Alpha-fetoprotein is a significant prognostic factor for gastric cancer: Results from a propensity score matching analysis after curative resection.

BACKGROUND: Prognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC) remains elusive so far due to disparities in cohort size and baseline characteristics in previous studies. A propensity score matching (PSM) analysis as well as multivariable model was performed for unbiased evaluation of the outcome in AFPGC. METHODS: Among 3034 gastric cancer patients who underwent curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea between 2002 and 2007, we identified 97 patients being positive for AFP either by elevation of serum-AFP levels >10 µg/L or by immunohistochemical staining. Due to marked disparities in baseline characteristics and cohort size, propensity-score-matching was performed which matched 87 AFPP-GC patients to the same number of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were compared using χ2-test. Survival curves were compared using the Kaplan-Meier-method and multivariable regression analysis was performed to evaluate the effect of AFP-positivity while adjusting the effects of confounding variables. RESULTS: AFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts. After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location, grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren histologic type and stage distribution. In multivariable regression analysis of the PSM-groups, only AFP-positivity and pathologic stage were predictive for overall survival (HR 2.98, CI 95% {1.7-5.1}, p < 0.0001). Five-year-survival rates were significantly worse for AFPP-GC patients (57.9% vs. 76.1%, p = 0.014). Recurrence was significantly more frequent in AFPP-GC patients (p = 0.003). CONCLUSION: AFP can be considered as an independent negative predictor of overall and recurrence-free survival in patients with gastric cancer.

Effect of endoscopy screening on stage at gastric cancer diagnosis: results of the National Cancer Screening Programme in Korea.

BACKGROUND: Although gastric cancer screening is common among countries with a high prevalence of gastric cancer, there is little data to support the effectiveness of this screening. This study was designed to determine the differences in stage at diagnosis of gastric cancer according to the screening history and screening method (upper gastrointestinal series (UGIS) vs endoscopy). METHODS: The study population was derived from the National Cancer Screening Programme (NCSP), a nationwide organised screening programme in Korea. The study cohort consisted of 19 168 gastric cancer patients who had been diagnosed in 2007 and who were invited to undergo gastric cancer screening via the NCSP between 2002 and 2007. RESULTS: Compared with never-screened patients, the odds ratios for being diagnosed with localised gastric cancer in endoscopy-screened patients and UGIS-screened patients were 2.10 (95% CI=1.90-2.33) and 1.24 (95% CI=1.13-1.36), respectively. CONCLUSIONS: Screening by endoscopy was more strongly associated with a diagnosis of localised stage gastric cancer compared with screening by UGIS.

Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study.

BACKGROUND: Metformin use has been associated with a decreased incidence and mortality of various cancers. AIM: To evaluate the association between metformin use and gastric cancer. METHODS: We randomly selected 100 000 type 2 diabetic patients from the 2004 Korean National Health Insurance claim database, and assessed gastric cancer incidence among 39 989 patients (aged 30-97 years) who were regularly treated with anti-diabetic drugs and followed-up from 2004 to 2010. In total, 26 690 patients had used metformin out of 32 978 diabetics who had not regularly used insulin (insulin non-users), and 5855 patients had used metformin out of 7011 regular insulin users. RESULTS: Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (P = 0.047, log-rank test). However, in patients on regular insulin, there was no difference of gastric cancer incidence according to metformin use. In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53-1.01) with borderline statistical significance (P = 0.059). Duration of metformin use was associated with the reduction in gastric cancer risk (AHR, 0.88; 95% CI 0.81-0.96, P = 0.003), especially in patients who used metformin for more than 3 years (AHR, 0.57; 95% CI, 0.37-0.87; P = 0.009). CONCLUSION: Metformin use >3 years in type 2 diabetics who do not use insulin is associated with a significantly reduced gastric cancer risk.

Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

BACKGROUND: Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. AIM: To validate the OLGA and OLGIM staging systems in a region with high risk of GC. METHODS: This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. RESULTS: More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P < 0.001), particularly among patients with intestinal-type GCs (62.2%) compared with diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. CONCLUSION: As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer.

Randomised clinical trial: the effects of Helicobacter pylori eradication on glandular atrophy and intestinal metaplasia after subtotal gastrectomy for gastric cancer.

