Racial differences in body composition and survival among older adults with gastrointestinal malignancies.

INTRODUCTION: Muscle and adipose tissue measures can be quantified from routinely obtained computed tomography (CT) images and are predictors of chemotherapy-related toxicities and survival among patients with gastrointestinal (GI) malignancies. Most studies to date have consisted of predominantly White patients, and the role of body composition among minoritized racial groups is unknown. We examined racial differences in body composition and survival among patients with GI malignancies. MATERIALS AND METHODS: This was a prospective cohort study of patients with GI malignancies. Single slices of axial CT images from L3 segments were analyzed using Slice-O-Matic software. The skeletal muscle area (cm2) was divided by height to obtain the skeletal muscle index (SMI, cm2/m2). Skeletal muscle radiodensity (SMD) in Hounsfield units (HU) was used for muscle composition. We compared body composition parameters between non-Hispanic (NH)-White and NH-Black participants. Cox models were used to examine the impact of body composition on survival. We proposed new race-specific cutoffs for body composition using optimal stratification. RESULTS: Five hundred forty patients were included, of which 24% were NH-Black. In Cox models stratified by race, each 5 cm2/m2 decrease in SMI was associated with increase in risk of all-cause mortality in NH-Black patients (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.04-1.49 p = 0.02). With the existing cut points, neither sarcopenia nor myosteatosis was associated with worse survival. Using a new cutoff for sarcopenia in NH-Black patients, NH-Black patients with sarcopenia (HR 2.31 95%CI 1.10-4.88 p = 0.03) and myosteatosis (HR 2.63 95% CI 1.25-5.53 p = 0.01) had worse survival. DISCUSSION: NH-Black older patients with GI cancers and sarcopenia or myosteatosis have worse overall survival.

Patient and provider factors predict non-surgical management for complex upper gastrointestinal cancers.

BACKGROUND: Surgery is the only potentially curative treatment for non-metastatic upper gastrointestinal cancers. We analyzed patient and provider characteristics associated with non-surgical management. METHODS: We queried the National Cancer Database for patients with upper gastrointestinal cancers from 2004 to 2018 who underwent surgery, refused surgery, or for whom surgery was contraindicated. Multivariate logistic regression identified factors associated with surgery being refused or contraindicated, and Kaplan-Meier curves assessed survival. RESULTS: We identified 249,813 patients based on our selection criteria-86.3% had surgery, 2.4% refused, and for 11.3%, surgery was contraindicated. Median overall survival was 48.2 months for patients who underwent surgery versus 16.3 and 9.4 months for the refusal and contraindicated groups. Medical and non-medical factors predicted both surgery refusals and contraindications, such as increasing age (odds ratio = 1.07 and 1.03, respectively, P < .001), Black race (odds ratio = 1.72 and 1.45, P < .001), comorbidities (Charlson-Deyo score 2+, odds ratio = 1.18 and 1.66, P < .001), low socioeconomic status (odds ratio = 1.70 and 1.40, P < .001), no health insurance (odds ratio = 3.26 and 2.34, P < .001), community cancer programs (odds ratio = 1.43 and 1.40, P < .001), low volume facilities (odds ratio = 1.82 and 1.52, P < .001), and stage 3 disease (odds ratio = 1.51 and 6.50, P < .001). On subset analysis (excluding patients age >70, Charlson-Deyo score 2+, and stage 3 cancer), non-medical predictors of both outcomes were similar. CONCLUSION: Refusal of and medical contraindications for surgery profoundly impact overall survival. The same factors (ie, race, socioeconomic status, hospital volume, and hospital type) predict these outcomes. These findings suggest variation and potential bias that may exist between physicians and patients discussing cancer surgery.

Disaggregated mortality from gastrointestinal cancers in Asian Americans: Analysis of United States death records.

