Young Jae Mok

Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

BACKGROUND D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer. METHODS The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). FINDINGS 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). INTERPRETATION Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. FUNDING F Hoffmann-La Roche and Sanofi-Aventis.

Surgical Outcomes for Gastric Cancer in the Upper Third of the Stomach

IntroductionThe proportion of gastric cancers affecting the upper third of the stomach has been increasing. At our surgical service we perform total and proximal gastrectomy for this condition. The purpose of this study was to investigate the surgical outcome of the two operative procedures and determine an optimal surgical approach.MethodsData from 147 patients who underwent resection for gastric cancer affecting the proximal one-third of the stomach were retrospectively analyzed. The patients were classified into a total gastrectomy (TG) group or a proximal gastrectomy (PG) group, and the clinicopathologic characteristics and surgical results were compared. We analyzed survival rates using Kaplan-Meier methods and made comparisons using a log-rank test across the same stage of the gastric cancer.ResultsFrom 1992 to 2000, a total of 104 total gastrectomies and 43 proximal gastrectomies for gastric cancer affecting the upper one-third of the stomach were performed. Our investigation revealed significantly different clinicopathologic characteristics in Borrmann type, length of the resection margin, degree of lymph node dissection, and lymph node stage. During the procedure, a combined resection of other organs was performed in 30 TG and 27 PG patients. Postoperative complications developed in 15 TG and 22 PG patients. The cancer recurrence rate was 4.8% for the TG group and 39.5% for the PG group; it was highest when the length of the proximal resection margin was < 1 cm. When we compared 5-year survival rates between the two groups, each at the same cancer stage, a significant difference was noted for stage III and IV gastric cancers.ConclusionsProximal gastrectomy may be performed during the early stage of proximal gastric cancer; but because of the high frequency of complications and cancer recurrence, an additional procedure should be expected afterward. When the cancer stage is advanced, total gastrectomy should be performed with sufficient length of the proximal resection margin.

Expression of estrogen receptors in gastric cancer and their clinical significance.

The male predominance of gastric cancer suggests that female sex hormones may have a protective effect against gastric cancer. We evaluated the expression of estrogen receptors in gastric cancer tissue and cells and the clinical significance of ER‐β expression in gastric cancer.

Gastric cancer histology: clinicopathologic characteristics and prognostic value.

Gastric cancer can be divided into two major histologic categories, that is, differentiated and undifferentiated types. In the present study, we sought to clarify the prognoses and clinicopathologic characteristics of signet ring cell carcinoma and mucinous carcinoma, both of which are mucin‐producing tumors of the undifferentiated type.

Preoperative evaluation of gastric cancer: value of spiral CT during gastric arteriography (CTGA).

AbstractBackground: To evaluate the utility of dual-phase spiral computed tomography during gastric arteriography (CTGA) in the preoperative staging of gastric cancers. Methods: We performed CTGA in 21 patients with pathologically proven gastric cancers. CTGA findings were prospectively analyzed and correlated with surgical and pathologic findings. Dual-phase scans were performed at 10 s (early) and 60–100 s (delayed) after injection of 120 mL of contrast medium at an injection rate of 6 mL/s through a preset 5-Fr catheter positioned in the celiac trunk. Spiral CT scans were assessed for enhancing pattern of the normal gastric wall, tumor detectability, and accuracy of tumor staging. Results: Normal gastric mucosa was clearly visible as two or three layers in all patients on early-phase scans and in eight patients on delayed-phase scans. The primary tumors were correctly detected with CTGA in seven (88%) of the eight early gastric cancers and in all 13 (100%) advanced gastric cancers. The accuracy of CTGA for T staging was 50% and 77% in early and advanced gastric cancers, respectively. The overall accuracy for tumor detection and T staging was 95% and 67%, respectively. The accuracy of CTGA for the degree of serosal invasion and regional lymph node metastasis was 77% and 76%, respectively. Conclusion: The CTGA technique improved tumor detection rate and accuracy of tumor staging, especially in early gastric cancer, and may be very useful in the preoperative staging of gastric cancer.

Follow-up study of peripheral blood carcinoembryonic antigen mRNA using reverse transcription-polymerase chain reaction as an early marker of clinical recurrence in patients with curatively resected gastric cancer

In this study, we evaluated the clinical significance of detecting carcinoembryonic antigen (CEA) mRNA in the peripheral blood samples of patients with gastric cancer. We analyzed the peripheral blood of 46 patients with gastric cancer who had undergone curative resection. The presence of CEA mRNA was serially monitored using a CEA-specific reverse transcription–polymerase chain reaction (RT-PCR) every 2 months. The clinical recurrence rates according to category were as follows: 100% (3 of 3) in the positive conversion, 0% (0 of 18) in the negative conversion, 50% (3 of 6) in the always-positive, and 10.5% (2 of 19) in the always-negative category. The recurrence rate was 66.7% (6 of 9) in the positive group and 5.4% (2 of 37) in the negative group (P ≤0.00022). Multiple logistic regression analysis demonstrated that only group variable had a significant effect on clinical recurrence (P = 0.015). We conclude that RT-PCR analysis of CEA mRNA in the peripheral blood seems to be a promising tool for the early detection of micrometastatic circulating tumor cells in gastric carcinoma patients and that it can be useful used to identify patients at risk for recurring.

