsa-miR-361-3p) were significantly down-regulated in tumors harboring the FBWX7 mutation. Unsupervised hierarchical clustering analysis showed that up-regulation of these seven miRNAs may result in high mitotic indices, indicating the role of miRNAs in tumor progression. Among the down-regulated miRNAs, hsa-miR-769-5p was strongly correlated with extracellular matrix–receptor interaction and lysine degradation. Among the clinicopathological factors, up-regulated hsa-miR-3934-5p was linked to an increased mitotic count. No change in miRNA expression was associated with a tumor size >1 cm, lymphovascular invasion, or Ki-67 index. In summary, we identified different miRNA signatures involved in FBXW7 mutations or high mitotic indices in rectal NETs, which may play a critical role in tumor behavior.

Data regarding driver mutation profiles in tonsillar squamous cell carcinomas (TSCCs) remain scarce, limiting the understanding of its pathogenesis and unexpected behavior in the updated staging system. We investigated the incidence of clinically relevant mutations and their contribution in the prognosis of the condition, and their association with human papillomavirus (HPV) infection and adjuvant therapy. We subjected 43 surgically resected TSCC samples to targeted next-generation sequencing, determined their HPV status using polymerase chain reaction, and performed The Cancer Genomic Atlas and Gene Set Enrichment analyses. Thirty-five TSCC samples (81.4%) showed at least one oncogenic/likely oncogenic mutation among twenty-nine cancer-related genes. The top five mutated genes were TP53 (46.5%), PIK3CA (25.6%), PTEN (18.6%), EGFR (16.3%), and SMAD4 (14.0%). The EGFR pathway was the most frequently affected (51.2%), followed by the p53 (48.8%), PI3K (39.5%), and RTK (34.9%) pathways. The gene set enrichment analysis confirmed that the genes involved in signal transduction, such as growth factor receptors and second messengers, EGFR tyrosine kinase inhibitors, and PI3K signaling pathways, were mostly related with TSCCs. TP53 mutation was an independent prognostic factor predicting worse overall survival in the adjuvant therapy group. RTK mutations were related to survival in all patients and in the HPV-positive group, but multivariate analyses showed no significance. In conclusion, oncogenic/likely oncogenic mutations were relatively high in TSCCs, and TP53 and RTK mutations may be candidate predictors for poor prognosis in the adjuvant therapy and HPV-positive groups, respectively, under the updated staging system.

We report herein a 46-year-old woman who presented with mucinous breast carcinoma that appeared as a coarse and densely calcified mass on mammography. The lesion was a 4.6-cmsized palpable, hyperechoic, calcified mass with posterior shadowing on ultrasonography. This finding is a unique feature of mucinous breast carcinoma and is also observed in unusual breast cancer variants such as metaplastic breast cancer with chondroid differentiation, extraosseous osteosarcoma, and breast chondrosarcoma. The lesion showed a slow-growing pattern throughout the 4-year observation period. Mammography performed 4 years ago revealed faint, grouped microcalcifications; the lesion increased in size over 2 years, presenting as a well-circumscribed, calcified mass, mimicking dystrophic calcification. As several unusual variants of breast cancer, including mucinous carcinoma, may present as coarse and densely calcified masses on mammography, immediate biopsy should be considered when they are observed.

Background and Aim Data on the trends in the prevalence of chronic liver disease (CLD) in Korea are scarce. This study aimed to evaluate whether the CLD prevalence changed between 1998–2001 and 2016–2017. Methods Data were extracted from the Korea National Health and Nutrition Examination Survey (1998–2001 to 2016–2017; n=25,893). Non-alcoholic fatty liver disease (NAFLD) was defined as a hepatic steatosis index >36 in the absence of any other evidence of CLD. The definition of alcohol-related liver disease (ALD) was excessive alcohol consumption (≥210 g/week for men and ≥140 g/week for women) and an ALD/NAFLD index >0. Results The prevalence of NAFLD increased from 18.6% (95% confidence interval [CI], 17.8–19.5%) in 1998–2001 to 21.5% (95% CI, 20.6–22.6%) in 2016–2017. During the same time period, increases were observed in the prevalence of obesity (27.0 vs. 35.1%), central obesity (29.4 vs. 36.0%), diabetes (7.5 vs. 10.6%), and excessive drinking (7.3 vs. 10.5%). ALD prevalence also increased from 3.8% (95% CI, 3.4–4.2%) to 7.0% (95% CI, 6.4–7.6%). In contrast, chronic hepatitis B decreased from 5.1% (95% CI, 4.6–5.5%) to 3.4% (95% CI, 3.0–3.8%). The prevalence of chronic hepatitis C was approximately 0.3% in 2016–2017. Conclusions The prevalence of NAFLD and ALD increase among Korean adults. Our results suggest potential targets for interventions to reduce the future burden of CLD.

