Jong Yeul Lee

Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis‐associated colon cancer in mice

Statins, HMG‐CoA reductase inhibitors could be associated with the risk reduction of colorectal cancer. We previously demonstrated that simvastatin inhibits NF‐κB signaling in human intestinal epithelial cells and ameliorates acute murine colitis. The aim of our study was to evaluate the effects of simvastatin on the apoptotic pathways related to NF‐κB signaling in colon cancer cells, and on anticancer effects in 2 different animal models. We treated cell lines (COLO 205 and HCT 116) with simvastatin or vehicle and determined apoptosis by cell cycle analysis, Annexin V‐FITC staining, caspase‐3 activity assay and confocal microscopy. We assessed the expression of antiapoptotic factors by RT‐PCR and Western blotting. In the colitis‐associated colon cancer (CAC) model, we induced colonic tumors in C57/BL6 mice by azoxymethane and dextran sulfate sodium administration, and evaluated simvastatins effect on tumor growth. In the xenograft model, we evaluated its effect on the inoculated tumor growth. In both cell lines, simvastatin caused dose‐ and time‐dependent cell death. Annexin V staining significantly increased after simvastatin treatment. It augmented caspase‐3 activity and downregulated the expression of Bcl‐2, Bcl‐xL, cIAP1 and cFLIP. In the CAC model, simvastatin significantly reduced tumor development. In the xenograft model, tumors from animals treated with simvastatin had smaller volumes, larger necrotic areas, lower expression of VEGF and higher apoptotic scores. In conclusion, simvastatin inhibited colon cancer development by induction of apoptosis and suppression of angiogenesis. These results suggest that simvastatin could be a potential chemopreventive and therapeutic agent of CAC as well as de novo colon cancer.

Technical feasibility and safety of laparoscopy‐assisted total gastrectomy in gastric cancer: A comparative study with laparoscopy‐assisted distal gastrectomy

Only a few surgeons with much experience of laparoscopic surgery perform laparoscopy‐assisted total gastrectomy (LATG), because of its technical difficulty and concern about subsequent complications. The aim of this study was to evaluate the technical feasibility and safety of LATG as compared with laparoscopy‐assisted distal gastrectomy (LADG) in gastric cancer.

Covered versus uncovered self-expandable metallic stents for palliation of malignant pyloric obstruction in gastric cancer patients: a randomized, prospective study.

BACKGROUND Self-expandable metallic stents (SEMSs) provide effective palliation of malignant pyloric obstruction in patients with inoperable gastric cancer. OBJECTIVE To compare the effectiveness and side effects of covered and uncovered SEMSs for the palliation of malignant pyloric obstruction. DESIGN Prospective, randomized, single-center study. SETTING Tertiary-care cancer center hospital. PATIENTS This study involved 80 patients with pyloric obstruction related to inoperable gastric cancer. INTERVENTION Covered or uncovered SEMS placement. MAIN OUTCOME MEASUREMENTS Technical and clinical success rates as well as the patency rate at 8 weeks after placement. RESULTS Both groups had a technical success rate of 100% with no immediate complications. Both groups also had comparable clinical success rates (covered SEMS, 95% [38 of 40] and uncovered SEMS, 90% [36 of 40], P = .68) and 8-week patency rates (covered SEMS, 61.3% [19 of 31] and uncovered SEMS, 61.1% [22 of 36], P > .99). Stent migration within 8 weeks was more common in the covered SEMS group (25.8% [8 of 31]) than in the uncovered SEMS group (2.8% [1 of 36], P = .009), whereas re-stenosis because of tumor ingrowth was more common in the uncovered SEMS group (25.0% [9 of 36] vs 0% [0 of 31] in the covered SEMS group, P = .003). Overall patient survival and stent patency did not differ between groups (P = .27 and 0.61 by log-rank test, respectively). LIMITATIONS The study population was limited to gastric cancer patients, and stent designs were changed in the midst of the study period. CONCLUSION Both the covered and uncovered SEMSs are effective and have comparable 8-week patency in patients with malignant pyloric obstruction, despite different patterns of late stent failure.

Effect of repeated endoscopic screening on the incidence and treatment of gastric cancer in health screenees.