BACKGROUND: Helicobacter pylori eradication is recommended for early gastric cancer (GC) patients after resection. AIM: To evaluate whether H. pylori eradication improves glandular atrophy and intestinal metaplasia (IM) in GC patients undergoing subtotal gastrectomy. METHODS: This randomised, double-blind trial was performed in tertiary care setting. Distal GC patients with H. pylori infection were randomised to receive proton pump inhibitor-based triple therapy or placebo. The histology was evaluated using the updated Sydney system before and at 36 months after surgery. The endpoints were the comparison of atrophy and IM score changes between the allocated groups and according to final H. pylori status. RESULTS: Overall, 190 patients were randomised to the treatment and placebo groups. For lesser curvature of the corpus, mean atrophy and IM scores did not differ between the treatment and placebo groups. However, the H. pylori-eradicated patients had significantly lower mean scores than the H. pylori-persistent patients regarding atrophy (0.55 ± 0.95 vs. 1.05 ± 1.10 respectively; P = 0.0046) and IM (0.66 ± 0.99 vs. 1.05 ± 1.16 respectively; P = 0.0284). The percentage change from baseline was more marked in the H. pylori-negative than in the H. pylori-positive groups (-58.6% vs. -11.0% for atrophy and -60.5% vs. -35.6% for IM respectively). For greater curvature, mean atrophy score was lower in the H. pylori-negative group than in the H. pylori-positive group (0.14 ± 0.50 vs. 0.41 ± 0.75 respectively; P = 0.0281). The percentage change was -36.4% vs. 86.3%. CONCLUSION: Helicobacter pylori eradication in GC patients is beneficial, as reflected by lower scores of atrophy and IM at 36 months after subtotal gastrectomy. (ClinicalTrials.gov number, NCT01002443).

Effect of chemotherapy on the outcome of self-expandable metallic stents in gastric cancer patients with malignant outlet obstruction.

BACKGROUND AND STUDY AIM: Chemotherapy has been suggested to affect the outcome of pyloric stent placement. This study aimed to investigate the association between the response to chemotherapy and pyloric stent outcome. PATIENTS AND METHODS: Data from 113 patients with inoperable gastric cancer who received chemotherapy after pyloric stent placement at the National Cancer Center hospital were analyzed retrospectively. Chemotherapy response was assessed using the Response Evaluation Criteria in Solid Tumors. A Cox proportional hazards model was used to evaluate the effect of chemotherapy response on the complications of stents. RESULTS: The stent migration rate was 15.9% (18/113) and the re-stenosis rate was 30.1% (34/113). The response rates to chemotherapy were higher in the first-line group than in the salvage chemotherapy group (second-line or more) (44.8% [26/58] vs. 3.6% [2/55], respectively; P < 0.001). The proportion of patients with long time-to-progression (> 8 weeks) was also higher in the first-line than the salvage chemotherapy group (81.0% [47 /58] vs. 61.8% [34 /55], respectively; P = 0.036). Although, the response to chemotherapy was not associated with stent migration or re-stenosis, a long time-to-progression (adjusted hazard ratio [aHR] = 0.29, 95% confidence interval [CI] 0.13-0.67) and first-line chemotherapy (aHR = 0.45, 95%CI 0.22-0.93) were protective factors against re-stenosis in the multivariate analysis. In patients who received first-line chemotherapy, the median duration of patency of covered and uncovered stents was 20 weeks (95%CI 11-29) and 33 weeks (95 %CI 18-48), respectively (P = 0.317). CONCLUSIONS: A long time-to-progression and first-line chemotherapy were significant protective factors against re-stenosis. In chemotherapy-naïve gastric cancer patients with pyloric obstruction, placement of an uncovered stent followed by chemotherapy can be considered to increase stent patency.

The influence of hospital volume and surgical treatment delay on long-term survival after cancer surgery.

BACKGROUND: We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer patients. METHODS: Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers. RESULTS: Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival [adjusted hazard ratio (aHR) = 1.36-1.86] than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal [aHR = 1.28; 95% confidence interval (CI), 1.17-1.40] and breast (aHR = 1.59; 95% CI, 1.37-1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78-3.81). CONCLUSION: Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.

Aspirin use and bleeding risk after endoscopic submucosal dissection in patients with gastric neoplasms.

