Family History of Gastric Cancer and Helicobacter pylori Treatment.

BACKGROUND: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period. RESULTS: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). CONCLUSIONS: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).

Clinical Practice Guideline for Gastritis in Korea.

Gastritis is a disease characterized by inflammation of the gastric mucosa. It is very common and has various classification systems such as the updated Sydney system. As there is a lot of evidence that Helicobacter pylori infection is associated with the development of gastric cancer and that gastric cancer can be prevented by eradication, H. pylori gastritis has been emphasized recently. The incidence rate of gastric cancer in Korea is the highest in the world, and due to the spread of screening endoscopy, atrophic gastritis and intestinal metaplasia are commonly diagnosed in the general population. However, there have been no clinical guidelines developed in Korea for these lesions. Therefore, this clinical guideline has been developed by the Korean College of Helicobacter and Upper Gastrointestinal Research for important topics that are frequently encountered in clinical situations related to gastritis. Evidence-based guidelines were developed through systematic review and de novo processes, and eight recommendations were made for eight key questions. This guideline needs to be periodically revised according to the needs of clinical practice or as important evidence about this issue is published in the future.

Efficacy of endoscopic management for anastomotic leakage after gastrectomy in patients with gastric cancer.

BACKGROUND: Anastomotic leakage (AL) after gastrectomy in gastric cancer patients is associated with high mortality rates. Various endoscopic procedures are available to manage this postoperative complication. The aim of study was to evaluate the outcome of two endoscopic modalities, clippings and stents, for the treatment of AL. PATIENTS AND METHODS: There were 4916 gastric cancer patients who underwent gastrectomy between December 2007 and January 2016 at the National Cancer Center, Korea. A total of 115 patients (2.3%) developed AL. Of these, 85 patients (1.7%) received endoscopic therapy for AL and were included in this retrospective study. The endpoints were the complete leakage closure rates and risk factors associated with failure of endoscopic therapy. RESULTS: Of the 85 patients, 62 received endoscopic clippings (with or without detachable snares), and 23 received a stent insertion. Overall, the complete leakage closure rate was 80%, and no significant difference was found between the clipping and stent groups (79.0% vs. 82.6%, respectively; P = 0.89). The complete leakage closure rate was significantly lower in the duodenal and jejunal stump sites (60%) than esophageal sites (86.1%) and gastric sites (94.1%; P = 0.026). The multivariate analysis showed that stump leakage sites (adjusted odds ratio [aOR], 4.51; P = 0.031) and the presence of intra-abdominal abscess (aOR, 4.92; P = -0.025) were associated with unsuccessful leakage closures. CONCLUSIONS: Endoscopic therapy using clippings or stents is an effective method for the postoperative management of AL in gastric cancer patients. This therapy can be considered a primary treatment option due to its demonstrated efficacy, safety, and minimally invasive nature.

Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer.

BACKGROUND: Patients with early gastric cancers that are limited to gastric mucosa or submucosa usually have an advanced loss of mucosal glandular tissue (glandular atrophy) and are at high risk for subsequent (metachronous) development of new gastric cancer. The long-term effects of treatment to eradicate Helicobacter pylori on histologic improvement and the prevention of metachronous gastric cancer remain unclear. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, we assigned 470 patients who had undergone endoscopic resection of early gastric cancer or high-grade adenoma to receive either H. pylori eradication therapy with antibiotics or placebo. Two primary outcomes were the incidence of metachronous gastric cancer detected on endoscopy performed at the 1-year follow-up or later and improvement from baseline in the grade of glandular atrophy in the gastric corpus lesser curvature at the 3-year follow-up. RESULTS: A total of 396 patients were included in the modified intention-to-treat analysis population (194 in the treatment group and 202 in placebo group). During a median follow-up of 5.9 years, metachronous gastric cancer developed in 14 patients (7.2%) in the treatment group and in 27 patients (13.4%) in the placebo group (hazard ratio in the treatment group, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.03). Among the 327 patients in the subgroup that underwent histologic analysis, improvement from baseline in the atrophy grade at the gastric corpus lesser curvature was observed in 48.4% of the patients in the treatment group and in 15.0% of those in the placebo group (P<0.001). There were no serious adverse events; mild adverse events were more common in the treatment group (42.0% vs. 10.2%, P<0.001). CONCLUSIONS: Patients with early gastric cancer who received H. pylori treatment had lower rates of metachronous gastric cancer and more improvement from baseline in the grade of gastric corpus atrophy than patients who received placebo. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT02407119 .).

