Keun Won Ryu

Assessment of lymph node metastases using 18F-FDG PET in patients with advanced gastric cancer

PurposeThe aim of this study was to assess the diagnostic accuracy of 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) with respect to lymph node (LN) metastasis in patients with advanced gastric cancer, and to ascertain the factors that affect this accuracy.MethodsSeventy-three patients with advanced gastric cancer, verified in all cases by endoscopic biopsy, were enrolled in this prospective study. We conducted FDG PET and other routine preoperative studies, including abdominal computed tomography (CT). Patients underwent either curative-intent gastrectomy and lymphadenectomy (n=67) or exploratory laparotomy. The Japanese system for the classification of gastric cancer was used for LN assessment.ResultsFDG PET was able to detect primary lesions in 70 of the 73 cases. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value of FDG PET for LN metastasis were 40%, 95%, 91% and 56%, respectively. Signet-ring cell carcinoma was associated with the lowest sensitivity (15%), whereas other cell types could be detected with moderate sensitivity (30–71%) and high specificity (93–100%). According to multiple logistic regression, the standardised uptake value for primary tumours was the only independent variable to be significantly related to sensitivity for LN metastasis (p=0.02, odds ratio=1.14). CT was superior to PET in terms of sensitivity (p<0.0001), and PET was superior to CT in terms of specificity (p<0.0001) and PPV (p=0.05).ConclusionFDG PET exhibits good specificity for LN staging of gastric cancer, and FDG uptake in the primary tumour is significantly related to the accuracy of FDG PET. Despite some clear limitations, FDG PET proved useful in the LN staging of FDG-avid gastric 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.

A Phase-II Clinical Trial of Laparoscopy-Assisted Distal Gastrectomy with D2 Lymph Node Dissection for Gastric Cancer Patients

ObjectivesThis study was conducted to determine whether laparoscopy-assisted distal gastrectomy (LADG) with complete D2 lymph node dissection for gastric cancer is a safe and effective surgical option.MethodsDuring an 8-month period, 64 patients, who were diagnosed preoperatively as having T1-2, N0-1 or M0 gastric cancer, were prospectively enrolled to undergo LADG with D2 lymph node dissection; two surgeons with experience of over 50 cases of laparoscopic gastrectomy performed the procedures. The compliance rate, defined as cases with no more than one missing lymph node station according to the Japanese Research Society of Gastric Cancer (JRSGC) lymph node grouping, for the open gastrectomy with D2 lymph node dissection was 66.0% in a pilot study and was used for calculations of sample size. Compliance rate and other surgical outcomes, including the number of retrieved lymph nodes from each lymph node station, morbidities, mortalities and conversion rate, were analyzed.ResultsThe compliance rate was 67.2% and was similar to that of open distal gastrectomy reported in the pilot study. The mean number of retrieved lymph nodes was 50.1 (range 20–100). The most frequently missed lymph node station was no. 5 (31.2%) followed by no. 3 (25.0%). There were no missed lymph nodes at stations no. 6 and 9. The complication rate was 3.1% (2/66); there were two conversions (3.0%) and no mortalities.ConclusionsThe current study suggests that LADG with D2 lymph node dissection is oncologically feasible, and phase-III clinical trials will be needed.

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.

Weekly docetaxel in combination with capecitabine in patients with metastatic gastric cancer.

Docetaxel (T) and capecitabine (X) are active agents against gastric cancer with synergistic antitumor effects. We conducted the current phase II study to assess the response rate and toxicity of combination TX regimen in patients with metastatic gastric cancer. Eligible patients were treated with docetaxel (36 mg/m2 intravenously) on days 1 and 8 and capecitabine (1000 mg/m2 orally twice a day) on days 1–14 of a 3-week schedule until progression occurred. From December 2001 to May 2003, 55 patients with median age of 54 years (range, 22–73 years) were enrolled; 47 patients had measurable lesions. A total of 358 courses of treatment were given, with a median of 5 (range, 1–22+) per patient. Objective responses were documented in 19 of 47 patients with measurable lesions (response rate, 40.4%; 95% confidence interval [CI], 25.9–54.9), with the median response duration of 5.6 months (range, 2.1–13.6+). At a median follow up of 15.9 months for all of 55 study patients, the median time to progression and survival were 4.5 months (95% CI, 3.4–5.6) and 12.0 months (95% CI, 7.5–16.6), respectively. Hematologic toxicities were mild to moderate, and the observed grade 3 nonhematologic toxicities, the most frequent of which was stomatitis, were generally manageable. Four patients experienced pneumonitis, but all of them responded to steroid treatment. The TX regimen was relatively well tolerated and effective against metastatic gastric cancer, with the added advantage of being an outpatient regimen.

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.

Circulating numbers of endothelial progenitor cells in patients with gastric and breast cancer

Angiogenic factors like VEGF or G-CSF were reported to mobilize endothelial progenitor cells (EPCs) from the bone marrow. These EPCs were shown to be incorporated in the neovessels of developing tumors. Although the concentrations of angiogenic factors in the peripheral blood were reported to be elevated in cancer patients, the number of circulating EPCs has not been previously investigated. In this study, the number of EPCs circulating in the blood in 16 healthy controls and 71 newly diagnosed cancer patients was examined by a culture assay of peripheral blood mononuclear cells. The number of circulating EPCs was not found to be increased in cancer patients, although the plasma levels of VEGF were elevated. It is suggested that VEGF, at concentrations typical of those observed in the blood of cancer patients, does not mobilize EPCs into the peripheral blood.

Phase 3 Trial of Postoperative Chemotherapy Alone Versus Chemoradiation Therapy in Stage III-IV Gastric Cancer Treated With R0 Gastrectomy and D2 Lymph Node Dissection

PURPOSE To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. METHODS AND MATERIALS The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. RESULTS Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). CONCLUSIONS Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.