Prevalence and Clinical Implications of Ascites in Gastric Cancer Patients after Curative Surgery.

We aimed to determine the frequency and clinical significance of ascites that developed during the follow-up period in patients who underwent curative resection for gastric cancer. The study included 577 patients with gastric cancer who underwent curative gastrectomy. Among them, 184 showed ascites in postoperative follow-up images. Benign ascites was observed in 131 of 490 patients without recurrence, 48 patients (of 87) with recurrence had malignancy-related ascites, and the remaining 5 patients had ascites only prior to recurrence. In most patients without recurrence (97.7%) and in 50% of patients with malignancy-related ascites, the ascites was small in volume and located in the pelvic cavity at the time that it was first identified. However, with the exception of nine patients, malignancy-related pelvic ascites occurred simultaneously or after obvious recurrence. Of those nine patients who had minimal pelvic ascites before obvious recurrence, only one had a clear association with a malignancy-related ascites. In the multivariate analysis, an age of ≤45 was the only independent risk factor for the occurrence of benign ascites. A small volume of pelvic ascites fluid is common in young gastric cancer patients who do not have recurrence after gastrectomy, regardless of sex. It is rare for ascites to be the first manifestation of recurrence.

In vitro comparison of wear of three orthodontic bite materials and opposing enamel.

OBJECTIVE: Orthodontic bite turbos are used to separate the maxillary and mandibular arch when disocclusion is needed for brackets placement or extrusion of teeth. Bite turbos should have adequate wear resistance to maintain disocclusion but also avoid abrasion of the opposing enamel. The objective of this study was to measure the wear of three materials used as bite turbos and opposing enamel wear. MATERIALS AND METHODS: 10mm×8mm×4mm specimens (n=8) of Transbond™LR (3M™) Transbond™ Plus (3M™) and Triad®gel (Dentsply) were prepared in silicone molds. Cusps of extracted premolars were prepared to a standard cone shape. Extracted maxillary incisors were used as reference for flat enamel surfaces. The experiments were performed on the modified UAB wear testing device at 20N for 200,000 cycles at 1Hz. All surfaces were scanned with a non-contact profilometer at 10micron resolution. Volumetric wear was measured with superimposition software and data analysed with one-way ANOVA and Tukey post-hoc. RESULTS: Significant differences were seen in the wear of materials and opposing enamels (P<.01). Material wear ranked: Triad®gel (.878±.196mm3)>Transbond™ Plus (.317±.062mm3)>Transbond™ LR (.136±.027mm3)>Enamel (.053±.04mm3). Opposing enamel ranked: Transbond™ LR (.158±.086mm3)=Enamel (.128±.035mm3)=Transbond™ Plus (.126±.025mm3)>Triad®gel (.039±.008mm3). CONCLUSIONS: All bite turbo materials wore more than natural enamel but caused equal or less wear to opposing enamel than tooth-tooth contact. Triad®gel underwent 2.5× and 6× the wear of Transbond™ Plus and Transbond™ LR respectively. The bite turbo material used may be selected based on preference for longevity.

The Prognostic Significance of Compliance with Postoperative Adjuvant Chemotherapy in Patients with Stage III Gastric Cancer: an Observational Study.

PURPOSE: Postoperative adjuvant chemotherapy is usually prescribed to improve the survival of patients with advanced gastric cancer who undergo curative surgery. This study was designed to determine the impact that the degree of compliance with chemotherapy has on the prognosis of patients with gastric cancer. MATERIALS AND METHODS: Among 252 patients with stage III gastric cancer who underwent curative surgery between July 2004 and December 2014, 85 patients were postoperatively treated with S-1, the oral fluoropyrimidine derivative, 23 received no chemotherapy, and 144 received other regimens. Overall survival was compared between the complete compliance group (who received 8 cycles of S-1 chemotherapy, n=44) and the incomplete compliance group (who received less than 8 cycles of S-1 chemotherapy, n=41). Factors that influenced patient compliance with chemotherapy were also analyzed. RESULTS: The overall 5-year survival rate was significantly different between the complete chemotherapy and incomplete chemotherapy groups (80.0% vs. 42.7%, P<0.001). Based on univariate and multivariate survival analyses of patients who received S-1 chemotherapy, the independent prognostic factors were tumor, node, and metastasis (TNM) stage (IIIa vs. IIIb vs. IIIc) and compliance with chemotherapy. TNM stage and age are significant factors that influence compliance with chemotherapy. CONCLUSIONS: TNM stage and compliance with chemotherapy are independent prognostic factors in patients with stage III gastric cancer who received postoperative chemotherapy. TNM stage and age are significant factors that influence patient compliance with chemotherapy.