Ten-day bismuth-containing quadruple therapy versus 7-day proton pump inhibitor-clarithromycin containing triple therapy as first-line empirical therapy for the Helicobacter pylori infection in Korea: a randomized open-label trial.

BACKGROUND: This randomized, open-label trial aimed to compare the efficacy of 10-day bismuth-containing quadruple therapy (BQT) with 7-day proton-pump inhibitor-clarithromycin containing standard triple therapy (STT) as an empirical first-line Helicobacter pylori therapy. METHODS: Participants with H. pylori infection were randomly assigned to either 10-day BQT (daily doses of bismuth 300 mg, four times; lansoprazole 30 mg, twice; metronidazole 500 mg, three times; and tetracycline 500 mg, four times) or 7-day STT (lansoprazole 30 mg; amoxicillin 1,000 mg; and clarithromycin 500 mg; each given twice daily). Participants who failed initial therapy were crossed over to the alternative treatment regimen. Primary outcome was the eradication rates of first-line treatment by intention-to-treat analysis. RESULTS: Study participants (n = 352) were randomized to receive either 10-day BQT (n = 175) or 7-day STT (n = 177). The BQT-group achieved a significantly higher eradication rate than the STT-group in the intention-to-treat analysis (74.3% vs 57.1%, respectively; P = 0.001), modified intention-to-analysis (87.2% [130/149] vs 68.7% [101/147], respectively; P < 0.001) and per-protocol analysis (92.9% [105/113] vs 70.1% [94/134], respectively; P < 0.001). Although there was no serious adverse event, the compliance was lower with BQT than STT as a higher proportion of participants in the BQT-group discontinued therapy because of adverse events than those in the STT-group (23.1% vs 9.1%, respectively; P = 0.001) CONCLUSIONS: Ten-day BQT had higher eradication rates compared to that of the 7-day STT as an empirical first-line treatment for H. pylori eradication in Korea. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02557932. Registered 23 September 2015, https://clinicaltrials.gov/ct2/show/NCT02557932?term=NCT02557932&draw=2&rank=1 .

Comparison of the performance of risk scoring systems for tumor bleeding in patients with inoperable gastric cancer.

BACKGROUND: The Glasgow - Blatchford bleeding score (GBS) and admission and full Rockall scores are widely used risk scoring systems to stratify risk and determine the need for intervention in patients with upper gastrointestinal bleeding. We evaluated the performance of these risk scoring systems in patients with gastric cancer and tumor bleeding. METHODS: This retrospective study included patients with inoperable gastric cancer who presented with tumor bleeding at the National Cancer Center, Korea, between 2001 and 2015. The GBS, and admission and full Rockall scores were calculated. Primary outcome was the performance of the risk scoring systems in predicting the need for urgent interventions (endoscopic therapy, transarterial embolization, and surgery). The risk factors associated with urgent intervention were analyzed. RESULTS: Of 357 patients with tumor bleeding, 118 (33.1 %; 116 endoscopic therapy, 2 trans-arterial embolization) required urgent intervention. The full Rockall score was better at predicting the need for urgent intervention (area under the receiver operating characteristic curve = 0.78; P < 0.001) than the GBS (0.56) and admission Rockall score (0.56). Hemostatic intervention was not performed in patients with a full Rockall score ≤ 6 (103 patients, 28.9 %). On multivariate analysis, endoscopic stigmata of recent hemorrhage of Forrest classes Ia - IIb were significant factors associated with urgent intervention. CONCLUSIONS: The full Rockall score was superior to the GBS and admission Rockall score in predicting the need for urgent intervention for tumor bleeding. Thus, endoscopic evaluation is required to determine the need for urgent intervention in patients with gastric cancer and tumor bleeding.

