MPI-GWAS: a supercomputing-aided permutation approach for genome-wide association studies

Permutation testing is a robust and popular approach for significance testing in genomic research that has the advantage of reducing inflated type 1 error rates; however, its compu-tational cost is notorious in genome-wide association studies (GWAS). Here, we developed a supercomputing-aided approach to accelerate the permutation testing for GWAS, based on the message-passing interface (MPI) on parallel computing architecture. Our application, called MPI-GWAS, conducts MPI-based permutation testing using a parallel computing approach with our supercomputing system, Nurion (8,305 compute nodes, and 563,740 central processing units [CPUs]). For 107 permutations of one locus in MPI-GWAS, it was calculated in 600 s using 2,720 CPU cores. For 107 permutations of ~30,000–50,000 loci in over 7,000 subjects, the total elapsed time was ~4 days in the Nurion supercomputer. Thus, MPI-GWAS enables us to feasibly compute the permutation-based GWAS within a reason-able time by harnessing the power of parallel computing resources.

Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. @*Results@#The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity. @*Results@#The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

The prognostic value of postoperative tumor marker conversion for gastric cancer

Purpose@#Preoperative positivity of serum tumor markers has been associated with poor long-term survival among patients with gastric cancer. However, there have been a considerable number of patients who have experienced a normalization of tumor markers (negative conversion) after curative treatment. This study aimed to evaluate the correlation between postoperative tumor marker conversion and survival after gastrectomy among gastric carcinoma patients. @*Methods@#We analyzed the clinical data of 129 patients who underwent curative gastrectomy with elevated preoperative carcinoembryonic antigen or carbohydrate antigen 19-9 between January 2009 and December 2013. @*Results@#Positive tumor markers converted to negative markers 6 months after surgery in 91 patients (70.5%). The patients with a negative conversion of tumor markers had significantly better outcomes than those without negative conversion (overall survival [OS] 63.9 months vs. 41.1 months, P<0.001; disease-free survival [DFS] 59.3 months vs. 33.2 months, P<0.001). Multivariate analyses showed that tumor marker conversion and lymph node metastasis were independent predictors of OS and DFS. During follow-up, tumor markers became elevated again (positive reconversion) in 23 patients (25.3%), with a negative conversion of tumor markers at 6 months after gastrectomy. Among the patients with a positive reconversion of tumor markers, gastric cancer recurred in 18 patients (78.3%). @*Conclusion@#Negative tumor marker conversion after curative gastrectomy strongly predicts a better prognosis. Patients without negative tumor marker conversion and those with positive reconversion after normalization should be carefully monitored because of the high possibility of recurrence.

Chronological changes in quality of life and body composition after gastrectomy for locally advanced gastric cancer

Purpose@#We evaluated the changes in body composition (BC) and quality of life (QoL) in patients who underwent gastrectomy for advanced gastric cancer. @*Methods@#BC data using segmental multifrequency bioelectrical impedance analysis and QoL data from the EORTC (European Organisation for the Research and Treatment of Cancer) gathered via QLQ-C30 and QLQ-STO22 questionnaires were obtained from 300 patients preoperatively and at 1, 2, and 3 years after surgery. In total, 114 patients underwent total gastrectomy (TG group) and 186 underwent distal gastrectomy (DG group). @*Results@#According to BC analysis, at 3 years postoperatively, the average body weight (P = 0.002), protein mass (P = 0.028), body fat mass (P = 0.009), skeletal muscle mass (P = 0.037), and visceral fat area (P = 0.012) was significantly decreased in the TG group than in the DG group compared to the preoperative. In the QLQ-C30, physical functioning (P = 0.001), role functioning (P = 0.013), and fatigue (P = 0.005) showed significantly worse QoL in the TG group than in the DG group at 2 and 3 years postoperatively. In the QLQ-STO22, pain (P = 0.001), reflux symptoms (P = 0.009), eating restrictions (P = 0.001), anxiety (P = 0.008), taste (P = 0.011), and body image (P = 0.014) showed greater continuous deterioration postoperatively in the TG group than in the DG group. @*Conclusion@#Persistent deterioration of BC and QoL is a serious concern following total gastrectomy. Long-term management of BC is required after gastrectomy and efforts should be made to improve the QoL in patients as soon as possible, postoperatively.

