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Background: Although second-line therapy is often considered for advanced gastric cancer patients, the optimal candidates are not well defined. Methods: We retrospectively collected baseline parameters, tumour features, and treatment data for 868 advanced gastric cancer patients exposed to multiple treatment lines at 19 Italian centres. Cross-tables and chi-square tests were used to describe categorical features. To predict the impact of clinical variables on progression-free survival and overall survival, Kaplan-Meier and Cox regression analyses were performed. Results: At the start of second-line therapy, median age was 64.8 years (25th-75th percentiles: 55.2-71.9 years). Overall, 43% of patients received single-agent chemotherapy, 47.4% a doublet, and 7.3% a triplet. Median second-line progression-free survival was 2.8 months (25th-75th percentiles: 1.8-5.2 months) and median second-line overall survival was 5.6 months (25th-75th percentiles: 2.9-10.0 months). Multivariate analysis showed that performance status, LDH level, neutrophils/lymphocytes ratio, and progression-free survival in the first-line therapy all impacted on prognosis. Based on these four prognostic factors, a prognostic index was constructed that divided patients into good, intermediate, and poor risk groups; median second-line overall survival for each group was 7.7, 4.5, and 2.0 months, respectively (log-rank p < 0.0001). Conclusions: Advanced gastric cancer patients with a favourable ECOG performance status, lower LDH levels, and a lower neutrophils/lymphocytes ratio at the start of second-line therapy seem to have better outcomes, regardless of age and intensity of treatment. A longer progression-free survival in the first-line therapy also had positive prognostic value. Our real-life study might help clinicians to identify the patients who may benefit most from a second-line therapy. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive techniques for gastric cancer surgery have recently been introduced in the Netherlands, based on a proctoring program. The aim of this population-based cohort study was to evaluate the short-term oncological outcomes of minimally invasive gastrectomy (MIG) during its introduction in the Netherlands. Methods: The Netherlands Cancer Registry identified all patients with gastric adenocarcinoma who underwent gastrectomy with curative intent between 2010 and 2014. Multivariable analysis was performed to compare MIG and open gastrectomy (OG) on lymph node yield (≥15), R0 resection rate, and 1-year overall survival. The pooled learning curve per center of MIG was evaluated by groups of five subsequent procedures. Results: Between 2010 and 2014, a total of 277 (14%) patients underwent MIG and 1633 (86%) patients underwent OG. During this period, the use of MIG and neoadjuvant chemotherapy increased from 4% to 39% ( p < 0.001) and from 47% to 62% ( p < 0.001), respectively. The median lymph node yield increased from 12 to 20 ( p < 0.001), and the R0 resection rate remained stable, from 86% to 91% ( p = 0.080). MIG and OG had a comparable lymph node yield (OR, 1.01; 95% CI, 0.75-1.36), R0 resection rate (OR, 0.86; 95% CI, 0.54-1.37), and 1-year overall survival (HR, 0.99; 95% CI, 0.75-1.32). A pooled learning curve of ten procedures was demonstrated for MIG, after which the conversion rate (13%-2%; p = 0.001) and lymph node yield were at a desired level (18-21; p = 0.045). Conclusion: With a proctoring program, the introduction of minimally invasive gastrectomy in Western countries is feasible and can be performed safely. [ABSTRACT FROM AUTHOR]

Background: Pulmonary thromboembolism (PE) is one of the life-threatening complications of gastric cancer surgery. D-dimer assay is a safe and rapid tool to exclude the presence of deep venous thrombosis (DVT). In July 2012, we started preoperative DVT screening of patients scheduled for gastric cancer surgery using a combination of D-dimer measurements and lower extremity venous ultrasonography to prevent PE. Methods: Between July 2012 and August 2015, 976 consecutive patients underwent gastric cancer surgery with preoperative D-dimer screening. Lower extremity venous ultrasonography was performed in patients with a positive D-dimer assay result (greater than 1.0 μg/ml). The incidence of and risk factors for preoperative DVT and the incidence of PE were examined in patients undergoing gastric cancer surgery. Results: Of the 976 patients, 176 (18.0%) showed positive D-dimer assay results, and in 13 (1.3%) DVT was diagnosed by lower extremity ultrasonography. Our analysis identified neoadjuvant chemotherapy as a risk factor for preoperative detection of DVT in patients undergoing gastric cancer surgery ( P = 0.021). The incidence of PE was 0.1% (1/976). Conclusion: Preoperative gastric cancer patients receiving neoadjuvant chemotherapy seem to be at higher risk for the development of DVT. [ABSTRACT FROM AUTHOR]

