Salvage radiation therapy for postoperative locoregionally recurrent non-small cell lung cancer: a single-center experience

Purpose@#To determine the effectiveness of salvage radiation therapy (RT) in patients with locoregional recurrence (LRR) following initial curative resection of non-small cell lung cancer (NSCLC) and identify the prognostic factors affecting survival. @*Materials and Methods@#Between January 2009 and January 2019, 54 patients with LRR after NSCLC surgery were treated with salvage RT (83.3%) or concurrent chemoradiation therapy (16.7%). Twenty-three (42.6%), 21 (38.9%), and 10 (18.5%) patients had local, regional, and both recurrences, respectively. The median RT dose was 66 Gy (range, 37.5 to 70 Gy). The radiation target volume included recurrent lesions with or without regional lymphatics depending on the location and recurrence type. @*Results@#The median follow-up time from the start of RT was 28.3 months (range, 2.4 to 112.4 months) and disease-free interval (DFI) from surgery to recurrence was 21.0 months (range, 0.5 to 92.3 months). Tumor response after RT was complete response, partial response, stable disease, and progressive disease in 17, 29, 5, and 3 patients, respectively. The rates of freedom from local progression at 1 and 2 years were 77.2% and 66.0%, respectively. The median survival duration after RT was 24.8 months, and the 2-year overall survival (OS) rate was 51.1%. On univariate analysis, initial stage, recurrence site, DFI, and tumor response after RT were significant prognostic factors for OS. DFI ≥12 months and tumor response after RT were statistically significant factors on multivariate Cox analysis for OS. @*Conclusion@#Our results demonstrated the effectiveness of salvage RT for LRR of NSCLC following curative surgery.

Salvage radiation therapy for postoperative locoregionally recurrent non-small cell lung cancer: a single-center experience

Purpose@#To determine the effectiveness of salvage radiation therapy (RT) in patients with locoregional recurrence (LRR) following initial curative resection of non-small cell lung cancer (NSCLC) and identify the prognostic factors affecting survival. @*Materials and Methods@#Between January 2009 and January 2019, 54 patients with LRR after NSCLC surgery were treated with salvage RT (83.3%) or concurrent chemoradiation therapy (16.7%). Twenty-three (42.6%), 21 (38.9%), and 10 (18.5%) patients had local, regional, and both recurrences, respectively. The median RT dose was 66 Gy (range, 37.5 to 70 Gy). The radiation target volume included recurrent lesions with or without regional lymphatics depending on the location and recurrence type. @*Results@#The median follow-up time from the start of RT was 28.3 months (range, 2.4 to 112.4 months) and disease-free interval (DFI) from surgery to recurrence was 21.0 months (range, 0.5 to 92.3 months). Tumor response after RT was complete response, partial response, stable disease, and progressive disease in 17, 29, 5, and 3 patients, respectively. The rates of freedom from local progression at 1 and 2 years were 77.2% and 66.0%, respectively. The median survival duration after RT was 24.8 months, and the 2-year overall survival (OS) rate was 51.1%. On univariate analysis, initial stage, recurrence site, DFI, and tumor response after RT were significant prognostic factors for OS. DFI ≥12 months and tumor response after RT were statistically significant factors on multivariate Cox analysis for OS. @*Conclusion@#Our results demonstrated the effectiveness of salvage RT for LRR of NSCLC following curative surgery.

Prognostic significance of lymph node ratio after neoadjuvant chemoradiation therapy for esophageal squamous cell carcinoma

Purpose@#We retrospectively evaluated the prognostic significance of lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma who underwent neoadjuvant concurrent chemoradiation therapy (NCRT) followed by surgery. @*Materials and Methods@#In total, 270 patients who underwent NCRT followed by surgery between August 2005 and December 2015 were included. They were divided into three groups: LNR 0 (n = 196), LNR low (0 0.1; n = 11). The primary endpoint was overall survival (OS), and the secondary endpoints were freedom from local recurrence (FFLR), distant metastasis-free survival (DMFS), and disease-free survival (DFS). @*Results@#The median number of retrieved lymph nodes per patient was 33. Pathologically, 74 patients had positive lymph nodes. The median follow-up duration was 36.1 months, and the median survival period was 68.4 months. There was a significant correlation between LNR and the number of positive lymph nodes (correlation coefficient = 0.763, p < 0.001). There was a substantial difference in the OS among the LNR groups, with 2-year survival rates of 79.0%, 54.0%, and 9.1% in the LNR 0, LNR low, and LNR high groups, respectively (p < 0.001). A marked decrease in FFLP, DMFS, and DFS was observed with the increasing LNR. In subgroup analysis, the survival results of patients with clinically positive lymph node were similar from those of entire cohort. @*Conclusion@#LNR is a significant prognostic factor in patients with esophageal squamous cell carcinoma who underwent NCRT followed by surgery. Additional treatment and closer follow-up would be necessary for patients with a high LNR.