Comparison of the mechanical properties of translucent zirconia and lithium disilicate.

STATEMENT OF PROBLEM: Three mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) possesses excellent mechanical properties but is relatively opaque. Five mol% yttria-stabilized zirconia polycrystal (5Y-ZP) offers improved translucency, but many of its clinical properties have not been compared with those of 3Y-TZP and lithium disilicate. PURPOSE: The purpose of this in vitro study was to compare the flexural strength, translucency parameter, bond strength, and enamel and material wear of 5Y-ZP (Katana UTML) with 3Y-TZP (Katana HT) and lithium disilicate (e.max CAD). MATERIAL AND METHODS: Flexural strength bars were sectioned (n=10, 25×4×2 mm), sintered or crystallized, polished, and fractured at 1 mm/min. Translucency specimens (1 mm thick) were fabricated (n=10). Their L*a*b* values were measured against a black-and-white background with a spectrophotometer, and ΔE00 was calculated. Zirconia bond strength specimens were airborne-particle abraded with 50 µm alumina followed by the application of a 10-methacryloxydecyl dihydrogen phosphate-containing primer (Clearfil Ceramic Primer). Lithium disilicate bond strength specimens were etched with 5% hydrofluoric acid followed by application of a silane-containing primer (Clearfil Ceramic Primer). A Tygon tube filled with resin cement (Panavia SA) was fixed to the surface of the ceramics and light-polymerized. After 1 day or 150 days of water storage, the resin cement was debonded in a macroshear test (n=10). The cusps of extracted human molars were isolated and mounted into the University of Alabama at Birmingham wear-testing device. Wear testing was performed with a 20-N load for 300000 cycles in 33% glycerin. The volumetric wear of polished zirconia, lithium disilicate, and enamel were measured along with the wear of the opposing enamel cusps using a noncontact profilometer (n=8). The data were compared by ANOVA and Tukey-Kramer analysis (α=.05). RESULTS: No statistical difference was seen between the bond strengths (P=.155) or the opposing enamel wear (P=.533) of different ceramics. A statistically significant difference was seen between the flexural strength (P<.001), translucency parameter (P<.001), and wear (P<.001) of the materials. The flexural strength values (MPa) were 1194 ±111 (Katana HT), 688 ±159 (Katana UTML), and 450 ±53 (e.max LT). The translucency parameter values were 6.96 ±0.53 (Katana HT), 8.30 ±0.24 (Katana UTML), 9.28 ±0.36 (e.max LT), and 12.64 ±0.48 (e.max HT). Bond strength values (MPa) at 1 and 150 days were 34.22 ±5.14 and 28.37 ±6.03 (Katana HT), 35.04 ±5.69 and 25.03 ±6.44 (Katana UTML), and 35.50 ±3.45 and 22.32 ±3.45 (e.max LT). Material and enamel wear (mm3) were 0 and 0.24 ±0.19 (Katana HT), 0 and 0.23 ±0.09 (Katana UTML), 0.28 ±0.13 and 0.31 ±0.10 (e.max CAD), and 0.09 ±0.03 and 0.31 ±0.14 (enamel). CONCLUSIONS: 5Y-TZP has a flexural strength and translucency parameter between those of 3Y-TZP and lithium disilicate. Both the short-term and long-term bond strength of 5Y-ZP and 3Y-TZP was shown to be similar to lithium disilicate. 5Y-ZP demonstrated no measurable material wear and opposing enamel wear similar to that of all the other materials tested.

Recurrence of gastric cancer in patients who are disease-free for more than 5 years after primary resection.