Background: The feasibility of the use of the enhanced recovery after surgery (ERAS) protocol in patients with gastric cancer remains unclear. Methods: This study was a single-center, prospective randomized trial involving patients with gastric cancer undergoing curative gastrectomy. The primary end point was the length of postoperative hospital stay. Secondary end points were the postoperative complication rate, admission costs, weight loss, and amount of physical activity. Results: From July 2013 to June 2015, we randomized 148 patients into an ERAS protocol group ( n = 73) and a conventional protocol group ( n = 69); six patients withdrew from the study. The hospital stay was significantly shorter in the ERAS protocol group than in the conventional protocol group (9 days vs 10 days; P = 0.037). The ERAS protocol group had a significantly lower rate of postoperative complications of grade III or higher (4.1% vs 15.4%; P = 0.042) and reduced costs of hospitalization (JPY 1,462,766 vs JPY 1,493,930; P = 0.045). The ratio of body weight to preoperative weight at 1 week and 1 month after the operation was higher in the ERAS protocol group (0.962 vs 0.957, P = 0.020, and 0.951 vs 0.937, P = 0.021, respectively). The ERAS protocol group recorded more physical activity in the first week after surgery. Conclusions: The ERAS protocol is safe and efficient, and seems to improve the postoperative course of patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Since the INT-0116 trial reported a survival advantage, postoperative chemoradiotherapy (CRT) has been a care standard for US patients in whom gastric adenocarcinoma has been diagnosed. We sought to estimate the association between treatment and survival among the older US Medicare population. Methods: This is a retrospective cohort study of Medicare beneficiaries aged 65-79 years with stage IB-III gastric adenocarcinoma diagnosed between 2002 and 2009 in a Surveillance, Epidemiology, and End Results region. Patients were categorized on the basis of treatment: (1) gastrectomy only and (2) gastrectomy plus adjuvant CRT. We examined factors associated with receipt of adjuvant CRT, including stage at diagnosis, comorbidity, and tumor subtype. Overall survival was measured from 90 days after gastrectomy until death or the censoring date of December 31, 2010. Results: Of the 1519 patients who underwent gastrectomy, 41.7% received adjuvant CRT. Factors associated with adjuvant CRT included age younger than 75 years at cancer diagnosis and stage II or stage III cancer. The median overall survival from the time of gastrectomy was 25.1 months (interquartile range 43.7 months) for gastrectomy only and 26.9 months (interquartile range 40.9 months) for adjuvant CRT. Multivariable and propensity-score-stratified models demonstrated a survival benefit associated with adjuvant CRT [hazard ratio (HR) 0.58; 95% confidence interval (CI) 0.50-0.67], although the magnitude was greater for stage II tumors (HR 0.50; 95% CI 0.39-0.61) and stage III tumors (HR 0.58; 95% CI 0.45-0.73) than for stage IB tumors (HR 1.02; 95% CI 0.71-1.45). Conclusions: Adjuvant CRT, in conjunction with gastrectomy, was associated with a survival benefit among older patients with stage II or stage III tumors. [ABSTRACT FROM AUTHOR]

Background: The Japanese Gastric Cancer Association (JGCA) initiated a new nationwide gastric cancer registry in 2008 and reported the treatment outcomes of patients with primary gastric cancer who underwent surgical therapy in 2001 and 2003. However, the outcomes of endoscopic therapy have not been reported yet. Methods: The JGCA conducted a retrospective nationwide registry in 2013 to investigate the short-term and long-term outcomes of endoscopic mucosal resection or endoscopic submucosal dissection in patients with gastric cancer treated from January 2004 through December 2006. This registry used a computerized database with terminology in accordance with the JGCA classification (13th and 14th editions) and the Japanese Gastric Cancer Treatment Guidelines from 2010. Results: Accurate data on 12,647 patients were collected from 126 participating hospitals and analyzed. The treatment procedure was endoscopic submucosal dissection in 81% of the patients and endoscopic mucosal resection in 19%. En bloc and R0 resections were achieved in 89% and 79% of the patients respectively. The total proportion of patients who underwent curative resection was 69.2%; 43.8% of patients underwent curative resection for absolute indication lesions, and 25.4% underwent curative resection for expanded indication lesions. Emergency surgery was performed to treat bleeding or perforation in very few patients (0.3% and 0.4% respectively). The 5-year follow-up rate after endoscopic resection was 70%. The 5-year overall survival rate was 91.6% in patients with absolute indications and 90.3% in patients with expanded indications after curative resection and 86.5% in patients who underwent noncurative resection. The 5-year disease-specific survival rates were 99.9%, 99.7%, and 98.7% in patients with absolute indications who underwent curative resection, patients with expanded indications who underwent curative resection, and patients who underwent noncurative resection respectively. Conclusion: Endoscopic resection of gastric cancer resulted in favorable short-term and long-term outcomes nationwide in Japan. Further efforts to increase the follow-up rate are needed. [ABSTRACT FROM AUTHOR]