Advantages of Distal Subtotal Gastrectomy over Total Gastrectomy in the Quality of Life of Long-Term Gastric Cancer Survivors

Purpose@#This study evaluated differences and shifting patterns in the health-related quality of life (HRQoL) of 5-year gastric cancer survivors after either a distal subtotal gastrectomy (DSG) or total gastrectomy (TG). @*Materials and Methods@#We analyzed the prospectively collected HRQoL data of 528 patients who survived 5 years without recurrence using the European Organization for the Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Quality of Life Questionnaire-Stomach module according to the type of surgery. The purpose was to identify the proportion of patients with deteriorating HRQoL and to assess the clinical significance of these changes. @*Results@#Deteriorating HRQoL was prevalent in both groups, including a large proportion of the DSG group. Decreased overall health status and scores on several function scales were less in the DSG group, while increases on the symptom scales were higher in the TG group. For most of the scales, gaps in HRQoL during the early postoperative period did not merge within the 5 years. Scores on the diarrhea and body image scales revealed “moderate changes” in both groups. @*Conclusions@#During the 5-year period after surgery, the TG group suffered from inferior HRQoL compared to the DSG group. However, a large proportion of the DSG group also suffered HRQoL deterioration. In general, the TG group experienced more HRQoL decline, with diarrhea and body image being the major concerns for both groups. To improve HRQoL after gastrectomy, patients must be better informed about post-gastrectomy symptoms. These symptoms must be vigorously investigated, and medical interventions should be available parallel to nutritional support. Favorable evidence of function-preserving gastrectomy should be established and disseminated to improve the HRQoL of early gastric cancer patients.

Information-Stressors and Cancer Patients’ Quality of Life: Responses to Deviant Information-Stressors Due to Pre-Postoperative Stage Discordance / 전남의대학술지

This study assessed preoperative quality of life (QoL) of gastric cancer patients exposed to inconsistent illness information by pre-post-operative stage discordance. The impact of information-stressors on patients’ QoL was investigated to determine information processing as a potential target for QoL management. Early-stage gastric cancer (EsGC) and late-stage gastric cancer (LsGC) groups based on their final stage were categorized by the consistency of preoperative staging information that was being shared. Those with consistent preoperative staging information were rated as EsGC (n=1,420) and LsGC (n=153) controls. EsGC and LsGC patients with misdirected information about their LsGC and EsGC were categorized as EsGC/iLsGC (n=32) and LsGC/iEsGC (n=55), respectively. Preoperative QoL data was obtained using EORTC QLQ-C30 and -STO22. QoL outcomes of EsGC/iLsGC and LsGC/iEsGC were compared with those of the EsGC and LsGC controls. QoL outcomes of the EsGC/iLsGC group matched that of EsGC control, but were significantly better than those of LsGC control on multiple scales including global health status/QoL, physical/role/social-functioning, and ten symptom scales/items. On the other hand, QoL outcomes of LsGC/iEsGC group were significantly better than those of LsGC control on multiple scales (global health status/ QoL, physical/role-functioning, and nine symptom scales/items) while they roughly matched with those of EsGC control. Intensified information-stressors did not exacerbate QoL beyond the influence of the patients’ medical condition, while de-intensified information-stressor improved QoL. Fear of negatively impacting QoL should not prevent the sharing of stressful illness information. As the de-intensified information- stressor improves QoL, information processing is recommended as a potential target for QoL management in cancer patients.