BACKGROUND: Late recurrence of gastric cancer is rare and there are few data on recurrence in patients who are disease free for >5 years after gastrectomy. The aim of this study was to evaluate the predictors and status of tumor recurrence among these patients. METHODS: Clinicopathologic characteristics, patterns of recurrence, and postrecurrence survival were analyzed in patients who were diagnosed as disease free at 5 years postoperatively and thereafter experienced recurrence. Independent factors associated with the late recurrence were analyzed. RESULTS: Among 1,573 patients who underwent curative surgery from June 1992 to December 2006, 348 patients had recurrence. Of them, 7.6% (n = 25) suffered from late recurrence after 5 years after gastrectomy. Among patients who were diagnosed as disease free at 5 years after surgery, it accounted for 2.8% (25/902). Cases with late recurrence were characterized by more aggressive clinicopathologic features than those without recurrence. The median time to recurrence was 88.8 months (range, 64.8-238.0); of the 25 patients, 18 (72.0%) had recurrence within 8 years after surgery. The most common pattern was peritoneal recurrence (n = 19; 76.0%). The estimated median survival after recurrence was 9.4 months. On multivariate analysis, pT4 classification was the only independent risk factor for late recurrence. There were 185 patients with pT4 tumor who had no recurrence at 5 years after surgery; 19 (10.3%) had late recurrence. CONCLUSION: pT4 tumor was the only important predictor of late recurrence. Whether extended follow-up for T4 tumors affects survival needs to be demonstrated in more large-scale studies.

The Ratio-Based N Staging System Can More Accurately Reflect the Prognosis of T4 Gastric Cancer Patients with D2 Lymphadenectomy Compared with the 7th American Joint Committee on Cancer/Union for International Cancer Control Staging System.

PURPOSE: The utility of N classification has been questioned after the 7th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) was published. We evaluated the correlation between ratio-based N (rN) classification with the overall survival of pathological T4 gastric cancer patients who underwent D2 lymphadenectomy. MATERIALS AND METHODS: We reviewed 222 cases of advanced gastric cancer patients who underwent curative gastrectomy between January 2006 and December 2015. The T4 gastric cancer patents were classified into four groups according to the lymph node ratio (the number of metastatic lymph nodes divided by the retrieved lymph nodes): rN0, 0%; rN1, ≤13.3%; rN2, ≤40.0%; and rN3, >40.0%. RESULTS: The rN stage showed a large down stage migration compared with pathological T4N3 (AJCC/UICC). There was a significant difference in overall survival between rN2 and rN3 groups in patients with pT4N3 (P=0.013). In contrast, the difference in metastatic lymph nodes was not significant in these patients (≥16 vs. <15; P=0.177). In addition, the rN staging system showed a more distinct difference in overall survival than the pN staging system for pathological T4 gastric cancer patients. CONCLUSIONS: Our results confirm that rN staging could be a good alternative for pathological T4 gastric cancer patients who undergo D2 lymphadenectomy. However, before applying this system to gastric cancer patients who undergo D2 lymphadenectomy, a larger sample size is required to further evaluate the usefulness of the rN staging system for all stages, including less advanced stages.

Discordant findings between preoperative endoscopy and postoperative pathology as an independent prognostic factor in gastric cancer patients.

BACKGROUND: Endoscopically diagnosed early gastric cancers (EGCs) are sometimes revealed to be advanced gastric cancers (AGCs) on pathologic examination of the resected specimen, and also endoscopically diagnosed AGCs are often determined to be EGCs. This study was designed to determine the impact on prognosis of the discordant finding between preoperative endoscopy and postoperative pathology in gastric cancer patients. METHODS: Patients with gastric cancer stages pT1a-T4a who underwent curative gastrectomy between 2004 and 2010 were included in the study. The preoperative endoscopic findings and clinicopathologic features were analyzed. The prognostic impact on recurrence-free survival of discordance between endoscopic and pathologic examinations was analyzed using multivariate analysis. RESULTS: Among 367 patients diagnosed with EGC on preoperative endoscopy, 40 (11 %) had AGC on final pathologic examination; this was more common in female patients, upper one-third location of the cancer, poorly differentiated tumor, combined gross type (elevated and depressed), lymphovascular invasion and lymph node metastasis. Among 350 patients diagnosed with AGC on preoperative endoscopy, 66 (19 %) had EGC pathologically; this was more frequent in patients with tumor in the lower and/or middle third of the stomach, differentiated tumor, Borrmann type 1 and absence of lymph node metastasis. The endoscopic appearance of AGC was identified as a poor prognostic factor related to recurrence-free survival in patients with EGC, whereas discordance did not influence recurrence-free survival in patients with AGC. CONCLUSIONS: Discordant preoperative endoscopic appearance may be an indicator of biologic aggressiveness and a reliable prognostic factor in EGC, but not in AGC.

