Clinical characteristics and prognostic factors of gastroenteropancreatic neuroendocrine tumors: a single center experience in China.

BACKGROUND/AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a unique subgroup of tumors in the digestive system but with great clinical heterogeneity. The information on clinical characteristics and prognostic factors of Chinese patients is rather limited. METHODOLOGY: We retrospectively analyzed the clinical features, prognostic factors of this disease in a consecutive cohort (N=294) between January 2007 and December 2012. RESULTS: Functioning tumors accounted for 9.2%. Rectum was the most predominant GEP-NETs locations. Abdominal pain occurred in 46.5% patients which was the most common initial symptom. G1, G2 and G3 tumors accounted for 41.5%, 34.7% and 23.8%, respectively. Endoscopy provided the highest detection rate of 95.7%. Consistence between endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNAB) and surgically obtained histological Ki-67 index was 36.4%. Serum CgA test showed a 80.0% consistence with the tissue biopsy. The median follow up duration was 2.8 years (0.02-5.90 years), the median survival was 4.8 years, overall 5-year survival rate was 69.6%. We found colonic localization, tumor size larger than 20 mm, G3 tumor and metastasis were associated with worse outcome (p<0.05). CONCLUSION: We found both consistence and differences in GEP-NETs characteristics between our study and previous reports.

Gut neuroendocrine tumor blood qPCR fingerprint assay: characteristics and reproducibility.

BACKGROUND: We have developed a PCR-based tool that measures a 51-gene panel for identification of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) in peripheral blood. This manuscript assesses the robustness (performance metrics) of this tool with a specific focus on the effects of individual parameters including collection, storage, acid suppressive medication [proton pump inhibitor (PPI)], age, sex, race and food on accuracy. METHODS: Performance metrics were evaluated using a gold standard (mRNA derived from three individual human neuroendocrine tumor cell lines) and clinical samples using qPCR. RESULTS: One hundred percent of the 51 transcripts were amplified in the gold standard (NEN cell line-derived mRNA) (CQ<35, average efficiency 1.94). The inter- and intra-assay variations were 1%-2%. In clinical samples, 50 of 51 targets (98%) were amplified. The inter- and intra-assay reproducibility ranged between 0.4% and 1.2%. The coefficient of variation (CV) was 5.3%. Expression of the reference gene, ALG9, was robust [low variation, low M-value, high (99.5%) PCR efficiency] and unaffected by sample processing. Test meals, long-term PPI use (>1 year), age, sex and ethnicity had no effect on the signature. Expression of two genes, ALP2 and CD59 correlated strongly with RNA integrity (R=0.72, p<0.001) and could be used to assess storage and processing. CONCLUSIONS: The 51 marker gene signature was robust and reproducible, exhibiting acceptable inter- and intra-assay metrics (<5%). Feeding, PPI intake, age, sex and ethnicity do not affect the signature. Expression levels of APLP2 and CD59 are effective surrogate markers of proper sample collection and processing.

Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England.

BACKGROUND: Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years. METHODS: Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test. RESULTS: 72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups. CONCLUSIONS: Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes.

Breast and bowel cancer screening uptake patterns over 15 years for UK south Asian ethnic minority populations, corrected for differences in socio-demographic characteristics.