BACKGROUND AND STUDY AIM: The risk of bleeding after endoscopic submucosal dissection (ESD) in patients with early gastric neoplasms who do not discontinue aspirin for the procedure has not been established. We aimed to investigate whether post-ESD gastric bleeding is increased in patients who take aspirin. PATIENTS AND METHODS: Patients who underwent ESD for early gastric neoplasms at the National Cancer Center Hospital, Korea, between November 2008 and January 2011 were enrolled. The risk of post-ESD bleeding was evaluated using Poisson regression analysis. RESULTS: We categorized 514 patients into three groups according to aspirin intake at the time of the procedure: patients who never used aspirin (n=439), patients who interrupted aspirin use for 7 days or more (n=56), and patients who continuously used aspirin (n=19). Post-ESD bleeding occurred in 4.1% (21/514) overall, and was more frequent in continuous aspirin users (4/19 [21.1%]) than in those who never used aspirin (15/439 [3.4%]) (P=0.006) and those with interrupted aspirin use (2/56 [3.6%]) (P=0.033). Multivariate analysis showed that use of aspirin by itself was associated with post-ESD bleeding (relative risk [RR] 4.49; 95% confidence interval [95%CI] 1.09-18.38). The resumption of clopidogrel combined with aspirin use (RR 26.71, 95%CI 7.09-100.53), and increased iatrogenic ulcer size (RR 1.52, 95%CI 1.14-2.02), were significantly associated with post-ESD bleeding. CONCLUSIONS: Continuous aspirin use increases the risk of bleeding after gastric ESD. Aspirin use should be stopped in patients with a low risk for thromboembolic disease to minimize bleeding complications.

Three-gene predictor of clinical outcome for gastric cancer patients treated with chemotherapy.

To identify transcriptional profiles predictive of the clinical benefit of cisplatin and fluorouracil (CF) chemotherapy to gastric cancer patients, endoscopic biopsy samples from 96 CF-treated metastatic gastric cancer patients were prospectively collected before therapy and analyzed using high-throughput transcriptional profiling and array comparative genomic hybridization. Transcriptional profiling identified 917 genes that are correlated with poor patient survival after CF at P<0.05 (poor prognosis signature), in which protein synthesis and DNA replication/recombination/repair functional categories are enriched. A survival risk predictor was then constructed using genes, which are included in the poor prognosis signature and are contained within identified genomic amplicons. The combined expression of three genes-MYC, EGFR and FGFR2-was an independent predictor for overall survival of 27 CF-treated patients in the validation set (adjusted P=0.017), and also for survival of 40 chemotherapy-treated gastric cancer patients in a published data set (adjusted P=0.026). Thus, combined expression of MYC, EGFR and FGFR2 is predictive of poor survival in CF-treated metastatic gastric cancer patients.

Comparison of surgical performance and short-term clinical outcomes between laparoscopic and robotic surgery in distal gastric cancer.

AIMS: The authors aimed to compare the surgical performance and the short-term clinical outcomes of robotic assisted laparoscopic distal gastrectomy (RADG) with laparoscopy-assisted distal gastrectomy (LADG) in distal gastric cancer patients. METHOD: From April 2009 to August 2010, 62 patients underwent LADG and 30 patients underwent RADG for preoperative stage I distal gastric cancer by one surgeon at the National Cancer Center, Korea. Surgical performance was measured using lymph node (LN) dissection time and number of retrieved LNs, which were viewed as surrogates of technical ease and oncologic quality. RESULTS: In clinicopathologic characteristics, mean age, depth of invasion and stage were significantly different between the LADG and RADG group. Mean dissection time at each LN station was greater in the RADG group, but no significant intergroup difference was found for numbers of retrieved LNs. Furthermore, proximal resection margins were smaller, and hospital costs were higher in the RADG group. In terms of the RADG learning curve, mean LN dissection time was smaller in the late RADG group (n = 15) than in the early RADG group (n = 15) for 4sb/4d, 5, 7-12a stations, but numbers of retrieved LNs per station were similar. CONCLUSION: With the exception of operating time and cost, the numbers of retrieved LNs and the short-term clinical outcomes of RADG were found to be comparable to those of LADG, despite the surgeon's familiarity with LADG and lack of RADG experience. Further studies are needed to evaluate objectively ergonomic comfort and to quantify the patient benefits conferred by robotic surgery.

CYP2A6 and ERCC1 polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients.

BACKGROUND: We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin. METHODS: Among MGC patients (n=108), who received S-1 (40 mg m(-2) b.i.d., days 1-14) and cisplatin (60 mg m(-2), day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487). RESULTS: Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3%; P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death. CONCLUSION: Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.

Risk of high-grade dysplasia or carcinoma in gastric biopsy-proven low-grade dysplasia: an analysis using the Vienna classification.

