Ho Young Chung

Factors related to lymph node metastasis and the feasibility of endoscopic mucosal resection for treating poorly differentiated adenocarcinoma of the stomach

BACKGROUND AND AIM Endoscopic mucosal resection (EMR) is currently not accepted as an alternative treatment to surgery in early gastric cancer (EGC) of the undifferentiated histologic type. The present retrospective analysis examined the correlation of various histologic factors with the presence of lymph node metastasis (LNM). PATIENTS AND METHODS A retrospective analysis on 234 patients with poorly differentiated EGC who underwent radical gastrectomy with D2 lymph node dissection was undertaken. Several clinicopathologic factors were investigated to identify predictive factors for LNM: age, sex, type of operation, tumor location, tumor size, gross type, ulceration, lymphatic invasion, and depth of invasion. RESULTS Of the 234 lesions with poorly differentiated EGC, half (n = 116) already showed submucosal invasion in the resection specimen; 25.9 % of those (30/116) were limited to the upper third (SM1). Of the lesions confined to the mucosa, LNM was found in 3.4 % (4/118). With minor submucosal infiltration (SM1), the LNM rate was lower (0/30) in our patient population. Only with SM2/3 infiltration did the LNM rate sharply rise to around 30 %. The cut-off for submucosal infiltration depth was 500 microm (0/32 LNM), above which LNM rates were substantial (31.2 %; 24/77). There was limited correlation between the SM1-3 classification and actual measurement of submucosal infiltration depth. In a multivariate analysis, tumor size ( P = 0.033), depth of invasion ( P = 0.004), and lymphatic invasion ( P < 0.001) were associated with LNM. CONCLUSION Poorly differentiated EGC confined to the mucosa or with minimal submucosal infiltration (<or= 500 microm) could be considered for curative EMR due to the low risk of LNM. Given the limited case number of subgroups, these findings should be confirmed by more data from other centers, which should also focus on local recurrence after EMR in poorly differentiated EGC.

Investigation of Vascular Endothelial Growth Factor Gene Polymorphisms and Its Association with Clinicopathologic Characteristics in Gastric Cancer

Objective: Vascular endothelial growth factor (VEGF) is known to be a potent proangiogenic factor. This study evaluates the potential association of three VEGF gene polymorphisms (–460T > C, +405G > C, and 936C > T) with the susceptibility to and clinicopathologic characteristics of gastric cancer. Methods: The VEGF genotypes were determined using paraffin-embedded tissue from 413 patients who underwent a surgical resection and peripheral blood lymphocytes from 413 healthy controls by PCR-RFLP assay. Results: There was no difference in the allele frequency of –460T > C polymorphism. However, for the +405G > C polymorphism, the +405C allele was associated with a significantly decreased susceptibility to gastric cancer [odds ratio (OR) 0.686; 95% confidence interval (CI) 0.564–0.834]. Although there was no significant difference in the distribution of the 936C > T polymorphism between the two groups, the 936T allele was associated with a decreased susceptibility to gastric cancer (OR 0.757; 95% CI 0.591–0.970). In the haplotype analyses, the haplotype TCT (OR 0.405; 95% CI 0.263–0.624) was most closely associated with a decreased susceptibility to gastric cancer. However, no significant association was observed between the frequency of the genotypes or alleles and the clinicopathologic characteristics of gastric cancer. Conclusion: These observations imply that the VEGF gene polymorphisms may be associated with the susceptibility to gastric cancer. However, further studies of other VEGF sequence variants and their biological functions are needed to understand the role of the VEGF polymorphisms in determining the susceptibility to gastric cancer.

Prognostic value of Tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer

BACKGROUND This study explored the prognostic impact of tumor-infiltrating lymphocytes (TILs) and investigated whether three histologic subtypes (lymphoepithelioma-like carcinoma, carcinoma with Crohns disease-like lymphoid reaction, and conventional-type adenocarcinoma) could stratify a prognostic subset for patients with Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). MATERIALS AND METHODS After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. The evaluation of the percentage of intratumoral (iTu-) and stromal (str-) TILs was carried out, and the cases were also subclassified into three histologic subtypes as noted above. RESULTS Among the 120 patients, 73 patients (60.8%) and 60 patients (50.0%) were determined as str-TIL-positive and iTu-TIL-positive, respectively. In a univariate analysis, str-TIL-positivity was significantly associated with longer recurrence-free survival (RFS; P = 0.002) and disease-free survival (DFS; P = 0.008), yet not overall survival (OS; P = 0.145). While iTu-TIL-positivity has a tendency of favorable outcome indicator for DFS and OS, but statistically significant differences were not shown, respectively (RFS, P = 0.058; DFS, P = 0.151; OS, P = 0.191). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, lymphatic invasion, perineural invasion, and venous invasion; histologic subtype, WHO classification, and str-TIL-positivity were independently or tentatively associated with favorable RFS (hazard ratio [HR] = 12.193, 95% confidence interval [95% CI] 1.039-143.055, P = 0.047) or DFS (HR = 4.836, 95% CI 0.917-25.525, P = 0.063). CONCLUSION The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.