Abstract Background The concurrence of sarcoidosis and primary lung cancer is very rare. We report a very rare case with a delayed diagnosis of primary lung cancer due to its misdiagnosis as worsening of pulmonary sarcoidosis. Case presentation A 68-year-old man presented to the outpatient department for evaluation of a mass in the right hilar area with lymphadenopathies in subcarinal and both interlobar areas on chest computed tomography (CT). Sufficient core samples were obtained from subcarinal and bilateral interlobar lymph nodes using endobronchial ultrasonography (EBUS) guided transbronchial needle aspiration (TBNA). EBUS could not reach the right hilar lymph node due to its high angle. The pathologic findings were consistent with sarcoidosis. After 5 months, chest CT revealed aggravation of the right upper paratracheal lymphadenopathy. Assuming worsening of sarcoidosis, he was prescribed an oral corticosteroid for 5 months. However, follow-up chest CT showed a newly developed right lower paratracheal lymphadenopathy and worsening right hilar lymphadenopathy. Bronchoscopy and EBUS were performed once again. Transbronchial lung biopsy from the right upper lobe and EBUS-TBNA from the right lower paratracheal lymph node revealed adenocarcinoma from the lung. Conclusions Although coexistence of sarcoidosis and lung cancer is very rare, the clinician should consider the possibility of accompanying lung cancer in sarcoidosis patients who are not responding to initial corticosteroid therapy.

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

We assessed the efficacy of polydeoxyribonucleotide (PDRN) in accelerating the healing of diabetic wounds in a murine model of streptozotocin (STZ)-induced diabetes. After the creation of diabetic wounds, the mice of the PDRN SC, PDRN IP and PBS groups received a subcutaneous, an intra-peritoneal injection of PDRN and a subcutaneous injection of PBS, respectively. After euthanasia, time-dependent changes in the wound diameter and histologic scores were measured and vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and collagen types I and III were assessed for their expression levels. The PDRN SC and the PDRN IP groups showed a significantly smaller diameter of diabetic wounds, significantly higher histologic scores, a significantly greater expression of VEGF, a significantly lower expression of TGF-β1 and a significantly greater expression of collagen types I and III as compared with the PBS group (p < 0.05 or 0.0001). In conclusion, PDRN might be effective in promoting the healing of diabetic wounds in a murine model of STZ-induced diabetes.

The aim of this study was to investigate the effect of Canavalia gladiata extract (CGE) on the regulation of AMP-activated protein kinase (AMPK) in 3T3-L1 preadipocytes and evaluate the adipogenesis and lipogenesis mechanisms. In 3T3-L1 preadipocytes, lipid accumulation and differentiation were suppressed by 1.1, 1.3, and 1.4 times under the CGE treatment at 0.25, 0.5, and 1.0 mg/mL, respectively. The expression of the main genes involved in the inhibition of adipogenesis was evaluated at the mRNA level via a transcription-polymerase chain reaction. The extract at 1.0 mg/mL increased the mRNA expressions of AMPK and carnitine palmitoyl transferase-1 (CPT-1) by 1.9 and 1.2 times, respectively, while it decreased the expression of sterol regulatory element binding proteins-1c (SREBP-1c), peroxisome proliferator activated receptor-γ (PPAR-γ), CCAAT enhancer binding protein-α (C/EBP-α), and fatty acid synthase (FAS) by 1.1, 1.2, 1.8, and 1.5 times, respectively, indicating inhibition of the adipogenesis and lipogenesis potential of CGE. Gallic acid (4.02 mg/g) was identified as the main component of the CGE via LC-MS/MS and HPLC analysis. The results of this study suggested that CGE can be utilized as an anti-obesity food additive or medication by activating the AMPK-induced regulation and suppressing adipogenesis transcription factors.