Prognostic significance of lymphovascular invasion in node-negative gastric cancer.

BACKGROUND: The aim of this study was to investigate the prognostic value of lymphovascular invasion (LVI) in gastric cancer patients without lymph node metastasis. METHODS: A total of 699 patients with primary tumor pT1-3/pN0-1 gastric adenocarcinoma who underwent curative resection from 2001 to 2010 were categorized into 3 groups: One-hundred and eleven patients with pN0/LVI(+), 475 with pN0/LVI(-), and 103 with pN1. RESULTS: The tumors in patients with N0/LVI(+) had more aggressive clinicopathologic features than those in patients with N0/LVI(-). However, there was no significant difference in patient characteristics between patients with pN0/LVI(+) and those with pN1, except for histologic grade. There were no significant differences in the overall survival rate in patients with pN0/LVI(+) compared to those with pN0/LVI(-) or the pN1 stage. However, the recurrence-free survival rate of the pN0/LVI(+) group was lower than that of the pN0/LVI(-) group (p < 0.001), while no significant difference was observed between the pN0/LVI(+) and the N1 groups (p = 0.216). In multivariate analysis, LVI was identified as a poor prognostic factor related to recurrence-free survival in node-negative gastric cancer patients. pT3 stage and less than D2 lymphadenectomy were poor prognostic factors affecting recurrence-free survival, and less than D2 lymphadenectomy was an independent poor prognostic factor for overall survival in pN0/LVI(+) patients. CONCLUSIONS: LVI could be an indicator of biological aggressiveness and may be a reliable prognostic factor for node-negative gastric cancer. LVI should be considered in postoperative management of gastric cancer.

The distance of proximal resection margin dose not significantly influence on the prognosis of gastric cancer patients after curative resection.

PURPOSE: It is well known that the curative resection with an adequate proximal margin length is the most effective treatment in gastric cancer. However, despite surgeon's effort to achieve a sufficient proximal margin length, it is often difficult to obtain a recommended proximal margin length in some cases. Therefore, this study was planned to investigate the impact of the length of proximal margin on prognosis of overall survival. METHODS: Between June 1992 and December 2010, 1,888 gastric cancer patients who underwent gastrectomy with curative intent were reviewed. According to tumor's location (total vs. subtotal gastrectomy), pathologic T staging, and differentiation, univariate and multivariate analyses were performed to evaluate the impact of the discrepancies of proximal margin length on overall survival. Also, the impact of the discrepancies of proximal margin length on local recurrence was assessed. RESULTS: The 5-year survival rate of positive proximal margin group was 5.9%. In negative proximal margin groups, multivariate analysis showed that the discrepancies of proximal margin length have no impact on overall survival. Kaplan-Meier analyses showed that there is no association between discrepancy of proximal margin length and local recurrence. CONCLUSION: It takes effort to secure a negative proximal margin in the surgical treatment of gastric cancer because of the poor prognosis of positive proximal margin. In negative proximal margin patients, there's no need to achieve an additional proximal margin length for long-term survival benefit because there was no impact of proximal margin length on overall survival and local recurrence.

Comparison of the outcomes for laparoscopic gastrectomy performed by the same surgeon between a low-volume hospital and a high-volume center.

