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Across the nation, patients with locally advanced gastric cancer (LAGC) are managed with modalities including upfront surgery (US) and perioperative chemotherapy (PCT). Preoperative therapies have demonstrated survival benefits over US and thus long-term outcomes are expected to vary between the options. However, as these 2 modalities continue to be regularly employed, we sought to perform a decision analysis comparing the costs and quality-of-life associated with the treatment of patients with LAGC to identify the most cost-effective option. We designed a decision tree model to investigate the survival and costs associated with the most commonly utilized management modalities for LAGC in the United States: US and PCT. The tree described costs and treatment strategies over a 6-month time horizon. Costs were derived from 2022 Medicare reimbursement rates using the third-party payer perspective for physicians and hospitals. Effectiveness was represented using quality-adjusted life-years (QALYs). One-way, two-way, and probabilistic sensitivity analyses were utilized to test the robustness of our findings. PCT was the most cost-effective treatment modality for patients with LAGC over US with a cost of $40,792.16 yielding 3.11 QALYs. US has a cost of $55,575.57 while yielding 3.15 QALYs; the incremental cost-effectiveness ratio (ICER) was $369,585.25. One-way and two-way sensitivity analyses favored PCT in all variations of variables across their standard deviations. Across 100,000 Monte Carlo simulations, 100% of trials favored PCT. In our model simulating patients with LAGC, the most cost-effective treatment strategy was PCT. While US demonstrated improved QALYs over PCT, the associated cost was too great to justify its use. [ABSTRACT FROM AUTHOR]

Background: Stomach cancer incidence presents significant racial/ethnic disparities among racial/ethnic minority groups in the United States, particularly among Asian and Hispanic immigrant populations. However, population‐based evaluation of disparities by nativity has been scarce because of the lack of nativity‐specific population denominators, especially for disaggregated Asian subgroups. Population‐based stomach cancer incidence and tumor characteristics by detailed race/ethnicity and nativity were examined. Methods: Annual age‐adjusted incidence rates were calculated by race/ethnicity, sex, and nativity and tumor characteristics, such as stage and anatomic subsite, were evaluated using the 2011–2015 California Cancer Registry data. For Hispanic and Asian populations, nativity‐specific population counts were estimated using the US Census and the American Community Survey Public Use Microdata Sample data. Results: During 2011–2015 in California, 14,198 patients were diagnosed with stomach cancer. Annual age‐adjusted incidence rates were higher among foreign‐born individuals than their US‐born counterparts. The difference was modest among Hispanics (∼1.3‐fold) but larger (∼2‐ to 3‐fold) among Chinese, Japanese, and Korean Americans. The highest incidence was observed for foreign‐born Korean and Japanese Americans (33 and 33 per 100,000 for men; 15 and 12 per 100,000 for women, respectively). The proportion of localized stage disease was highest among foreign‐born Korean Americans (44%); a similar proportion was observed among US‐born Korean Americans, although numbers were limited. For other Asians and Hispanics, the localized stage proportion was generally lower among foreign‐born than US‐born individuals and lowest among foreign‐born Japanese Americans (23%). Conclusions: Nativity‐specific investigation with disaggregated racial/ethnic groups identified substantial stomach cancer disparities among foreign‐born immigrant populations. Substantial racial/ethnic disparities in stomach cancer exist in the United States, with the largest disparities found for foreign‐born Korean and Japanese Americans. Comparisons of incidence rates and stage distribution underscore the importance of implementing targeted prevention and screening strategies for high‐risk racial/ethnic subgroups and immigrant populations in the United States. [ABSTRACT FROM AUTHOR]

Introduction Risk factors for gastric cancer in the United States are not well understood, especially in populations with a low proportion of immigrants. We conducted a matched case–control study in a Veteran Affairs Medical Center to identify risk factors for gastric cancer. Materials and Methods Gastric cancer patients and age- and sex-matched controls were identified in a 1:4 ratio from January 1, 1997 to October 31, 2018. Demographic, medical, endoscopic, and histologic data were extracted. We performed conditional logistic regression to estimate odds ratios and 95% CIs for associations between potential risk factors and gastric cancer. Results Most gastric cancer cases were diagnosed on initial endoscopy (71.4%). Of these, the most common presenting stage was stage IV (40.8%). Risk factors for gastric cancer included Black and Asian race and never or current (compared to former) drinkers, although Helicobacter pylori eradication and pernicious anemia were associated with decreased risk. Conclusions The high proportion of late-stage gastric cancer diagnoses highlights the need for improved risk stratification as well as screening and surveillance protocols in the U.S. population. Racial disparities among veterans in an equal-access system necessitate further investigation into the etiology of these disparities. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer ranks as the 5th most prevalent cancer and the 4th leading cause of cancer-related deaths worldwide. Various treatment modalities, including surgical resection, chemotherapy, and radiotherapy, are available for gastric cancer patients. However, disparities related to age, sex, race, socioeconomic factors, insurance status, and demographic factors often lead to delayed time to treatment. Methods: In this retrospective study, conducted between 2004 and 2019, we utilized data from the National Cancer Database (NCDB) to investigate the factors contributing to disparities in the time to first treatment, surgery, chemotherapy, and radiotherapy among gastric cancer patients. Our analysis incorporated several variables, and statistical analysis was conducted to provide valuable insights into these disparities. Results: We observed notable disparities in the timing of treatment for various demographic groups, including age, sex, race, insurance status, geographic location, and facility type. These disparities include longer time to treatment in males (32.67 vs 30.75), Native Americans (35.10 vs 31.09 in Asians), low-income patients (32 vs 31.15), patients getting treatment in an academic setting (36.11 vs 29.61 in community setting), significantly longer time to chemotherapy in 70+ age group (51.13 vs 40.38 in <40 y age group), black race (55.81 vs 47.05 in whites), low income people (49.64 vs 46.74), significantly longer time to radiotherapy in females (101.61 vs 79.75), blacks and Asians (109.68 and 113.96 respectively vs 92.68 in Native Americans) etc. There are various other disparities in time to surgery, chemotherapy, and radiotherapy. Conclusions: Understanding these disparities is crucial in developing targeted strategies to improve timely access to appropriate treatments and enhance outcomes for gastric cancer patients. Future research with updated data and prospective study designs can provide a more comprehensive understanding of the factors influencing patient outcomes in gastric cancer. [ABSTRACT FROM AUTHOR]

While clinical practice guidelines for hereditary diffuse gastric cancer are well established, there is no consensus on the approach for familial intestinal gastric cancer (FIGC). In low‐incidence gastric cancer (GC) areas such as the United States or most European countries, there are no evidence‐based recommendations on endoscopic assessment in FIGC families. We aim to describe the yield of GC surveillance in these families, and to identify epidemiological risk factors for the development of GC and its precursor lesions. This is a multicenter observational study involving nine tertiary Spanish hospitals, in which all individuals fulfilling FIGC criteria who underwent endoscopic surveillance were included between 1991 and 2020. Forty‐one healthy individuals of 31 families were recruited. The median number of upper gastrointestinal endoscopies per individual was 3 (interquartile range, IQR, 1‐4). The median interval time between tests was 2 years (IQR 1.5‐2.5), and the median follow‐up was 9 years (IQR 3‐14.5). In 18 (43.9%) subjects, a precursor lesion of GC was found during follow‐up, and in 2 (4.9%), an early GC was identified, in which curative treatment was offered. Helicobacter pylori (Hp) infection proved to be independently associated with an increased risk of developing precursor lesions or GC, adjusted by age, gender and follow‐up, with an Odds Ratio of 6.443 (1.36‐30.6, P value.019). We present the first outcomes that support endoscopic surveillance with biopsies and detection of Hp in FIGC families, although the periodicity has yet to be defined. [ABSTRACT FROM AUTHOR]