The prognostic value of postoperative tumor marker conversion for gastric cancer

Purpose@#Preoperative positivity of serum tumor markers has been associated with poor long-term survival among patients with gastric cancer. However, there have been a considerable number of patients who have experienced a normalization of tumor markers (negative conversion) after curative treatment. This study aimed to evaluate the correlation between postoperative tumor marker conversion and survival after gastrectomy among gastric carcinoma patients. @*Methods@#We analyzed the clinical data of 129 patients who underwent curative gastrectomy with elevated preoperative carcinoembryonic antigen or carbohydrate antigen 19-9 between January 2009 and December 2013. @*Results@#Positive tumor markers converted to negative markers 6 months after surgery in 91 patients (70.5%). The patients with a negative conversion of tumor markers had significantly better outcomes than those without negative conversion (overall survival [OS] 63.9 months vs. 41.1 months, P<0.001; disease-free survival [DFS] 59.3 months vs. 33.2 months, P<0.001). Multivariate analyses showed that tumor marker conversion and lymph node metastasis were independent predictors of OS and DFS. During follow-up, tumor markers became elevated again (positive reconversion) in 23 patients (25.3%), with a negative conversion of tumor markers at 6 months after gastrectomy. Among the patients with a positive reconversion of tumor markers, gastric cancer recurred in 18 patients (78.3%). @*Conclusion@#Negative tumor marker conversion after curative gastrectomy strongly predicts a better prognosis. Patients without negative tumor marker conversion and those with positive reconversion after normalization should be carefully monitored because of the high possibility of recurrence.

Chronological changes in quality of life and body composition after gastrectomy for locally advanced gastric cancer

Purpose@#We evaluated the changes in body composition (BC) and quality of life (QoL) in patients who underwent gastrectomy for advanced gastric cancer. @*Methods@#BC data using segmental multifrequency bioelectrical impedance analysis and QoL data from the EORTC (European Organisation for the Research and Treatment of Cancer) gathered via QLQ-C30 and QLQ-STO22 questionnaires were obtained from 300 patients preoperatively and at 1, 2, and 3 years after surgery. In total, 114 patients underwent total gastrectomy (TG group) and 186 underwent distal gastrectomy (DG group). @*Results@#According to BC analysis, at 3 years postoperatively, the average body weight (P = 0.002), protein mass (P = 0.028), body fat mass (P = 0.009), skeletal muscle mass (P = 0.037), and visceral fat area (P = 0.012) was significantly decreased in the TG group than in the DG group compared to the preoperative. In the QLQ-C30, physical functioning (P = 0.001), role functioning (P = 0.013), and fatigue (P = 0.005) showed significantly worse QoL in the TG group than in the DG group at 2 and 3 years postoperatively. In the QLQ-STO22, pain (P = 0.001), reflux symptoms (P = 0.009), eating restrictions (P = 0.001), anxiety (P = 0.008), taste (P = 0.011), and body image (P = 0.014) showed greater continuous deterioration postoperatively in the TG group than in the DG group. @*Conclusion@#Persistent deterioration of BC and QoL is a serious concern following total gastrectomy. Long-term management of BC is required after gastrectomy and efforts should be made to improve the QoL in patients as soon as possible, postoperatively.

Impact of body mass index on quality of life after distal gastrectomy for gastric cancer

PURPOSE: Few studies have evaluated changes in quality of life (QoL) in relation to changes in body mass index (BMI) after gastrectomy. This study aimed to evaluate the impact of postoperative changes in BMI on QoL after distal gastrectomy in gastric cancer patients. METHODS: QoL data from the European Organization for the Research and Treatment of Cancer (EORTC) gathered via the QLQ-C30 and QLQ-STO22 questionnaires were obtained from 1,036 patients preoperatively and at 1 year postoperatively. The patients were divided into 2 groups: group 1 - decreased postoperative BMI and group 2 - unchanged or increased postoperative BMI. RESULTS: There were 577 patients in group 1 and 459 in group 2. According to global health status and functional scales, emotional functioning (P = 0.035) was significantly worse in group 1 than in group 2 at 1 year postoperatively. Furthermore, there were significant decreases in QoL symptom scale scores, including fatigue (P = 0.016), nausea and vomiting (P = 0.002), and appetite loss (P = 0.001) scores, in group 1 compared with group 2. Regarding QLQ-STO22, reflux symptoms (P = 0.020), anxiety (P = 0.003), and body image (P = 0.003) were significantly worse in group 1 than in group 2 at 1 year after surgery. CONCLUSION: BMI changes after distal gastrectomy influence QoL. Focus on controlling gastrointestinal symptoms and providing psychological support is essential in patients with decreased BMI after surgery. Patients should be offered follow-up care to assist them in maintaining BMI, for example, through dietary-behavior modifications and via intensive nutritional support, to prevent QoL deterioration after distal gastrectomy.