BACKGROUND: The volume-outcome relationship in laparoscopic surgery is controversial. This study was designed to identify differences in laparoscopic gastrectomy outcomes between a low-volume hospital and a high-volume center and to provide guidelines for overcoming the problems associated with a low-volume hospital. METHODS: From April 2009 to November 2012, one surgeon performed 134 totally laparoscopic distal gastrectomies (TLDGs) at a high-volume center (HVC; ASAN Medical Center) and at a low-volume hospital (LVH; Hanyang University Guri Hospital). All laparoscopically assisted gastrectomies were excluded from this study. During the early period of laparoscopic gastrectomy at the low-volume hospital, TLDG with Roux-en-Y gastrojejunostomy (RYGJ) was performed according to the surgeon's choice. The reconstruction method was classified as gastroduodenostomy (GD) or RYGJ. Early surgical outcomes achieved at the LVH were investigated and compared with those obtained at the HVC. RESULTS: The early surgical outcomes differed significantly between the two hospitals. In particular, the postoperative complication rate for the patients who underwent TLDG RYGJ at the LVH was higher than at the HVC (LVH 15.4 % vs. HVC 0 %; p = 0.037). Furthermore, significant differences were observed in the mean operation time (TLDG GD: LVH 141.0 min vs. HVC 117.4 min, p = 0.001; TLDG RYGJ: LVH 186.3 min vs. HVC 134.6 min, p = 0.009) and length of hospital stay (TLDG GD: LVH 8.1 days vs. HVC 7.2 days, p = 0.044; TLDG RYGJ: LVH 11.5 day vs. HVC 6.8 day, p = 0.009). CONCLUSIONS: Although all the operations were performed by one experienced surgeon, the early surgical outcomes differed significantly between the low- and high-volume hospitals. Low-volume hospitals often lack well-trained surgical professionals such as first assistants and scrub nurses. Therefore, the authors recommend that a surgeon who works at an LVH should assess potential personnel shortages and find a solution before operating.

The influence of post-operative surveillance on the prognosis after curative surgery for gastric cancer.

BACKGROUND/AIMS: Although routine post-operative surveillance after curative resection for gastric cancer is recommended, there are few reports on the value of postoperative follow-up. The aim of this study was to assess the possible role of post-operative surveillance as a prognostic factor after curative resection for gastric cancer. METHODOLOGY: A total of 192 gastric cancer patients who suffered recurrences after curative resection between January 2001 and June 2012 were included in this study. Clinicopathological factors and survival were retrospectively analyzed according to the presence or absence of symptoms related to tumor recurrence at the time of relapse. RESULTS: One-hundred-and-twenty-six of the patients (65.6%) had asymptomatic recurrences. Peritoneal recurrence (60.6%) predominated among the symptomatic recurrences, whereas locoregional recurrences (42.1%) were dominant among the asymptomatic recurrence. Median recurrence-free survival times did not differ between the two groups (p=0.507). However, median post-recurrence (p<0.001) and overall survival times (p=0.022) were longer in the asymptomatic group. CONCLUSIONS: Time to recurrence did not differ between the symptomatic and asymptomatic recurrence groups, but post-recurrence survival and overall survival were better in the asymptomatic group. Prior to the execution of a large scale randomized controlled trial, close follow-up should be considered.

The impact of old age on surgical outcomes of totally laparoscopic gastrectomy for gastric cancer.

BACKGROUND: Old age is regarded as the risk factor of major abdominal surgery due to the lack of functional reserve and the increased presence of comorbidities. This study aimed to evaluate the impact of old age on the surgical outcomes of totally laparoscopic gastrectomy for gastric cancer. METHODS: This study enrolled 389 gastric cancer patients who underwent totally laparoscopic gastrectomy at Hanyang University Guri Hospital and ASAN Medical Center. The patients were classified into two groups according to age as those older than 70 years and those younger than 70 years. Early surgical outcomes such as operation time, postoperative complications, time to first flatus, days until soft diet began, and hospital stay were evaluated. RESULTS: No patient was converted to open surgery. The two groups differed significantly in terms of overall postoperative complication rate, time to first flatus, days until soft diet began, and hospital stay. The patients who underwent Roux-en-Y gastrojejunostomy differed in incidence of postoperative ileus but not in severe postoperative complication rate. CONCLUSIONS: The results of this study demonstrated that old age can have an effect on the surgical outcomes of totally laparoscopic gastrectomy. This study especially showed that elderly patients are affected by the return of bowel movement after totally laparoscopic gastrectomy. On the other hand, however, it is presumed that old age has not had a serious impact on surgical outcomes in totally laparoscopic gastrectomy because no difference in the severe postoperative complication rate was observed.

Role of metastasectomy on overall survival of patients with metastatic gastric cancer.

