Background/Aims: AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancer (GC), especially Epstein-Barr virus (EBV)-associated and microsatellite instability high GC.The loss of ARID1A expression has been reported as a poor prognostic marker in GC. However, the relationships between ARID1A alteration and EBV-associated and microsatellite instability high GC, which are known to have a favorable prognosis, has hampered proper evaluation of the prognostic significance of ARID1A expression in GC. We aimed to analyze the true prognostic significance of ARID1A expression by correcting confounding variables. Methods: We evaluated the ARID1A expression in a large series (n=1,032) of advanced GC and analyzed the relationships between expression pattern and variable parameters, including clinicopathologic factors, key molecular features such as EBV-positivity, mismatch repair protein deficiency, and expression of p53 and several receptor tyrosine kinases including human epidermal growth factor receptor 2, epidermal growth factor receptor, and mesenchymal-epithelial transition factor. Survival analysis of the molecular subtypes was done according to the ARID1A expression patterns. Results: Loss of ARID1A expression was found in 52.5% (53/101) of mutL homolog 1 (MLH1)-deficient and 35.8% (24/67) of EBV-positive GCs, compared with only 9.6% (82/864) of the MLH1-proficient and EBV-negative group (p<0.001). The loss of ARID1A expression was associated only with MLH1 deficiency and EBV positivity. On survival analysis, the loss of ARID1A expression was associated with worse prognosis only in MLH1-proficient and EBV-negative GC. Multivariate analysis revealed that both loss of ARID1A and decreased ARID1A expression were independent worse prognostic factors in patients with advanced GC. Conclusions Only in MLH1-proficient and EBV-negative GC, the loss of ARID1A expression is related to poorer prognosis.

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

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

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

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.

PUPOSE: Through a survey on an Internet homepage, we conducted research concerning the need of patients and their families for information on gastric cancer. We also assessed their interest in gastric cancer. MATERIALS AND METHODS: We analyzed 619 inquiries presented from June 2002 to September 2003 and 524 replies submitted to a questionnaire survey delivered by the Internet homepage (www.gastriccancer.co.kr) from August to October 2003 to gastric cancer patients and their families. RESULTS: Analysis of Inquiries: The classified inquiries listed in order of frequency are as follows: treatment, prognosis, stages, symptoms, pathophysiology, diagnostic modalities, favorable food, etiology, follow-up, etc. Among the inquiries about treatment, the most frequent subgroup was about the scope of surgery or perioperative implications. Next came questions concerning chemotherapy. Among the questions from patients yet to be operated, on those about operability and the prognosis were most frequent. Among the patients who had undergone a resection, questions on complications and the corresponding prognosis were most frequent. The concern from patients with inoperable or recurrent cancers was related to terminal care and/or chemotherapy. Analysis of Questionnaires: The respondents acquired information on gastric cancer from the Internet (40%), doctors (32%), the mass media (15%) and acquaintances (13%). Only 6% of the respondents were sufficiently satisfied with the information provided by doctors. Among the respondents, 89.9% were interested in complementing treatment with folk remedies while only 5% were not. CONCLUSION: Patients and their families were eager to get information about gastric cancer. However, many of them found the doctors' information to be insufficient. Our suggestion is that the public health, academic societies, medical institutions, and public organizations should endeavor to provide through an activated Internet network correct information on gastric cancer.
Complement System Proteins ; Surveys and Questionnaires ; Drug Therapy ; Follow-Up Studies ; Friends ; Humans ; Internet* ; Mass Media ; Medicine, Traditional ; Prognosis ; Public Health ; Surveys and Questionnaires* ; Societies, Medical ; Stomach Neoplasms ; Terminal Care

The overall prognosis of gastric cancer has gradually improved over the past decades with growing awareness of potential carcinogens, surveillance programs and early diagnosis, as well as advances in surgical techniques and multimodality treatments. Nevertheless, the outcome of advanced stage disease still remains poor with currently available treatments, and a worldwide consensus on the standard management thereof has not been established. To improve prognosis and quality of life in gastric cancer patients, both standardization and individualization of managements are imperative. Diagnostic tests and surgical procedures need to be further sophisticated and standardized based on more recent evidences from ongoing and future randomized controlled trials, while comprehensive management should be individualized to each patient. Future challenges lie with how to optimize personalized therapies by deciphering biological complexity of gastric cancer and incorporating molecular biomarkers in clinical practice to forecast prognosis and to guide targeted therapeutics in adjunct to current standards of care.
Disease Management ; Gastrectomy ; Humans ; Lymph Node Excision ; Stomach Neoplasms/*diagnosis/drug therapy/etiology/surgery

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*

PURPOSE: This study was performed to find out the risk factors for recurrence and prognosis of early gastric cancer (EGC) patients by evaluating the recurrence, overall survival, and disease-specific survival after curative resection. METHODS: Out of 4217 patients who had undergone gastric resections for gastric adenocarcinoma from 1987 to 1997, the records of 1264 curatively resected EGC patients were reviewed retrospectively. Risk factors that determined recurrence, overall survival, and stomach cancer specific survival were investigated by using uni-variate and multi -variate analyses. RESULTS: Among the 1264 patients, 62 patients (4.9%) were diagnosed as having recurrent cancer and 162 patients died during follow-up. Of these 162 patients, 53 (4.2% of 1264, 32.7% of 162) patients died of gastric cancer whereas 92 died of non-gastric cancer causes and 17 died of unknown causes. In uni-variate analyses, the depth of invasion and lymph node metastasis were risk factors for recurrence and gastric cancer-specific survival while age, histologic type, depth of invasion, and lymph node metastasis were risk factors for overall survival. In multi-variate analysis, lymph node metastasis was the only risk factor for recurrence and gastric cancer-specific survival, while age was the only risk factor for overall survival. In a detailed analysis of prognoses based on lymph node metastasis, recurrence and gastric cancer related death were more frequently noted in patients with 3 or more lymph node metastasis and with extra- perigastric lymph node metastasis. CONCLUSION: Although EGC patients treated by curative resection showed good prognosis, those with lymph node metastasis have risks of recurrence and gastric cancer- related death. Considering the high rate of recurrence and gastric cancer-related death, more attention should be given to EGC patients with 3 or more lymph node metastases and/or extra-perigastric lymph node metastases. Adjuvant chemotherapy might be recommended for these high-risk patients.
Adenocarcinoma ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms* ; Survival Rate*