Quality of Life of Long-Term Survivors after a Distal Subtotal Gastrectomy

PURPOSE The aim of this study was to investigate the impact of a distal subtotal gastrectomy on the quality of life (QoL). MATERIALS AND METHODS The QoL data of 126 patients were obtained on their 5th annual follow-up visit after a curative distal subtotal gastrectomy for gastric cancer (Group A). The QoL data of 130 age- and gender-adjusted healthy population were obtained from the individuals who visited the health screening center for a medical check-up (Group B). There were 42 women and 84 men in the study group and their mean age was 56.0±11.1 years. QoL was assessed using the Korean versions of the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) and QLQ-STO22. RESULTS The EORTC QLQ-C30 global health status and QoL scores of Group A and Group B were 63.9±22.7 and 61.3±22.1, respectively (p=0.361). Group A revealed a better score for emotional functioning (84.1±16.1 and 75.2±21.4, respectively; p<0.001), cognitive functioning (82.0±16.4 and 75.0±21.4, respectively; p=0.004) and fatigue (27.7±20.8 and 33.8±23.2, respectively; p=0.028). However, Group A revealed a worse score for nausea and vomiting (14.8±20.0 and 10.2±16.0, respectively; p=0.042), financial difficulties (14.8±22.9 and 7.1±16.1, respectively; p=0.002), reflux (16.7±17.7 and 10.1±17.0, respectively; p=0.003), eating restrictions (13.6±15.2 and 6.6±10.2, respectively; p<0.001) and body image (23.3±25.4 and 16.2±24.6, respectively; p=0.023). CONCLUSION The QoL of long-term survivors after a distal subtotal gastrectomy is still influenced by the surgery itself even though they are considered to be free of disease.

No Association of Vascular Endothelial Growth Factor-A (VEGF-A) and VEGF-C Expression with Survival in Patients with Gastric Cancer

PURPOSE Although the vascular endothelial growth factor (VEGF) superfamily has been identified to critically influence tumor-related angiogenesis, the prognostic significance of a VEGF expression in gastric cancer is still controversial. Accordingly, the present study analyzed the VEGF-A and VEGF-C expressions and their impact on the prognosis of patients with gastric cancer. MATERIALS AND METHODS Three hundred seventy-five consecutive patients who underwent surgical resection for gastric adenocarcinoma with a curative intent were enrolled in the present study. Immunohistochemical staining for VEGF-A and VEGF-C was performed using the formalin fixed, paraffin embedded tumor tissues. RESULTS Positive VEGF-A and VEGF-C expressions were observed in 337 (90.1%) and 278 (74.9%) cases, respectively. The survival analysis showed that the expression of VEGF-A and VEGF-C had no effect on the OS and DFS. On the multivariate analysis that included age, gender and the TNM stage, no significant association between the grade of the VEGF-A or VEGF-C expression and survival was observed. CONCLUSION The current study suggests that the tissue expression of VEGF-A or VEGF-C alone is not an independent prognostic marker for patients with surgically resected gastric adenocarcinoma.

Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer : Daegu Gyeongbuk Oncology Group

The present study was conducted to evaluate the efficacy and safety of a combination regimen of docetaxel plus oxaliplatin in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous docetaxel 65 mg m−2 plus oxaliplatin 120 mg m−2 on day 1 based on a 3-week cycle. Forty-two patients were enrolled in the current study, among whom 39 were assessable for efficacy and all assessable for toxicity. One complete response and 18 partial responses were confirmed, giving an overall response rate of 45.2% (95% confidence interval (CI); 31.7–59.7%). At a median follow-up of 7.7 months, the median time to progression and median overall survival was 5.7 (95% CI; 4.3–7.2) months and 9.9 (95% CI; 7.8–12.0) months, respectively. Grade 3/4 neutropenia occurred in 11 patients (26.1%) and febrile neutropenia was observed in four patients (9.5%). The common non-haematologic toxicity was fatigue (grade 1/2, 61.9%) and nausea (grade 1/2, 47.7%). The combination of docetaxel and oxaliplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

Long-term Quality of Life After Distal Subtotal and Total Gastrectomy: Symptom- and Behavior-oriented Consequences.