BACKGROUND: A number of studies have reported low uptake of cancer screening programmes by South Asian populations in the UK. However, studies to date have not adjusted findings for differences in demographics and socio-economic status of these populations. SUBJECTS: All residents in Coventry and Warwickshire, UK, eligible for screening. Uptakes compared for round 1 (2000-02) and round 2 (2003-05) of a national bowel cancer screening pilot, and for rounds 1, 2 and 5 of the established NHS breast cancer screening programme (commenced 1989). DATA: Bowel screening data were analysed for 123,367 invitees in round 1 and 116,773 in round 2 (total 240,140 cases). Breast screening data were analysed for 61,934, 62,829 and 86,749 invitees in rounds 1, 2 and 5 respectively (total 211,512 cases). ANALYSIS: Screening uptake was compared for two broad meta-categories (South Asian and non-Asian) and for five Asian subgroups (Hindu-Gujarati; Hindu-Other; Muslim; Sikh; South Asian Other). Univariate and multivariate analyses examined screening uptake and various demographic attributes of invitees, including age, gender, deprivation and ethnic group. RESULTS: South Asians demonstrated significantly lower (p < 0.001) unadjusted bowel screening uptake; 32.8% vs. 61.3% for non-Asians (round 1). Rates were particularly low for the Muslim subgroup: 26.1% (round 1), 21.5% (round 2). For breast screening, a smaller difference was observed between South Asians and non-Asians; initially 60.8% vs. 75.4% (round 1) and later 66.8% vs. 77.7% (round 5). Thus, the disparity reduced gradually over time, alongside an overall trend of increased uptake. However, figures remained consistently low for Muslims (51% in rounds 1 and 5). After adjusting for age, deprivation (and gender), bowel screening uptake remained significantly lower for all South Asian subgroups. After similar adjustments, breast screening uptake remained lower for all subgroups except Hindu-Gujaratis. For Muslims registered with an Asian (vs. non-Asian) GP, bowel screening uptake was significantly lower (p < 0.001). However, breast screening uptake for Muslims with an Asian (vs. non-Asian) GP showed no difference (p = 0.12) in the same period. Colonoscopy and breast assessment uptakes were similar for both meta-categories, but Asian response time appeared slower for colonoscopy. The percentage of abnormal FOBT results was significantly higher for South Asian invitees. A slight increase in abnormal mammograms was observed for Muslims over time (2.7% to 4.2% in rounds 1 and 5 respectively). CONCLUSION: The lower cancer screening uptakes observed for the South Asian population cannot be attributed to socio-economic, age or gender population differences. Although breast screening disparities have reduced over time, significant differences remain. We conclude that both programmes need to implement and assess interventions to reduce such differences.

Prospective integration of cultural consideration in biomedical research for patients with advanced cancer: recommendations from an international conference on malignant bowel obstruction in palliative care.

In the setting of an international conference on malignant bowel obstruction as a model for randomized controlled trials (RCTs) in palliative care, we discuss the importance of incorporating prospective cultural considerations into research design. The approach commonly used in biomedical research has traditionally valued the RCT as the ultimate "way of knowing" about how to best treat a medical condition. The foremost limitation of this approach is the lack of recognition of the impact of cultural viewpoints on research outcomes. We propose that interest relevant to cultural viewpoints should be emphasized in conceptualizing and interpreting research questions, designs, and results. In addition to recognizing our cultural biases as individuals and researchers, we recommend two major shifts in designing and implementing RCTs: 1) inclusion of a multidisciplinary team of researchers to inform the diversity of perspectives and expertise brought to the research, and 2) use of mixed methods of inquiry, reflecting both deductive and inductive modes of inference.

Small intestinal cancer: a population-based study of incidence and survival patterns in the United States, 1992 to 2006.

BACKGROUND: The etiology of cancers of the small intestine is largely unknown. To gain insight into these rare malignancies, we evaluated contemporaneous incidence and survival patterns. METHODS: Using small intestine cancer data from 12 population-based registries of the Surveillance, Epidemiology and End Results Program, we calculated age-adjusted and age-specific incidence rates (IRs), IR ratios, and relative survival (RS) rates. RESULTS: In total, 10,945 small intestine cancers (IR = 2.10/100,000 person-years) were diagnosed during 1992 to 2006, including carcinomas (n = 3,412; IR = 0.66), neuroendocrine cancers (n = 4,315; IR = 0.83), sarcomas (n = 1,084; IR = 0.20), and lymphomas (n = 2,023, IR = 0.38). For all histologic groups, males had significantly higher IRs than females, and distinct age-specific gender patterns were limited to intermediate-/high-grade lymphomas. Neuroendocrine cancer rates varied significantly by race, with rates highest among blacks and lowest among Asians/Pacific Islanders. Carcinoma IRs were highest among blacks; sarcoma IRs were highest among Asians/Pacific Islanders; and lymphoma IRs were highest among whites. Age-specific IR patterns were similar across racial/ethnic groups. During 1992 to 2006, duodenal cancer IRs increased more markedly than those for other subsites. RS varied little by gender or race. Neuroendocrine cancers had the most favorable RS, and carcinomas had the least favorable. The greatest improvement in 5-year RS from 1992 to 1998 to 1999 to 2005 was observed for sarcomas and lymphomas. CONCLUSIONS: Distinct small intestine cancer IR patterns according to histologic subtype suggest different underlying etiologies and/or disease biology, with susceptibility varying by gender, racial/ethnic groups, and subsite. Temporal patterns support a possible role for diagnostic bias of duodenal cancers. IMPACT: Future epidemiologic studies of small intestine cancer should consider histologic subtype by gender, race/ethnicity, and subsite.

