Gastric cancer (GC) is one of the deadliest malignancies in the world. Currently, clinical treatment decisions are mostly made based on the extent of the tumor and its anatomy, such as tumor-node-metastasis staging. Recent advances in genome-wide molecular technology have enabled delineation of the molecular characteristics of GC. Based on this, efforts have been made to classify GC into molecular subtypes with distinct prognosis and therapeutic response. Simplified algorithms based on protein and RNA expressions have been proposed to reproduce the GC classification in the clinical field. Furthermore, a recent study established a single patient classifier (SPC) predicting the prognosis and chemotherapy response of resectable GC patients based on a 4-gene real-time polymerase chain reaction assay. GC patient stratification according to SPC will enable personalized therapeutic strategies in adjuvant settings. At the same time, patient-derived xenografts and patient-derived organoids are now emerging as novel preclinical models for the treatment of GC. These models recapitulate the complex features of the primary tumor, which is expected to facilitate both drug development and clinical therapeutic decision making. An integrated approach applying molecular patient stratification and patient-derived models in the clinical realm is considered a turning point in precision medicine in GC.
Biomarkers, Tumor ; Chemotherapy, Adjuvant ; Classification ; Decision Making ; Drug Therapy ; Heterografts ; Humans ; Molecular Targeted Therapy ; Organoids ; Precision Medicine ; Prognosis ; Real-Time Polymerase Chain Reaction ; RNA ; Stomach Neoplasms

Familial or hereditary breast cancer has genetic heterogeneity and is transmitted vertically in an autosomal dominant fashion. About 5 to 10% of breast cancers are caused by the inheritance of mutations in dominant susceptibility genes. We retrospectively reviewed 50 breast cancer patients from 44 families. These patients had treated their breast cancer at the Department of Surgery, Yonsei University College of Medicine, from 1981 to 1996. There were no statistically significant differences between the familial breast cancers and the sporadic breast cancers in such clinicopathologic characteristics as major complaint, tumor location, tumor size, metastasis to axillary lymph nodes, stage distribution, histology distribution and hormone receptor status. For familial camcers, the mean survival was 125 months, the overal 5-year survival rate was 85%, and the overall 5-year disease-free survival rate was 70%.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Genetic Heterogeneity ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Retrospective Studies ; Survival Rate ; Wills

PURPOSE: Adenosquamous carcinoma, a rare malignant tumor of the stomach, is characterized by two different cell components, one adenomatous and the other squamous component. Its clinicopathologic feature and prognosis are quite different from the ordinary adenocarcinomas. We report our experience of 9 such cases. MATERIALS AND METHODS: Clinical and pathologic features were reviewed for the 9 patients who undenwent gastrectomies and were confirmed as adenosquamous carcinoma by pathologists during the 10-year period of from 1987 to 1998. Postoperative adjuvant therapy and prognosis were also reviewed. RESULTS: The ages of 6 male and 3 female patients ranged from 30 to 59, with the median age of 48. Total gastrectomy was done in 4 cases, while other underwent subtotal gastrectomy. Curative resection was done in four cases. Fourteeen additional organs were resected concomitantly due to suspicious tumor invasion and among them 9 organs were histologically confirmed for tumor invasion. The mean tumor size was 7.4 cm (2.5-27 cm) and all cases were pathologically advanced. One case showed peritoneal seeding and 3 cases showed hepatic metastases. There were 7 cases of stage IV disease by the UICC TNM classification (5th ed.) and the other two were stage II and stage IIlb respectively. Eight cases received postoperative adjuvant chemotherapy comprising S-FU, DDP, adriamycin, picibanil or VP-16. Of 9 patients, 6 died and the overall 5-year survival rate was 15.3%. CONCLUSION: Adenosquamous cancer of stomach is regarded as a disease of unfavorable prognosis, which was confirmed by this study. The treatments were not quite different from those for other stomach cancers. Although more cases and further investigations are essential for complete understanding of the clinical prognosis and proper treatment of the gastric adenosquamous cancer, early diagnosis, curative resection and close postoperative follow-ups are currently available options for better outcome of this disease.
Adenocarcinoma ; Carcinoma, Adenosquamous* ; Cellular Structures ; Chemotherapy, Adjuvant ; Classification ; Doxorubicin ; Early Diagnosis ; Etoposide ; Female ; Follow-Up Studies ; Gastrectomy ; Humans ; Male ; Neoplasm Metastasis ; Picibanil ; Prognosis ; Stomach ; Stomach Neoplasms ; Survival Rate