Background: Gastric carcinoma with lymphoid stroma (GCLS) is characterized by undifferentiated carcinoma mixed with prominent lymphoid infiltration. GCLS has unique clinicopathological features and a better prognosis compared to other types of gastric cancer. We analyzed the clinicopathological features of early GCLS in relation to lymph node metastasis (LNM). Methods: We performed a retrospective analysis of 241 patients diagnosed with GCLS confined to the mucosa or the submucosa between March 1998 and December 2015. Their data were compared with those from 1219 patients who underwent resection for differentiated early gastric cancer (EGC). Results: Of the 241 patients analyzed, 33 (13.7%) had intramucosal cancers and 208 (86.3%) had cancers that penetrated the submucosa. Compared to differentiated EGC, early GCLS was more prevalent in younger individuals and in men, tended to be proximally located, was highly associated with Epstein-Barr virus (EBV) infection (89.2%), and had a lower risk of LNM. The 5-year disease-specific survival rate of patients with early GCLS was 98.3% but depended significantly on LNM status ( p < 0.001) and EBV infection status ( p = 0.039). The risk of LNM from mucosal GCLS and submucosal GCLS was 0% [95% confidence interval (CI) 0-9.1] and 10% (95% CI 6.8-15.2), respectively. On multivariate analysis, LNM was found to be associated with tumor size ( p = 0.022) and lymphovascular invasion ( p = 0.002) in addition to tumor depth. Conclusions: Early GCLS has distinct clinicopathological features depending on age, sex, tumor location, EBV infection status, and LNM status. Tailored therapies, including endoscopic treatment, are needed based on the distinct clinicopathological features of early GCLS. [ABSTRACT FROM AUTHOR]

Follow-up after gastrectomy for gastric cancer has several purposes, including management of side effects of surgery, oncological recurrence surveillance, psychological support, and data collection for research. How follow-up after gastrectomy, and especially recurrence surveillance, is performed differs immensely between different Western countries, despite guidelines from Western oncological organizations quite unanimously advocating symptom-driven surveillance, without scheduled cross-sectional imaging, endoscopies, or analysis of tumor markers. Given a complete lack of randomized data, the available body of observational data does not support intensive routine surveillance for recurrent disease. Moreover, studies of other cancers have shown a negative emotional impact of routine surveillance. There is an apparent need for randomized controlled trials to address the issue of optimized strategies for postgastrectomy recurrence surveillance. [ABSTRACT FROM AUTHOR]