Asian Americans (AAs) are heterogeneous, and aggregation of diverse AA populations in national reporting may mask high-risk groups. Gastrointestinal (GI) cancers constitute one-third of global cancer mortality, and an improved understanding of GI cancer mortality by disaggregated AA subgroups may inform future primary and secondary prevention strategies. Using national mortality records from the United States from 2003 to 2017, we report age-standardized mortality rates, standardized mortality ratios and annual percent change trends from GI cancers (esophageal, gastric, colorectal, liver and pancreatic) for the six largest AA subgroups (Asian Indians, Chinese, Filipinos, Japanese, Koreans and Vietnamese). Non-Hispanic Whites (NHWs) are used as the reference population. We found that mortality from GI cancers demonstrated nearly 3-fold difference between the highest (Koreans, 61 per 100 000 person-years) and lowest (Asian Indians, 21 per 100 000 person-years) subgroups. The distribution of GI cancer mortality demonstrates high variability between subgroups, with Korean Americans demonstrating high mortality from gastric cancer (16 per 100 000), and Vietnamese Americans demonstrating high mortality from liver cancer (19 per 100 000). Divergent temporal trends emerged, such as increasing liver cancer burden in Vietnamese Americans, which exacerbated existing mortality differences. There exist striking differences in the mortality burden of GI cancers by disaggregated AA subgroups. These data highlight the need for disaggregated data reporting, and the importance of race-specific and personalized strategies of screening and prevention.

Circulating miR-21 as a potential biomarker in human digestive system carcinoma: a systematic review and diagnostic meta-analysis.

Purpose: Gastrointestinal cancers (GICs) account for about a quarter of cancers. Lately, the circulating microRNAs as a non-invasive biomarker for identifying and monitoring diseases have been recognized. Several studies have examined the role of miR-21 in digestive system carcinoma. We conducted a meta-analysis to assess the diagnostic role of miR-21 in GICs.Methods: Seventeen studies involving 1700 individuals were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, SROC, and Q* index were calculated based on true-positive, true-negative, false-negative, and false-positive. Moreover, the subgroup analyses have been performed for miR-21 based on sample types (serum/plasma), normalized genes (U6, miR-16, and miR-39), and ethnicity.Results: The pooled sensitivity 0.722 (95% CI: 0.70-0.74), specificity 0.820 (95% CI: 0.801-0.838), PLR 4.375 (95% CI: 3.226-5.933), NLR 0.308 (95% CI: 0.239-0.398), DOR 16.06 (95% CI: 9.732-26.53) as well as AUC 0.86, and Q* index 0.79 represented the high-grade diagnostic precision of miR-21 in identifying GICs (ESCC, GC, CRC, HCC, and PC).Conclusion: This meta-analysis demonstrated that circulating miR-21 levels can be used to monitor the digestive system carcinomas. Therefore, miR-21 can be a useful biomarker of progression and fair diagnosis in GICs patients.

Racial Differences in Gastroenteropancreatic Neuroendocrine Tumor Treatment and Survival in the United States.

OBJECTIVES: The objective of this study was to evaluate racial differences in cancer treatment and survival in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients. METHODS: Using the Surveillance, Epidemiology, and End Results Registry, we identified patients with GEP-NETs of the stomach, small intestine (SI), colon, rectum, appendix, and pancreas diagnosed between 1973 and 2014. Demographic, cancer, and treatment information were collected and compared using χ2 tests. Multivariable logistic and Cox regression were used to determine disparities in receiving treatment and overall survival. RESULTS: We identified 19,031 GEP-NET patients: 2839 were non-Hispanic Blacks, 12,832 non-Hispanic Whites, 2098 Hispanics, and 1262 Asians. African Americans and Hispanics with SI and pancreatic NETs were less likely to be treated with surgery (odds ratio, 0.6; 95% confidence interval [CI], 0.46-0.69; odds ratio, 0.71; 95% CI, 0.51-0.99, respectively). African American race was not an independent predictor of survival; there was a strong trend in stomach, SI, and pancreas NETs (hazard ratio [HR], 1.31; 95% CI, 1-1.7; HR, 1.2; 95% CI, 0.99-1.45; HR, 1.22; 95% CI, 1-1.48, respectively). CONCLUSIONS: Our study provides evidence of racial disparities in treatment and survival across GEP-NET primary sites and racial groups. Further studies should be performed to improve our understanding of the reason for these disparities.

Size and Importance of Socioeconomic Status-Based Disparities in Use of Surgery in Nonadvanced Stage Gastrointestinal Cancers.