Objective:This study assessed long-term quality of life (QoL) after subtotal gastrectomy (STG) and total gastrectomy (TG) by comparing groups matched by a set of patient factors at and beyond postoperative 5 years. The cause of QoL gaps based on symptomatic and behavioral consequences of surgery were investigated. Background:Survivors after STG and TG were matched by a set of patient factors (age, sex, stage, chemotherapy, and postoperative period). QoL data were obtained from 53 and 36 pairs of survivors at and beyond postoperative 5 years, respectively. Methods:The European Organization for Research and Treatment of Cancer QoL Questionnaire (QLQ)-C30 and QLQ-STO22 were used to assess QoL. QoL comparisons between STG and TG groups were made for 5-year survivors and long-term survivors. Results:Five-year survivors after TG showed significantly worse QoL in social functioning, nausea and vomiting, eating restrictions, and taste. For long-term survivors, QoL inferiority of the TG group was observed only in eating restrictions. Among 4 items constituting eating restrictions, the TG group tended to exhibit worse QoL in 2 items (enjoyable meals and social meals). Conclusions:Although 5-year survivors after TG still suffer from QoL inferiority from symptomatic and behavioral consequences of surgery, inferiority from behavioral consequences will persist even after symptomatic inferiority to STG survivors is no longer valid. Efforts to ameliorate persistent QoL inferiority in TG survivors should be directed toward restoring dietary behaviors, where TG survivors are prevented from enjoyable meals and social meals.

Quality of life in cancer survivors 5 years or more after total gastrectomy: A case-control study

INTRODUCTION This study investigated how total gastrectomy (TG), along with memories of cancer, affect the subjective wellness of survivors long after surgery. Rational approaches for effectively improving the quality of life (QoL) of these survivors were suggested. METHODS Between 2008 and 2013, QoL data of gastric cancer patients who underwent a curative TG, were obtained at 5-year postoperative follow-up visits (5-year survivors) and at visits beyond 5 years (long-term survivors). The control groups for these survivor groups were constructed from volunteers who visited our health-examination center for annual medical checkups. The Korean versions of the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the gastric cancer specific module, the EORTC QLQ-STO22, were used to assess QoL. RESULTS Five-year survivors showed worse QoL compared to the control group in role functioning, social functioning, nausea/vomiting, appetite loss, financial difficulties, reflux, eating restrictions, taste, and body image, and better QoL in the emotional and cognitive functioning scales. In long-term survivors, deterioration in QoL were still apparent in financial difficulties, reflux, and eating restrictions, while QoL differences in the remaining scales had diminished. DISCUSSION Surviving 5 years after TG does not result in living in a carefree state in terms of QoL. After 5 postoperative years, survivors still need extended care for deteriorated QoL indicators due to symptomatic, behavioral, and financial consequences of surgery. CONCLUSION While relevant clinical and institutional approaches are required for corresponding declines in QoL, such efforts must extend beyond 5 postoperative years.

Laparoscopy Assisted versus Open Distal Gastrectomy with D2 Lymph Node Dissection for Advanced Gastric Cancer: Design and Rationale of a Phase II Randomized Controlled Multicenter Trial (COACT 1001)

Purpose Laparoscopy-assisted distal gastrectomy for early gastric cancer has gained acceptance and popularity worldwide. However, laparoscopy-assisted distal gastrectomy for advanced gastric cancer is still controversial. Therefore, we propose this prospective randomized controlled multi-center trial in order to evaluate the safety and feasibility of laparoscopy assisted D2-gastrectomy for advanced stage gastric cancer. Materials and Methods Patients undergoing distal gastrectomy for advanced gastric cancer staged cT2/3/4 cN0/1/2/3a cM0 by endoscopy and computed tomography are eligible for enrollment after giving their informed consent. Patients will be randomized either to laparoscopy-assisted distal gastrectomy or open distal gastrectomy. Sample size calculation revealed that 102 patients are to be included per treatment arm. The primary endpoint is the non-compliance rate of D2 dissection; relevant secondary endpoints are three-year disease free survival, surgical and postoperative complications, hospital stay and unanimity rate of D2 dissection evaluated by reviewing the intraoperative video documentation. Discussion Oncologic safety is the major concern regarding laparoscopy-assisted distal gastrectomy for advanced gastric cancer. Therefore, the non-compliance rate of clearing the N2 area was chosen as the most important parameter for the technical feasibility of the laparoscopic procedure. Furthermore, surgical quality will be carefully reviewed, that is, three independent experts will review the video records and score with a check list. For a long-term result, disease free survival is considered a secondary endpoint for this trial. This study will offer promising evidence of the feasibility and safety of Laparoscopy-assisted distal gastrectomy for advanced gastric cancer.Trial Registration: NCT01088204 (international), NCCCTS-09-448 (Korea).

Recent advances in chemotherapy for advanced gastric cancer.

Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the choice of optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration, with a median survival of approximately 7-11 mo and survival at 2 years rarely more than 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, several molecular targeting agents are now under evaluation in international randomized studies, and trastuzumab, an anti-HER2 monoclonal antibody, has shown antitumor activity against HER-2 positive AGC. However, this benefit is limited to only about 20% of patients with AGC (patients with HER-2 positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of predictive and prognostic molecular markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.