Actual compliance to adjuvant chemotherapy in gastric cancer

PURPOSE: This study aims to investigate the actual compliance with chemotherapy and analyze several factors affecting the compliance in patients with gastric cancer. METHODS: From February 2012 to December 2014, we collected data of patients with gastric cancer who received adjuvant chemotherapy (TS-1 monotherapy or XELOX: capecitabine/oxaliplatin) in Korea. RESULTS: We collected data of 1,089 patients from 31 institutions. The completion rate and dose reduction rate by age (≥60 years vs. <60 years) were 57.5% vs. 76.8% (P < 0.001) and 17.9% vs. 21.3% (P = 0.354); by body mass index (BMI) (≥23 kg/m2 vs. <23 kg/m2) were 70.2% vs. 63.2% (P = 0.019) and 19.2% vs. 19.9% (P = 0.987), respectively. The compliance by American Society of Anesthesiologists physical status (ASA PS) classification was as follows: completion rate was 74.4%, 62.8%, and 60% (P = 0.001) and the dose reduction rate was 18.4%, 20.7%, and 17.8% (P = 0.946) in ASA PS classification I, II, and III, respectively. The completion rate of TS-1 and XELOX was 65.9% vs. 70.3% (P = 0.206) and the dose reduction rate was 15.7% vs. 33.6% (P < 0.001). Furthermore, the completion rate of chemotherapy by surgical oncologists and medical oncologists was 69.5% vs. 63.2% (P = 0.028) and the dose reduction rate was 17.4% vs. 22.3% (P = 0.035), respectively. CONCLUSION: The compliance was lower in patients who were older than 60 years, had BMI <23 kg/m2, and had higher ASA PS classification. Furthermore, the patients showed higher compliance when they received chemotherapy from surgical oncologists rather than from medical oncologists.

Bioelectrical Impedance Analysis for Prediction of Early Complications after Gastrectomy in Elderly Patients with Gastric Cancer: the Phase Angle Measured Using Bioelectrical Impedance Analysis

PURPOSE: Phase angle obtained using bioelectrical impedance analysis (BIA) provides a relatively precise assessment of the nutritional status of elderly patients. This study aimed to evaluate the significance of phase angle as a risk factor for complications after gastrectomy in elderly patients. MATERIALS AND METHODS: We evaluated 210 elderly patients (aged ≥65 years) who had undergone gastrectomy for gastric cancer between August 2016 and August 2017. The phase angle cutoff value was calculated using receiver operating characteristic curve analysis according to sex. A retrospective analysis regarding the correlation between early postoperative complications and well-known risk factors, including the phase angle, was performed. RESULTS: Multivariate analysis revealed that the presence of two or more comorbidities (odds ratio [OR], 3.675) and hypoalbuminemia (OR, 4.059) were independent risk factors for overall complications, and female sex (OR, 2.993) was independent risk factor for severe complications. A low phase angle (OR, 2.901 and 4.348, respectively) and total gastrectomy (OR, 4.718 and 3.473, respectively) were independent risk factors for both overall and severe complications. CONCLUSIONS: Our findings show that preoperative low phase angle predicts the risk of overall and severe complications. Our findings suggest that BIA should be performed to assess the risk of postoperative complications in elderly patients with gastric cancer.

Midterm body composition changes after open distal gastrectomy for early gastric cancer

PURPOSE: This study evaluated midterm changes in body composition after open distal gastrectomy for early gastric cancer. METHODS: Data from 138 gastric cancer patients who underwent open distal gastrectomy at Kyungpook National University Chilgok Hospital between January 2011 and December 2012 were collected and reviewed. Patients with pathological stage I gastric cancer and with no comorbidities at diagnosis were enrolled. Body composition data from segmental multifrequency bioelectrical impedance analysis were obtained preoperatively and at 1, 2, and 3 years after surgery. RESULTS: The mean body weight losses at 1 and 3 years after surgery were 6.1 kg and 5.8 kg, respectively (P < 0.001). The protein mass, skeletal muscle mass, and fat-free mass decreased continuously until 3 years after surgery (0.5 kg, 1.6 kg, and 2.4 kg, respectively; P < 0.001). The average body fat mass and visceral fat area loss at 1 year after surgery were 4.7 kg and 20.5 cm2, respectively (P < 0.001). After 1 postoperative year, the body fat mass and visceral fat areas increased continuously, up to 12.2 kg and 74.2 cm2 at 3 years after surgery, respectively (+1.4 kg and +1.2 cm2, respectively). CONCLUSION: More intense nutritional and exercise programs may be important after gastric cancer surgery, especially during the first postoperative year.