Low Frequency of Lymph Node Metastases in Patients in the United States With Early-stage Gastric Cancers That Fulfill Japanese Endoscopic Resection Criteria.

BACKGROUND & AIMS: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSIONS: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Effect of gastrectomy on blood pressure in early gastric cancer survivors with hypertension.

PURPOSE: We investigated the effect of gastrectomy on blood pressure (BP) in early gastric cancer survivors with hypertension and whether well-controlled BP was due solely to surgery-induced weight loss. METHODS: The study enrolled 66 early gastric cancer patients with hypertension, undergoing endoscopic submucosal dissection (ESD), or gastrectomy. Blood analyses, 24-h ambulatory BP monitoring, brachial ankle pulse wave velocity (baPWV), and echocardiography were measured prior to, 3 months after, and 1 year after ESD or gastrectomy. The primary endpoint was remission of hypertension at 1 year. RESULTS: The remission rate of hypertension was significantly higher in the gastrectomy group than in the ESD group (p = 0.006). Those with remission of hypertension had a significant weight loss (p < 0.001), decrease in body mass index (p < 0.001), 24-h total systolic BP (p = 0.047), baPWV (p = 0.042), triglycerides (p = 0.049) and apolipoprotein B/apolipoprotein A1 (p = 0.004), and an increase in high-density lipoprotein cholesterol (p < 0.001) at 1 year. Upon multivariate logistic regression analysis, gastrectomy [odds ratio (OR) = 7.77, 95% confidence interval (CI) = 2.05-35.89], diuretic use (OR = 3.76, 95% CI = 1.14-13.98), and lower 24-h total diastolic BP before treatment (OR = 0.90, 95% CI = 0.82-0.96) were predictive of remission of hypertension after adjusting for percent weight. CONCLUSIONS: In early gastric cancer survivors with hypertension, gastrectomy resulted in better BP control than did ESD, which may be due to the gastrectomy itself, beyond weight loss. Therefore, it should be remembered that the adequate reduction of antihypertensives may be necessary in early gastric cancer survivors after gastrectomy.

Three-year interval for endoscopic screening may reduce the mortality in patients with gastric cancer.

BACKGROUND: Endoscopic screening has been adopted in South Korea for the national screening of gastric cancer (GC). This study aimed to assess the effect on overall survival of GC patients and determine the optimal endoscopic screening interval. METHODS: The baseline characteristics and overall survival of GC patients treated at the National Cancer Center, Korea, between 2010 and 2016 were compared between those without a history of endoscopic evaluation (group N) and those in whom the interval between the last endoscopic evaluations and diagnosis of GC was ≤ 1, 1-2, 2-3, 3-4, or > 4 years (groups 1-5, respectively). RESULTS: A total of 2362 patients met the criteria for the study (1060 in group N and 1302 in groups 1-5). More patients in groups 1-5 were diagnosed with stage I GC (83.7, 83.7, 71.8, 78.2, and 71.6%, respectively) than in group N (62.4%, P < 0.001) and were treated endoscopically (38.8, 33.8, 24.7, 21.8, and 15.5%, respectively, vs. 13.5%; P < 0.001). Group 2 had less-advanced tumor stages (P = 0.001) and was more likely to have received endoscopic treatments (P = 0.026) than group 3. Hazard ratios for death were significantly lower in groups 2 (0.45; 95% confidence interval [CI], 0.32-0.64) and 3 (0.57; 95% CI, 0.33-0.98) than in group N; the decrease was not significant in group 4 (0.49, 95% CI, 0.20-1.20). CONCLUSIONS: Endoscopic screening every 3 years may reduce the mortality of GC patients, though screenings at least every 2 years may benefit patients with less-advanced stages.

The distribution pattern of metastatic lymph nodes after non-curative endoscopic resection in early gastric cancer.