BACKGROUND: The size and importance of socioeconomic status (SES)-based disparities in use of surgery for non-advanced stage gastrointestinal (GI) cancers have not been quantified. METHODS: The exposure in this study of patients age 18-80 with one of nine non-advanced stage GI cancers in the 2007-2015 SEER database was a census tract-level SES composite. Multivariable models assessed associations of SES with use of surgery. Causal mediation analysis was used to estimate the proportion of survival disparities in SES quintiles 1 versus 5 that were mediated by disparities in use of surgery. RESULTS: Lowest SES quintile patients underwent surgery at significantly lower rates than highest quintile patients in each cancer. SES-based disparities in use of surgery were large and graded in esophagus adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma, and pancreatic adenocarcinoma. Smaller but clinically relevant disparities were present in stomach, ampulla, and small bowel adenocarcinoma, whereas disparities were small in colorectal adenocarcinoma. Five-year all-stage overall survival (OS) was correlated with the size of disparities in use of surgery in SES quintiles 1 versus 5 (r = - 0.87; p = 0.003). Mean OS was significantly longer (range 3.5-8.9 months) in SES quintile 5 versus 1. Approximately one third of SES-based survival disparities in poor prognosis GI cancers were mediated by disparities in use of surgery. The size of disparities in use of surgery in SES quintiles 1 versus 5 was correlated with the proportion mediated (r = 0.98; p < 0.001). CONCLUSIONS: Low SES patients with poor prognosis GI cancers are at substantial risk of undertreatment. Disparities in use of surgery contribute to diminished survival.

[Status of non-steroidal anti-inflammatory drugs use in areas with a high incidence of upper gastrointestinal cancer in China: a multi-center cross-sectional survey].

Objective: To describe the status of non-steroidal anti-inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods: This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High-risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)" . From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health-related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ(2) test and Cochran-Armitage trend analysis method. Results: Of 35 910 subjects, the mean age was (54.6±7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend <0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend <0.05 for all). Conclusion: The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.

Perioperative Mortality Does Not Explain Racial Disparities in Gastrointestinal Cancer.

BACKGROUND: Racial minorities with gastrointestinal cancer suffer disproportionately poor overall and disease-specific survival. We used a nationally representative sample to examine the relationship between race/ethnicity and mortality and determine whether these disparities were observed in the perioperative period. MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) was used to examine patients undergoing surgery for cancers of the esophagus, stomach, pancreas, colon and rectum ("GI cancer") between 2008 and 2012. Logistic regression was used to evaluate whether race/ethnicity was associated with perioperative mortality after adjusting for sociodemographic characteristics, perioperative factors and presentation (ER vs elective). RESULTS: A total of 110,044 subjects were identified, including 75.8% Whites, 10.5% Black patients, 7.2% Hispanic patients, and 3.1% Asian/Pacific Islanders (API). Whites were generally older than minorities. In adjusted multivariable generalized linear mixed logistic models, no increase in perioperative mortality was seen for minorities. Worse outcomes were observed for those with higher Elixhauser comorbidity score (OR 6.90, CI 5.96-7.99), lower income region (OR 1.24, CI 1.10-1.40), males (OR 1.54, CI 1.42-1.68), and those without private insurance (Medicare OR 1.34, CI 1.16-1.55; Medicaid OR 1.27, CI 1.02-1.58; self-pay OR 1.64, CI 1.24-2.17). Differences in mortality were predominantly driven by comorbidities (pseudo %ΔR2 = 38.56%) and only minimally by race (pseudo %ΔR2 = 0.49%). CONCLUSION: Minority groups do not suffer higher rates of perioperative mortality for GI cancer surgeries after controlling for clinical and demographic factors. Future work to address cancer disparities should focus on areas in the cancer care trajectory such as cancer screening, surveillance, socioeconomic factors, and access.

The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients' Demographics.

BACKGROUND: We report our experience with malignant pleural effusion (MPE) and the impact of patients' demographics on the differential diagnosis at the primary site. METHODS: After IRB approval, we searched our pathology database from January 2013 to January 2017 for patients with positive pleural effusions (PEs). Patients' demographics and clinical histories were noted. RESULTS: 474 patients were identified (288 females [61%] and 186 males [39%]), ranging in age from 19 to 64 years old. Ethnicity was distributed as follows: Caucasian (n = 330, 70%), African American (n = 114, 24%) and Asian (n = 30, 6%). The most common primary sites were the lung (n = 180, 37%), followed by the breast (n = 81, 17%), and the gynecologic system (67, 13%). The lung was the most common primary for all ethnicities (n = 190, 40%). The second-most common primary site was the breast in African Americans and Caucasians and upper gastrointestinal (GI) tract in Asians. In 5 cases (1%), the primary tumor could not be determined. CONCLUSION: Cytology examination is a useful method to diagnose primary sites of PE. Pulmonary primary is the most common cause of effusion in all ethnicities. In African American and Caucasian patients, the breast was the second-most common site of MPE, while in Asian patients it was the upper GI tract.