Objectives: Gastric cancer in the United States has a low survival rate mainly because of the late stage of diagnosis. Furthermore, there are no well-established guidelines concerning screening and surveillance even for higher risk patients such as those with nondysplastic noncardia gastrointestinal metaplasia (GIM), and thus they are not routinely performed. This study was designed to provide new evidence-based data that can be used to support the implementation of biennial surveillance guidelines in individuals with nondysplastic noncardia GIM. This practice can help detect early malignant lesions, thereby decreasing morbidity and mortality. We evaluated the cost-effectiveness of surveillance endoscopies for noncardia gastric cancer in populations with two different pathological diagnoses: mixed GIM and incomplete GIM (iGIM). Methods:Markov state transition models were developed using a cohort simulation of 1000 hypothetical patients. Analysis was conducted for both mixed and iGIM. Quality-adjusted life-years and transition probabilities were derived from the published medical literature. Costs associated with endoscopy, cancer care, and surgery were based on Medicare reimbursement. Awillingness-to-pay threshold of $100,000 per quality-adjusted life-year was used to determine cost-effectiveness. Results: Our study determined that it is significantly cost-effective to perform biennial endoscopy surveillance in patients who have been incidentally found to have noncardia mixed GIM, with a cost savings of $5783.84 per person, and in those with iGIM, with a cost savings of $8093.08 per person. Conclusions: Biennial endoscopy surveillance should be considered in all individuals found to have mixed or incomplete noncardia GIM on endoscopy. Furthermore, screening specifically for iGIM after differentiating between the two groups can lead to further cost savings. As such, we recommend that pathologists routinely differentiate between the two and recommend robust routine surveillance of iGIM. [ABSTRACT FROM AUTHOR]

Background: Recently, numerous publications on Helicobacter pylori (H. pylori) have been published, but bibliometric analyses on this research field are scarce. To address this gap, we conducted a bibliometric analysis to provide a comprehensive overview and to explore the current research states and hotspots in this field. Materials and Methods: Publications on H. pylori from 2002 to 2021 were retrieved from the Web of Science Core Collection database (WoSCC). Trends in publications and citations were analyzed using Excel 2021. VOSviewer and Citespace were used to perform bibliometrics analysis. Results: 36,266 publications on H. pylori were retrieved from the WoSCC database. In general, we observed an increasing trend in the number of publications over the past 20 years. The United States was the most productive and influential country, with the largest proportion of both publications and total citations. Helicobacter, US Department of Veterans Affairs, and Graham, David were the most productive journals, institutions and authors, respectively. Further analysis the co‐occurrence and burst detection of keywords revealed that the most common keywords were "Helicobacter pylori," "gastric cancer," and "gastritis," all keywords were divided into eight main clusters, and the most important current research hotspot was the relationship between H. pylori infection and the changes of gut microbiota. Conclusions: The United States has been the most productive and influential country on H. pylori research, and H. pylori‐related research remains an active research field. The relationship between H. pylori infection and the changes of gut microbiota is a research hotspot attracting significant attention. [ABSTRACT FROM AUTHOR]

Background: There is a high prevalence of malnutrition in cancer patients, which seriously affects the anti-cancer therapy effect and outcomes, causing a huge disease burden worldwide. Appropriate nutritional support is important for cancer prevention and control. The aim of this study was to explore the development trends, hotspots, and frontiers of Medical Nutrition Therapy (MNT) on Cancer from a bibliometric perspective, and provide new insights for future research and clinic practices. Methods: The global literature of MNT on Cancer published between 1975 and 2022 were searched in the Web of Science Core Collection Database (WOSCC). After refining the data, descriptive analysis and data visualization were performed with bibliometric tools (CiteSpace, VOSviewer, and R package "bibliometrix"). Results: A total of 10,339 documents with a timespan from 1982 to 2022 were included in this study. The number of documents had increased continuously over the past 40 years, especially with a steep rise from 2016 to 2022. The majority of scientific production outputs were from the United States, which had the most core research institutions and authors. The published documents could be clustered into three themes respectively labeled by terms "double-blind", "cancer" and "quality-of-life". "gastric cancer", "outcome", "inflammation", "sarcopenia" and "exercise" were the most prominent keywords in recent years. "breast-cancer", "colorectal-cancer", "expression", "risk", "in-vitro", "quality-of-life", "cancer" and "life" might represent the newly emerged topics. Conclusions: There were a good research foundation and reasonable disciplinary structure in the field of medical nutrition therapy for cancer at present. The core research team was mainly located in the United States, England, and other developed countries. According to the current trends in publications, more articles shall be published in the future. Nutritional metabolism, malnutrition risk, and the impact of nutritional therapy on prognosis might be research hotspots. In particular, it was important to focus on specific cancer, such as breast cancer, colorectal cancer, and gastric cancer, which might be the frontiers. [ABSTRACT FROM AUTHOR]

Our study aimed to estimate the epidemiological trends of gastric cancer in the United States from 1992 to 2019. This population‐based study used the US Surveillance, Epidemiology and End Results‐12 database as a fundamental cohort to analyze gastric cancer incidence, incidence‐based mortality (IBM), overall survival (OS) and cancer‐specific survival (CSS) probabilities from 1992 to 2019. The Global Burden of Disease study (1990‐2018) was used as a likely validation cohort. Age‐period‐cohort analyses were performed to explore the underlying causes of trend changes. We found that the incidence rate of gastric cancer decreased from 1992 to 2019. IBM also decreased significantly from 1997 to 2019. The 3‐year OS and CSS of gastric cancer increased from 22.3% to 28.7% and 25.7% to 33.5%, respectively. However, the proportion of distant gastric cancer cases had unexpectedly increased rapidly from 33.1% in 1992 to 44.7% in 2019. Age‐period‐cohort modeling found that the incidence and IBM rates remained stable in the groups aged below 50 years, while that in all age groups older than 50 years showed a significant downward trend. High incidence and mortality risks were observed in the younger birth cohorts (birth year after 1990). To conclude, we observed a decline in incidence and mortality rates of gastric cancer in the United States in the past decades. We determined that progression of primary and tertiary preventive measures is the main reason for the reduction in the disease burden of gastric cancer. However, secondary preventive measures for gastric cancer still need to be strengthened. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Surgical resection is the gold standard of treatment. In the United States, race and socioeconomic status are associated with the diagnosis of GC; however, no studies have examined these as independent risk factors for surgical outcomes. Our study sought to investigate socioeconomic factors and GC surgical outcomes using a national cancer registry. GC patients between 2004 and 2016 were identified using the National Cancer Database. Univariate and multivariate logistic regression was used to analyze associations between socioeconomic factors and 30-d mortality, 90-d mortality, and unplanned readmission rate. A total of 96,990 patients who received nonpalliative surgical treatment for GC were identified. When controlling for other clinical and socioeconomic factors, older age, male sex, higher comorbidities, larger tumor size, advanced stage disease, and inadequate resection were correlated with worse 30- and 90-d mortality. Additionally, 30-d and 90-d mortality was significantly lower when the patient's income (odds ratio [OR] = 0.77 and OR = 0.43, respectively, for >$63,333/y versus <$40.227/y) and the percentage of residents with a high school degree in their zip code (OR = 0.69 and OR = 0.52, respectively, for <6.3% no high school degree versus ≥ 17.6%) were higher. No significant disparate trends were identified in terms of race and insurance status or in unplanned readmissions on multivariate analysis. Lower income and the level of education at the place of residence were independently associated with higher 30-d and 90-d mortality in this study, highlighting the potential for a major socioeconomic disparity in this population. • Thirty-day and 90-d mortality was up to 57% higher in patients with income < $40,227/y. • Thirty-day and 90-d mortality was up to 48% higher in zip codes with low education (≥17.6% residents with no high school degree). • Private insurance correlated with lower 30-d mortality. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (Hp) is causal in benign and malignant gastrointestinal diseases. Accordingly, current guidelines recommend Hp eradication in patients with active infection. Unfortunately, treatment failure is common, exposing patients to complications associated with persistent Hp infection and consequences of repeated treatment, including promotion of antibiotic resistance. In the United States (US), data regarding eradication rates with available therapies are limited. Moreover, the clinical and economic burden of eradication treatment failure have not been thoroughly described. We aimed to characterize Hp eradication rates and the clinical consequences and associated costs of persistent Hp infection among US adults. We conducted focused literature reviews using initial searches in Embase, MEDLINE, and Cochrane Database of Systematic Reviews via Ovid followed by manual searches to identify relevant publications. Hp eradication rates were suboptimal, with most studies reporting rates ≤80% with clarithromycin-based triple therapy and bismuth quadruple therapy. There was direct evidence supporting numerous benefits of successful Hp eradication, including decreased risk of recurrent or complicated peptic disease and non-cardia gastric cancer. Cost benefits of eradication were related to mitigation of conditions associated with persistent Hp infection, (e.g. complicated peptic ulcer disease, and gastric cancer) which altogether exceed US$5.3 billion. [ABSTRACT FROM AUTHOR]

Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and comparative review of each country’s guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations. [ABSTRACT FROM AUTHOR]

Objectives: Little is known about the current status and the changing trends of hospitalization and palliative care consultation of patients with gastric cancer in the United States. The aim of this study was to evaluate the changing trend in the number of hospitalization, palliative care consultation, and palliative procedures in the US during a recent 10-year period using a nationwide database.Methods: This was a retrospective study that analyzed the National Inpatient Sample (NIS) database of 2009-2018. Patients aged more than 18 years who were diagnosed with a gastric cancer using International Classification of Diseases (ICD)-9 and 10 codes were included. Palliative care consultation included palliative care (ICD-9, V66.7; ICD-10, Z51.5) and advanced care planning (ICD-9, V69.89; ICD-10, Z71.89). Palliative procedures included percutaneous or endoscopic bypass, gastrostomy or enterostomy, dilation, drainage, nutrition, and irrigation for palliative purpose.Results and Discussion: A total of 86,430 patients were selected and analyzed in this study. Using a compound annual growth rate (CAGR) approach, the annual number of hospitalizations of gastric cancer patients was found to be decreased during 2009-2018 (CAGR: -0.8%, P = 0.0084), while utilization rates of palliative care and palliative procedures increased (CAGR: 9.3 and 1.6%, respectively; P < 0.0001). Multivariable regression analysis revealed that palliative care consultation was associated with reduced total hospital charges (-$34,188, P < 0.0001).Conclusion: Utilization of palliative care consultation to patients with gastric cancer may reduce use of medical resources and hospital costs. [ABSTRACT FROM AUTHOR]

Background Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse. Objectives We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk. Methods Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers. Results During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non–statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite. Conclusions Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted. [ABSTRACT FROM AUTHOR]

Background: The efficacy of endoscopic ultrasound (EUS) for determining the T category of gastric cancer is variable. The aim of this study was to evaluate the superiority of EUS by using the 6th edition American Joint Committee on Cancer (AJCC) staging system for stomach cancer compared to the new 7th/8th edition.Methods: A retrospective analysis of clinical and EUS imaging features of 348 gastric carcinoma patients who underwent radical resection were retrospectively analyzed. Differences between the 6th and 7th/8th edition T staging systems for preoperative EUS evaluation were compared.Results: The accuracy of EUS T staging was 72.4% for the 7th/8th edition and 78.4% for the 6th edition. T3 stage accuracy was significantly worse when the T3 group status was changed. The tumor location, echoendoscope type, and histological type were associated with inaccuracy. We further analyzed the EUS image features for each tumor T stage and found that an indistinctly visible muscularis propria (MP) or with obvious thickening was considered an indicator of lesions involved in the MP with a sensitivity of 81.3%; an MP completely disappeared and accompanied with a serosal layer intact may be a marker that the lesion invaded to the subserosa. We also found that irregularities in the outer edge of the gastric wall were markers of gastric serosal layer penetration with a positive predictive value of 92.2%.Conclusions: The increased complexity of the 7th/8th edition T staging system is accompanied by worsening of the predictive accuracy for EUS as compared to the 6th edition. Furthermore, the tumor location, echoendoscope type, histological type, and EUS image features for each tumor T stage should warrant attention. [ABSTRACT FROM AUTHOR]

Background: Quality measurement has become a priority for national healthcare reform, and valid measures are necessary to discriminate hospital performance and support value‐based healthcare delivery. The Commission on Cancer (CoC) is the largest cancer‐specific accreditor of hospital quality in the United States and has implemented Quality of Care Measures to evaluate cancer care delivery. However, none has been formally tested as a valid metric for assessing hospital performance based on actual patient outcomes. Methods: Eligibility and compliance with the Quality of Care Measures are reported within the National Cancer Database, which also captures data for robust patient‐level risk adjustment. Hospital‐level compliance was calculated for the core measures, and the association with patient survival was tested using Cox regression. Results: Seven hundred sixty‐eight thousand nine hundred sixty‐nine unique cancer cases were included from 1323 facilities. Increasing hospital‐level compliance was associated with improved survival for only two measures, including a 35% reduced risk of mortality for the gastric cancer measure G15RLN (HR 0.65, 95% CI 0.58–0.72) and a 19% reduced risk of mortality for the colon cancer measure 12RLN (HR 0.81, 95% CI 0.77–0.85). For the lung cancer measure LNoSurg, increasing compliance was paradoxically associated with an increased risk of mortality (HR 1.14, 95% CI 1.08–1.20). For the remaining measures, hospital‐level compliance demonstrated no consistent association with patient survival. Conclusion: Hospital‐level compliance with the CoC's Quality of Care Measures is not uniformly aligned with patient survival. In their current form, these measures do not reliably discriminate hospital performance and are limited as a tool for value‐based healthcare delivery. [ABSTRACT FROM AUTHOR]

Lymph node (LN) yield is a key quality indicator that is associated with improved staging in surgically resected gastric cancer. The National Comprehensive Cancer Network recommends a yield of ≥15 LNs for proper staging, yet most facilities in the United States fail to achieve this number. The present study aimed to identify factors that could affect LN yield on a facility level and identify outlier hospitals. This was a retrospective review of adults (aged ≥18 y) with gastric cancer (Tumor-Node-Metastasis Stages I-III) who underwent gastrectomy. Data were analyzed from the National Cancer Database (2004-2016). Multivariate analysis identified patient and tumor characteristics, whereas an observed-to-expected ratio of identified outlier hospitals. Facility factors were compared between high and low outliers. A total of 26,590 patients were included in this study. Of these patients, only 50.3% had an LN yield ≥15. The multivariate model of patient and tumor characteristics demonstrated a concordance index was 0.684. A total of 1245 facilities were included. There were 198 low outlier LN yield hospitals and 135 high outlier LN yield hospitals (observed-to-expected ratio of 0.42 ± 0.24 versus 1.38 ± 0.19, P < 0.0001). There was a difference in facility type between low and high outliers (P < 0.0001). High LN yield hospitals had a larger surgical volume than low LN yield hospitals (median 8.4 [4.9, 13.5] versus 3.5 [2.4, 5.2]; P < 0.0001). Nearly half of the population exhibited low compliance to National Comprehensive Cancer Network recommendations. Facility-level disparities exist as high yearly surgical volume and academic facility status distinguished high-performing outlier hospitals. [ABSTRACT FROM AUTHOR]

Gastric cancer is not a top‐10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard‐of‐care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD‐L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein‐Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity. [ABSTRACT FROM AUTHOR]