Health issues associated with gout and increased occurrence of osteoporosis or fractures have been raised; however, the results are elusive. Herein, we explored the possible link between gout and incident osteoporosis/osteoporotic fractures based on long-term follow-up nationwide data. This study enrolled 16,305 patients with gout and 65,220 controls who were matched by propensity score at a 1:4 ratio on the basis of sex, age, income, and residence from the Korean National Health Insurance Service-Health Screening Cohort database (2002–2015). A Cox proportional hazard model was employed to identify the relevance between gout and incident osteoporosis/fractures, following adjustment for various covariates. In the follow-up period, osteoporosis developed in 761 individuals with gout and 2805 controls (incidence rates: 8.0 and 7.3/1000 person-years, respectively), and each osteoporotic fracture in the distal radius (2.8 vs. 2.7/1000 person-years), hip (1.3 vs. 1.3/1000 person-years), and spine (4.5 vs. 4.5/1000 person-years) occurred in gout and control groups, respectively. After adjustment, the gout group presented an 11% higher development of osteoporosis (95% confidence interval = 1.02–1.20) than the controls (p = 0.011). Subgroup analyses maintained the augment of incident osteoporosis in sufferers with gout, particularly in either men or

Growing evidence suggests that genetic and epigenetic factors, including environmental factors, contribute to the development of oral squamous cell carcinoma (OSCC). Here, we investigated the transcriptional silencing of the CD24, CD44, CD133, and CD147 genes, which are well-known cancer stem cell surface markers in various cancer types, including OSCC. We first examined the correlation between the transcriptional expression level and reactivation by 5-aza-2′-deoxycytidine (5-aza-dC) and the promoter methylation levels of the four genes in several OSCC cell lines. We observed promoter hypermethylation for the CD24, CD133, and CD147 genes at 70%, 75%, and 70%, respectively, in OSCC cell lines compared to normal oral mucosa tissues (CD133 and CD147 extracted from The Cancer Genome Atlas (TCGA) database were negatively correlated, supporting their epigenetic regulation in primary OSCC tumors. The methylation status of CD133 and CD147 was associated with poor survival in patients with OSCC using the TCGA database. Our findings provide additional insight into the abnormal DNA methylation of CD133 and that CD147 could be used for the diagnosis and therapeutic treatment of patients with OSCC.

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (>20 years) based on the Korean Genome and Epidemiology Study data (2005–2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.

The effect of proton pump inhibitor (PPI) use on migraine risk remains controversial. We explored the odds of migraines in relation to prior PPI use and treatment duration. Data from the Korean National Health Insurance Service-Health Screening Cohort (2002–2015) were analyzed in this nested case-control study involving 28,159 participants with incident migraines and 112,636 controls (1:4 matched by sex, age, income, and residential region). The baseline covariates were balanced by performing propensity score overlap weighting-based adjustments, and the effect of prior PPI use (past vs. current) and treatment duration (

We explored the genetic and environmental inter-relationships among osteoporosis, fracture, arthritis, and bone mineral density concordance in monozygotic twins compared to those in dizygotic twins. This cross-sectional research assessed data of 1032 monozygotic and 242 dizygotic twin pairs aged >20 years included in the Healthy Twin Study data of the Korean Genome and Epidemiology Study between 2005 and 2014. Outcomes of interest included illness concordance and absolute differences in dual-energy X-ray absorptiometry (DEXA) T-scores. We found comparable concordances of osteoporosis, fractures, osteoarthritis, and rheumatoid arthritis between monozygotic and dizygotic twins. Medical histories of osteoporosis, fractures caused by accident or falling, osteoarthritis, and rheumatoid arthritis were not distinct between monozygotic and dizygotic twins. Accidental fracture occurrence in both monozygotic twins showed significantly lower odds than that in dizygotic twins. Genetic influence on liability to fracture risk might thus be maintained. DEXA T-scores for bone mineral density indicated more comparable tendencies within monozygotic twin pairs than within dizygotic ones, suggesting the relative importance of genetic contribution to bone mineral density. The relative importance of genetic factors in bone mineral density is sustained between monozygotic twins; overt disease expression of osteoporosis, fractures, or arthritis may be affected by environmental factors.