Background: The objectives of this national study were to examine the short-term safety and long-term survival benefit associated with surgical resection of hepatic metastases from gastric cancer. Methods: Patients from the Hospital Episode Statistics database were classified by disease and treatment approach. Gastric cancer: 1. Without liver metastases treated by gastrectomy (GG). 2. With liver metastases treated by gastrectomy and hepatectomy (GGH). 3. With liver metastases treated by gastrectomy without hepatectomy (GGNH). 4. With liver metastases treated with no surgery (GNS). Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. Results: During the study period, 87,482 were patients diagnosed with gastric cancer, of whom 13,841 underwent partial or total gastrectomy. Of those who underwent gastrectomy, 336 had a diagnosis of liver metastases and 78 of these had a hepatectomy. Propensity-matched analysis showed no significant differences in 30- or 90-day mortality between the GGH and GG groups. The GGH group had significantly improved 1-year mortality (35.9 % vs. 50.0 %, p = 0.049) and 5-year mortality (61.5 % vs. 75.7 %, p = 0.031) compared to the GGNH group, and compared to the GNS group, the GCH group had 1-year mortality (35.9 % vs. 84.6 %, p < 0.001) and 5-year mortality (61.5 % vs. 90.8 %, p < 0.001). Conclusions: This study showed that hepatectomy for synchronous gastric cancer hepatic metastases may carry survival benefits in selected patients. The data presented should not be a rationale to change current clinical practice but rather a stimulus to prospectively study the role of surgery in a selected group of patients who are currently treated with palliative chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive surgical techniques are increasingly being implemented in oncologic care. This study assesses the impact of minimally invasive surgery on oncologic and perioperative outcomes in the management of gastric cancer in the USA. Methods: From the American College of Surgeons and American Cancer Society National Cancer Data Base, we identified 6427 patients who underwent gastrectomy for cancer from 2010 to 2012. Treatment groups were categorized with an intention-to-treat paradigm as robotic, laparoscopic, and open surgery. Univariate and multivariate analyses were performed to estimate the impact of the surgical approach on oncologic and perioperative outcomes. Results: Of patients undergoing definitive surgical intervention, 3.5 % ( n = 223) underwent robotic gastrectomy, 23.1 % ( n = 1487) underwent laparoscopic gastrectomy, and 73.4 % ( n = 4717) underwent open surgery. Minimally invasive gastrectomy was more frequently performed on white ( P = 0.018), privately insured patients ( P = 0.049) treated at academic centers ( P < 0.0001) in the eastern USA ( P < 0.0001). After demographics, comorbidities, and tumor-related factors had been controlled for, patients who underwent laparoscopic gastrectomy had the postoperative length of stay decreased by 1.08 days ( P < 0.0001) and greater odds of having at least 15 lymph nodes resected (odds ratio 1.16, P = 0.023). Use of robotic surgery did not have a statistically significant effect on the postoperative length of stay relative to open surgery ( P = 0.222) but the patients so treated had greater odds of having at least 15 lymph nodes resected (odds ratio 1.51, P = 0.005). There were no differences in R0 resection rates or perioperative mortality on the basis of the surgical approach alone. Conclusions: These findings suggest that use of minimally invasive surgery for gastric cancer in the USA is impacting the adequacy of oncologic resection but is not yet having a clinically significant impact on perioperative outcomes relative to a conventional open approach. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. Methods: SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Results: Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. Conclusions: This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs. [ABSTRACT FROM AUTHOR]

Background and aim: The ability to differentiate between mucosal (M) or microinvasive submucosal (SM1: depth of less than 500 µm) and invasive submucosal (SM2: depth of 500 µm or more) cancer is paramount when choosing the method of treatment for early gastric cancer (EGC). The 'non-extension sign' relates to a localized increase in thickness and rigidity due to massive submucosal invasion by a cancer. The present study sought to assess the ability of conventional endoscopy (CE) to correctly identify SM2 cancer using only the non-extension sign. Methods: This is a retrospective study based on a prospectively collected database. EGCs had been diagnosed according to invasion depth as M-SM1 or SM2. In terms of the endoscopic diagnostic criterion, lesions positive for the non-extension sign were classified as SM2 cancers, while those negative for the non-extension sign were classified as M-SM1 cancers. Histopathological findings were used as the gold standard. Results: We examined a total of 863 lesions from 704 patients, comprising 104 true-positive, 733 true-negative, 9 false-positive, and 17 false-negative lesions. This yielded a sensitivity of 92.0 % (95 % confidence interval (CI), 87.0-97.0 %), a specificity of 97.7 % (95 % CI, 96.7-98.8 %), a positive predictive value of 85.9 % (95 % CI, 79.7-92.1 %), a negative predictive value of 98.8 % (95 % CI, 98.0-99.6 %), and a diagnostic accuracy of 96.9 % (95 % CI, 95.8-98.1 %). Conclusion: The non-extension sign may be useful for accurately determining the suitability of minimally invasive endoscopic treatment. Nevertheless, considering the limitations of retrospective analysis, a further prospective study is warranted to confirm the diagnostic reliability of the non-extension sign. [ABSTRACT FROM AUTHOR]

