Laparoscopy-assisted versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: Results From a Randomized Phase II Multicenter Clinical Trial (COACT 1001).

OBJECTIVE: This randomized, phase II, multicenter clinical trial was conducted to evaluate the feasibility of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection compared with open distal gastrectomy (ODG) for the treatment of advanced gastric cancer (AGC). SUMMARY OF BACKGROUND DATA: D2 lymph node dissection has been accepted as standard treatment for AGC. Although LADG is widely performed in early gastric cancer (EGC), the feasibility of LADG in AGC has not been proven yet. METHODS: Patients with cT2-T4a and cN0-2 (AJCC 7 staging system) distal gastric cancer were randomly but not blindingly assigned to LADG or ODG groups using fixed block sizes with a 1:1 allocation ratio. The primary endpoint was the noncompliance rate of the lymph node dissection, which was used to evaluate feasibility. Secondary endpoints included 3-year disease-free survival (DFS), 5-year overall survival, complications, and surgical stress response. RESULTS: Between June 2010 and October 2011, 204 patients enrolled and underwent either LADG (n = 105) or ODG (n = 99). Of these, 196 patients (100 in LADG and 96 in ODG) were included in the intention-to-treat analysis. There were no significant differences in the overall noncompliance rate of lymph node dissection between LADG and ODG groups (47.0% and 43.2%, respectively; P = 0.648). In the subgroup analysis, the noncompliance rate in the LADG group was significantly higher than the ODG group for clinical stage III disease (52.0% vs 25.0%, P = 0.043). No difference was found in the 3-year DFS rate between the groups (LADG, 80.1%; ODG, 81.9%; P = 0.448). Differences in postoperative complication rates and surgical stress response were found to be insignificant between the 2 arms. CONCLUSIONS: LADG was feasible for AGC treatment based on the noncompliance rate of D2 lymph node dissection. Subgroups analysis data suggest that further studies are needed for stage III gastric cancer.

Intratumoural PD-L1 expression is associated with worse survival of patients with Epstein-Barr virus-associated gastric cancer.

BACKGROUND: This study investigated the clinical relevance and prognostic impact of the overall expression of programmed cell death protein ligand-1 (PD-L1) and programmed cell death protein ligand-2 (PD-L2), in patients with Epstein-Barr virus-associated gastric cancer (EBVaGC). METHODS: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with EBVaGC identified by EBV-encoded RNA in situ hybridisation was retrospectively analysed using immunohistochemistry (IHC). For each IHC marker, positivity was separately in intraepithelial tumour cells (iTu-) and immune cells in the tumour stroma area (str-). RESULTS: Among 116 eligible patients, 57 (49.1%) and 66 patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive, respectively, whereas 23 (21.6%) and 45 patients (38.8%) were determined as iTu-PD-L2 positive and str-PD-L2 positive, respectively. Intraepithelial tumour cell PD-L1 positivity was found to be significantly associated with lymph node (LN) metastasis (P=0.012) and a poor disease-free survival (DFS) (P=0.032), yet not overall survival (P=0.482). In a multivariate analysis, iTu-PD-L1 positivity was independently associated with a poor DFS (P=0.006, hazard ratio=12.085). In contrast, str-PD-L2-positivity was related to a lower T category (P=0.003), absence of LN metastasis (P=0.032) and perineural invasion (P=0.028). Intraepithelial tumour cell and str-PD-L2 positivity showed a trend towards an improved DFS, although not significant (P=0.060 and P=0.073, respectively). CONCLUSIONS: Intraepithelial tumour cells PD-L1 expression can be used to predict a poor outcome in patients with EBVaGC and can represent a rational approach for PD-1/PD-L pathway-targeted immunotherapy.

Effect of Intravenous Ferric Carboxymaltose on Hemoglobin Response Among Patients With Acute Isovolemic Anemia Following Gastrectomy: The FAIRY Randomized Clinical Trial.

IMPORTANCE: Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes. OBJECTIVE: To evaluate the efficacy and safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy. DESIGN, SETTING, AND PARTICIPANTS: The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included. INTERVENTIONS: Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients). MAIN OUTCOMES AND MEASURES: The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12. RESULTS: Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% [200 patients] for the ferric carboxymaltose group vs 54.0% [115 patients] for the placebo group; absolute difference, 38.2% [95% CI, 33.6%-42.8%]; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL [95% CI, 150.2-209.5]; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% [95% CI, 13.1%-18.3%]; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% [95% CI, 3.3%-7.6%]; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients [6.8%], including injection site reactions [5 patients] and urticaria [5 patients]) than the placebo group (1 patient [0.4%]), but no severe adverse events were reported in either group. CONCLUSION AND RELEVANCE: Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01725789.