Background/Aims: The aim of this study was to develop ‘Koreans Gut Quotient Measurement Scales (GQ)’, in which Koreans respond to questionnaires about the subjective feelings and symptoms of their intestinal health status. Methods: Among 66 items pooled from previous studies and 4 items that were added following a focus group interview, 15 items were chosen using the Delphi survey. The content validity was evaluated using the content validity ratio. Data collected from 1,120 people from the general public in Korea were analyzed to verify the reliability and validity of GQ. Results: The finalized GQ consisted of 17 items (including two exploratory measurement items) that were classified into three independent factors based on exploratory factor analysis (EFA): ‘perceived intestine discomfort’, ‘bowel movement discomfort’, and ‘bowel movement control discomfort’. The discriminant and convergent validity of GQ were identified using EFA, reliability test, and confirmatory factor analysis. In addition, the criterion-related validity of GQ was identified using correlation and multiple regression analysis. Conclusions: The GQ, which is a simplified intestinal health index developed based on an easy questionnaire for the public to understand, can be used as a tool for the public to evaluate their own intestinal health and determine when to visit clinics.

Adipose-derived stem cells (ADSCs) are potential therapeutics considering their self-renewal capacity and ability to differentiate into all somatic cell types in vitro. The ideal ADSC-based therapy is a direct injection into the relevant organs. The objective of this study was to investigate the viability and safety of intra-organ human ADSC (h-ADSC) xenotransplants in vivo. Subcutaneous adipose tissue from the abdominal area of 10 patients was sampled. h-ADSCs were isolated from adipose tissue samples and identified using immunofluorescence antibodies. Multi-differentiation potential assays for adipocytes, osteocytes, and chondrocytes were performed. Cultured h-ADSCs at passage 4 were transplanted into multiple organs of 17 rats, including the skin, subcutaneous layer, liver, kidney, pancreas, and spleen. The h-ADSC-injected organs excised after 100 days were examined, and the survival of h-ADSCs was measured by quantitative real-time polymerase chain reaction (qRT-PCR) using specific human and rat target genes. h-ADSCs confirmed by stem cell phenotyping were induced to differentiate into adipogenic, osteogenic, and chondrogenic lineages in vitro. All rats were healthy and exhibited no side effects during the study; the transplanted h-ADSCs did not cause inflammation and were indiscernible from the native organ cells. The presence of transplanted h-ADSCs was confirmed using qRT-PCR. However, the engrafted survival rates varied as follows: subcutaneous fat (70.6%), followed by the liver (52.9%), pancreas (50.0%), kidney (29.4%), skin (29.4%), and spleen (12.5%). h-ADSCs were successfully transplanted into a rat model, with different survival rates depending on the organ.

Chordomas are rare, locally aggressive bone malignancies with poor prognoses. However, those with minimal or no bone involvement are more easily resectable because of their well-delineated margins and thus have better prognoses. Such extraosseous chordomas of the spine are localized both intradurally and extradurally. Only a few case reports have focused on extraosseous, extradural spinal chordomas. Radiologically, this type of chordoma has a dumbbell shape; however, dumbbell-shaped spinal tumors are traditionally thought to be neurogenic tumors (i.e., schwannomas or neurofibromas). We herein report a unique case involving a woman with a dumbbell-shaped extraosseous chordoma protruding predominantly into the retropharyngeal space. A 44-year-old woman presented for evaluation of a left submandibular mass. A T2-hyperintense, gadolinium-enhancing mass was found in her cervical spinal canal, protruding through the C2/3 neural foramen into the retropharyngeal space with minimal vertebral involvement. The initial diagnosis was a neurogenic tumor, most likely a schwannoma. After subtotal removal, the pathologic diagnosis was a chordoma. Because chordomas and schwannomas have significantly different prognoses, caution is warranted when a dumbbell-shaped tumor is identified in the spine with minimal or no vertebral deterioration on radiology. This report also provides the first thorough review of extraosseous dumbbell-shaped intraspinal–extraspinal chordomas.

ObjectivePneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP.MethodsWe retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC).ResultsThe IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016).ConclusionsPatients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

Objective This study was conducted to evaluate the effects of Rhus succedanea extract addition on in vitro ruminal fermentation and microbial growth. Methods Two ruminally-fistulated steers consuming 600 g/kg timothy- and 400 g/kg cracked corn-based concentrate with free access to water and mineral block were used as rumen fluid donors. In vitro batch fermentation, with timothy as a substrate, was conducted for up to 72 h, with Rhus succedanea extracts added to achieve final concentrations of 0, 10, 30, 50, 70, and 90 mg/L. Results Effective dry matter (DM) degradability rate linearly decreased (p = 0.046) depending on extract dosing levels. Total gas production after 24 to 72 h incubation tended to decrease following extract addition, beginning with 50 mg/L starting dose (significance of quadratic effects: p = 0.006, p