BACKGROUND AND OBJECTIVES: Additional surgery should be done after non-curative endoscopic resection (ER) in early gastric cancer (EGC) due to the risk of lymph node metastasis (LNM). However, the distribution pattern of LNM in these patients is complicated and unpredictable. The aim of this study is to identify any different distribution patterns of LNM in patients with EGC who underwent additional surgery after non-curative (ER) comparing to those without ER. METHODS: Patients who underwent surgery for EGC between 2001 and 2016 were included. Enrolled patients were divided into two groups, those who underwent additional surgery after non-curative ER and those who underwent direct surgery without a history of ER. Demographics, tumor characteristics and LNM distribution pattern were analyzed. RESULTS: Among 4295 patients with EGC, 404 patients had a history of preoperative ER, and 3891 patients did not. After the application of exclusion criteria, 23 (7.1%) of 322 patients undergoing additional surgery had LNM. The additional surgery group showed less LNM, fewer nodal stations and more restricted distribution pattern of LNM. CONCLUSIONS: The distribution pattern of LNM in EGC is complicated. However, more restricted locoregional LNM could be expected in cases of additional surgery after non-curative ER than after direct surgery.

Body mass index and mortality in patients with gastric cancer: a large cohort study.

BACKGROUND: The effects of obesity on prognosis in gastric cancer are controversial. AIMS: To evaluate the association between body mass index (BMI) and mortality in patients with gastric cancer. METHODS: A single-institution cohort of 7765 patients with gastric cancer undergoing curative gastrectomy between October 2000 and June 2016 was categorized into six groups based on BMI: underweight (< 18.5 kg/m2), normal (18.5 to < 23 kg/m2), overweight (23 to < 25 kg/m2), mildly obese (25 to < 28 kg/m2), moderately obese (28 to < 30 kg/m2), and severely obese (≥ 30 kg/m2). Hazard ratios (HRs) for overall survival (OS) and disease-specific survival (DSS) were calculated using Cox proportional hazard models. RESULTS: We identified 1279 (16.5%) all-cause and 763 (9.8%) disease-specific deaths among 7765 patients over 83.05 months (range 1.02-186.97) median follow-up. In multivariable analyses adjusted for statistically significant clinicopathological characteristics, preoperative BMI was associated with OS in a non-linear pattern. Compared with normal-weight patients, underweight patients had worse OS [HR 1.42; 95% confidence interval (CI) 1.15-1.77], whereas overweight (HR 0.84; 95% CI 0.73-0.97), mildly obese (HR 0.77; 95% CI 0.66-0.90), and moderately obese (HR 0.77; 95% CI 0.59-1.01) patients had better OS. DSS exhibited a similar pattern, with lowest mortality in moderately obese patients (HR 0.58; 95% CI 0.39-0.85). Spline analysis showed the lowest all-cause mortality risk at a BMI of 26.67 kg/m2. CONCLUSION: In patients undergoing curative gastric cancer surgery, those who were overweight or mildly-to-moderately obese (BMI 23 to < 30 kg/m2) preoperatively had better OS and DSS than normal-weight patients.

Non-exposure simple suturing endoscopic full-thickness resection (NESS-EFTR) versus laparoscopic wedge resection: a randomized controlled trial in a porcine model.