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.

Body composition changes after totally laparoscopic distal gastrectomy with delta-shaped anastomosis: a comparison with conventional Billroth I anastomosis.

BACKGROUND: The purpose of this study was to compare body composition changes of patients undergoing totally laparoscopic distal gastrectomy (TLDG) with delta-shaped anastomosis (DSA) versus conventional laparoscopic distal gastrectomy (CLDG). METHODS: Data from gastric cancer patients who underwent laparoscopic distal gastrectomy for histologically proven gastric cancer in KNUMC from January 2013 to May 2014 were collected and reviewed. We examined 85 consecutive patients undergoing TLDG or CLDG: 41 patients underwent TLDG and 44 patients underwent CLDG. Body composition was assessed by segmental multifrequency bioelectrical impedance analysis. We compared the changes in nutritional parameters and body composition from preoperative status between the two groups at postoperative 6 and 12 months. RESULTS: All of the postoperative changes in the body composition and nutritional indices were similar between the two groups with the exception of visceral fat areas (VFAs) and albumin levels. VFAs increased at 6 months postoperatively in the TLDG group and a significant difference was shown at 12 months postoperatively between the TLDG and CLDG groups (86.7 ± 22.8 and 74.7 ± 21.9 cm(2), respectively, P < 0.05). Postoperative albumin levels were higher in the TLDG group with statistical significance at 6 and 12 months after surgery (6 months, P = 0.028; 12 months, P = 0.012). CONCLUSIONS: The influence of TLDG with DSA on nutrition and body composition seemed comparable to those of CLDG. Six months postoperatively, VFAs and albumin levels were recovered in the TLDG group but not in the CLDG group. Thus, TLDG seems to be a novel surgical method.

Taxanes in the Treatment of Advanced Gastric Cancer.

Although rapid advances in treatment options have improved the prognosis of advanced gastric cancer (AGC), it remains a major public health problem and the second leading cause of cancer-related deaths in the world. Taxanes (paclitaxel and docetaxel) are microtubule stabilizing agents that inhibit the process of cell division, and have shown antitumor activity in the treatment of AGC as a single or combination chemotherapy. Accordingly, this review focuses on the efficacy and tolerability of taxanes in the first- or second-line chemotherapy setting for AGC.

Long-term Shifting Patterns in Quality of Life After Distal Subtotal Gastrectomy: Preoperative- and Healthy-based Interpretations.

OBJECTIVE: The study assessed long-term shifting patterns in quality of life (QoL) after distal subtotal gastrectomy relative to an estimated healthy population QoL (HPQoL), and compared them to shifting patterns interpreted in terms of a preoperative QoL baseline. BACKGROUND: QoL data from 127 gastric cancer patients who underwent open distal subtotal gastrectomy were obtained at the preoperative period and at 6, 12, 18, 24, and 36 months after surgery. QoL data obtained from 127 age- and sex-adjusted healthy individuals were used to estimate HPQoL. METHODS: The study used the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) and a gastric cancer module (QLQ-STO22) to assess QoL. Comparisons were made between preoperative-based and healthy-based interpretations of longitudinal QoL shifting patterns. RESULTS: Among the persistently deteriorated QoL variables indicated by the preoperative-based interpretation (physical functioning, role functioning, cognitive functioning, nausea and vomiting, dyspnea, diarrhea, dysphagia, eating restrictions, dry mouth, and body image), eating restrictions and body image concerns were the only factors indicated by a healthy-based interpretation. In this interpretation, financial difficulties were evident at the preoperative period and persisted for at least 36 months. When preoperative QoL was used as a baseline, decreased QoL due to financial difficulties was not revealed. CONCLUSIONS: Persistent QoL deterioration after distal subtotal gastrectomy is primarily due to financial difficulties, eating restrictions, and body image concerns. Preoperative-based interpretation of postoperative QoL may exaggerate the persistency of reduced QoL and conceal on-going QoL deterioration after surgery.

Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial.

BACKGROUND: The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. METHODS: CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II-IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m(2) twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m(2) on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov, NCT00411229. FINDINGS: We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54-70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio [HR] 0·58, 95% CI 0·47-0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63-73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47-58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51-0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74-82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64-73) in the observation group. Adverse event data were not collected after the primary analysis. INTERPRETATION: Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer. FUNDING: F Hoffmann La-Roche and Sanofi.

Prognostic value of postoperative CA19-9 normalization in patients with advanced gastric cancer.

BACKGROUND/AIMS: CA19-9 is known to have positive correlation with depth of invasion, nodal involvement, and peritoneal metastasis in gastric adenocarcinoma. In patients with high preoperative CA19-9 serum levels who underwent curative gastrectomy, we evaluated the prognostic impact of postoperative normalization of CA 19-9. METHODOLOGY: Among 1,439 patients who underwent curative gastrectomy for advanced gastric adenocarcinoma, data of 102 patients with advanced gastric adenocarcinoma whose preoperative serum CA19-9 level was higher than cutoff value (37 U/mL) were reviewed. If serum CA19-9 level had fallen below 37 U/mL at 6 months after surgery, the CA19-9 level was considered normalized. RESULTS: CA19-9 levels were normalized in 79 patients but not in 23 patients. There were statistically significant differences in prognosis according to depth of invasion, presence of lymph node metastasis, extent of gastric resection, and postoperative CA19-9 normalization on univariate analyses. Multivariate analysis revealed that pathological lymph node metastasis (p<0.001) and postoperative CA19-9 normalization were independent prognostic factors (p=0.001). CONCLUSIONS: In patients with advanced gastric adenocarcinoma who underwent curative gastric resection, postoperative normalization of CA19-9 can be a surrogate for potentially curative surgical treatment and can be used as a good prognostic factor.

Pilot study of adjuvant chemotherapy with 3-week combination of S-1 and cisplatin for patients with stage II-IV (M0) gastric cancer.

PURPOSE: The feasibility of a 3-week combination of S-1 and cisplatin as an adjuvant chemotherapy for patients with curatively resected gastric cancer was investigated. EXPERIMENTAL DESIGN: Korean patients with stage II-IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection were enrolled. The S-1 was administered orally at 80 mg/m(2) divided into two daily doses for 14 days, while the cisplatin was administered at 60 mg/m(2) intravenously over 2 h every 21 days. The patients received a maximum of six cycles. RESULTS: From January 2006 to July 2010, 74 patients were included in this study. The median patient age was 56 years (range, 22-71), and 51.4% (38/74) of the patients had a performance status of 0. The median number of chemotherapy cycles administered was 6 (range, 1-6). The median relative dose intensity was 86.4% for S-1 and 80.0% for cisplatin. With a median follow-up duration of 13.9 months, the median relapse-free survival (RFS) and overall survival (OS) have not yet been reached. Fifteen relapses (20.3%) were documented. Plus, the estimated RFS rate was 60.5% at 3 years. The treatments were generally well tolerated. The most frequently observed grade 3-4 hematological toxicity was neutropenia (35.1%), and only 1 cycle of neutropenic fever occurred. The most frequently observed grade 3-4 non-hematological toxicities were nausea (4.1%) and asthenia (4.1%), and all the other grade 3-4 non-hematological toxicities were observed in less than 3% of the patients. CONCLUSIONS: Postoperative adjuvant S-1 plus cisplatin for 18 weeks was found to be feasible for patients with stage II-IV (M0) gastric adenocarcinoma following complete surgical resection.

General perioperative management of gastric cancer patients at high-volume centers.

BACKGROUND: Gastric cancer is very common in Korea and Japan, where many hospitals annually perform high numbers of gastrectomies for gastric cancer. The aim of this study was to compare the general management of gastric cancer in high-volume centers in Korea and Japan. METHODS: We undertook a survey of the general management of gastric cancer at high-volume centers (over 200 cases/year) and analyzed the answers. RESULTS: In six of 14 hospitals surveyed, antimicrobial prophylaxis for elective gastrectomy was administered until postoperative day 3. A Levin tube and an abdominal drain were routinely inserted in seven and ten hospitals, respectively. Laboratory tests, such as complete blood cell count, liver function test, electrolytes, and blood urea nitrogen/creatinine were performed frequently on postoperative days 1, 2, 3, and 5. Sips of water after open distal gastrectomy were restarted up to postoperative day 3 in twelve hospitals. The surgical pathology was reported up to postoperative day 10 in thirteen hospitals. Twelve hospitals provided a regular patient education program and only one hospital provided an integrated education program which included the participation of a surgeon, an oncologist, a nurse, and a nutritionist. CONCLUSIONS: The general management of gastric cancer in 14 high-volume centers was not so different among the centers. The general management protocols noted here are expected to provide useful information for perioperative care.