PURPOSE: The role of metastasectomy has been debatable and unclear in the treatment for patients with metastatic gastric cancer. Therefore, this study was designed to evaluate the role of metastasectomy on the overall survival of these patients. MATERIALS AND METHODS: In 2,406 patients who underwent gastrectomy for gastric cancer between 1998 and 2010, 188 (7.8%) patients had their first surgery for metastatic gastric cancer. To minimize the bias of systemic chemotherapy, 99 patients who received postoperative chemotherapy (fewer than 2 cycles) were excluded. The primary gastrectomy or metastasectomy had not been enforced in the following cases. Patients with far advanced peritoneal dissemination, multiple liver and lung metastasis (more than 2), and a poor general condition (Eastern Cooperative Oncology Group>2) were excluded. Based on the metastasectomy, the patients were classified into two groups, gastrectomy with metastasectomy and gastrectomy only group. RESULTS: There was no significant difference between both groups in clinicopathological characteristics except for the mean age (P=0.047). The univariate analysis for overall survival show statistical significances in metastasectomy (P=0.026), distal gastrectomy (P=0.047), and combined resection of another organ (P=0.047) group. With a multivariate analysis, metastasectomy was a significant factor in patient survival after surgery (odds ratio 1.679; P=0.034). CONCLUSIONS: Based on our results, we assume that a detailed strategy for surgery is needed to improve the overall survival of patients with metastatic gastric cancer. Therefore, we suggest that a metastasectomy can help prolong overall survival in some patients with metastatic gastric cancer.

Tumor size as a prognostic factor in gastric cancer patient.

PURPOSE: The purpose of this study is to investigate the prognostic significance of tumor size for 5-year survival rate in patients with gastric cancer. MATERIALS AND METHODS: A total of 1,697 patients with gastric cancer, who underwent potentially curative gastrectomy, were evaluated. Patients were divided into 4 groups as follows, according to the median size of early and advanced gastric cancer, respectively: small early gastric cancer (tumor size ≤3 cm), large early gastric cancer (tumor size >3 cm), small advanced gastric cancer (tumor size ≤6 cm), and large advanced gastric cancer (tumor size >6 cm). The prognostic value of tumor size for 5-year survival rate was investigated. RESULTS: In a univariate analysis, tumor size is a significant prognostic factor in advanced gastric cancer, but not in early gastric cancer. Multivariate analysis showed that tumor size is an independent prognostic factor for 5-year survival rate in advanced gastric cancer (P=0.003, hazard ratio=1.372, 95% confidence interval=1.115~1.690). When advanced gastric cancer is subdivided into 2 groups, according to serosa invasion: Group 1; serosa negative (T2 and T3, 7th AJCC), and Group 2; serosa positive (T4a and T4b, 7th AJCC), tumor size is an independent prognostic factor in Group 1 (P=0.011, hazard ratio=1.810, 95% confidence interval=1.149~2.852) and in Group 2 (P=0.033, hazard ratio=1.288, 95% confidence interval=1.020~1.627), respectively. CONCLUSIONS: Tumor size is an independent prognostic factor in advanced gastric cancer irrespective of the serosa invasion, but not in early gastric cancer.

Prognostic factors on overall survival in lymph node negative gastric cancer patients who underwent curative resection.

PURPOSE: To assess independent prognostic factors for lymph node-negative metastatic gastric cancer patients following curative resection is valuable for more effective follow-up strategies. MATERIALS AND METHODS: Among 1,874 gastric cancer patients who received curative resection, 967 patients were lymph node-negative. Independent prognostic factors for overall survival in lymph node-negative gastric cancer patients grouped by tumor invasion depth (early gastric cancer versus advanced gastric cancer) were explored with univariate and multivariate analyses. RESULTS: There was a significant difference in the distribution of recurrence pattern between lymph node-negative and lymph node-positive group. In the lymph node-negative group, the recurrence pattern differed by the depth of tumor invasion. In univariate analysis for overall survival of the early gastric cancer group, age, macroscopic appearance, histologic type, venous invasion, lymphatic invasion, and carcinoembryonic antigen level were significant prognostic factors. Multivariate analysis for these factors showed that venous invasion (hazard ratio, 6.695), age (≥59, hazard ratio, 2.882), and carcinoembryonic antigen level (≥5 ng/dl, hazard ratio, 3.938) were significant prognostic factors. Multivariate analysis of advanced gastric cancer group showed that depth of tumor invasion (T2 versus T3, hazard ratio, 2.809), and age (hazard ratio, 2.319) were prognostic factors on overall survival. CONCLUSIONS: Based on our results, independent prognostic factors such as venous permeation, carcinoembryonic antigen level, and age, depth of tumor invasion on overall survival were different between early gastric cancer and advanced gastric cancer group in lymph node-negative gastric cancer patients. Therefore, we are confident that our results will contribute to planning follow-up strategies.