Prognostic significance of lymph node ratio after neoadjuvant chemoradiation therapy for esophageal squamous cell carcinoma

Purpose@#We retrospectively evaluated the prognostic significance of lymph node ratio (LNR) in patients with esophageal squamous cell carcinoma who underwent neoadjuvant concurrent chemoradiation therapy (NCRT) followed by surgery. @*Materials and Methods@#In total, 270 patients who underwent NCRT followed by surgery between August 2005 and December 2015 were included. They were divided into three groups: LNR 0 (n = 196), LNR low (0 0.1; n = 11). The primary endpoint was overall survival (OS), and the secondary endpoints were freedom from local recurrence (FFLR), distant metastasis-free survival (DMFS), and disease-free survival (DFS). @*Results@#The median number of retrieved lymph nodes per patient was 33. Pathologically, 74 patients had positive lymph nodes. The median follow-up duration was 36.1 months, and the median survival period was 68.4 months. There was a significant correlation between LNR and the number of positive lymph nodes (correlation coefficient = 0.763, p < 0.001). There was a substantial difference in the OS among the LNR groups, with 2-year survival rates of 79.0%, 54.0%, and 9.1% in the LNR 0, LNR low, and LNR high groups, respectively (p < 0.001). A marked decrease in FFLP, DMFS, and DFS was observed with the increasing LNR. In subgroup analysis, the survival results of patients with clinically positive lymph node were similar from those of entire cohort. @*Conclusion@#LNR is a significant prognostic factor in patients with esophageal squamous cell carcinoma who underwent NCRT followed by surgery. Additional treatment and closer follow-up would be necessary for patients with a high LNR.

A Filtering Method for Identification of Significant Target mRNAs of Coexpressed and Differentially Expressed MicroRNA Clusters.

MicroRNA (miRNA) binding is primarily based on sequence, but structure-specific binding is also possible. Various prediction algorithms have been developed for predicting miRNA target genes; the results, however, have relatively high levels of false positives, and the degree of overlap between predicted targets from different methods is poor or null. We devised a new method for identifying significant miRNA target genes from an extensive list of predicted miRNA target gene relationships using hypergeometric distributions. We evaluated our method in statistical and semantic aspects using a common miRNA cluster from six solid tumors. Our method provides statistically and semantically significant miRNA target genes. Complementing target prediction algorithms with our proposed method may have a significant synergistic effect in finding and evaluating functional annotation and enrichment analysis for miRNA.

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development.

BACKGROUND: Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. OBJECTIVE: The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. METHODS: This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. RESULTS: In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and external users for managing 11,645 studies and 146,943 subjects. CONCLUSIONS: The CTMS was introduced in the Asan Medical Center to manage the large amounts of data involved with clinical trial operations. Inter- and intraunit control of data and resources can be easily conducted through the CTMS system. To our knowledge, this is the first CTMS developed in-house at an academic medical center side which can enhance the efficiency of clinical trial management in compliance with privacy and security laws.

Establishment of Kawasaki disease database based on metadata standard.

Kawasaki disease (KD) is a rare disease that occurs predominantly in infants and young children. To identify KD susceptibility genes and to develop a diagnostic test, a specific therapy, or prevention method, collecting KD patients' clinical and genomic data is one of the major issues. For this purpose, Kawasaki Disease Database (KDD) was developed based on the efforts of Korean Kawasaki Disease Genetics Consortium (KKDGC). KDD is a collection of 1292 clinical data and genomic samples of 1283 patients from 13 KKDGC-participating hospitals. Each sample contains the relevant clinical data, genomic DNA and plasma samples isolated from patients' blood, omics data and KD-associated genotype data. Clinical data was collected and saved using the common data elements based on the ISO/IEC 11179 metadata standard. Two genome-wide association study data of total 482 samples and whole exome sequencing data of 12 samples were also collected. In addition, KDD includes the rare cases of KD (16 cases with family history, 46 cases with recurrence, 119 cases with intravenous immunoglobulin non-responsiveness, and 52 cases with coronary artery aneurysm). As the first public database for KD, KDD can significantly facilitate KD studies. All data in KDD can be searchable and downloadable. KDD was implemented in PHP, MySQL and Apache, with all major browsers supported.Database URL: http://www.kawasakidisease.kr.

CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

OBJECTIVES: Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. METHODS: Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. RESULTS: In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. CONCLUSIONS: A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

Establishing semantic interoperability of biomedical metadata registries using extended semantic relationships.

Achieving semantic interoperability is critical for biomedical data sharing between individuals, organizations and systems. The ISO/IEC 11179 MetaData Registry (MDR) standard has been recognized as one of the solutions for this purpose. The standard model, however, is limited. Representing concepts consist of two or more values, for instance, are not allowed including blood pressure with systolic and diastolic values. We addressed the structural limitations of ISO/IEC 11179 by an integrated metadata object model in our previous research. In the present study, we introduce semantic extensions for the model by defining three new types of semantic relationships; dependency, composite and variable relationships. To evaluate our extensions in a real world setting, we measured the efficiency of metadata reduction by means of mapping to existing others. We extracted metadata from the College of American Pathologist Cancer Protocols and then evaluated our extensions. With no semantic loss, one third of the extracted metadata could be successfully eliminated, suggesting better strategy for implementing clinical MDRs with improved efficiency and utility.

GOChase-II: correcting semantic inconsistencies from Gene Ontology-based annotations for gene products.

BACKGROUND: The Gene Ontology (GO) provides a controlled vocabulary for describing genes and gene products. In spite of the undoubted importance of GO, several drawbacks associated with GO and GO-based annotations have been introduced. We identified three types of semantic inconsistencies in GO-based annotations; semantically redundant, biological-domain inconsistent and taxonomy inconsistent annotations. METHODS: To determine the semantic inconsistencies in GO annotation, we used the hierarchical structure of GO graph and tree structure of NCBI taxonomy. Twenty seven biological databases were collected for finding semantic inconsistent annotation. RESULTS: The distributions and possible causes of the semantic inconsistencies were investigated using twenty seven biological databases with GO-based annotations. We found that some evidence codes of annotation were associated with the inconsistencies. The numbers of gene products and species in a database that are related to the complexity of database management are also in correlation with the inconsistencies. Consequently, numerous annotation errors arise and are propagated throughout biological databases and GO-based high-level analyses. GOChase-II is developed to detect and correct both syntactic and semantic errors in GO-based annotations. CONCLUSIONS: We identified some inconsistencies in GO-based annotation and provided software, GOChase-II, for correcting these semantic inconsistencies in addition to the previous corrections for the syntactic errors by GOChase-I.

Two Cases of Granulosa Cell Tumor of the Ovary / 대한산부인과학회지

Granulosa cell tumors are relatively low-grade malignancies accounting for about 1 to 2% of all primary ovarian neoplasms and have an indolent growth pattern. There are two types of tumors, adult type granulosa cell tumor (AGCT) and juvenile type granulosa cell tumor (JGCT), and each tumor reveals different clinical or histopathological features. The clinical manifestations are mostly associated with estrogen produced by tumor, which are vaginal bleeding or menstrual irregularity in AGCT and precocious puberty in JGCT. Although most patients are diagnosed in early stage with favorable prognosis, some recur after several years. So, continuous follow up is required. Recently, we experienced two cases of adult type granulosa cell tumor and report with a brief review of literatures.

A case of ruptured omental pregnancy / 대한산부인과학회지

Abdominal pregnancy is a rare form of ectopic pregnancy, which has been classified as early and advanced abdominal pregnancies. In case of early abdominal pregnancy, we may miss the diagnosis because the symptoms and clinical characteristics are non-specific. However, recently, the early diagnosis is made because of the development of quantitative beta-hCG measurement, transvaginal ultrasonography and the development of laparoscopy. Omental pregnancy is a very rare form of abdominal pregnancy, which is hard to detect early. When ruptured, it accompanies with massive hemorrhage. So, early diagnosis and treatment is essential to prevent high morbidity, mortality and serious complications. Definite diagnosis is made by cytopathologic examination of tissue specimen after surgery. We have experienced a case of ruptured early omental pregnancy and reviewed it briefly.

Two Cases of Endometriosis at the Subcutaneous Tissue of the Abdominal Scar after Cesarean Section / 대한산부인과학회잡지

Endometriosis is generally confined to the pelvic viscera and the peritoneum, but it can proliferate in other areas like pleura, skin, extremities, lung, gallbladder, stomach, kidney and surgical scar. Scar endometriosis usually occurs in the surgical scar of previous cesarean sections, hysterotomy and episiotomy. The occurrence of endometrioma in cesarean scar is an infrequent event, usually presenting as a tender abdominal wall mass. We report two cases of abdominal wall endometrioma after cesarean section, which is presented with a brief review of the literature.