BACKGROUND: Current endoscopic full-thickness resection (EFTR) methods produce transmural communication and expose the tumor to the peritoneum. An EFTR method with a simple suturing technique that does not expose the gastric mucosa to the peritoneum (non-exposure simple suturing, NESS) was recently developed. To date, there have been no prospective studies that compare EFTR with laparoscopic wedge resection in human or animal. The aim of this study was to compare outcomes between NESS-EFTR and laparoscopic wedge resection (LWR) using the linear staplers in a randomized animal study. METHODS: NESS-EFTR includes steps of laparoscopic seromuscular suturing, EFTR of the inverted stomach wall, and endoscopic mucosal suturing with endoloops and clips. Sixteen pigs underwent NESS-EFTR (n = 8) or LWR (n = 8). The resected locations were the cardia, fundus, upper body anterior and greater curvature, antrum lesser and greater curvature side. The pigs were killed 3 weeks after surgery. Rates of successful complete resection (en-bloc resection with clear margins), successful closure, and complications were evaluated. RESULTS: The complete resection rates in the NESS-EFTR and LWR groups were 100 and 75%, respectively (P = 0.467). All wounds were successfully closed in both groups. Resected tissues were significantly larger in the LWR group (mean ± SD: 8.0 ± 0.8 cm vs. 4.4 ± 0.5 cm, P < 0.001). Procedure time was significantly shorter in the LWR group (31.7 ± 10.0 min vs. 118.1 ± 23.4 min, P < 0.001). Early deaths due to complications only occurred in the LWR group (a leakage at cardia and a stenosis at the antrum lesser curvature side). CONCLUSIONS: Incomplete resection and complications were occurred in only LWR group. NESS-EFTR was feasible and safe in animal.

Recovery of Food Intake after Gastrectomy for Gastric Cancer: Based on a Large-Scale Gastric Cancer Cohort.

BACKGROUND: This study was aimed at evaluating the food intake and nutritional status of patients who underwent gastrectomy for gastric cancer based on a large-scale gastric cancer cohort. METHODS: An observational prospective cohort study for gastric cancer has been conducted since 2010. From the cohort data, we selected the data for patients who completed at least 2 days of 3-day diet diaries and who underwent subtotal gastrectomy (STG) or total gastrectomy (TG). As a control group, patients who underwent endoscopic submucosal dissection were also included. The collected diet data were converted to macro- and micronutrients using computerized software, and the nutrient intakes were compared. RESULTS: Among 6,556 patients who participated in the cohort study from 2011 to 2016, 1,289 patients who completed at least 2 days of 3-day diet diaries were included in this study. During the postoperative 3-month period, body weight was significantly decreased in the and TG groups. However, there was no difference in nutrient intake among the 3 groups except vitamin D and calcium intake. Similar results were observed during the postoperative 12 months period. CONCLUSIONS: Postoperative body weight loss and anemia might originate from altered absorptive function and metabolic change after gastrectomy rather than decreased nutrient intake.

Survival benefit of additional surgery after noncurative endoscopic resection in patients with early gastric cancer.

BACKGROUND AND AIMS: Excellent long-term outcome is expected for early gastric cancers (EGCs) after endoscopic submucosal dissection (ESD). However, if ESD is considered noncurative at the pathologic evaluation, additional surgery is recommended. We evaluated whether long-term outcome is compromised if additional surgery is not performed for EGCs that are out-of-indication. METHODS: We retrospectively analyzed a cohort of patients with EGC not meeting ESD indications whose initial treatment was either ESD (n = 219) or surgery (n = 1799). Among them, 127 patients who underwent additional surgery after initial ESD and 67 patients who did not were matched using propensity scores to patients who initially underwent standard surgery, at a 1:1 ratio. Overall mortality and gastric cancer recurrence were compared. RESULTS: The overall mortality and gastric cancer recurrence rates were not significantly different between the 127 patients who underwent initial ESD with additional surgery and the corresponding initial standard surgery patients. However, the overall mortality of the 67 patients who underwent ESD without additional surgery (5-year mortality, 26.0%; 95% CI, 13.5%-49.9%) was higher than that of the matched initial standard surgery patients (5-year mortality, 14.5%; 95% CI, 6.3%-33.6%; P = .04). Gastric cancer recurrence was also higher in ESD patients without additional surgery (5-year recurrence, 17.0%; 95% CI, 7.6%-37.8%) than in the matched initial surgery group (0%; P = .002). In multivariate analyses, ESD without additional surgery was a significant risk factor for overall mortality and gastric cancer recurrence. CONCLUSIONS: Additional surgery should be encouraged after non-curative ESD to obtain long-term outcomes comparable with those of initial standard surgery. (Clinical trial registration number: NCC2015-0093.).

Effect of biopsy site on detection of gastric cancer high-risk groups by OLGA and OLGIM stages.