Association between COX-2 -1195G>A polymorphism and gastrointestinal cancer risk: A meta-analysis.

AIM: To perform a meta-analysis to investigate the association between cyclooxygenase-2 (COX-2) -1195G>A gene polymorphism and gastrointestinal cancers. METHODS: Publications related to the COX-2 -1195G>A gene polymorphism and gastrointestinal cancers published before July 2016 were retrieved from PubMed, EMBASE, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using Stata11.0 software. The strength of the association was evaluated by calculating the combined odds ratios (ORs) and the corresponding 95%CIs. The retrieved publications were excluded or included one by one for sensitivity analysis. In addition, the funnel plot, Begg's rank correlation test, and Egger's linear regression method were applied to analyse whether the included publications had publication bias. RESULTS: A total of 24 publications related to the COX-2 -1195G>A gene polymorphism were included, including 28 studies involving 11043 cases and 18008 controls. The meta-analysis results showed that the COX-2 -1195G>A gene polymorphism significantly correlated with an increased risk of gastrointestinal cancers, particularly gastric cancer (A vs G: OR = 1.35; AA/AG vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR = 1.35). Compared to the Caucasian population in America and Europe, the COX-2 -1195G>A gene polymorphism in the Asian population (A vs G: OR = 1.30; AA/AG vs GG: OR = 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37) significantly increased gastrointestinal cancer risk. The sensitivity analysis (P < 0.05) and the false positive report probability (P < 0.2) confirmed the reliability of the results. CONCLUSION: The results showed that the COX-2 -1195G>A gene polymorphism might be a potential risk factor for gastrointestinal cancers. Further validation by a large homogeneous study is warranted.

Small Numbers, Big Challenges: Adolescent and Young Adult Cancer Incidence and Survival in New Zealand.

PURPOSE: This study was undertaken to determine cancer survival and describe the unique spectrum of cancers diagnosed among New Zealand's adolescents and young adult (AYA) population. METHODS: Registrations for 1606 15-24 year olds diagnosed with a new primary malignant tumor between 2000 and 2009 were obtained from the New Zealand Cancer Registry and classified according to AYA diagnostic group and subgroup, age, sex, and prioritized ethnicity. Age-standardized incidence rates (IRs) per million person years and 5-year relative survival ratios were calculated. RESULTS: Cancer incidence was 228.6 per million for adolescents aged 15-19 years and 325.7 per million for young adults aged 20-24 years. Overall IRs were consistent across all ethnic groups but there were unique ethnic differences by tumor group including a higher incidence of bone tumors, carcinoma of the gastrointestinal tract, and gonadal germ cell tumors among Maori, a higher incidence of leukemia among Pacific peoples, and a higher incidence of melanoma among non-Maori/non-Pacific peoples. Five-year relative survival for adolescents (75.1%) and AYA overall (80.6%) appeared poorer than had been achieved in other high-income countries. Maori (69.5%) and Pacific (71.3%) AYA had lower 5-year survival compared to non-Maori/non-Pacific peoples (84.2%). CONCLUSION: The survival disparities observed require further investigation to identify and address the causes of these inferior outcomes. The newly established AYA Cancer Network Aotearoa has been tasked with improving cancer survival and care and ensuring equality of access for New Zealand AYAs with cancer.

Oral Bisphosphonates and Upper Gastrointestinal Cancer Risks in Asians with Osteoporosis: A Nested Case-Control Study Using National Retrospective Cohort Sample Data from Korea.

BACKGROUND: Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis. METHODS: We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases. RESULTS: A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied. CONCLUSIONS: This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.

Liver and Other Gastrointestinal Cancers Are Frequent in Mexican Americans.