Objectives Early gastric cancer (EGC) can be treated by minimally invasive endoscopic resection and has an excellent prognosis. The aim of this study was to investigate whether repeated esophagogastroduodenoscopy (EGD) screening is an effective method for detecting EGC that can be treated by endoscopic resection. Methods For patients diagnosed with gastric cancer in the Korean National Cancer Center screening program, we analyzed the incidence of gastric cancer, clinicopathological characteristics, and treatment modality according to whether they had (repeated screening group) or not (infrequent screening group) undergone EGD screening within 2 years before diagnosis. Results Of the 18 414 patients who underwent EGD, 81 (0.44%) were found to have gastric cancer. Incidence of gastric cancer in repeated screening group was lower than that of infrequent screening group (multiple adjusted odds ratio=0.45, 95% confidence interval: 0.26–0.77, P=0.004). The proportion of EGCs was 96% (25 of 26) n the repeated screening group and 71% (34 of 48) in the infrequent screening group (P=0.01). Mean (SD) tumor size was smaller [1.9 (1.2) vs. 3.0 (1.6) cm, P=0.01] and the proportion of intramucosal cancer was higher [81% (21 of 26) vs. 50% (24 of 48), P=0.02] in the former than in the latter. Endoscopic resection was performed more frequently in the repeated screening group [54% (14 of 26) vs. 23% (11 of 48), P=0.007]. Conclusion Repeated endoscopic screening within 2 years decreased the incidence of gastric cancer and endoscopic resection could be applied to more patients who underwent EGD screening within 2 years.

Surgical Indication for Non-curative Endoscopic Resection in Early Gastric Cancer

BackgroundEndoscopic resection (ER) is an effective treatment for early gastric cancer (EGC) without lymph node metastasis. However, after ER additional surgery may be needed to manage the risks presented by residual cancer or lymph node metastasis.MethodsER was performed on 344 gastric adenocarcinomas between November 2001 and April 2006 at the Korean National Cancer Center under the strict pre-procedural indication. The authors performed operations in 43 patients due to: residual mucosal cancer, a mucosal cancer larger than 3 cm, or a submucosal cancer regardless of size or margin involvement. ER and surgical specimens were reviewed and analyzed for residual cancer and lymph node metastasis.ResultsBased on examinations of ER specimens, cancer was confined to the mucosal layer in 15 patients (34.9%) and invaded the submucosal layer in 28 patients (65.1%). Surgical specimens showed residual cancer in 17 patients (39.5%) and lymph node metastasis in four (9.3%). Neither residual cancer nor lymph node metastasis was found in patients with less than 500 μm submucosal invasion without margin involvement in ER specimens. In three of four patients with lymph node metastasis, the depth of submucosal invasion was 500 μm or more; the remaining patient had a 4-cm-sized differentiated mucosal cancer.ConclusionsWhen a pathologic evaluation of an ER specimen reveals more than 500 μm of submucosal invasion or a mucosal cancer of larger than 3 cm, surgery should be considered due to the risk of lymph node metastasis.

Sentinel Node Mapping and Skip Metastases in Patients with Early Gastric Cancer

ObjectivesThis study was designed to identify the characteristics of patients with early gastric cancers that have skip metastases. Background The possibility of lymph node metastasis is the most important factor to consider when deciding on the resection procedure for patients with early gastric cancer.MethodsFrom February 2003 through July 2008, 739 patients with early gastric adenocarcinoma underwent gastric resection at the National Cancer Center, Korea, and were included in this study. Patients with skip metastases were analyzed and compared with those without skip metastases.ResultsSkip metastases were found in 2.8% of patients with early gastric cancer. Tumor size and the presence of lymphatic invasion were associated with skip metastases by both univariate and multivariate analysis. All skip metastases were metastases to the extraperigastric lymph nodes that skipped across the perigastric lymph nodes. Sixteen patients (66.7%) with these metastases had metastatic lymph nodes at No. 7, 8, and 9 stations.ConclusionsTumor size should be considered during sentinel lymph node mapping to prevent false-negative results in patients with early gastric cancer. If sentinel nodes are not found in the perigastric lymph nodes, No. 7, 8, and 9 stations should be explored for prevention of false-negative sentinel node mapping results.