Gastric cancer imposes a global health burden. Although multimodal therapies have proven to benefit patients with advanced diseases after curative surgery, the prognosis of most advanced cancer patients still needs to be improved. Surgical extirpation is the mainstay of gastric cancer treatment. Indeed, without curative surgery, variations and combinations of chemotherapy and/or radiation cannot bring clinically meaningful success. Centered around D2 surgery, adjuvant and peri-operative multimodal therapies have improved survival in a certain group of gastric cancer patients. Moving toward a personalized cancer therapy era, molecular targeted strategies have been tested in clinical trials for gastric cancer. With some success and failures, we have learned valuable lessons regarding the biology of gastric cancer and the clinical relevance of biological therapies in addition to conventional treatments. Future treatment of gastric cancer will be shifted to molecularly tailored and genome information-based personalized therapy. Collaboration across disciplines and actively adopting emerging anti-cancer strategies, along with in-depth understanding of molecular and genetic underpinnings of tumor development and progression, are imperative to realizing personalized therapy for gastric cancer. Although many challenges remain to be overcome, we envision that the era of precision cancer medicine for gastric cancer has already arrived and anticipate that current knowledge and discoveries will be transformed into near-future clinical practice for managing gastric cancer patients.
Combined Modality Therapy ; Female ; Gastrectomy ; Humans ; *Precision Medicine ; Prognosis ; Stomach Neoplasms/*surgery

Axillary breast is one of the varieties of polymastia which is characterized by the presence of more than 2 breasts. It may cause symptoms during pregnancy, lactation, or in the premenopausal period. Unless there are obvious symptoms of lactation or the assistance of further imaging studies such as mammography and breast ultrasound, the diagnosis is often confused with subcutaneous lipoma. The incidence of axillary breast cancer is low but it should be investigated and treated properly in view of another breast cancer in the embryonic milk-line. In this paper we reviewed 4 cases of axillary breast cancer and documented some articles regarding aberrant breast and carcinoma arising from it. It is suggested that subcutaneous nodules of uncertain origin around the periphery of the breast should be viewed with suspicion and treated properly.
Adenocarcinoma, Mucinous/pathology* ; Adenocarcinoma, Mucinous/complications ; Adult ; Aged ; Breast/abnormalities* ; Breast Neoplasms/pathology* ; Breast Neoplasms/complications ; Carcinoma, Infiltrating Duct/pathology* ; Carcinoma, Infiltrating Duct/complications ; Case Report ; Female ; Human ; Middle Age

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.
Biology ; Chromosomal Instability ; Classification ; Far East ; Genome ; Humans ; Incidence ; Microsatellite Repeats ; Population Characteristics ; Stomach Neoplasms* ; Translational Medical Research

Background/Aims: Caudal type homeobox (CDX)-1 and -2 are reportedly involved in the development and progression of gastric cancer (GC). Although there are several reports on the prognostic significance of CDX-2 expression in GC, it remains controversial. In this study, we sought to validate the prognostic value of CDX-1 and -2 expression according to the histologic and molecular subtypes of GC. Methods: In total, 1,158 cases of advanced GC were investigated using immunohistochemical staining and tissue microarrays for CDX-1 and -2 expression, and survival analysis was performed according to different histological and molecular subtypes. Results: Of the 915 GCs with CDX-1 expression, 163 (17.8%) were Epstein-Barr virus (EBV)-positive or mismatch repair deficient (MMR-d), and the remaining 752 (82.2%) were EBV-negative or MMR-proficient (MMR-p). Of the 1,008 GCs with CDX-2 expression, 177 (17.5%) were EBV-positive or MMR-d, and the remaining 831 (82.5%) were EBV-negative or MMR-p. In the EBV-positive and MMR-d groups, CDX expression had no relationship with patient outcomes.In the EBV-negative and MMR-p groups, 404 (53.7%) and 523 (62.9%) samples were positive for CDX-1 and CDX-2 expression, respectively. Survival analysis demonstrated that CDX-1 and CDX-2 expression in all patients was correlated with favorable outcomes in terms of overall survival (multivariate analysis; p=0.018 and p=0.028, respectively). In the subgroup analysis, CDX-1 expression and CDX-2 expression were associated with favorable outcomes in EBV-negative and MMR-p intestinal (p=0.015 and p=0.010), and mixed and diffuse-type (p=0.019 and p=0.042) GCs, respectively. Conclusions The expression of CDX-1 and CDX-2 is a favorable prognostic factor in EBVnegative, MMR-p advanced GC.