Background: In Japan, S-1, an oral fluoropyrimidine, plus cisplatin is a standard regimen for advanced gastric cancer, whereas nab-paclitaxel is a treatment option. We aimed to evaluate the tolerance, pharmacokinetics, safety, and clinical efficacy of S-1 combined with nab-paclitaxel in patients with advanced gastric cancer in a phase 1 study. Methods: The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus nab-paclitaxel. The study was designed in accordance with a standard 3 + 3 method. Patients received 3-week cycles of treatment. S-1 was administered orally at 80 mg/m twice daily for 14 days, and nab-paclitaxel was administered as an intravenous infusion at 180, 220, or 260 mg/m on day 1 or 8. Results: Among the 16 patients enrolled, dose-limiting toxicity was observed in one patient at level 2a (S-1 80 mg/m twice daily plus nab-paclitaxel 220 mg/m on day 1). The MTD was not obtained, but the RD was established as level 3a (S-1 80 mg/m twice daily plus nab-paclitaxel 260 mg/m on day 1). The most common grade 3-4 toxicity was neutropenia (62.5 %). The overall response rate was 54.5 %. The pharmacokinetic profiles of coadministered S-1 and paclitaxel were comparable to those of nab-paclitaxel or S-1 alone. Conclusions: Based on the present results, the RD was determined as level 3a (S-1 80 mg/m twice daily plus nab-paclitaxel 260 mg/m on day 1). This combination therapy was well tolerated and showed antitumor efficacy in patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Capecitabine plus cisplatin (XP) is recognized as one of the global standard first-line chemotherapy regimens for patients with metastatic gastric cancer (mGC). Recent multinational phase III trials in mGC have been conducted with XP as the control arm, although no data on XP in Japanese patients with mGC have been published to date. The AVAGAST (XP ± bevacizumab in mGC) and ToGA (XP ± trastuzumab in human epidermal growth factor receptor 2 [HER2]-positive mGC) studies were the first two global studies including Japanese mGC patients. The aim of this analysis was to investigate the efficacy and safety of XP in Japanese mGC patients, using AVAGAST and ToGA subgroup data. Methods: Efficacy and safety analyses were carried out in Japanese patients with mGC receiving XP alone, based on results from the AVAGAST and ToGA studies. There were differences in the target populations between the two studies; for example, the ToGA study limited patients to those with HER2-positive tumors; therefore, efficacy was evaluated separately. Results: Ninety-four Japanese patients in the AVAGAST study and 50 in the ToGA study received XP alone. Median overall and progression-free survivals were 14.2 and 5.7 months, respectively, in the AVAGAST study, and 17.7 and 5.6 months, respectively, in the ToGA study. Overall response rates were 49.2 % in the AVAGAST and 58.5 % in the ToGA study. Adverse events were generally mild; the most common grade 3/4 events were neutropenia, anemia, anorexia, and nausea. Conclusions: XP is effective and well tolerated in Japanese patients with mGC, and could be one of the standard regimens for the first-line treatment in this cohort. [ABSTRACT FROM AUTHOR]

Background: A recent randomized controlled trial (Trastuzumab for Gastric Cancer [ToGA] study) established standard scoring criteria of human epidermal growth factor receptor 2 (HER2) for gastric cancer and demonstrated the efficacy of trastuzumab for treating metastatic gastric cancer. The aim of the present study was to evaluate the frequency of HER2-positive cases by application of the standard criteria in patients with resectable gastric cancer and to examine the relationships between HER2 expression and prognosis, mucin phenotype, p53 status, and clinicopathological features. Methods: A total of 213 patients were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry (IHC), HER2 amplification by in situ hybridization, and mucin and p53 expression by staining for CD10, MUC2, MUC5AC, MUC6, and p53. Results: HER2-positive tumors were identified in 25 patients (11.7 %). HER2-positive cases were more frequently found in men, older patients, and in the intestinal histological type ( P = 0.0048, 0.0309, and <0.0001, respectively). Although no association was found between HER2 overexpression and mucin phenotype, the expression of CD10 and p53 was significantly correlated with HER2 positivity ( P = 0.0079 and 0.013). The overall survival of HER2-negative and -positive patients was not significantly different. However, in patients with stage III/IV, overall survival was worse in HER2-positive patients ( P = 0.0149). In a comparison between dual-color in situ hybridization (DISH) and fluorescence in situ hybridization (FISH), four IHC2+/3+ cases that were DISH-positive were judged as negative by FISH. Conclusions: Our study indicated that HER2 expression was less frequent in resectable gastric cancer than in metastatic gastric cancer. The impact of HER2 expression on survival was limited. DISH was superior to FISH for evaluating cases with limited HER2 expression. [ABSTRACT FROM AUTHOR]