Background and Aims: High sodium consumption has been associated with an increased risk of gastric cancer. The mean daily sodium intake in the United States substantially exceeds the national recommended amount. The low sodium‐DASH diet has been shown to decrease the risk of cardiovascular disease in the United States, but its impact on gastric cancer has not been well studied. We therefore aimed to model the impact and cost‐effectiveness of the low sodium‐DASH diet for gastric cancer prevention in the U.S. population. Methods: A Markov cohort state‐transition model was developed to simulate the impact of the low sodium‐DASH diet on gastric cancer outcomes for the average 40‐year‐old in the United States compared to no intervention. Primary outcomes of interest were gastric cancer incidence and incremental cost‐effectiveness ratios (ICER). Results: Our model found that compared to the no intervention cohort, the risk of gastric cancer decreased by 24.8% for males and 21.2% for females on the low sodium‐DASH diet. 27 cases and 14 cases per 10,000 individuals were prevented for males and females, respectively, in the intervention group. The ICER for the low sodium‐DASH diet strategy was $287,726 for males and $423,878 for females compared to the no intervention strategy. Conclusions: Using a Markov model of gastric cancer risk, we found that adherence to a low sodium‐DASH diet could decrease the risk of gastric cancer. This intervention was not cost‐effective due to the high cost of a low sodium‐DASH accordant diet, but significantly improved for high‐risk populations and when the cost of the diet became slightly more affordable. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is more common in men than in women, but underlying reasons have not been completely understood. This study aimed to assess patterns of the sex difference in the incidence of gastric cancer in the United States.Methods: Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results Program, we analyzed the age-specific sex difference in the incidence of gastric cancer by ethnicity, anatomic site and histological type in the United States during 1992-2014. We assessed the temporal trends in the sex differences in the incidence of gastric cancer during the study period.Results: The male-to-female incidence ratio of cardia cancer increased with age until peaking at ages 55-69 years and decreased thereafter, while the ratio for non-cardia gastric cancer increased with age before ages < 60 years and remained stable onwards. The age-specific patterns in the sex difference of gastric cancer incidence varied between intestinal and diffuse histological types. The sex difference in the incidence of cardia cancer remained relatively stable except for that the absolute difference between the sexes in whites decreased on average by 0.8% per year from 1992 to 2014. The absolute incidence difference between the sexes in non-cardia gastric cancer decreased over time in whites, blacks, and Asian and Pacific islanders by approximately 4% per year. The male-to-female incidence ratio of non-cardia gastric cancer decreased over time in whites and blacks, but remained relatively stable in Asian and Pacific islanders.Conclusions: Both extrinsic and intrinsic factors may have contributed to the sex difference in gastric cancer. Sex hormones may play a role in the development of cardia cancer and intestinal type of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown an increase in the incidence of gastric cancer (GC) among young adults in Asia and Latin America. However, it is unknown if a similar trend is happening in the United States (US).Methods: A retrospective review of the National Cancer Data Base was conducted to identify patients diagnosed with gastric adenocarcinoma between the years of 2004 and 2013.Results: A total of 93 734 patients were included. The 2 age groups below 40 did not see a change in GC incidence; however, age groups above 40 had increasing incidence. Patients aged 18-25 had the largest proportion of stage 4 disease and a poor survival (median 11.5 months), compared to older patients.Conclusion: Despite the increasing trend of GC among individuals, the incidence of GC among young adults is not increasing. However, this subpopulation presents at more advanced stages (clinical stage 4) and thus has worse survival. [ABSTRACT FROM AUTHOR]

The necessity of extensive lymph node (LN) dissection/examination and adjuvant therapy for patients with early gastric cancer (EGC, Tis-T1, any N) remains controversial. We aim to refine treatment recommendations for patients with EGC through a reflective analysis for the survival gap between Eastern and Western countries. EGC patients diagnosed between 2004 and 2014 were identified from the National Cancer Database (NCDB) and a large medical center in China. Adequate LN yield was defined as ≥25 LNs examined. In the US cohort, 14.4% of (1104/7641) patients with EGC had ≥25 LNs examined. The 5-y overall survival (OS) was significantly better than those with <25 LNs (78.9% versus 68.5%, P < 0.001). Examination of ≥25 LNs was an independent predictor of better OS after adjusting all known prognostic factors. Patients with ≥25 LNs examined had significantly higher chance of having LN-positive disease compared to patients with <25 LNs (14.9% versus 10.7%, P < 0.001). A similar stage migration phenomenon was observed in Chinese cohort (LN positive: 25.2% versus 18.4% in ≥25 LNs and <25 LNs examined group, respectively, P = 0.02). In the US cohort, adjuvant therapy was associated with a significant survival benefit for LN-positive patients (5-y OS: 71.0% versus 43.0% for with/without adjuvant therapy, respectively, P < 0.001) but not in LN-negative patients (5-y OS: 71.2% versus 71.5%, P = 0.90). Adequate lymphadenectomy and LN examination are critical components of EGC management. Adjuvant therapy should be strongly encouraged for all EGC patients with LN-positive disease in the United States. • Adequate lymphadenectomy could significantly improve the OS of early gastric cancer. • Examining ≥25 LNs may lead to more accurate N stage identification and less stage migration. • The survival gap between Eastern and Western populations can be narrowed by quality of lymphadenectomy by surgeons and thorough evaluation of the surgical specimen by pathologists. • Adjuvant therapy should be strongly encouraged for all EGC patients with positive LN disease in the United States. [ABSTRACT FROM AUTHOR]

Gastric adenocarcinoma lymph node retrieval during gastrectomy and survival differ significantly between Asian and Western studies. It is unclear whether such disparities are the result of surgical technique, patient population, or other factors. In this observational study, we aimed to determine whether lymph node retrieval and outcomes differ between White, Black, and Asian American patients undergoing gastrectomy for adenocarcinoma. 47,217 cases of gastric resection for gastric adenocarcinoma and its subtypes were identified in the National Cancer Data Base (2000–2015). Differences in demographics, lymph node retrieval, operative outcomes, and survival were compared by self-reported race (White, Black, and Asian). Asians had greater median lymph node retrieval (17) compared to White (15) and Black (16) patients, P < 0.001. Lymph node ratio was lowest in Asian (0.03) compared to White (0.05) and Black (0.09) patients, P < 0.001. Postoperative mortality was lowest in Asian patients on multivariable analysis (90-day mortality adjusted odds ratio of 0.54, P < 0.001). Median survival was not yet reached for Asian patients but was 39.5 months for White and 43.0 months for Black patients (P < 0.001). Differences in survival by race persisted on multivariable analysis (Asian adjusted hazard ratio was 0.64, 95% CI: 0.59–0.70, P < 0.001). Asian-American patients with gastric cancer undergoing gastrectomy have greater lymph node retrieval, decreased lymph node ratio, decreased postoperative mortality, and increased long-term survival compared to White or Black Americans. Data suggest factors other than surgical technique and oncologic care may be responsible for gastric adenocarcinoma outcome differences seen between Asian and Western studies. [ABSTRACT FROM AUTHOR]

Background: Acid-suppressant medications, including proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs), are frequently prescribed and have been linked to increased risk of some gastrointestinal cancers.Aims: We examined whether post-diagnosis use of PPIs/H2RAs is associated with the risk of mortality in gastrointestinal cancer patients.Methods: We used data from patients with esophageal cancer, gastric cancer, or hepatocellular carcinomas (HCCs) in the national VA Central Cancer Registry diagnosed between 2002 and 2016. We identified PPI/H2RA prescriptions that were filled before and after cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3-month lag to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between the date of cancer diagnosis and the start of follow-up.Results: PPIs were used by the majority (54% post-diagnosis use) of patients. We found no association between post-diagnosis PPI use and cancer-specific mortality in esophageal adenocarcinoma (HR 0.93; 95% CI 0.84-1.02), esophageal squamous cell carcinoma (HR 0.99; 95% CI 0.87-1.12), or gastric cardia cancer (HR 1.04; 95% CI 0.89-1.22) patients. Post-diagnosis PPI use was, however, associated with the increased risk of cancer-specific mortality for patients with gastric non-cardia cancer (HR 1.50; 95% CI 1.29-1.74) and HCC (HR 1.31; 95% CI 1.23-1.40). The results were similar for associations with post-diagnosis use of H2RAs. There was no association with pre-diagnosis PPI/H2RA use.Conclusion: Post-diagnosis PPI/H2RA use was associated with the increased mortality in gastric non-cardia cancer and HCC patients. [ABSTRACT FROM AUTHOR]