BACKGROUND/AIMS: The operative link for gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems are recommended to assess the severity of gastritis, but the optimal biopsy sites have not been clearly defined. We aimed to investigate whether the scoring of the OLGA and OLGIM stages was affected by the use of different biopsy sites. METHODS: Between 2014 and 2015, to determine OLGA and OLGIM stages, seven biopsy samples were obtained from the antrum (lesser and greater curvatures [LG] of the antrum and lesser curvature of the angle) and corpus (LG and anterior and posterior walls [AP]) in 247 patients diagnosed with gastritis, gastric adenoma, or adenocarcinoma. The OLGA and OLGIM stages were scored using four different protocols: antrum + angle + corpus LG, antrum + angle + corpus AP, antrum + corpus LG, and antrum + corpus AP. High-risk group included patients who had OLGA or OLGIM stages III and IV. RESULTS: For the OLGA stage, the angle + antrum + corpus LG protocol placed more patients in the high-risk group (64.4%) than the angle + antrum + corpus AP (55.5%, P < .001), antrum+corpus LG (59.5%, P = .031), and antrum + corpus AP (47.8%, P < .001) protocols. Likewise, for the OLGIM stage, the angle + antrum + corpus LG protocol placed more patients in the high-risk group (48.6%) than the angle + antrum + corpus AP (46.2%, P = .134), antrum + corpus LG (36.8%, P < .001), and antrum + corpus AP (37.2%, P < .001) protocols. CONCLUSIONS: To prevent underestimation of OLGA and OLGIM stages, it is necessary to include an angle biopsy, and to obtain corpus biopsy specimens from lesser and greater curvature sites rather than from anterior and posterior wall sites.

Current status and challenges in sentinel node navigation surgery for early gastric cancer.

Although a number of feasibility studies for sentinel node (SN) concepts in gastric cancer have been conducted since 2000, there remains a debate regarding detailed detection techniques and oncological safety. Two important multicenter phase II clinical trials were performed in Japan that used different methods and reached different conclusions; one confirmed acceptable results with a false-negative rate of 7%, and the other showed an unacceptably high false-negative rate of 46.4%. The Sentinel Node Oriented Tailored Approach (SENORITA) trial is a multicenter randomized controlled phase III trial being performed in Korea. Patient enrollment is now complete and the long-term results are currently awaited. Recently, an image-guided SN mapping technique using infrared ray/fluorescence was introduced. This method might be a promising technology because it allows the clear visualization of SNs. With regard to the primary tumor, the non-exposed endoscopic wall-inversion surgery technique and non-exposure endolaparoscopic full-thickness resection with simple suturing technique have been reported. These methods prevent abdominal infection and tumor seeding and can be good alternatives to conventional laparoscopic gastric wedge resection. For indications, SN navigation surgery can be extended to patients who underwent non-curative endoscopic resection. Although a few studies have been performed on these patients, sentinel concepts may be beneficial to patients as they omit the need for additional gastrectomy. SN navigation surgery can lead to actual organ-preserving surgery and plays a key role in improving the quality of life of patients with early gastric cancer in the future.

Lymph node metastasis risk according to the depth of invasion in early gastric cancers confined to the mucosal layer.