Background/Aims: Caudal type homeobox (CDX)-1 and -2 are reportedly involved in the development and progression of gastric cancer (GC). Although there are several reports on the prognostic significance of CDX-2 expression in GC, it remains controversial. In this study, we sought to validate the prognostic value of CDX-1 and -2 expression according to the histologic and molecular subtypes of GC. Methods: In total, 1,158 cases of advanced GC were investigated using immunohistochemical staining and tissue microarrays for CDX-1 and -2 expression, and survival analysis was performed according to different histological and molecular subtypes. Results: Of the 915 GCs with CDX-1 expression, 163 (17.8%) were Epstein-Barr virus (EBV)-positive or mismatch repair deficient (MMR-d), and the remaining 752 (82.2%) were EBV-negative or MMR-proficient (MMR-p). Of the 1,008 GCs with CDX-2 expression, 177 (17.5%) were EBV-positive or MMR-d, and the remaining 831 (82.5%) were EBV-negative or MMR-p. In the EBV-positive and MMR-d groups, CDX expression had no relationship with patient outcomes.In the EBV-negative and MMR-p groups, 404 (53.7%) and 523 (62.9%) samples were positive for CDX-1 and CDX-2 expression, respectively. Survival analysis demonstrated that CDX-1 and CDX-2 expression in all patients was correlated with favorable outcomes in terms of overall survival (multivariate analysis; p=0.018 and p=0.028, respectively). In the subgroup analysis, CDX-1 expression and CDX-2 expression were associated with favorable outcomes in EBV-negative and MMR-p intestinal (p=0.015 and p=0.010), and mixed and diffuse-type (p=0.019 and p=0.042) GCs, respectively. Conclusions The expression of CDX-1 and CDX-2 is a favorable prognostic factor in EBVnegative, MMR-p advanced GC.

Purpose: To determine the limitations of current screening methods for lipid disorders and to suggest a new method that is effective for use in Korean adolescents. Methods: Data from the 6th Korea National Health and Nutrition Examination Survey (2013–2015) were analyzed. The diagnostic validity (sensitivity and specificity) of various cardiovascular risk factors currently used for lipid disorder screening was investigated, as was the diagnostic validity of non-HDL-cholesterol ≥145 mg/dL as a screening tool. Results: The prevalence of dyslipidemia and familial hypercholesterolemia (FH) among Korean adolescents was 20.4%±1.0% and 0.8%±0.3%, respectively. The current standard screening methods identified only 5.9%±1.4% and 30.3%±17.2% of the total number of dyslipidemia and FH cases, respectively. The diagnostic sensitivity and specificity of lipid profile analysis for dyslipidemia among obese adolescents were 19.5%±2.3% and 93.6%±0.8% and for FH were 30.3%±17.2% and 91.1%±0.8%, respectively. When adolescents with obesity, hypertension, or a family history of dyslipidemia or cardiocerebrovascular disease for over 3 generations were included in the screening, diagnostic sensitivity increased to 68.4%±2.8% for dyslipidemia and 83.5%±2.7% for FH. Universal screening of all adolescents based on non-HDL-cholesterol levels had sensitivities of 30.2%±2.7% and 100%, and specificities of 99.2%±0.3% and 94%±0.6% for dyslipidemia and FH, respectively. Conclusion New screening methods should be considered for early diagnosis and treatment of lipid disorders in Korean adolescents.

PURPOSE: In spite of a very poor prognosis for primary gastric cancer invading neighboring organs, combined resection of the involved adjacent organ may improve. Whether pancreaticoduodenectomy in advanced distal gastric cancer improves the survival is controversial. We conducted this study to evaluate the results of pancreaticoduodenectomy in advanced distal gastric cancer. METHODS: We retrospectively analysed 29 patients who underwent surgery at the Department of Surgery, Yonsei University College of Medicine, between January 1994 and December 2001. Patients included in this study had locally advanced distal gastric cancer, without evidence of distant metastases, which had invaded to the duodenum and/or pancreas head, or conglomerated infrapyloric lymph nodes. Patients were divided into two groups: pancreaticoduodenectomy (PD) (n=12), or palliative subtotal gastrectomy (PSTG) (n=17). We compared the clinicopathologic features, operative outcomes, recurrence and survival between these two groups. RESULTS: There were no differences in clinicopathologic features between the two groups. Operation time, incidence and amount of perioperative transfusion, postoperative hospital stay and morbidity were greater in the PD group than in the PSTG group. However, there was no postoperative mortality in either group. Five patients had systemic recurrence (liver, lung, and paraaortic LN metastases) in the PD group, while most patients experienced regional disease progression in the PSTG group. The survival of the PD group was significantly better than that of the PSTG group (P=0.0006). CONCLUSION: Pancreaticoduodenectomy can be safely performed and improves the prognosis for patients with locally far advanced distal gastric cancer that is associated with invasion into the duodenum and/or pancreas head, or conglomerated infrapyloric lymph nodes.
Disease Progression ; Duodenum ; Gastrectomy ; Head ; Humans ; Incidence ; Length of Stay ; Lung ; Lymph Nodes ; Mortality ; Neoplasm Metastasis ; Pancreas ; Pancreaticoduodenectomy* ; Prognosis ; Recurrence ; Retrospective Studies ; Stomach Neoplasms*