Gastric cancer remains third leading cause of global cancer mortality and is the fifth most common type of cancer in the United States. A select number of gastric cancers harbor alterations in EGFR and/or have amplification/overexpression in the HER2; 2–35 and 9–38%, respectively. The advent of next-generation sequencing of tissue and circulating tumor DNA has allowed for the massive expansion of targeted therapeutics to be employed in many settings. There have been a handful of trials using EGFR inhibitors with modest outcomes. Using novel strategies to target multiple co-mutations as well as identifying immunoregulatory molecule expression patterns will potentially drive future trials and improve gastric cancer patient outcomes. [ABSTRACT FROM AUTHOR]

To investigate whether endoscopic treatment is applicable to American patients and explores the predictors of lymph node metastasis (LNM) in early gastric cancer (EGC). Patients with EGC confined to either mucosa (T1a, n = 1799) and submucosa (T1b, n = 1689) were identified from the Surveillance, Epidemiology, and End Result database. Multivariate logistic regression, Kaplan–Meier method, and univariate/multivariate Cox regression were used to assess the correlation between invasion depth and LNM or prognosis. A nomogram for predicting LNM was constructed and internally validated. EGC limited to T1a exhibited a 2.4% incidence of LNM, which increased to 11.1% when the depth invaded T1b.LNM was present at 1.4%, 5.2%, and 5.0% for sizes ≤2, 2–5, and >5cm of low-grade T1a EGC, respectively, (p =.019) and at 4.8%, 12.4%, and 28.6% of T1b EGC, respectively (p <.001).The multivariate logistic model revealed that older age, T1b invasion, larger tumor size, and high-grade lesions were associated with a higher risk of LNM. Moreover, the T1a EGC patients had better cancer-specific survival (OS) and overall survival(CSS) compared with the T1b EGC patients (5-year OS: 77.2% versus 67.4%, p <.001; 5-year CSS: 90.6% versus 81.4%, p <.001). The discrimination of the prediction model was 0.745. Endoscopic treatment may only be suitable for patients in the US population who have low-grade T1a lesions of less than 2 cm in size. Patients with T1a lesions of greater than 2 cm in size, lesions with high-grade, and all T1b lesions may benefit from radical surgical resection with lymphadenectomy. [ABSTRACT FROM AUTHOR]

Background: Despite multiple clinical trials and practice guidelines for the treatment of gastric cancer, oncologic outcomes have not improved in the United States. One potential reason could be differences in the quality of surgery as performed in a controlled trial versus in practice. Methods: Using the National Cancer Database, rates of adherence with operative standards for gastrectomy for cancer were analyzed. Of the numerous evidence-based operative standards outlined in the manual, two were reliably measured in the NCDB: (1) achieving and R0 resection, and (2) having > 16 lymph nodes examined. Univariable and multivariable Cox proportional hazard modeling and logistic regression were performed. Results: A total of 28,705 patients with gastric adenocarcinoma who underwent curative-intent gastrectomy during 2004–2014 were identified. Only 36.5% of stage 0/I patients, and 41.8% of stage II/III patients, met minimum standards. Predictors for meeting standards included age < 65, fewer comorbidities, Asian/Pacific Islander race, and treatment at academic and high-volume centers. Patients who met standards had longer OS (stage 0/I: 104.9 versus 66.6 months; stage II/III: 40.6 versus 26.0 months; p < 0.001 for both). Meeting standards was a significant predictor for improved OS for both stage 0/I and II/III patients (HR = 0.665 and HR = 0.747, respectively, p < 0.001 for both). Conclusions: For standards that are measurable in the NCDB, adherence is poor. Improved adherence with operative standards may improve survival for gastric cancer patients in the U.S. There is a need for better measuring of, and adherence with, operative standards in gastrectomy for cancer. [ABSTRACT FROM AUTHOR]

Background: National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community.Methods: Patients with stage II to III gastric adenocarcinoma undergoing curative-intent resection (National Cancer Data Base, 2006-2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan-Meier analysis was used to assess survival.Results: There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10-year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline-concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values <.001). The median overall survival was 45.5 months for patients who received guideline-concordant care and 32.0 months for those who did not (P < .001, reference for all ORs: academic programs).Conclusions: Compliance with guidelines was associated with improved outcomes. Although the rate of compliance with NCCN guidelines is improving, integrated care networks may be an important way of improving the quality of gastric cancer care within the community. [ABSTRACT FROM AUTHOR]

Approximately 5.0% of gastric cancer (GC) patients are diagnosed before the age of 40 and are not candidates for screening programs in most countries and regions. The incidence of gastric cancer in young adults (GCYA) has declined over time in most countries except in the United States. Genetic alterations, environmental factors, and lifestyle may predispose some young adults to GC. According to molecular classifications, the cancer of most GCYA patients belongs to the genomically stable or microsatellite stable/epithelial-mesenchymal transition subtype, with the common genetic aberrations being mutations in CDH1. What characterizes GCYA are a higher prevalence in females, more aggressive tumor behaviors, diagnosis at advanced stages, fewer comorbidities and being better treatment candidates, and a similar or better survival outcome when compared with older patients. Considering the greater loss of life-years in younger patients, lowering the incidence of GC and diagnosing at a relatively early stage are the two most effective ways to decrease GC mortality. To achieve these goals, the low awareness of GCYA among general people, policy-makers, clinicians, and researchers should be changed. [ABSTRACT FROM AUTHOR]

Background: Although prior studies have shown that marital status affects the prognosis of patients with gastric cancer, its time-varying effects are not well understood. We aimed to investigate the changes in marital status' impact over a 10-year follow-up time among patients with gastric cancer (GC) in the United States. Materials and Methods: All patients with gastric cancer diagnosed between 2004 and 2008 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. Married patients and unmarried patients (single, separated, divorced or widowed) with complete survival time were selected for comparisons. A total of 14,545 patients who had clinical data and follow-up information available were enrolled. We used Kaplan–Meier analyses and time-dependent flexible parametric models to estimate time-varying hazard ratios (HRs). Results: Unmarried GC patients had worse overall and cancer-specific survival compared with married patients (log-rank test: P < 0.001 and P < 0.001, respectively). The time-varying analysis found that unmarried patients had a significantly higher risk of overall mortality during the 10-year follow-up time, with the lowest adjusted hazard ratio (HR) at 12 months after diagnosis (HR at 12 months, 1.08; 95% CI, 1.03–1.15). For cancer-specific mortality, the time-varying adjusted HR of unmarried patients was significantly higher initially (HR at 12 months, 1.08; 95% CI, 1.02–1.14) but decreased to null after 20 months (HR at 24 months = 1.04; 95% CI = 0.99–1.11). Conclusion: Unmarried patients had a higher risk of cancer-specific mortality during the 20 months after gastric cancer diagnosis, which may be an appropriate time frame for intervention. [ABSTRACT FROM AUTHOR]

Background: Vitamin D was first hypothesized to play a role in cancer chemoprevention in 1980 when it was observed that there was a higher rate of colon cancer in the Northern USA as compared with populations living in the South. While cholecalciferol (vitamin D3) has been tested in many cancer-cell lines, published results for ergocalciferol (vitamin D2) are lacking for most epithelial cell cancers, and combination studies of both D2 and D3 and vitamin A (retinoic acid) are lacking in general. The goal of the study was to investigate the effects of vitamins D2, D3, and A, alone and in combination on the growth of all gastric and colon cancer cell lines in vitro. Methods: Colon (SW480 and HCT-116) and gastric (AGS and NCI-N87) cell lines were treated with varying concentrations of D2, D3 and all-trans retinoic acid (ATRA) and combinations thereof. Cell viability and cytotoxicity were measured using the CellTiter-Glo® 2.0 assay, while caspase activities and cytotoxicity were determined using the Caspase-Glo® 3/7, Caspase 8, ApoTox-Glo™ Triplex assays. Autophagy was determined using the CYTO-ID® Autophagy Detection Kit 2.0. Gene expression studies were performed using qPCR. Results: Both vitamin D2 and D3 inhibited the growth of all cell lines tested, with IC50 ranging from 19-56 µM. However, when combined (1:1), the IC50 for the combination of D2 and D3 was significantly reduced to a range of 5-6.0 µM indicating synergism. ATRA also inhibited the growth of all cell lines tested with an IC50 range of 2.6 to 5.6 µM. When ATRA was combined with D2 and D3, the IC50s were significantly reduced to 0.65 to 1.4 µM, further indicating synergistic effects. In the gastric and colon cancer cell lines, the combination induced apoptosis via caspase 3/7 and 8, increased the Bax/Bcl-2 ratio, while in the SW480 colon cancer line, the combination also induced autophagy. Conclusion: Our data demonstrated that vitamins D2, D3 and ATRA inhibit the proliferation of colon and gastric cancer cells. The combinations of D2+D3 or ATRA+D2+D3 had synergistic effects or additive effects on all cell lines tested, increased Bax expression and the Bax/Bcl-2 ratio, and increased caspase 3/7 and 8 activities to favor apoptosis. In SW480 colon cancer cells the combination also induced autophagy. This data suggest that combinations of vitamins A and D have synergistic effects in colon and gastric cancers, and considering the potential clinical implications, further research is justified. [ABSTRACT FROM AUTHOR]