Impact of Body Mass Index on the Quality of Life after Total Gastrectomy for Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the impact of postoperative body mass index (BMI) shifts on the quality of life (QoL) following total gastrectomy in patients with gastric cancer. MATERIALS AND METHODS: QoL data collected from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and QLQ-STO22 questionnaires were obtained from 417 patients preoperatively and 1 year after surgery. Patients were divided into two groups based on changes in BMI: group 1 comprised patientswhose BMIrange category dropped, and group 2 included patients who maintained or rose to a higher category compared to their preoperative BMI category. RESULTS: There were 276 patients in group 1 and 141 in group 2. QoLs with respect to the global health status and functional scales were not significantly different between the groups 1 year after surgery. However, there were significantly greater decreases in QoL in group 1 due to gastrointestinal symptoms, such as nausea and vomiting (p=0.008), appetite loss (p=0.001), and constipation (p=0.038). Of the QLQ-STO22 parameters, dysphagia (p=0.013), pain (p=0.012), reflux symptoms (p=0.017), eating restrictions (p=0.007), taste (p=0.009), and body image (p=0.009) were associated with significantly worse QoL in group 1 than in group 2 1 year after surgery. CONCLUSION: Patients have significantly different QoLs depending on the BMI shift after total gastrectomy. Efforts to reduce the gap in QoL should include intensive nutritional support and restoration of dietary behaviors. Appropriate clinical and institutional approaches, plus active medical interventions, are required for maintaining patients’ BMIs after surgery.

Chronological Changes in Quality of Life after Distal Gastrectomy for Gastric Cancer

PURPOSE: Patient quality of life (QoL) may be severely disrupted following distal gastrectomy for gastric cancer. This issue should be addressed to improve postoperative care. MATERIALS AND METHODS: QoL data from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and its gastric cancer-specific module, were administered to 202 patients preoperatively, and 5 years postoperatively. Patients were classified into subgroups based on their answers to each questionnaire item: group I (good), answering “not at all”; group II (fair), answering “a little”; group III (poor), answering “quite a bit” or “very much.” RESULTS: At 5 years post-operation, the proportion of patients in group III on the functional scales ranged from 4.3% to 5.7%. The proportions of patients in group III with fatigue, insomnia, diarrhea, and financial difficulties were 8.9%, 9.0%, 11.5%, and 9.1%, respectively. The proportions of patients in group III with anxiety, dry mouth, body image concerns, and hair loss were 12.8%, 10.5%, 9.9%, and 12.6%, respectively. These proportions were less than 5% for other QoL symptom scales/items and for the gastric cancer-specific module. CONCLUSIONS: Most patients reported good or fair QoL following surgery. However, symptom management of fatigue, insomnia, diarrhea, anxiety, dry mouth, body image, and hair loss should be specifically targeted for long-term patient care in approximately 10% of patients.

Using Quality of Life Scales with Nutritional Relevance after Gastrectomy: a Challenge for Providing Personalized Treatment