Background: The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008. Methods: From 208 participating hospitals, 53 items including surgical procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed. Results: The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed. Conclusions: Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a global health problem accounting for 10% of all new cancer cases and 12% of all cancer deaths worldwide. Many clinical trials and meta-analyses have explored the value of neoadjuvant or adjuvant chemotherapy and radiation therapy in gastric cancer; however, these studies have produced conflicting results. The purpose of this guidance document was to determine whether patients with resectable gastric cancer should receive neoadjuvant or adjuvant therapy in addition to surgery. Outcomes of interest were overall survival, disease-free survival, and adverse events. Methods: A systematic review was undertaken to inform recommendations regarding neoadjuvant and adjuvant therapy in resectable gastric cancer in Ontario, Canada. MEDLINE and EMBASE databases, as well as American Society of Clinical Oncology (ASCO) annual meeting proceedings and American Society for Therapeutic Radiology and Oncology (ASTRO) proceedings were systematically searched from 2002 to 2010. Oral fluoropyrimidine trials were excluded owing to the unavailability of these agents in North America. Results: Overall, 22 randomized controlled trials (RCTs), 13 meta-analyses, and two secondary analyses were included. The systematic review informed the development of a clinical practice guideline with the following recommendations. Postoperative 5-fluorouracil-based chemoradiotherapy based on the Macdonald approach or perioperative ECF (epirubicin, cisplatin, fluorouracil) chemotherapy based on the Cunningham/MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) approach are both acceptable standards of care in North America. Choice of treatment should be made on a case-by-case basis. Adjuvant chemotherapy is a reasonable option for those patients for whom the Macdonald and MAGIC protocols are contraindicated. All patients with resectable gastric cancer should undergo a pretreatment multidisciplinary assessment to determine the best plan of care. Conclusions: Overall survival in patients with resectable gastric cancer is significantly improved with the use of either postoperative chemoradiation (Macdonald approach) or perioperative ECF (MAGIC protocol). [ABSTRACT FROM AUTHOR]

Background: Most gastric cancer patients present with advanced stage disease precluding curative surgical treatment. These patients may be considered for palliative resection or bypass in the presence of major symptoms; however, the utility of surgery for non-curative, asymptomatic advanced disease is debated and the appropriate treatment strategy unclear. Purpose: To evaluate the non-curative surgical literature to better understand the limitations and benefits of non-curative surgery for advanced gastric cancer. Methods: A literature search for non-curative surgical interventions in gastric cancer was conducted using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases from 1 January 1985 to 1 December 2009. All abstracts were independently rated for relevance by a minimum of two reviewers. Outcomes of interest were procedure-related morbidity, mortality, and survival. Results: Fifty-nine articles were included; the majority were retrospective, single institution case series. Definitions describing the treatment intent for gastrectomy were incomplete in most studies. Only five were truly performed with relief of symptoms as the primary indication for surgery, while the majority were considered non-curative or not otherwise specified. High rates of procedure-related morbidity and mortality were demonstrated for all surgeries across the majority of studies and treatment-intent categories. Median and 1-year survival were poor, and values ranged widely within surgical approaches and across studies. Conclusions: A lack of transparent documentation of disease burden and symptoms limits the surgical literature in non-curative gastric cancer. Improved survival is not evident for all patients receiving non-curative gastrectomy. Further prospective research is required to determine the optimal intervention for palliative gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome specifically associated with germline mutations to the E-cadherin (CDH1) gene. HDGC is characterized by autosomal dominance and high penetrance and a high cumulative risk for advanced gastric cancer. Our purpose in this study was to identify and synthesize findings from all articles on: (1) current recommendations for CDH1 screening and prophylactic gastrectomy; (2) CDH1 testing results in HDGC patients; and (3) prophylactic gastrectomy results in HDGC patients. Methods: Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1985 to 2009. Results: Seventy articles were included in this review. Among patients with a positive family history of gastric cancer, 1085 were screened from 454 families, and 38.4% tested positive. Mutation-positive families also had a considerable family history of breast and colon cancer. Of the 322 patients screened for CDH1 mutations by current HDGC screening criteria, 29.2% tested positive. Among the 76.8% of patients who underwent prophylactic gastrectomy following positive CDH1 test results, 87.0% had positive final histopathology results and 64.6% had signet ring cells identified. Some of the patients with negative final histopathology results had opted to undergo prophylactic gastrectomy prior to CDH1 testing, and were ultimately found to be negative for CDH1 mutations. Conclusion: CDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC. [ABSTRACT FROM AUTHOR]

Background: In gastric cancer, the utility of sentinel lymph node (SLN) biopsy has not been established. SLN may be a good predictor of the pathological status of other lymph nodes and thus the necessity for more extensive surgery or lymph node dissection. We aimed to identify and synthesize findings on the performance of SLN biopsies in gastric cancer. Methods: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. Titles and abstracts were independently rated for relevance by a minimum of two reviewers. Techniques, detection rates, accuracy, sensitivity, specificity, and false-negative rates (FNRs) were analyzed. Analysis was performed based on the FNR. Results: Twenty-six articles met our inclusion criteria. SLN detection using the dye method (DM) was reviewed in 18 studies, the radiocolloid method (RM) was used in 12 studies, and both dye and radiocolloid methods (DUAL) were used in 5 studies. The DM had an overall calculated FNR of 34.7% (95% confidence interval [CI] 21.2, 48.1). The RM had an overall calculated FNR of 18.5% (95% CI 9.1, 28.0). DUAL had an overall calculated FNR of 13.1% (95% CI −0.9, 27.2). Conclusion: Application of the SLN technique may be practical for early gastric cancer. The use of DUAL for identifying SLN may yield a lower FNR than either method alone, although statistical significance was not met. [ABSTRACT FROM AUTHOR]