Background: Adequate lymphadenectomy (AL) of 15+ lymph nodes comprises an important component of gastric cancer surgical therapy. Despite endorsement by the National Comprehensive Cancer Network and the Committee on Cancer, initial adoption of this paradigm has been relatively slow. The current analysis sought to perform an adjusted time-trend evaluation of the factors associated with AL and its dissemination.Methods: Utilizing the 2004-2015 National Cancer Database, 28,985 patients were identified who underwent gastrectomy for adenocarcinoma. An adjusted time-trend analysis was performed to estimate the adoption of AL overall. Multivariable logistic regression was utilized to assess factors associated with these observed trends. Interactions and stratified models determined disparate effects in vulnerable populations (older adults, ethnic minorities, low socioeconomic status).Results: The adjusted time-trend analysis demonstrated an overall 30% increase (28.8 to 58.7%) in receipt of AL (OR 1.10 increase/year; 95%CI 1.09-1.10) from 2004 to 2015. This trend persisted even after stratifying the models by age, race/ethnicity, and income (OR 1.07-1.12; p < 0.05). Slowest rates of adoption were seen amongst hospitals in the Midwest census region (OR 1.08, CI 1.06-1.90) and comprehensive community hospitals (OR 1.08, CI 1.06-1.91) and with African-American patients (OR 1.09, CI 1.06-1.11) (all p < 0.05).Conclusion: This multi-center evaluation demonstrates increased adoption of AL during gastric cancer surgery in the USA overall and amongst vulnerable populations, although regional and racial disparities were observed. Future studies are needed to investigate reasons underlying racial and regional differences in receipt of AL. [ABSTRACT FROM AUTHOR]

Germline CDH1 mutation carriers are at risk for early-onset diffuse gastric cancer (DGC) and female carriers have an additional risk of lobular breast cancer. The reported literature GC risk of 70% has led to the recommendation for germline mutation carriers to undergo prophylactic total gastrectomy (PTG). The objective of this research was to examine post-surgical clinical outcomes and to identify which of the domains/symptoms from the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30) were determinants of overall quality of life (QOL) in individuals undergoing PTG. Participants were recruited through multiple sources. Postsurgical clinical outcomes were obtained from hospital records. Participants completed validated questionnaires measuring generic and condition specific QOL (PROMIS, EORTC and SF 36v.II) at a single point in time. The mean QOL in this cohort was 70.6 (SD = 25.6), which is better than reference values from the general populations in USA and Canada Role and social function plus the symptoms anxiety, pain, taste, dyspnea and diarrhea were significant predictor variables for QOL (p < 0.05). Although this study reveals good overall QOL for individuals after PTG, attention should be given to managing symptoms as part of long term care to further enhance QOL. The function/symptom scores were associated with worse overall health and global health status and thus may mark a real need for more attentive post-surgical care. [ABSTRACT FROM AUTHOR]

Background: The drawback of intracorporeal esophagojejunostomy with the double-stapling technique (DST) using a transorally inserted anvil (OrVil™, Covidien, Mansfield, MA, USA) following laparoscopic total gastrectomy (LTG) is not only the high incidence of stenosis but also the presence of intractable stenosis that is refractory to endoscopic treatments.Methods: From November 2013 to December 2016, 24 patients with gastric cancer underwent intracorporeal circular-stapled esophagojejunostomy with the hemi-double-stapling technique (hemi-DST) using the OrVil™ in antecolic Roux-en-Y reconstruction with its efferent loop located on the left side of the patient following LTG to prevent twisting of the esophagojejunostomy and lifted jejunum, which might cause intractable stenosis of the esophagojejunostomy.Results: In this patient series, no twisting of the esophagojejunostomy and lifted jejunum was encountered intraoperatively or postoperatively. Two stenoses of the esophagojejunostomy occurred. Because neither was involved with twisting and both were localized at the anastomotic plane, endoscopic treatments including balloon dilation and electrocautery incisional therapy were successful in both cases. There were no patients with intractable stenosis in this series.Conclusions: Intracorporeal esophagojejunostomy with the hemi-DST using the OrVil™ in antecolic Roux-en-Y reconstruction with its efferent loop located on the left side of the patient can be one option for a circular stapling technique in LTG due to its prevention of intractable stenosis of the esophagojejunostomy that is refractory to endoscopic treatments. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is an important cause of death among racial/ethnic minorities in the U.S. The objective of this study was to investigate racial disparities in survival among gastric cancer patients within demographic and disease subgroups.Methods: Patients diagnosed with invasive epithelial gastric cancer between 2006 and 2015 were identified from the California Cancer Registry. Cox proportional hazards regression was used to identify factors associated with survival among non-Hispanic whites (NHWs, n = 7,475), non-Hispanic blacks (NHBs, n = 1,246), Hispanics (n = 6,274), and Asians/Pacific Islanders (APIs, n = 4,204). Survival was compared across race/ethnicity within subgroups of demographic and disease factors. Five-year relative survival was also calculated within subgroups.Results: There were notable differences in patient characteristics by race/ethnicity, but predictors of survival were similar for each group. Overall, APIs (HR = 0.83, 95% CI: 0.79, 0.88, p < 0.0001) and Hispanics (HR = 0.94, 95% CI: 0.90, 0.99, p = 0.0104) had better survival than NHWs, but NHBs and NHWs did not have different prognosis (HR = 1.06, 95% CI: 0.98, 1.15, p = 0.2237). The survival advantage of APIs persisted in nearly every demographic and disease subgroup, but Hispanics and NHBs had similar survival as NHWs in most groups. Race was not a significant predictor of survival among those with public or no insurance and patients with cardia tumors.Conclusions: There are some differences in survival by race/ethnicity, but race/ethnicity alone cannot explain disparate outcomes in gastric cancer. Future studies, particularly ones that investigate the role of population-specific etiological factors and molecular tumor profiles, are needed to further understand factors associated with survival. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive gastric or gastro-oesophageal junction cancer who received trastuzumab deruxtecan at the recommended doses for expansion.Methods: This was an open-label, dose-escalation and dose-expansion phase 1 trial done at eight hospitals and clinics in the USA and six in Japan. Eligible patients were at least 18 years old in the USA and at least 20 years old in Japan and had advanced solid tumours (regardless of HER2 expression in dose escalation or HER2 expression or mutation in dose expansion). The recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan were administered intravenously to patients once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. In this Article, all patients with HER2-positive gastric or gastro-oesophageal junction cancer with previous trastuzumab treatment who received trastuzumab deruxtecan were analysed together. The primary endpoints of the study were safety and preliminary activity (proportion of patients who achieved an objective response as assessed by the investigators). The activity evaluable set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion, and for whom both baseline and post-treatment activity data were available. The safety analysis set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. Enrolment for patients with gastric or gastro-oesophageal junction cancer has completed. This trial is registered at ClinicalTrials.gov, number NCT02564900, and ClinicalTrials.jp, number JapicCTI-152978.Findings: Between Aug 28, 2015, and Aug 10, 2018, 44 patients with HER2-positive gastric or gastro-oesophageal junction cancer received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. All patients had at least one treatment-emergent adverse event. The most frequent grade 3 or worse treatment-emergent adverse events included anaemia (13 [30%]) and decreases in neutrophil (nine [20%]), platelet (eight [18%]), and white blood cell (seven [16%]) counts. Serious treatment-emergent adverse events occurred in 11 (25%) patients. There were four pneumonitis cases (three grade 2 and one grade 3). There were no drug-related deaths due to treatment-emergent adverse events. 19 (43·2%; 95% CI 28·3-59·0) of 44 patients had a confirmed objective response.Interpretation: Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in heavily pretreated patients with HER2-positive gastric or gastro-oesophageal junction cancer. These results support further investigation of trastuzumab deruxtecan for HER2-positive gastric or gastro-oesophageal junction cancer post-trastuzumab.Funding: Daiichi Sankyo Co, Ltd. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to evaluate the racial and ethnic disparities in the incidence of gastric cancer and their temporal trends in the United States. Materials and Methods Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results database, we assessed such disparities during 1992-2014 in the United States using a variety of disparity metrics. Results The age-standardized incidence rate of non-cardia gastric cancer was highest in Asian and Pacific Islanders, while the incidence of cardia gastric was highest in non-Hispanic whites in men and was similarly low in all groups in women. The incidence of non-cardia gastric cancer decreased in all groups over time, particularly in Asian and Pacific Islanders (on average by 3% per year). The incidence of cardia gastric remained relatively stable in virtually all racial/ethnic groups. The racial and ethnic disparities in gastric cancer incidence steadily decreased over time as measured on the absolute scale, which was mainly driven by the reduced disparities in non-cardia gastric cancer. The range difference in the incidence of gastric cancer decreased on average by 4.1% per year in men and by 2.6% per year in women from 1992 to 2014. The between group variance decreased by 5.6% per year in men and by 3.4% per year in women. The relative-scale disparity measures generally remained stable over time. Conclusion This study demonstrates decreased racial and ethnic disparities in the incidence of gastric cancer over time in the United States, particularly as measured on the absolute scale. [ABSTRACT FROM AUTHOR]