Background MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post-transcriptional gene regulation. They are commonly deregulated in human malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Methods Six cases of resected NSCLC harboring the T790M mutation were examined. We performed miRNA time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially expressed between the two groups were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results miRNA PCR array profiling revealed three up-regulated miRNAs whose expression levels were altered 4.0-fold or more in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change, 4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The three differentially expressed miRNAs were validated by qRT-PCR, and they were found to be overexpressed in the T790M group relative to L858R group. In particular, expression levels of miR-1 and miR-124 were significantly higher in the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096). Conclusions MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated NSCLC.

Objective: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a rare autoimmune and paraneoplastic encephalitis caused by the N-methyl-d-aspartate receptor antibody which is related to tumors, such as teratomas of the ovaries. To our knowledge, this is the first reported case of Anti-NMDAR encephalitis associated with ovarian mucinous cystadenoma. Case report: A 23-year-old woman with a flu-like illness, confused mental status, and behavioral changes presented to the hospital. A right-sided ovarian tumor was detected during the work-up and was suspected to be a teratoma that might have caused the encephalitis. A laparoscopic right salpingo-oophorectomy (RSO) was performed. Histopathological examination revealed a mucinous cystadenoma. She recovered gradually and had complete resolution of symptoms after surgical removal of the mucinous cystadenoma and immunotherapy. Conclusion: Even though anti-NMDAR encephalitis is caused by ovarian teratoma because it contains various types of tissues, ovarian tumors in anti-NMDAR encephalitis may not be limited to ovarian teratomas. Keywords: Anti-NMDAR encephalitis, Ovarian tumor, Mucinous cystadenoma

Microtubule-associated tumor suppressor 1 (MTUS1) is thought to be downregulated in arious human cancers, which suggests its role as a tumor suppressor. This study investigated the clinicopathological significance of MTUS1 expression in lung adenocarcinoma. Tissue microarray blocks consisting of 161 cases were constructed, and immunohistochemical staining was used to assess MTUS1 expression. Correlations of MTUS1 expression and clinicopathological parameters were analyzed. In addition, we used public databases and performed bioinformatics analysis. Low level of MTUS1 was significantly associated with higher clinical stage (p = 0.006), higher tumor stage (p = 0.044), lymph node metastasis (p = 0.01), worse histologic grade (p = 0.007), lymphovascular invasion (p = 0.014), and higher Ki-67 proliferation index (p < 0.001). Patients with low MTUS1 expression also showed shorter disease-free survival (p = 0.002) and cancer-specific survival (p = 0.006). Analysis of data from the Cancer Genome Atlas confirmed that the mRNA expression of MTUS1 in lung adenocarcinoma was significantly lower than that of normal lung tissue (p = 0.02), and patients with decreased MTUS1 expression showed significantly shorter overall survival (p = 0.008). These results suggest that MTUS1 may be a potential biomarker for predicting clinical outcomes in lung adenocarcinoma patients.

The Ki-67 labeling index (LI) is an important prognostic factor in breast carcinoma. The Ki-67 LI is traditionally calculated via unaided microscopic estimation; however, inter-observer and intra-observer variability and low reproducibility are problems with this visual assessment (VA) method. For more accurate assessment and better reproducibility with Ki-67 LI, digital image analysis was introduced recently. We used both VA and automated digital image analysis (ADIA) (Ventana Virtuoso image management software) to estimate Ki-67 LI for 997 cases of breast carcinoma, and compared VA and ADIA results. VA and ADIA were highly correlated (intraclass correlation coefficient 0.982, and Spearman's correlation coefficient 0.966, p

The comparison of the genetic profiles between primary and metastatic colorectal cancer (CRC) is needed to enable the discovery of useful therapeutic targets against metastatic CRCs. We performed the targeted next generation sequencing assay of 170 cancer-associated genes for 142 metastatic CRCs, including 95 pairs of primary and metastatic CRCs, to reveal their genomic characteristics and to assess the genetic heterogeneity. The most frequently mutated gene in primary and metastatic CRCs was APC (71% vs. 65%), TP53 (54% vs. 57%), KRAS (45% vs. 44%), PIK3CA (16% vs. 19%), SMAD4 (15% vs. 14%) and FBXW7 (11% vs. 11%). The concordance in the top six frequently mutated genes was 85%, on average. The overall mutation frequencies were consistent with two sets of public data (TCGA and MSKCC). To the author’s knowledge, this is the first study to compare the genetic profiles of our cohort with that of the metastatic CRCs from MSKCC. Comparative sequencing analysis between primary and metastatic CRCs revealed a high degree of genetic concordance in the current clinically actionable genes. Therefore, the genetic investigation of archived primary tumor samples with the challenges of obtaining an adequate sample from metastatic sites appears to be sufficient for the application of cancer precision medicine in the metastatic setting.