Handsewn versus stapled gastroduodenostomy in patients with gastric cancer: long-term follow-up of a randomized clinical trial.

BACKGROUND: The role of circular staplers in gastroduodenostomy during subtotal gastrectomy for gastric cancer has not been defined clearly. METHODS: A randomized clinical trial included patients with gastric cancer who underwent subtotal gastrectomy with either stapled (99 patients) or handsewn gastroduodenostomy (98 patients). The anastomosis time and postoperative outcomes in the two groups were compared. RESULTS: Performance of stapled gastroduodenostomy was significantly quicker than handsewn gastroduodenostomy. There were no significant differences between the groups in postoperative course, morbidity and mortality rates, survival rate, and recurrence pattern. CONCLUSIONS: Stapled gastroduodenostomy with a circular stapler can reduce the anastomosis time with relative safety.

No association of the NFKB1 insertion/deletion promoter polymorphism with survival in patients with gastric cancer.

OBJECTIVE: The present study analyzed the functional insertion/deletion polymorphism in the promoter region of NFKB1 gene and their impact on the prognosis for patients with gastric adenocarcinoma. METHODS: Four hundred and seventy two consecutive patients with curatively resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and the -94 insertion/deletion ATTG polymorphism of NFKB1 determined using a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The NFKB1 promoter gene polymorphism was successfully amplified in 97.8% of the cases. There were no sexual differences in relation to the genotype and allele. No correlation was observed between the frequency of the genotype or allele and the T, N or M stage. The multivariate survival analysis showed no association between the NFKB1 -94 insertion/deletion promoter polymorphism and the disease-free survival or overall survival of the patients with gastric cancer. CONCLUSIONS: The functional NFKB1 promoter polymorphism was not found to be a prognostic marker for Korean patients with surgically resected gastric adenocarcinoma.

Localization of gastric cancer by CT gastrography: a prospective study.

BACKGROUND/AIMS: We evaluated the usefulness of CT gastrography in preoperative localization of gastric cancer. METHODOLOGY: CT gastrographic images of 213 patients with gastric cancer were evaluated for localization of tumor. For the precise localization we developed a software module to measure the shortest distances from tumor to the esophagogastric junction and to the pylorus on the images. After gastrectomy, these were compared with the shortest distances on surgical specimen. RESULTS: The localization rates of advanced and early gastric cancer were 100.0% and 88.8%, respectively. There were significantly linear relationship between the shortest distances measured on CT gastrographic images and those on surgical specimen. CONCLUSION: CT gastrography could be a useful preoperative localization tool.

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.

Exon 9 Mutation of PIK3CA Associated With Poor Survival in Patients With Epstein-Barr Virus-associated Gastric Cancer.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (GC) is known to harbor a significant enrichment of of phosphatidylinositol 4, 5-biphosphate 3- kinase catalytic subunit alpha isoform (PIK3CA). Therefore, this study investigated the clinical relevance and prognostic role of PIK3CA mutations in patients with EBV-GC. MATERIALS AND METHODS: After reviewing 1,318 consecutive cases of surgically resected GC, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. PIK3CA mutations were identified in formalin-fixed and paraffin-embedded surgical specimens from 112 patients with EBV-GC with available tumor tissue samples. Real-time polymerase chain reaction was used to evaluate hot-spot mutations of exons 1, 4, 7, 9, and 20 of PIK3CA. RESULTS: Among the 112 patients, the frequency of PIK3CA mutations was 25.0% (n=28), and among the 28 patients harboring a PIK3CA mutation, most mutations were identified in exon 9 (n=21, 18.8%). The presence of PIK3CA mutation was also correlated with a higher T category (p<0.001) and N category (p<0.001), as well as the presence of perinueral invasion (p<0.001) and venous invasion (p<0.001). In a univariate analysis, PIK3CA mutation showed no association with overall survival (OS) (p=0.184) or disease-free survival (DFS) (p=0.150). Patients harboring exon 9 PIK3CA mutations exhibited a significantly shorter OS (p=0.023) and DFS (p=0.013) than the patients lacking an exon 9 PIK3CA mutation, yet without statistical significance in the multivariate analysis. Notably, exon 9 E542K mutation of PIK3CA was associated with the worst DFS (p=0.011). CONCLUSION: The current data show that PIK3CA mutations appear to play an important role in carcinogenesis and tumor aggressiveness in EBV-GC, and also support the concept that exon 9 mutation of PIK3CA is a prognostic indicator for predicting patient outcomes and a rationale for therapeutic targeting in EBV-GC.