PURPOSE: This study evaluated the changes in nutritional status based on quality of life (QoL) item-level analysis to determine whether individual QoL responses might facilitate personal clinical impact. MATERIALS AND METHODS: This study retrospectively evaluated QoL data obtained by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Stomach (QLQ-STO22) as well as metabolic-nutritional data obtained by bioelectrical impedance analysis and blood tests. Patients were assessed preoperatively and at the 5-year follow-up. QoL was analyzed at the level of the constituent items. The patients were categorized into vulnerable and non-vulnerable QoL groups for each scale based on their responses to the QoL items and changes in the metabolic-nutritional indices were compared. RESULTS: Multiple shortcomings in the metabolic-nutritional indices were observed in the vulnerable groups for nausea/vomiting (waist-hip ratio, degree of obesity), dyspnea (hemoglobin, iron), constipation (body fat mass, percent body fat), dysphagia (body fat mass, percent body fat), reflux (body weight, hemoglobin), dry mouth (percent body fat, waist-hip ratio), and taste (body weight, total body water, soft lean mass, body fat mass). The shortcomings in a single index were observed in the vulnerable groups for emotional functioning and pain (EORTC QLQ-C30) and for eating restrictions (EORTC QLQ-STO22). CONCLUSIONS: Long-term postoperative QoL deterioration in emotional functioning, nausea/vomiting, pain, dyspnea, constipation, dysphagia, reflux, eating restrictions, dry mouth, and taste were associated with nutritional shortcomings. QoL item-level analysis, instead of scale-level analysis, may help to facilitate personalized treatment for individual QoL respondents.

Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer / 전남의대학술지

This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 patients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC.

A Survival Analysis of Gastric or Colorectal Cancer Patients Treated With Surgery: Comparison of Capital and a Non-capital City / 예방의학회지

OBJECTIVES: The objective of the present study was to compare prognosis of patients with gastric or colorectal cancer according to places where they received surgeries. METHODS: The cancer patients underwent surgeries in sampled hospitals located in Daegu were matched 1:1 to the patients who visited sampled hospitals in Seoul using propensity score method. After the occurrences of death were examined, Kaplan-Meier method was used for survival analysis and the log-rank test was performed to compare the survival curves. RESULTS: A total of six out of 291 gastric cancer patients who had surgeries in Daegu died (2.1%) and ten deaths (3.4%) occurred from patients went Seoul hospitals. Out of 84 gastric cancer patients who had chemotherapy after surgeries in Daegu, 13 (15.5%) patients died while 18 (21.4%) deaths occurred among patients underwent surgeries in Seoul. Six deaths (6.9%) out of 87 colorectal cancer patients who had surgeries in Daegu were reported. Five patients (5.7%) died among the patients underwent surgeries in Seoul. Among the colorectal cancer patients with chemotherapy after surgeries, 13 patients (12.4%) who visited hospitals in Daegu and 14 (13.3%) patients who used medical centers in Seoul died. There were no significant differences according to places where patients used medical services. CONCLUSIONS: The result of this study is expected to be used as basic data for policy making to resolve centralization problem of cancer patients and to help patients to make rational choices in selection of medical centers.

Clinical Significance of p53 Protein Expression, Beta-catenin Expression and HER2 Expression for Epstein-Barr Virus-associated Gastric Cancer / 전남의대학술지

This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 patients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC.

Validation of the 7th AJCC/UICC staging system for gastric cancer and a proposal for a new TNM system based on a prognostic score: a retrospective multicenter study

PURPOSE: We validate the 7th American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system for gastric cancer and propose a new staging system that reflects the prognostic significances of each of T and N category. METHODS: Data from 5,957 patients who underwent curative gastrectomies from 2000 to 2007 at 4 university hospitals in Daegu Metropolitan city in Korea were analyzed for the validation of the 7th AJCC/UICC staging system for gastric cancer. The hazard ratios of the respective T and N categories were estimated and converted to weightings and summated to make prognostic score (P-score). Homogeneity and stage grouping were determined according to the P-scores. RESULTS: In the 7th AJCC/UICC staging system for gastric cancer, poor discrimination was noted between stages IIB and IIIA (P = 0.152). In addition, heterogeneity in stage IIB (P = 0.021) and a small gap in 5-year survival rates (1.7%) between stages IA and IB were noted. A new proposed staging system was generated on the basis of P-scores and demonstrated more discrimination between stages and more homogeneity within stages. The new staging system reflects the different prognostic impacts of N3a and N3b. CONCLUSION: Several controversial issues of the 7th AJCC/UICC staging system for gastric cancer were reconfirmed in the present analysis. The TNM system based on P-score appears to be more scientifically accurate than the 7th AJCC/UICC staging system for gastric cancer.