BACKGROUND AND AIMS: Therapeutic guidelines have not yet been established for low-grade gastric adenomas/dysplasias (LGD), which have a low risk of progression to high-grade adenomas/dysplasias (HGD) or to invasive carcinomas. This study aimed to evaluate risk factors for HGD/carcinoma that indicate a need for resection in biopsy-proven LGD lesions. PATIENTS AND METHODS: In total, 236 LGD lesions from 208 consecutive patients treated with endoscopic resection (ER) were retrospectively studied between 2004 and 2008. The Vienna classification was used for histological diagnosis. A generalized estimating equation (GEE) logistic regression model was used for multivariate analysis. RESULTS: Among the 236 LGD lesions, the final pathology diagnosed 9 (3.8 %) as invasive carcinoma (category 5), 71 (30.1 %) as HGD (category 4), 148 (62.7 %) as LGD (category 3), and 8 (3.4 %) as negative/indefinite for dysplasia (category 1/2). Lesions ≥ 1 cm were classified as HGD/carcinoma in 39.4 % of patients (65/165). Multivariate analysis indicated that size of ≥ 1 cm (OR 1.93 [95 % CI, 1.06 - 3.52]), depressed morphology (OR 3.81 [95 % CI, 1.22 - 11.9]), and erythema (OR 2.49 [95 % CI, 1.31 - 4.72]) were significantly associated with HGD/carcinoma. The OR increased to 47.6 (95 % CI, 4.27 - 530.65) when the risk factors were all positive. The sensitivity and negative predictive value for ≥ 1 risk factors were 93.8 % and 90.9 %, respectively. As the number of risk factors of a lesion increased, the specificity and positive predictive value also increased. CONCLUSIONS: Endoscopic resection can be recommended if a low-grade dysplastic lesion has at least one of the following risk factors: depressed morphology, surface erythema, or a size of 1 cm or greater. For lesions that have none of the three risk factors, follow-up endoscopy is recommended.

Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of S-1/irinotecan/oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and the association between treatment outcome and uridine diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms. PATIENTS AND METHODS: Patients with previously untreated MGC received S-1 40 mg/m(2) b.i.d. on days 1-14 and irinotecan 150 mg/m(2) plus oxaliplatin 85 mg/m(2) on day 1 every 3 weeks. RESULTS: Forty-four patients were enrolled. In intent-to-treat analysis, the objective response rate was 75%, including the complete response (CR) rate of 14%. The median time to progression and overall survival was 10.2 and 17.6 months, respectively. Ten (26%) of the 39 patients with primary gastric tumor showed biopsy-confirmed gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. The most common grade 3 nonhematologic toxic effects were abdominal pain (18%), anorexia (16%), and diarrhea (14%). UGT1A polymorphisms were associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, and UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), and grade 3 abdominal pain (UGT1A1*6). CONCLUSIONS: The TIROX regimen induced marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. UGT1A genotype may be predictive of TIROX toxicity.

Risk factors for lymph node metastasis in patients with early gastric cancer and signet ring cell histology.

BACKGROUND: Early gastric cancer with signet ring cell histology has been reported as a favourable histological type. The aim of this study was to identify risk factors associated with lymph node metastasis in patients with this type of early gastric cancer. METHODS: A cross-sectional study of patients with early gastric cancer with differentiated and signet ring cell histology undergoing surgery was conducted. Risk factors were evaluated using multiple logistic regression analysis with odds ratios and 95 per cent confidence intervals. RESULTS: In 1362 patients undergoing gastrectomy for early gastric cancer, the rate of lymph node metastasis was similar for tumours with signet ring cell and differentiated histological findings (10.7 versus 9.0 per cent respectively; P = 0.307). Logistic regression analysis showed that depth of tumour invasion was predictive of lymph node metastasis in patients with signet ring cell histology (P < 0.001). Tumour size was not associated with lymph node metastasis in either univariable or multivariable analysis. Lesions smaller than 2 cm were not uncommon in patients with signet ring cell gastric tumours and lymph node metastases (six of 48; 13 per cent). CONCLUSION: Patients with early gastric cancer with signet ring cell-type histology are probably best treated by gastrectomy with lymph node dissection.

Risk of hemorrhagic gastropathy associated with colonoscopy bowel preparation using oral sodium phosphate solution.