This study aimed to investigate the optimal addition of terpene-based Pinus densiflora and Mentha canadensis extracts, with antioxidant and methane reduction effects, as feed supplements to ruminants. Two cannulated steers (450 ± 30 kg), consuming Timothy Hay and a commercial concentrate (60:40, w/w) twice daily (at 09:00 and 17:30) at 2% of body weight, with free access to water and a mineral block, were used as rumen fluid donors. In vitro fermentation experiments, with Timothy Hay as the substrate, were conducted with P. densiflora and M. canadensis extracts as supplements to achieve concentrations of 30, 50, and 70 mg/L on a Timothy Hay basis. Fibrobacter succinogenes decreased in proportion upon P. densiflora and M. canadensis extract supplementation at 50 mg/L, while the dry matter degradability of the feed was not significantly different (p < 0.05). Methane emission was significantly lower in the 50 and 70 mg/L treatment groups, for both extracts, at 12 h (p < 0.05). Based on methane production and antioxidant activity, our study suggests that 30 mg/L addition is the most appropriate level of supplementation.

The vital signs or laboratory test results of sepsis patients may change before clinical deterioration. This study examined the differences in prognostic performance when systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA) scores, National Early Warning Score (NEWS), and lactate levels were repeatedly measured. Scores were obtained at arrival to triage, 1 h after fluid resuscitation, 1 h after vasopressor prescription, and before leaving the emergency room (ER) in 165 patients with septic shock. The relationships between score changes and in-hospital mortality, mechanical ventilation, admission to the intensive care unit, and mortality within seven days were compared using areas under receiver operating characteristic curve (AUROCs). Scores measured before leaving the ER had the highest AUROCs across all variables (SIRS score 0.827 [0.737–0.917], qSOFA score 0.754 [0.627–0.838], NEWS 0.888 [0.826–0.950], SOFA score 0.835 [0.766–0.904], and lactate 0.872 [0.805–0.939]). When combined, SIRS + lactate (0.882 [0.804–0.960]), qSOFA + lactate (0.872 [0.808–0.935]), NEWS + lactate (0.909 [0.855–0.963]), and SOFA + lactate (0.885 [0.832–0.939]) showed improved AUROCs. In patients with septic shock, scoring systems show better predictive performances at the timepoints reflecting changes in vital signs and laboratory test results than at the time of arrival, and combining them with lactate values increases their predictive powers.

Background: Chronic placental inflammation, such as villitis of unknown etiology (VUE) and chronic chorioamnionitis (CCA), is considered a placental manifestation of maternal anti-fetal rejection. The aim of this study is to investigate its frequency in twin pregnancies compared to singleton pregnancies. Methods: Three hundred twin placentas and 1,270 singleton placentas were consecutively collected at a tertiary medical center in Seoul, Republic of Korea from 2009 to 2012. Hematoxylin and eosin sections of tissue samples (full-thickness placental disc and chorioamniotic membranes) were reviewed. Results: Non-basal VUE was more frequent in twin placentas than in singleton placentas (6.0% vs 3.2%, p < .05). In preterm birth, CCA was found less frequently in twin placentas than in singleton placentas (9.6% vs 14.8%, p < .05), reaching its peak at an earlier gestational age in twin placentas (29–32 weeks) than in singleton placentas (33–36 weeks). CCA was more frequent in twin pregnancies with babies of a different sex than with those with the same sex (13.8% vs 6.9%, p=.052). Separate dichorionic diamniotic twin placentas were affected by chronic deciduitis more frequently than singleton placentas (16.9% vs 9.7%, p

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma that most commonly involves the central nervous system and skin. To our knowledge, no state-of-the art imaging findings have been reported for hepatic IVLBCL in the English literature. We report the first case of hepatic involvement of IVLBCL along with a literature review.