Clinical significance and prognostic role of hypoxia-induced microRNA 382 in gastric adenocarcinoma.

Hypoxia and angiogenesis are critical components in the progression of solid cancer, including gastric cancers (GCs). miR-382 has been identified as a hypoxia-induced miR (hypoxamiR), but the clinical significance in GCs has not been identified yet. To explore the clinical and prognostic importance of miR-382 in GCs, the surgical specimens of 398 patients with GCs in KNU hospital in Korea, the total of 183 patients was randomly selected using simple sampling methods and big data with 446 GCs and 45 normal tissues from the data portal (https://portal.gdc.cancer.gov/) were analysed. Expression of miR-382 as well as miR-210, as a positive control hypoxamiR by qRT-PCR in histologically malignant region of GCs showed significantly positive correlation (R = 0.516, p<0.001). High miR-210 and miR-382 expression was significantly correlated with unfavorable prognosis including advanced GCs (AGC), higher T category, N category, pathologic TNM stage, lymphovascular invasion, venous invasion, and perinueral invasion, respectively (all p<0.05). In univariate analysis, high miR-210 expression was significantly associated with worse overall survival (OS) (p = 0.036) but not high miR-382. In paired 60 gastric normal and cancer tissues, miR-382 expression in cancer tissues was significantly higher than normal counterpart (p = 0.003), but not miR-210 expression. However, by increasing the patient number from the big data analysis, miR-210 as well as miR-382 expression in tumor tissues was significantly higher than the normal tissues. Our results suggest that miR-382, as novel hypoxamiR, can be a prognostic marker for advanced GCs and might be correlated with metastatic potential. miR-382 might play important roles in the aggressiveness, progression and prognosis of GCs. In addition, miR-382 give a predictive marker for progression of GCs compared to the normal or preneoplastic lesion.

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.

Comparison of laparoscopic proximal gastrectomy with double-tract reconstruction and laparoscopic total gastrectomy in terms of nutritional status or quality of life in early gastric cancer patients.

BACKGROUND: This study aimed to evaluate the surgical outcomes of laparoscopic proximal gastrectomy (LPG) reconstructed by the double-tract method in comparison to those of laparoscopic total gastrectomy (LTG). METHODS: A retrospective review of the prospectively established database identified early gastric cancer patients who underwent LPG (n = 34) or LTG (n = 46) between January 2011 and December 2015. Baseline characteristics and surgical outcomes including postoperative complications, changes in body composition, nutritional status, and quality of life (QOL) after surgery were compared between the LPG and LTG patients. RESULTS: Operating time was significantly longer in the LTG group (240.7 ± 43.9 vs. 211.7 ± 32.8 min, p = 0.007). The incidence of grade II or more complications and the hospital stay were comparable between the groups. There was no significant difference between the groups in terms of body composition using a bioelectrical impedance method in 1 year postoperatively. Nutritional status assessed by serum hemoglobin, iron, vitamin B12, albumin, total protein, and total cholesterol levels and postoperative changes in quality of life up to 2 years after surgery were also similar between the groups. Vitamin B12 supplementation was required in 75.4% of the patients in the LTG group and 46.5% in the LPG group within 2 years after surgery (p = 0.005). CONCLUSION: LPG with double-tract reconstruction appears superior in preventing vitamin B12 deficiency compared to LTG, particularly after 1 year after the surgery, although it offered little benefit in terms of postoperative body composition changes and QOL.

Impact of Body Mass Index on the Quality of Life after Total Gastrectomy for Gastric Cancer.

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.