Background: Accurate preoperative staging is important in determining the appropriate treatment of gastric cancer. Recently, endoscopic ultrasound (EUS) has been introduced as a staging modality. However, reported test characteristics for EUS in gastric cancer vary. Our purpose in this study was to identify, synthesize, and evaluate findings from all articles on the performance of EUS in the preoperative staging of gastric cancer. Methods: Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 1 December 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Meta-analysis for the performance of EUS was analyzed by calculating agreement (Kappa statistic), and pooled estimates of accuracy, sensitivity, and specificity for all EUS examinations, using histopathology as the reference standard. Subgroup analyses were also performed. Results: Twenty-two articles met our inclusion criteria and were included in the review. EUS pooled accuracy for T staging was 75% with a moderate Kappa (0.52). EUS was most accurate for T3 disease, followed by T4, T1, and T2. EUS pooled accuracy for N staging was 64%, sensitivity was 74%, and specificity was 80%. There was significant heterogeneity between the included studies. Subgroup analyses found that annual EUS volume was not associated with EUS T and N staging accuracy ( P = 0.836, 0.99, respectively). Conclusion: EUS is a moderately accurate technique that seems to describe advanced T stage (T3 and T4) better than N or less advanced T stage. Stratifying by EUS annual volume did not affect EUS performance in staging gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The overall prognosis and survival of patients with advanced gastric cancer are generally poor. Extended lymphadenectomy is recommended for patients with advanced gastric cancer; however, splenectomy and distal pancreatectomy performed with an extended lymph node dissection may be associated with increased morbidity and mortality. Method: Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 31 December 2009. Studies on gastric carcinoma investigating extended lymphadenectomy with splenectomy and/or pancreaticosplenectomy that reported data on surgical outcomes or survival were selected. Results: Forty studies were included in this review. Decreased complication rates were demonstrated with spleen preservation in two prospective studies and three retrospective studies, and with pancreas preservation in five retrospective studies. No randomized controlled trial showed survival benefit or detriment for preservation of spleen or pancreas in extended lymphadenectomy. Improved survival was demonstrated with spleen preservation in two prospective and eight retrospective studies, and with pancreas preservation in one prospective and four retrospective studies. Conclusions: Preservation of the spleen and pancreas during extended lymphadenectomy for gastric cancer decreases complications with no clear evidence of improvement or detriment to overall survival. [ABSTRACT FROM AUTHOR]

Background: Gastric perforation is a rare presentation of gastric cancer and is thought to be a predictor of advanced disease and, thus, poor prognosis. Guidelines do not exist for the optimal management strategy. We aimed to identify, review, and summarize the literature pertaining to perforation in the setting of gastric cancer. Methods: A qualitative, systematic review of the literature was performed from January 1, 1985, to January 1, 2010. Searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were performed using search terms related to gastric cancer surgery. Abstracts were examined by two independent reviewers and a standardized data collection tool was used to extract relevant data points. Summary tables were created. Results: Nine articles were included. Perforation was reported to occur in fewer than 5% of gastric cancer patients. Preoperative diagnosis of a gastric cancer was rated and occurred in 14-57% of patients in the papers reviewed. Mortality rates for emergency gastrectomy ranged from 0 to 50% and for simple closure procedures the rates ranged from 8 to 100%. Patients able to receive an R0 gastrectomy demonstrated better long-term survival (median 75 months, 50% 5-year) compared with patients who had simple closure procedures. Conclusions: Gastric cancer patients presenting with a gastric perforation demonstrate improved overall survival with an R0 resection; however, implementation of this management technique is complicated by infrequent preoperative gastric cancer diagnosis, and inability to perform an oncologic resection due to patient instability and intra-abdominal contamination. [ABSTRACT FROM AUTHOR]