Long-term survival after endoscopic resection versus surgery in early gastric cancers.

BACKGROUND AND STUDY AIM Endoscopic resection for early gastric cancers that meet the expanded indication is considered to be an investigational treatment. The study aim was to evaluate long-term outcomes of endoscopic resection compared with surgery for early gastric cancers meeting the expanded indication. METHODS We retrospectively reviewed data from patients who underwent endoscopic resection or surgery for gastric cancers meeting the expanded indication between 2001 and 2009. Overall survival rate was the primary outcome; gastric cancer recurrence rates and complication rates were secondary outcomes. RESULTS Among 457 patients included, 165 underwent endoscopic resection and 292 surgery, with median follow-up duration of 58.6 months. The 5-year overall survival rates were 97.5 % and 97.0 % for endoscopic resection and surgery, respectively; Kaplan-Meier analysis showed no significant difference (P = 0.425). The 5-year gastric cancer recurrence rate was higher for endoscopic resection than for surgery (4.8 % vs. 0.3 %; P < 0.001) mainly because of metachronous cancers which developed only in the endoscopic resection group (9/165, 5.5 %). Most of the metachronous cancers (88.9 %) were curatively treated with endoscopic resection. Early complication rates were similar between the groups (P = 0.557), but the endoscopic resection group had more grade III or higher complications according to the Clavien-Dindo classification compared with the surgery group (4.8 % vs. 1.4 %, P = 0.026). Late complications occurred only following surgery (4.8 %, P = 0.004), and most (92.9 %) were grade III or higher. CONCLUSIONS Endoscopic resection may be an optimal alternative to surgery for gastric cancers that meet the expanded indication criteria, because of a comparable long-term overall survival rate.

Is the New Seventh AJCC/UICC Staging System Appropriate for Patients with Gastric Cancer?

BACKGROUND The purpose of this study was to compare the clinical usefulness of the seventh Union Internationale Contre le Cancer/American Joint Committee on Cancer (AJCC/UICC) staging system vs the sixth AJCC/UICC staging system in patients with gastric cancer. STUDY DESIGN Included were 1,799 patients who underwent surgery for gastric cancer between January 2001 and June 2005 at the National Cancer Center (South Korea). For the sixth and seventh AJCC/UICC staging systems, survival outcomes stratified by stage, by T classification, and by N classification were summarized using Kaplan-Meier curves and compared statistically using a log rank test; survival differences were quantified using hazard ratios estimated from a Cox regression model. The 2 systems were compared in terms of prognostic performances using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion (AIC) in the Cox regression analysis. RESULTS Significant survival differences between each stage were not found using the seventh staging system, especially for stages IB, IIA, and IIB (p = 0.14 and p = 0.11). The sixth staging system had higher linear trend chi-square score and likelihood ratio chi-square score, which means better discriminatory ability, monotonicity, and homogeneity, and had smaller AIC, which indicates better optimistic prognostic stratification, especially in the N classification. The modified staging system combining the T classification of the seventh AJCC/UICC system and the N classification of the sixth system showed better prognostic performance compared with each separate version (sixth or seventh) of the staging system. CONCLUSIONS The seventh AJCC/UICC staging system is not more clinically useful than the sixth system in surgically treated patients with gastric cancer because of an inappropriate N classification. A new TNM system is required with a different N classification.

Feasibility of laparoscopic sentinel basin dissection for limited resection in early gastric cancer

The clinical applications of sentinel node (SN) biopsies in early gastric cancer are limited because of low sensitivity. Sentinel basin (SB) dissection has been suggested as alternative to SN biopsy to improve sensitivity. The aim of this study was to examine the feasibility of laparoscopic SB dissection.

Biopsy site for detecting Helicobacter pylori infection in patients with gastric cancer

Background:  Helicobacter pylori eradication is recommended in post‐gastric cancer resection, but premalignant changes may prevent the detection of H. pylori. The aim of this study was to determine appropriate biopsy site for detecting H. pylori in gastric cancer patients.