Benefit of Post-operative Surveillance for Recurrence after Curative Resection for Gastric Cancer

BackgroundAlthough most clinicians perform surveillance after gastrectomy, there is no consensus on the optimal follow-up schedule. This study aimed to evaluate the benefit of postoperative surveillance for recurrence after curative resection for gastric cancer.MethodWe retrospectively studied 110 patients who had recurrences after undergoing curative gastrectomies between 2000 and 2004 at Korea University Hospital. We analyzed the clinico-pathologic factors and oncologic results according to the presence of recurrence symptoms.ResultsFifty-five (50%) patients had symptomatic recurrences. There were significant differences in recurrence patterns; locoregional (29.1%) and peritoneal recurrences (27.3%) were dominant in asymptomatic group; peritoneal (47.3%) and hematogenous recurrences (25.5%) were dominant in symptomatic group. The median recurrence-free survival was not different for both groups (p = 0.054). However, median overall and post-recurrence survival was poor in the symptomatic group (p = 0.004, p < 0.001). The presence of symptoms and short disease-free survival were independent poor prognostic factors for post-recurrence survival.ConclusionPatients with asymptomatic recurrences could have increased survival compared to symptomatic patients. Although our post-operative surveillance could not be any benefit to improve outcomes for recurrent gastric cancer, it is important to discriminate the nature of recurrent gastric cancer by the presence of symptoms for planning further treatment.

Inflammatory myofibroblastic tumor of the stomach with peritoneal dissemination in a young adult: imaging findings.

Inflammatory myofibroblastic tumors are lesions that most often affect young adults and children. These tumors have been found in numerous extrapulmonary sites but rarely in the stomach. It is unknown whether this process is reactive or neoplastic. They are infiltrative lesions and often extend through the gastric wall, sometimes reaching adjacent organs including the esophagus, duodenum, peritoneal cavity, spleen, pancreas, and liver. These features mimic malignancy on endoscopy and radiology. We report the ultrasound, color Doppler ultrasound, and helical computed tomographic findings of a gastric inflammatory myofibroblastic tumor with peritoneal dissemination in a young adult. To our knowledge, this is the first report of color Doppler ultrasound and helical computed tomographic findings of this rare disease entity.

Incidence and Long-term Outcome of Young Patients With Gastric Carcinoma According to Sex Does Hormonal Status Affect Prognosis?

BACKGROUND We investigated the clinicopathological features and evaluated the prognostic impact of age and sex on patients with gastric cancer. DESIGN Retrospective study from 1993 to 2000. SETTING Korea University Medical Center. PATIENTS A total of 1299 patients with gastric cancer were divided into young (n = 175 [13.5%]) and older (n = 1124 [86.5%]) groups with an age cutoff of 40 years. MAIN OUTCOME MEASURES Clinicopathological characteristics were investigated and survival analysis was performed according to sex for each age group. RESULTS Tumor differentiation was significantly different between the 2 age groups. Among male patients, the young group had more undifferentiated tumors than the older group (P < .001) but, in female patients, both differentiation (P < .001) and operative methods (P = .008) were significantly different between the young and older groups. In male patients, the 10-year survival rate of the young group was higher (62.5%) than that of the older group (44.6%) (P = .03). Although it was not statistically significant, the survival rate of the older female group was higher than that of the young group (56.2% vs 51.9%). On multivariate analysis, tumor stage (P < .001) and sex (P = .042) were proved to be independent prognostic factors. CONCLUSIONS Only tumor differentiation was an important difference between the 2 age groups, and prognosis was not affected by age. However, when sex was added to age as a factor, the older male and young female groups had an unfavorable prognosis. Therefore, we propose that sex hormones such as estrogens contribute to the survival differences, and further studies are needed to confirm this possibility.

Clinical Significance of Immunohistochemically-Identified Lymphatic and/or Blood Vessel Tumor Invasion in Gastric Cancer

BACKGROUND Tumor invasion and lymph node metastasis are significant prognostic factors for gastric cancer, and lymphatic and vascular tumor invasion are also significant risk factors for gastric cancer recurrence. Recently, the immunohistochemical detection of lymphatic and blood vessel tumor invasion (LBVI) has been shown to have a higher sensitivity and specificity than hematoxylin-eosin staining methods. MATERIALS AND METHODS One hundred forty-nine gastric cancer patients who underwent curative resection at Korea University Hospital between November 2003 and December 2006 served as the study subjects. Lymphatic vessel invasion was evaluated by immunostaining with the new selective marker, D2-40, and blood vessel invasion was assessed with anti-CD31 antibody. Patients were divided according to the presence of LBVI, clinicopathologic factors were compared, and postoperative surgical outcomes were analyzed. RESULTS LBVI was present in 66 patients (44.3%). LBVI was significantly correlated with depth of tumor invasion (P < 0.001), lymph node stage (P < 0.001), and lymph node micrometastasis (P = 0.013). Cancer recurrence was more common in the LBVI group (P = 0.007), and peritoneal seeding was the most prevalent type of recurrence (P = 0.028). Univariate analysis showed tumor size, depth of tumor invasion, lymph node stage, and LBVI to have a significant impact on survival. Based on multivariate analysis, however, depth of tumor invasion and lymph node stage were correlated with survival. CONCLUSION Immunohistochemical demonstration of LBVI is an additional prognostic marker, and provides useful information for planning treatment strategies in gastric cancer patients.