BACKGROUND: Early gastric cancers (EGCs) within the mucosal layer of the gastric wall have a small risk of lymph node (LN) metastasis. METHODS: We reviewed clinicopathology data for patients who underwent surgery for EGC between 2001 and 2013 at the National Cancer Center, Korea. Poisson regression analyses were performed to compare the risk of LN metastasis according to the depth of tumor invasion in patients with mucosal EGCs. RESULTS: Among the 1776 EGC patients included, 580 (32.7 %) had tumors confined to the lamina propria (LP; LP group) and 1196 (67.3 %) had tumors invading the muscularis mucosae (MM; MM group). Seventy-one patients (4.0 %) had LN metastasis, and the MM group had a significantly higher rate of LN metastasis (59 patients, 4.9 %) than the LP group (12 patients, 2.1 %; P = 0.004). A multivariate analysis showed that tumors invading the MM (adjusted risk ratio 1.95; P = 0.045) were significantly associated with LN metastasis in addition to well-known risk factors, including tumor size greater than 3 cm, presence of ulceration, undifferentiated histologic type, and lymphovascular invasion. The incidence of LN metastasis was 1.87 % (95 % confidence interval 0.23-6.59 %) within tumors invading the MM that met the expanded criterion for endoscopic resection of differentiated histologic type of size 3 cm or smaller with ulceration. LN metastasis was not found in tumors meeting the absolute criteria for endoscopic resection. CONCLUSIONS: EGCs invading the MM had a higher rate of lymph node metastasis than those confined to the LP. Further study is needed to evaluate whether different curative treatment criteria are needed for LP-confined and MM-invading EGCs.

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival.

BACKGROUND: We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome. METHODS: Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system] received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2) twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1. RESULTS: From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and worse survival than those with wild/wild or wild/variant genotypes. CONCLUSION: Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.

Risk of lymph node metastasis in differentiated type mucosal early gastric cancer mixed with minor undifferentiated type histology.

BACKGROUND: The possibility of lymph node metastasis is critical to the assessment of the indication for endoscopic submucosal dissection. The differentiation of tumors is an important predicting factor for lymph node metastasis. Even though gastric cancers frequently show intratumoral heterogeneity, most studies have not considered the effects of the minor histologic components. The purpose of this study was to investigate the relationship between the presence of undifferentiated type histology (UD-min) within differentiated type tumors and lymph node metastases in early gastric cancer confined to the mucosal layer. METHODS: A retrospective study of 847 patients who underwent surgery for differentiated early gastric cancer, confined to mucosa, was conducted. We analyzed the proportion of the undifferentiated type components of the tumor and their relationship with lymph node metastasis. RESULTS: The overall rate of lymph node metastasis was 1.7 % (14/847 patients) and 215 differentiated tumors (25.4 %) have UD-min. UD-min was associated with female sex, younger age, larger tumor size, and the presence of ulcer. Lymph node metastasis rate with or without UD-min was 5.1 % (11/215) versus 0.5 % (3/632), respectively (p < 0.001). UD-min was found to be associated with lymph node metastasis in the multivariate analyses (odds ratio [OR] = 4.39, CI 1.08-17.89). When three risk factors (tumor size >2 cm, ulcer, and UD-min) were present concurrently, the rate of lymph node metastasis was high (10 %). CONCLUSIONS: The presence of an UD-min component should be considered when assessing curative resection status of endoscopic submucosal dissection for differentiated type mucosal cancer.

Optimal submucosal invasion of early gastric cancer for endoscopic resection.

BACKGROUND: A small differentiated gastric cancer with minute submucosal invasion after endoscopic resection is regarded as the curative resection criterion of an expanded indication. However, recent studies have shown a high incidence of lymph node metastasis in those meeting the expanded criteria. The aim of this study was to evaluate the validity of the 500 µm criterion and to determine an optimal cutoff value for the expanded indication. METHODS: We reviewed the clinicopathological data of 1,322 patients who underwent curative resection for submucosal gastric cancer between 2001 and 2013. The full thickness of the submucosa and the incidence of lymph node metastasis according to the depth of the submucosal invasion were evaluated. The sensitivity, specificity, and positive and negative predictive values were calculated with receiver operating characteristic (ROC) curve analysis. RESULTS: The mean full thickness of the submucosa was 2,605 ± 1,760 µm, and the incidence of lymph node metastasis in 103 tumors meeting the expanded indication was 3.9 % (4/103). In the ROC analysis, the area under the curve was 0.664 (95 % confidence interval 0.538-0.791; p = 0.017), and the highest negative predictive value of 98 % was observed when the cutoff value was 300 µm. CONCLUSIONS: This study suggests that a range reduction in the depth of submucosal invasion is required to obtain a high negative predictive value. Further large-scale studies are required to validate the optimal cutoff value proposed in this study.