BACKGROUND: Disease patterns in Mexican American health-disparity populations differ from larger US populations. AIMS: This study is aimed to determine frequency of gastrointestinal cancers in Mexican Americans. METHODS: We analyzed self-reported data from the Cameron County Hispanic Cohort where we find high rates of risk factors for cancer: obesity (48.5 %) and diabetes (30.7 %). Participants provided cancer histories about themselves and first- and second-degree relatives. Logistic regression models assessed risk factors. Frequencies of cancer sites were ranked and validated using concurrent age local cancer registry data. RESULTS: Among 9,249 individuals (participants and their relatives), there were 1,184 individuals with reports of cancer. Among cohort participants under 70 years of age, the most significant risk factor for all-cause cancers was diabetes (OR 3.57, 95 % CI 1.32, 9.62). Participants with metabolic syndrome were significantly more likely to report cancer in relatives [1.73 (95 % CI 1.26, 2.37]. Among cancers in fathers, liver cancer was ranked third, stomach fourth, colorectal sixth, and pancreas tenth. In mothers, stomach was third, liver fourth, colorectal seventh, and pancreas eleventh. The unusual prominence of these cancers in Mexican Americans, including liver cancer, was supported by age-adjusted incidence in local registry data. CONCLUSIONS: Gastrointestinal system cancers, particularly, liver cancer, in a Mexican American health disparity cohort and their relatives rank higher than in other ethnicities and are associated with high rates of diabetes and metabolic syndrome. Effective prevention of diabetes and low-tech, high-quality screening strategies for gastrointestinal cancers are needed in health disparity communities.

Relationship between apurinic endonuclease 1 Asp148Glu polymorphism and gastrointestinal cancer risk: An updated meta-analysis.

AIM: To evaluate the relationship between apurinic endonuclease 1 (APE1) Asp148Glu polymorphism and the susceptibility to gastrointestinal (GI) cancers. METHODS: We searched PubMed, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure (CNKI) databases updated on July 15, 2014 for relevant studies. Only case-control studies comparing APE1 Asp148Glu polymorphism and GI cancer risk were included. We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data. Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls. Review Manager version 5.1 was used to perform the meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models. We also conducted subgroup analyses stratified by ethnicity and cancer type. Publication bias was evaluated using Begg's test. RESULTS: The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population (G vs T: OR = 1.18; 95%CI: 1.05-1.32; TG vs TT: OR = 1.28; 95%CI: 1.08-1.52; TG + GG vs TT: OR = 1.32; 95%CI: 1.10-1.57). Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians (G vs T: OR = 1.27; 95%CI: 1.07-1.51; GG vs TT: OR = 1.58; 95%CI: 1.05-2.38; TG vs TT: OR = 1.30; 95%CI, 1.01- 1.67; and TG + GG vs TT: OR = 1.38; 95%CI: 1.07-1.78), but not in Caucasians. Further subgroup analysis by cancer type indicated that APE1 Asp148Glu polymorphism may contribute to gastric cancer risk. However, Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model. CONCLUSION: This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk, especially in gastric cancer.

[C-KIT in gastrointestinal stromal tumors and associated malignancies: A Study in a population with genetic isolation]. / C-kit en tumores estromales gastrointestinales y neoplasias asociadas: estudio en población con aislamiento genético.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Numerous studies have reported the association between GIST and other neoplasms. OBJECTIVES: The aim of this study was to investigate the possible association between GIST and other tumors in a genetically isolated population. METHODS: A retrospective study was conducted of patients with GIST between 2002 and 2009 at our center. Epidemiological, pathological and family data in patients with GIST alone (group A) were compared with those in patients with GIST associated with other neoplasms (group B). A possible common genetic mechanism was investigated between GIST and associated malignancies by testing the detection of the immunohistochemical marker, CD117, in all tumors. RESULTS: Twenty-two patients with GIST were identified, 10 in group A (45%) and 12 in group B (55%). In group B, the associated tumor was malignant in 6 patients (50%) and benign in another 6 (50%). Of the 22 patients with GIST, 8 (36%) had a family history of malignancies. Of these 8 patients, 7 (87.5%) were in group B (p=0.03) and 3 (37.5%) showed the same pathological type of neoplasm as their relatives. All GIST were positive for CD117 whereas associated malignancies were negative for this marker. CONCLUSION: We did not find immunohistochemical positivity for CD117 in malignancies associated with GIST. Given the special characteristics of the study population, the association between GIST and associated malignancies may be incidental.

Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial.

BACKGROUND: The randomized, double-blind, placebo-controlled GRID trial tested the oral multikinase inhibitor regorafenib in 199 patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib, and showed a significant improvement in progression-free survival (PFS) versus placebo [hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.19-0.39; p < 0.0001]. METHODS: A subgroup analysis of Japanese patients in the GRID study was performed to compare the efficacy and safety of oral regorafenib 160 mg once daily with matching placebo, in combination with best supportive care. The primary study endpoint was progression-free survival (PFS); safety was evaluated through the incidence of adverse events (AEs). RESULTS: Seventeen Japanese patients were randomized to regorafenib (n = 12) or placebo (n = 5). Patient demographics were consistent with those of the overall study population. PFS was significantly longer with regorafenib than placebo (HR 0.08; 95 % CI 0.02-0.45; p = 0.000164). Centrally assessed disease control rates were 58 % and 20 % in the regorafenib and placebo groups, respectively (p = 0.080796). Treatment-related adverse events (AEs) were reported in all regorafenib-treated patients and 60 % of placebo recipients; the most frequent AE was hand-foot skin reaction (HFSR) (92 % versus 20 %, respectively). CONCLUSION: Regorafenib showed efficacy and a manageable safety profile in Japanese patients with advanced GIST, consistent with the overall GRID study population. AEs, such as HFSR and maculopapular rash, were observed more frequently in Japanese patients. Although dose modification was frequently reported, only one patient with hepatic failure discontinued regorafenib because of AEs.

A risk of digestive tract neoplasms susceptibility in miR-146a and miR-196a2.

Genome-wide association studies have identified many genes associated with digestive tract neoplasms. However, the published findings have been conflicting. The aim of our study was to evaluate the involvement of two polymorphisms (miR-146a rs2910164, miR-196a2 rs11614913) in digestive tract neoplasms risk and explore how miR-146a and miR-196a2 influence this risk. Systemic research of the PubMed, EBSCO, CBM and VIP databases was performed. The software STATA 12.0 was used to calculate odd ratios and 95% confidence intervals. There were 14 studies (6,053 cases and 6,527 controls) available for rs2910164 and 15 studies (5,648 cases and 6,607 controls) involved in rs11614913. Rs2910164G>C was statistically significantly associated with digestive tract neoplasms (OR 1.134, 95% CI 1.076-1.194, P < 0.001). In the subgroup analysis by ethnicity, significant association was observed in Asian individuals (OR 1.145, 95% CI 1.084-1.209, P < 0.001). We found a correlation between rs11614913 and only colorectal cancer (OR 1.325, 95% CI 1.102-1.594, P = 0.003). This study suggested that digestive tract neoplasms might associate with miR-146a variants, but not miR-196a2 variants.

Clinico-pathological characteristics and prognostic factors of gastrointestinal stromal tumors among a Chinese population.

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the digestive tract. GISTs include a group of heterogeneous tumors with different morphology, biologic behavior, and genetic characteristics, so their epidemiology, clinico-pathological features and prognosis is distinct in different countries. The objective of this study is to analyze clinico-pathological characteristics and prognostic factors of GISTs among Chinese population. We investigated 112 GIST patients were diagnosed between July 2008 and January 2013 at the First Affiliated Hospital of Guangxi Medical University. Histologic evaluation and immunohistochemistry analysis was performed on paraffin-embedded tissue from the 112 GISTs. Overall survival analysis was carried out using the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed according to Cox's proportional hazards model. Three and 5-year OS rates were 71.4 and 58.6% respectively. Univariate analysis showed that the following factors were significant in predicting OS: tumor site, tumor size, metastasis, resection margin status, cell type, invasion of adjacent organ, invasion of smooth muscle, mitotic rate, P53 and adjuvant therapy with imatinib (P<0.05). Multivariate analysis showed that tumor size, metastasis, resection margin status, mitotic rate, P53 and adjuvant therapy with imatinib were independent prognostic factors associated with OS. This may aid in the prediction of clinical evolution and guide treatments in patients with GIST in China.

Association between the interleukin-17A -197G>A (rs2275913) polymorphism and risk of digestive cancer.

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13- 1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.