Phospholipase D1 mediates bFGF-induced Bcl-2 expression leading to neurite outgrowth in H19-7 cells.

The purpose of the present study was to investigate the role of PLD (phospholipase D) in bFGF (basic fibroblast growth factor)-induced Bcl-2 expression and to examine whether overexpressed Bcl-2 influences neurite outgrowth in immortalized hippocampal progenitor cells (H19-7 cells). We found that Bcl-2 expression was maximally induced by bFGF within 24 h, and that this effect was reduced by inhibiting PLD1 expression with PLD1 small interfering RNA or by overexpressing DN (dominant-negative)-PLD1, whereas PLD1 overexpression markedly induced Bcl-2 expression. bFGF treatment activated Ras, Src, PI3K (phosphoinositide 3-kinase), PLCγ (phospholipase Cγ) and PKCα (protein kinase Cα). Among these molecules, Src and PKCα were not required for Bcl-2 expression. PLD activity was decreased by Ras, PI3K or PLCγ inhibitor, suggesting that PLD1 activation occurred through Ras, PI3K or PLCγ. We found that Ras was the most upstream molecule among these proteins, followed by the PI3K/PLCγ pathway, indicating that bFGF-induced PLD activation took place through the Ras/PI3K/PLCγ pathway. Furthermore, PLD1 was required for activation of JNK (c-Jun N-terminal kinase), which led to activation of STAT3 (signal transducer and activator of transcription 3) and finally Bcl-2 expression. When Bcl-2 was overexpressed, neurite outgrowth was stimulated along with induction of neurotrophic factors such as brain-derived neurotrophic factor and neurotrophin 4/5. In conclusion, PLD1 acts as a downstream effector of bFGF/Ras/PI3K/PLCγ signalling and regulates Bcl-2 expression through JNK/STAT3, which leads to neurite outgrowth in H19-7 cells.

Clinicopathological characteristics of alpha-fetoprotein-producing gastric cancer.

PURPOSE: α-fetoprotein (AFP)-producing gastric cancer is a rare tumor with high rates of liver metastasis and a poor prognosis. Many studies have been performed but there have been no comprehensive investigations of the clinicopathological and prognosis. MATERIALS AND METHODS: Six hundred ninety four patients with gastric cancer who underwent a curative gastric resection in Hanyang University Hospital from February 2001 to December 2008 were evaluated retrospectively after excluding active or chronic hepatits, liver cirrhosis and preoperative distant metastasis. Among them, thirty five patients had an elevated serum level of AFP (>7 ng/ml) preoperatively. The clinicopathological features of AFP-producing gastric cancer were analyzed. RESULTS: There was poorer differentiation, a higher incidence of lymph node metastasis, more marked lymphatic and vascular invasion in the AFP-positive group than in the AFP-negative group. The 5-year survival rate of the AFP-positive group was significantly poorer than that in the AFP-negative group (66% vs. 80%, P=0.002). A significantly higher incidence of liver metastasis was observed in the AFP-positive group than in the AFP-negative group (14.3% vs. 3.6%, P=0.002) with a shorter median time period from the operation to the metachronous liver metastasis (3.7 months vs. 14.1 months, P=0.043). Multivariate survival analysis revealed the depth of invasion, degree of lymph node metastasis and AFP-positivity to be the independent prognostic factors. CONCLUSIONS: AFP-producing gastric cancers have an aggressive behavior with a high metastatic potential to the liver. In addition, their clinicopathological features are quite different from the more common AFP-negative gastric cancer.

Bone metastasis in gastric cancer patients.