Background: Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric cancers, and are emerging as potential treatments for HER2-positive metastatic colorectal cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations. We aimed to assess the activity of pertuzumab and trastuzumab in patients with HER2-amplified metastatic colorectal cancer.Methods: MyPathway is an ongoing, phase 2a, multiple basket study. Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer with measurable or evaluable disease and an Eastern Cooperative Oncology Group performance status score of 2 or less, enrolled from 25 hospitals or clinics in 16 states of the USA. Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously). The primary endpoint was the proportion of patients who achieved an objective response based on investigator-reported tumour responses. Analyses were done per protocol. This ongoing trial is registered with ClinicalTrials.gov, number NCT02091141.Findings: Between Oct 20, 2014, and June 22, 2017, 57 patients with HER2-amplified metastatic colorectal cancer were enrolled in the MyPathway study and deemed eligible for inclusionin this cohort analysis. Among these 57 evaluable patients, as of Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20-45). The most common treatment-emergent adverse events were diarrhoea (19 [33%] of 57 patients), fatigue (18 [32%] patients), and nausea (17 [30%] patients). Grade 3-4 treatment-emergent adverse events were recorded in 21 (37%) of 57 patients, most commonly hypokalaemia and abdominal pain (each three [5%] patients). Serious treatment-emergent adverse events were reported in ten (18%) patients and two (4%) of these adverse events (ie, chills and infusion-related reaction) were considered treatment related. There were no treatment-related deaths.Interpretation: Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer.Funding: F Hoffmann-La Roche/Genentech. [ABSTRACT FROM AUTHOR]

Background: Our aim was to evaluate the prognostic value of the number of lymph nodes examined (eLNs) in patients with node-negative gastric cancer (GC) and further to adjust the American Joint Committee on Cancer (AJCC) 8th staging system based on the number of eLNs.Methods: Node-negative GC patients diagnosed during 1988-2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included. On the basis of a primary cohort of 4159 node-negative GC patients, we built the adjusted AJCC 8th staging system, which was then internally validated by a bootstrap method, and externally validated with an independent cohort of 5565 node-negative GC patients.Results: The median number of eLNs was 10. For the training set, the optimal eLNs thresholds were determined to be 9 for node-negative GC patients. The adjusted AJCC 8th staging system for node-negative GC patients based on the number of eLNs had a significantly higher Harrell's concordance index than the initial AJCC 8th staging system (C-index, 0.635 versus 0.616; P < 0.001). Thus, the adjusted AJCC 8th staging system had superior prognostic stratification. Similar results were found in the validation set.Conclusions: For node-negative GC patients in the United States, the adjusted AJCC 8th staging system based on the number of eLNs predicted survival more accurately and discriminatively. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer is decreasing nationally but remains pervasive globally. We evaluated our experience with gastric cancer at a safety-net hospital with a substantial immigrant population.Methods: Demographics, pathology, and treatment were analyzed for gastric adenocarcinoma at our institution (2004-2017). Chi-square analyses were performed for dependence of staging on demographics. Survival was evaluated with Kaplan-Meier and Cox regression analyses.Results: We identified 249 patients (median age 65 years). Patients were predominantly born outside the USA or Canada (74.3%), non-white (70.7%), and federally insured (71.4%), and presented with late-stage disease (52.2%). Hispanic ethnicity, Central American birthplace, Medicaid insurance, and zip code poverty > 20% were associated with late-stage presentation (all p < 0.05). Univariate analyses showed decreased survival for patients with late-stage disease, highest zip code poverty, and age ≥ 65 (all p < 0.05). On multivariate analysis, survival was negatively associated with late-stage presentation (HR 4.45, p < 0.001), age ≥ 65 (1.80, p = 0.018), and H. pylori infection (2.02, p = 0.036).Conclusion: Hispanic ethnicity, Central American birthplace, Medicaid insurance, and increased neighborhood poverty were associated with late-stage presentation of gastric cancer with poor outcomes. Further study of these populations may lead to screening protocols in order to increase earlier detection and improve survival. [ABSTRACT FROM AUTHOR]

Background: In the USA, a quarter of elderly patients do not receive any treatment for regional gastric cancer, which results in poorer outcomes. We sought to identify factors associated with undertreatment of regional gastric cancer in this population, as well as to assess overall survival in the undertreated population.Methods: Elderly patients (aged ≥ 65 years) diagnosed with regional gastric cancer between 2001 and 2009 were identified from the Surveillance Epidemiology and End Results (SEER)-Medicare linked databases. Treatment was defined as receiving any medical or surgical therapy for gastric cancer. Logistic regression analysis was used to identify factors associated with failure to receive treatment. Overall survival was analyzed using the Kaplan-Meier method and Cox proportional hazard model.Results: Of 5972 patients with regional gastric cancer, 1586 (26.5%) received no treatment. Median age was 78 years; 56.1% of patients were men. On multivariable analysis, the factors strongly associated with lack of therapy were age ≥ 80 years, black race, lower education level, and diagnosis before 2007. As expected, patients who received therapy had better overall survival (log-rank test, p < 0.001). Specifically, median survival and 5-year survival were 16.5 months and 20.5% for treated patients, compared with 9.1 months and 19.0% for untreated patients.Conclusions: Elderly patients with gastric cancer have better overall 5-year survival after receiving treatment for their cancer. Disparities in the use of treatment for curable cancers are associated with older age, black race, lower educational level, and diagnosis before 2007. [ABSTRACT FROM AUTHOR]