BACKGROUND AND STUDY AIMS: Oral sodium phosphate (NaP) solution is widely used for colonoscopy bowel preparation and it may cause aphthous ulcers in the colon. Our aim was to evaluate whether oral NaP solution is associated with gastric mucosal lesions. METHODS: A total of 20 070 individuals underwent esophagogastroduodenoscopy (EGD) with colonoscopy, and 4271 individuals underwent EGD without colonoscopy, for cancer screening. Oral NaP solutions were used for bowel preparation prior to colonoscopy. Hemorrhagic gastropathy was graded using a five-point scale for erosive mucosal injury. The effect of NaP bowel preparation on hemorrhagic gastropathy was estimated using multiple logistic regression analysis with odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: The incidence of hemorrhagic gastropathy was 1.6 % (70/4271) in the EGD only group and 4.0 % (809/20 070) in the EGD with colonoscopy group ( P < 0.001, unadjusted OR 2.55, 95 %CI 1.99 - 3.27). The ORs for mild (grade 1 - 2), moderate (grade 3), and severe (grade 4) hemorrhagic gastropathy according to NaP use were 1.92 (95 %CI 1.45 - 2.54), 4.72 (95 %CI 2.65 - 8.47), and 5.99 (95 %CI 1.46 - 24.63), respectively. After adjustment for confounding factors, NaP solution was a significant risk factor for acute hemorrhagic gastropathy in the multivariate analysis (OR 1.92, 95 %CI 1.34-2.74). In addition, male sex, a body mass index (kg/m (2)) of less than 20, concurrent use of antihypertensive or nonsteroidal anti-inflammatory drugs, and duodenal ulcers were independently associated with the development of hemorrhagic gastropathy. HELICOBACTER PYLORI infection and atrophic gastritis were negatively associated with hemorrhagic gastropathy. CONCLUSION: Oral NaP bowel preparation for colonoscopy was associated with hemorrhagic gastropathy.

Obesity and weight gain as risk factors for erosive oesophagitis in men.

BACKGROUND: Although obesity and weight gain increase the risk for symptoms of gastro-oesophageal reflux disease, their association with erosive oesophagitis is still unclear in the male population. AIM: To evaluate, in men, the association of body mass index (BMI) and weight gain with endoscopically proven erosive oesophagitis. METHODS: A total of 8571 Korean men in a comprehensive screening cohort were enrolled. Effects of BMI and abdominal obesity on erosive oesophagitis were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression analysis. We also evaluated the association between erosive oesophagitis and BMI change after 1-3 years. RESULTS: The prevalence of erosive oesophagitis was 6.4% (552/8571). In univariate analysis, the ORs for erosive oesophagitis increased as BMI or waist circumference increased (P for trend <0.001, both). In multivariate analysis, OR for erosive oesophagitis increased as BMI increased (P for trend = 0.002), while the significance of waist circumference was attenuated (P for trend = 0.13). Increase in BMI (>or=1 kg/m2) was associated with persistence of erosive oesophagitis (OR = 2.83, 95% CI: 1.01-7.92, P = 0.04) and new development of the disease (OR = 2.13, 95% CI: 1.38-3.28, P = 0.001) compared with BMI change less than 1 kg/m2. CONCLUSIONS: Elevated BMI and weight gain have a significant association with erosive oesophagitis.

Learning curve for identification of sentinel lymph node based on a cumulative sum analysis in gastric cancer.

BACKGROUND/AIMS: Lymph node metastasis is the most important point to consider when deciding on the modality of resection in patients with early gastric cancer. This study was conducted to evaluate the learning curve for identification of sentinel lymph nodes in patients with gastric cancer. METHODS: The investigators included the results from 2 prospective series of sentinel lymph node mapping. Cumulative sum (CUSUM) analysis was performed to assess the learning curves for identification of sentinel lymph nodes at CUSUM target success rates of 95%. RESULTS: One surgeon performed 135 sentinel lymph node mappings for 2 prospective series. The success rate exceeded 90%. The learning period for gastric cancer sentinel node mapping was calculated to be 26 cases for achieving a 95% success rate. Multiple logistic regression analysis for successful detection of sentinel nodes showed that surgical experience of sentinel lymph node mapping was an independent factor for successful detection of sentinel nodes. CONCLUSIONS: This study suggests that the learning period for identification of sentinel lymph nodes in gastric cancer would be 26 cases. In clinical trials for gastric cancer with sentinel lymph node mapping, the learning curve should be considered to minimize bias due to surgical factors.

Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma.

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1-14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30-45 mg m(-2) b.i.d.) and docetaxel (25-40 mg m(-2)); MTD was 45 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel and RD was 40 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8-79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9-8.1) and 13.7 months (95% CI: 9.9-17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.