ObjectivesThis study considered whether there could be a change of mortality and length of stay as a result of inter-hospital transfer, clinical department, and size of hospital for patients with organophosphates and carbamates poisoning via National Patients Sample data of the year 2009, which was obtained from Health Insurance Review and Assessment Services (HIRA). The utility and representativeness of the HIRA data as the source of prognosis analysis in poisoned patients were also evaluated.MethodsOrganophosphate and carbamate poisoned patients' mortality and length of stay were analyzed in relation to the initial and final treating hospitals and departments, as well as the presence of inter-hospital transfers.ResultsAmong a total of 146 cases, there were 17 mortality cases, and the mean age was 56.8 ± 19.2 years. The median length of stay was 6 days. There was no inter-hospital or inter-departmental difference in length of stay. However, it significantly increased when inter-hospital transfer occurred (transferred 11 days vs. non-transferred 6 days; p = 0.037). Overall mortality rate was 11.6%. The mortality rate significantly increased when inter-hospital transfer occurred (transferred 23.5% vs. non-transferred 7.0%; p = 0.047), but there was no statistical difference in mortality on inter-hospital and inter-department comparison at the initial treating facility. However, at the final treating facility, there was a significant difference between tertiary and general hospitals (5.1% for tertiary hospitals and 17.3% for general hospitals; p = 0.024), although there was no significant inter-departmental difference.ConclusionsWe demonstrated that hospital, clinical department, length of stay, and mortality could be analyzed using insurance claim data of a specific disease group. Our results also indicated that length of stay and mortality according to inter-hospital transfer could be analyzed, which was previously unknown.

BackgroundGastric cancer is one of the leading cancer types in incidence and mortality, especially in Asia. In order to improve survival, identification of a catalogue of molecular alterations underlying gastric cancer is a critical step for developing and designing genome-directed therapies.Methodology/principal findingsThe Center for Cancer Genome Discovery (CCGD) at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection platform, termed OncoMap v4, interrogates 474 "hotspot" mutations in 41 genes that are relevant for cancer. We performed OncoMap v4 in formalin-fixed paraffin-embedded (FFPE) tissue specimens from 237 gastric adenocarcinomas. Using OncoMap v4, we found that 34 (14.4%) of 237 gastric cancer patients harbored mutations. Among mutations we screened, PIK3CA mutations were the most frequent (5.1%) followed by p53 (4.6%), APC (2.5%), STK11 (2.1%), CTNNB1 (1.7%), and CDKN2A (0.8%). Six samples harbored concomitant somatic mutations. Mutations of CTNNB1 were significantly more frequent in EBV-associated gastric carcinoma (P = 0.046). Our study led to the detection of potentially druggable mutations in gastric cancer which may guide novel therapies in subsets of gastric cancer patients.Conclusions/significanceUsing high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma.

Given the high incidence of metastatic esophageal squamous cell carcinoma, especially in Asia, we screened for the presence of somatic mutations using OncoMap platform with the aim of defining subsets of patients who may be potential candidate for targeted therapy.We analyzed 87 tissue specimens obtained from 80 patients who were pathologically confirmed with esophageal squamous cell carcinoma and received 5-fluoropyrimidine/platinum-based chemotherapy. OncoMap 4.0, a mass-spectrometry based assay, was used to interrogate 471 oncogenic mutations in 41 commonly mutated genes. Tumor specimens were prepared from primary cancer sites in 70 patients and from metastatic sites in 17 patients. In order to test the concordance between primary and metastatic sites from the patient for mutations, we analyzed 7 paired (primary-metastatic) specimens. All specimens were formalin-fixed paraffin embedded tissues and tumor content was >70%.In total, we have detected 20 hotspot mutations out of 80 patients screened. The most frequent mutation was PIK3CA mutation (four E545K, five H1047R and one H1047L) (N = 10, 11.5%) followed by MLH1 V384D (N = 7, 8.0%), TP53 (R306, R175H and R273C) (N = 3, 3.5%), BRAF V600E (N = 1, 1.2%), CTNNB1 D32N (N = 1, 1.2%), and EGFR P733L (N = 1, 1.2%). Distributions of somatic mutations were not different according to anatomic sites of esophageal cancer (cervical/upper, mid, lower). In addition, there was no difference in frequency of mutations between primary-metastasis paired samples.Our study led to the detection of potentially druggable mutations in esophageal SCC which may guide novel therapies in small subsets of esophageal cancer patients.