PURPOSE: Bone metastasis from stomach cancer occurs only rarely and it is known to have a very poor prognosis. This study examined the clinical characteristics and prognosis of patients who were diagnosed with stomach cancer and bone metastasis. MATERIALS AND METHODS: The subjects were 19 patients who were diagnosed with stomach cancer at Hanyang University Medical Center from June 1992 to August 2010 and they also had bone metastasis. The survival rate according to many clinicopathologic factors was retrospectively analyzed. RESULTS: 11 patients out of 18 patients (61%) who received an operation were in stage IV and the most common bone metastasis location was the spine. Bone scintigraphy was mostly used for diagnosing bone metastasis and PET-CT and magnetic resonance imaging were used singly or together. The serum alkaline phosphatase at the time of diagnosis had increased in 12 cases and there were clinical symptoms (bone pain) in 16 cases. Treatment was given to 14 cases and it was mostly radiotherapy. There were 2 cases of discovering bone metastasis at the time of diagnosing stomach cancer. The interval after operation to the time of diagnosing bone metastasis for the 18 cases that received a stomach cancer operation was on average 14.9±17.3 months and the period until death after the diagnosis of bone metastasis was on average 3.8±2.6 months. As a result of univariate survival rate analysis, the group that was treated for bone metastasis had a significantly better survival period when the bone metastasis was singular rather than multiple, as compared to the non-treatment group, yet both factors were not independent prognosis factors on multivariate survival analysis. CONCLUSIONS: An examination to confirm the status of bone metastasis when conducting a radio-tracer test after the initial diagnosis and also after an operation is needed for stomach cancer patients, and bone scintigraphy is the most helpfully modality. Making the diagnosis at the early stage and suitable treatments are expected to enhance the survival rate and improve the quality of life even for the patients with bone metastasis.

Clinicopathologic Characteristics of Gastric Cancer Patients according to the Timing of the Recurrence after Curative Surgery.

PURPOSE: There are few studies that have focused on the predictors of recurrence after gastrectomy for gastric carcinoma. This study analyzed the patients who died of recurrent gastric carcinoma and we attempted to clarify the clinicopathologic factors that are associated with the timing of recurrence. MATERIALS AND METHODS: From June 1992 to March 2009, 1,795 patients underwent curative gastric resection at the Department of Surgery, Hanyang University College of Medicine. Among them, 428 patients died and 311 of these patients who died of recurrent gastric carcinoma were enrolled in this study. The clinicopathologic findings were compared between the 72 patients who died within one year after curative gastrectomy (the early recurrence group) and the 92 patients who died 3 years after curative gastrectomy (the late recurrence group). RESULTS: Compared with the late recurrence group, the early recurrence group showed an older age, a more advanced stage, a poorly differentiated type of cancer and a significantly higher tendency to have lymphatic invasion, vascular invasion and perineural invasion.Especially in the gastric cancer patients with a more advanced stage (stage III and IV), the early recurrence group was characterized by a significantly higher preoperative serum carcino embryonic antigen level, perineural invasion and a relatively small number of dissected lymph nodes. CONCLUSIONS: The clinicopathologic characteristics of recurrent gastric cancer are significantly different according to the stage of disease, and even in the same stage. For the early detection of recurrence after curative surgery, it is important to recognize the clinicopathological factors that foretell a high risk of recurrence. It is mandatory to make an individualized surveillance schedule according to the clinicopathologic factors.

Evaluation of the 7th UICC TNM Staging System of Gastric Cancer.

Since January of 2010, the seventh edition of UICC tumor node metastasis (TNM) Classification, which has recently been revised, has been applied to almost all cases of malignant tumors. Compared to previous editions, the merits and demerits of the current revisions were analyzed. Many revisions have been made for criteria for the classification of lymph nodes. In particular, all the cases in whom the number of lymph nodes is more than 7 were classified as N3 without being differentiated. Therefore, the coverage of the N3 was broad. Owing to this, there was no consistency in predicting the prognosis of the N3 group. By determining the positive cases to a distant metastasis as TNM stage IV, the discrepancy in the TNM stage IV compared to the sixth edition was resolved. In regard to the classification system for an esophagogastric (EG) junction carcinoma, it was declared that cases of an invasion to the EG junction should follow the classification system for esophageal cancer. A review of clinical cases reported from Asian patients suggests that it would be more appropriate to follow the previous editions of the classification system for gastric cancer. In addition, in the classification of the TNM stages in the overall cases, the discrepancy in the prognosis between the different stages and the consistency in the prognosis between the same TNM stages were achieved to a lesser extent as compared to that previously. Accordingly, further revisions are needed to develop a purposive classification method where the prognosis can be predicted specifically to each variable and the mode of the overall classification can be simplified.