Background: Complete resection is the only definitive treatment available for gastric cancer. Factors associated with positive margins and their survival effects have been the subject of many studies, but the appropriate management for these patients is still debated. The objective of this review is to examine positive margins after gastric cancer resections by exploring predictive factors, impact on survival, and optimal strategies for re-resection. Methods: A systematic electronic literature search was conducted using Medline and EMBASE from January 1, 1998, to December 31, 2009. Studies on gastric or gastroesophageal junction adenocarcinoma that either investigated the predictors for positive margin or employed multivariate methods to analyze the survival effects of positive margins were selected. Results: Twenty-two studies incorporating 19355 patients were included in this review. Positive margins were associated with larger tumor size, deeper wall penetration, more extensive gastric involvement, greater nodal involvement, higher stage, diffuse histology, higher Borrmann type, lymphatic vessel involvement, and total gastrectomy. Patient survival was independently associated with margin status, and this survival effect was more prominent in early cancers in most studies that performed subgroup analyses. Conclusions: The probability of acquiring positive margins is highly dependent on the biology and the extent of the tumor. There is a significant negative effect on survival, which is more prominent in cancers at early stages, making re-resection or a second operation important. Patients with more advanced disease can be offered more extensive surgery to remove disease, but this should be balanced against the risks of more extensive resections. [ABSTRACT FROM AUTHOR]

Background: Surgery is the only curative treatment for patients with gastric cancer. However, the extent of lymph node dissection is still debated. Therefore, with the publication of newer trial results, we conducted an updated meta-analysis of D1 versus D2 randomized controlled trials comparing outcomes. Methods: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985, to December 31, 2010. Meta-analyses were performed using RevMan v5 software. Both short- and long-term outcomes were analyzed. Subgroup analyses of T stage and spleen/pancreas resection versus preservation were performed. Results: Outcomes of 5 randomized trials involving 1642 patients (845 D1, 797 D2) enrolled from 1982 to 2005 were included. Despite the addition of the more recent trials, overall hospital mortality and reoperation rates were still higher in D2 cases. Subgroup analysis of recent trials and spleen/pancreas preservation revealed no significant difference in hospital mortality between groups. Five-year overall survival was similar between D1 versus D2 trials. Sub-analysis by tumor depth and spleen/pancreas preservation detected trends for improved survival with D2 lymphadenectomy in T3/T4 patients and those with spleen/pancreas preservation. Conclusion: Earlier trials show that D2 dissections have higher operative mortality, while recent trials have similar rates. A trend of improved survival exists among D2 patients who did not undergo resection of the spleen or pancreas, as well as for patients with T3/T4 cancers. [ABSTRACT FROM AUTHOR]

Background: Complete resection of a gastric cancer and adjacent lymph nodes offers the only chance for cure of the disease. However, disease recurrence occurs in 22-51% of cases, and its prognosis is very poor. Many clinicians perform post-operative follow-up for these patients, although there is no consensus on the regimen, frequency of visits, mode of testing, or the rationale of a follow-up program. Purpose: The objective of this systematic review was to identify the evidence for surveillance in patients with resected gastric cancer, specifically examining the interval of follow-up and the modalities utilized. Methods: Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1st 1998 to December 1st 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Results: Five articles were selected. A total of 810 patients underwent post-operative follow-up. History and physical examination, hematological and chemistry profile, endoscopy (esophagogastroduodenoscopy [EGD]), and computed tomography (CT) were the most frequently employed modalities. CT detected the majority of recurrences in the included studies. The survival post-recurrence was significantly higher in the asymptomatic group compared with symptomatic group in three studies, but this may simply reflect lead-time bias. No differences in overall survival (OS) were found. Conclusion: The included studies failed to show an improvement in OS with more intense surveillance. Further prospective studies are required to determine whether a subgroup of patients may benefit from more intensive follow-up. [ABSTRACT FROM AUTHOR]

Background: Nodal status is one of the most important prognostic factors in gastric adenocarcinoma (GC). As such, it is important to assess an appropriate number of lymph nodes (LNs) in order to accurately stage patients. However, the number of LNs assessed in each GC case varies, and in many cases the number examined per gastric specimen is less than current recommendations. Purpose: We aimed to identify and synthesize findings from all articles evaluating the association of clinicopathological features and long-term outcomes with the number of LNs assessed among GC patients. Methods: Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1998 to 2009. Results: Twenty-five articles were included in this review. Extensive resection, increased tumor size, and greater TNM staging were all associated with a greater number of LNs assessed. The disease-free survival was longer and recurrence rate was lower in patients with more LNs assessed. Overall survival, as well as survival by TNM and clinical stage, was improved among patients with an increased number of LNs assessed, but much of this appears to be due to stage migration, with the effect more pronounced in more advanced disease. Conclusion: More LNs assessed resulted in less stage migration and possibly better long-term outcomes. Although current guidelines suggest 16 LNs to be assessed, especially in advanced GC, a higher number of LNs should be assessed. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the author discusses systematic reviews and meta-analyses of studies on gastric cancer management.

An introduction is presented in which the editor discusses perioperative management of gastric cancer.