Background: The incidence of gastric cancer, while declining in many places worldwide, is characterized by considerable geographical variability. The USA has large racial, ethnic and regional variation; we collected data from all 50 states to better characterize recent changes in gastric cancer incidence nationwide.Methods: Annual gastric cancer incidence rates from 1999 to 2013 were extracted from the United States Cancer Statistics (USCS) registry. Secular trends of gastric cancer incidence were examined overall and by sociodemographic factors and states. We used Joinpoint regression to compute annual percent change (APC) and average annual percent change (AAPC) and corresponding 95% confidence intervals (CIs). SEER 13 registries data were extracted to examine the secular trends by cardia and non-cardia gastric cancers.Results: Overall gastric cancer incidence decreased until 2007 (APC = -1.55, 95% CI: -1.88, -1.21), and remained stable thereafter (APC = -0.32, 95% CI: -0.84, 0.20). However, rates increased among persons <50 years of age (AAPC = 0.89, 95% CI: 0.61, 1.16), especially among non-Hispanic white females and Hispanic females. Incidence of non-cardia gastric cancer increased among persons <50 years of age (AAPC = 0.69, 95% CI: -0.06, 1.44), whereas rates of gastric cardia cancer remained unchanged. States with rapid increases in high-risk population groups (e.g. Hispanic females aged <50), including California and Texas, had highest annual increases in gastric cancer incidence.Conclusions: Divergent trends for gastric cancer incidence were observed in the USA. Incidence rates, particularly for non-cardia gastric cancer, were stable or increasing among persons aged  <50 years. [ABSTRACT FROM AUTHOR]

Introduction: The incidence, survival, and propensity for nodal metastasis in early-stage gastric signet ring cell carcinoma have not been defined in the United States. These data are critical determinants for treatment allocation.Methods: Cases of gastric signet ring cell carcinoma were extracted from the national SEER database for the years 2004-2013. Age-standardized incidence was derived. Survival was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of nodal metastasis. Exclusion criteria included neoadjuvant radiotherapy and lack of histologic or nodal data.Results: A total of 10,624 cases were initially identified. The analysis cohort included 506 cases with early T-stage N0M0 disease following exclusions. The incidence was 0.094 per 100,000 person-years. The 5-year survival rate was 82.8%. Tumor stage (p < 0.001) and size (p < 0.001) were independent predictors of nodal metastasis. The incidence of nodal involvement for T1a tumors <2 cm was 5.4% (p < 0.004).Conclusion: The incidence of potentially resectable signet ring gastric carcinoma has not changed significantly over the past decade. While presenting with predominantly high-grade histology, early T-stage disease has a high survival rate. Small T1a tumors have low rates of nodal metastasis, suggesting that an endoscopic resection could be considered in this subset. [ABSTRACT FROM AUTHOR]

Background: A novel prediction model for accurate determination of 5-year overall survival of gastric cancer patients was developed by an international collaborative group (G6+). This prediction model was created using a single institution's database of 11,851 Korean patients and included readily available and clinically relevant factors. Already validated using external East Asian cohorts, its applicability in the American population was yet to be determined.Study Design: Using the Surveillance, Epidemiology, and End Results (SEER) dataset, 2014 release, all patients diagnosed with gastric adenocarcinoma who underwent surgical resection between 2002 and 2012, were selected. Characteristics for analysis included: age, sex, depth of tumor invasion, number of positive lymph nodes, total lymph nodes retrieved, presence of distant metastasis, extent of resection, and histology. Concordance index (C-statistic) was assessed using the novel prediction model and compared with the prognostic index, the seventh edition of the TNM staging system.Results: Of the 26,019 gastric cancer patients identified from the SEER database, 15,483 had complete datasets. Validation of the novel prediction tool revealed a C-statistic of 0.762 (95% CI 0.754 to 0.769) compared with the seventh TNM staging model, C-statistic 0.683 (95% CI 0.677 to 0.689), (p < 0.001).Conclusions: Our study validates a novel prediction model for gastric cancer in the American patient population. Its superior prediction of the 5-year survival of gastric cancer patients in a large Western cohort strongly supports its global applicability. Importantly, this model allows for accurate prognosis for an increasing number of gastric cancer patients worldwide, including those who received inadequate lymphadenectomy or underwent a noncurative resection. [ABSTRACT FROM AUTHOR]

Background: Stomach cancer was a leading cause of cancer-related deaths early in the 20th century and has steadily declined over the last century in the United States. Although incidence and death rates are now low, stomach cancer remains an important cause of morbidity and mortality in black, Asian and Pacific Islander, and American Indian/Alaska Native populations.Methods: Data from the CONCORD-2 study were used to analyze stomach cancer survival among males and females aged 15 to 99 years who were diagnosed in 37 states covering 80% of the US population. Survival analyses were corrected for background mortality using state-specific and race-specific (white and black) life tables and age-standardized using the International Cancer Survival Standard weights. Net survival is presented up to 5 years after diagnosis by race (all, black, and white) for 2001 through 2003 and 2004 through 2009 to account for changes in collecting Surveillance, Epidemiology, and End Results Summary Stage 2000 data from 2004.Results: Almost one-third of stomach cancers were diagnosed at a distant stage among both whites and blacks. Age-standardized 5-year net survival increased between 2001 to 2003 and 2004 to 2009 (26.1% and 29%, respectively), and no differences were observed by race. The 1-year, 3-year, and 5-year survival estimates were 53.1%, 33.8%, and 29%, respectively. Survival improved in most states. Survival by stage was 64% (local), 28.2% (regional), and 5.3% (distant).Conclusions: The current results indicate high fatality for stomach cancer, especially soon after diagnosis. Although improvements in stomach cancer survival were observed, survival remained relatively low for both blacks and whites. Primary prevention through the control of well-established risk factors would be expected to have the greatest impact on further reducing deaths from stomach cancer. Cancer 2017;123:4994-5013. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Background: During the past 40 years, esophageal/gastric cardia adenocarcinoma (EA/GCA) incidence increased in Westernized countries, but survival remained low. A parallel increase in sugar intake, which may facilitate carcinogenesis by promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in association with EA/GCA incidence and survival.Methods: We pooled 500 EA cases, 529 GCA cases and 2027 controls from two US population-based case-control studies with cases followed for vital status. Dietary intake, assessed by study-specific food frequency questionnaires, was harmonized and pooled to estimate 12 measures of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard ratios [95% confidence intervals (CIs)] were calculated using multinomial logistic regression and Cox proportional hazards regression, respectively.Results: EA incidence was increased by 51-58% in association with sucrose (ORQ5vs.Q1 = 1.51, 95% CI = 1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1 = 1.55, 95% CI = 1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1 = 1.58, 95% CI = 1.13-2.21). Body mass index (BMI) and gastro-esophageal reflux disease (GERD) modified these associations (Pmultiplicative-interaction ≤ 0.05). For associations with sucrose and sweetened desserts/beverages, respectively, the OR was elevated for BMI < 25 (ORQ4-5vs.Q1-3 = 1.79, 95% CI = 1.26-2.56 and ORQ4-5vs.Q1-3 = 1.45, 95% CI = 1.03-2.06), but not BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.05, 95% CI = 0.76-1.44 and ORQ4-5vs.Q1-3 = 0.85, 95% CI = 0.62-1.16). The EA-glycaemic index association was elevated for BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.38, 95% CI = 1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3 = 0.88, 95% CI = 0.62-1.24). The sucrose-EA association OR for GERD < weekly was 1.58 (95% CI = 1.16-2.14), but for GERD ≥ weekly was 1.01 (95% CI = 0.70-1.47). Sugar/carbohydrate measures were not associated with GCA incidence or EA/GCA survival.Conclusions: If confirmed, limiting intake of sucrose (e.g. table sugar), sweetened desserts/beverages, and foods that contribute to a high glycaemic index, may be plausible EA risk reduction strategies. [ABSTRACT FROM AUTHOR]

Objective To quantify the population-risk of developing gastric cancer (GC) following breast cancer (BC). Methods GC incidence following a ductal or lobular BC were separately compared to incidence in the general United States population using SEER data. Results GC rates were similar to the general population for ductal BC. Women aged 35–75 with lobular BC had a significantly higher incidence of GC; women aged 40–44 had the highest risk. Conclusion The risk of secondary GC is high among young women diagnosed with lobular BC. More studies investigating the etiology and prevalence of familial GC syndromes at the population-level are needed. [ABSTRACT FROM AUTHOR]

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations. [ABSTRACT FROM AUTHOR]