Adenocarcinoma of the small bowel: a 60-yr perspective derived from M. D. Anderson Cancer Center Tumor Registry.

OBJECTIVES: To analyze subsite distribution of small bowel adenocarcinoma (SBA) over a 60-yr interval and to determine the impact of age, gender, and ethnicity on SBA cross-referenced for selected variables including anatomic distribution. METHODS: Data from 1944 to 2003 were extracted from the M. D. Anderson Cancer Center Tumor Registry (MDACCTR) and analyzed by age, gender, ethnicity, anatomic site, and time intervals. RESULTS: A total of 523 confirmed cases with 460 specified for subsite were identified. Peak incidence occurred in the sixth decade with male predominance (58%). Relative distribution for subsites was stable over the period of study; however, site-specific incidence differed significantly with age. Although jejunal SBA comprised only 21% of site-specific total (SST), 49% occurred in 0-49 age group rendering duodenal SBA (59% of SST) more common with increasing age (p < 0.001). A higher percentage of women presented at younger age; however, the difference was not significant (p = 0.061). Subsite distribution was similar for both genders, but varied significantly among ethnicities (p = 0.048) with Hispanics and African Americans having a higher percentage of duodenal SBA. The age and gender distribution among ethnicities varied significantly. African Americans having SBA presented at a younger age (p < 0.001), and comprised a higher percentage of women (p = 0.026). CONCLUSION: Differences exist for SBA subsite distribution within age and ethnic groups but not gender. Unlike colon cancer, SBA subsite distribution has been stable during the last six decades. Different risk factors for SBA appear to affect different subsites. Site- and age-related distribution impacts on diagnostic evaluation for SBA.

Incidence of small bowel cancer in the United States and worldwide: geographic, temporal, and racial differences.

OBJECTIVE: To examine the demographic and geographic patterns of small bowel cancer incidence in the United States and worldwide. METHODS: Incidence data from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 to 2000 were used to analyze the four histologic types of small bowel cancer, adenocarcinomas, carcinoid tumors, lymphomas, and sarcomas. International comparisons were made using data from Cancer Incidence in Five Continents (CIVIII). Geographic correlations between small bowel and both large bowel and stomach cancer incidence, were performed. RESULTS: Men had higher rates than women for all types of small bowel cancer. Blacks had almost double the incidence of carcinomas and carcinoid tumors compared to whites (10.6 vs. 5.6 per million people; 9.2 vs. 5.4 per million people, respectively). Small bowel cancer incidence has risen, with the greatest increase for carcinoid tumors (21%) and black men (120%). A geographic correlation between small and large bowel cancer incidence, but not small bowel and stomach cancer, were observed. CONCLUSIONS: Small bowel cancer incidence in the U.S. is higher in blacks compared to whites, particularly for carcinomas and carcinoid tumors. Small bowel cancer incidence is rising, particularly in black men. The geographic correlation between large and small bowel cancer suggests shared etiologies.

Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973-2000: increase in the signet ring cell type.

CONTEXT: During the last 50 years, the incidence and mortality of gastric cancer has declined in many countries. This decline has primarily included the intestinal type (Lauren classification). However, there is an impression among pathologists that the diffuse type, especially the signet ring cell subtype, has become more prevalent. OBJECTIVES: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, we analyzed the trends of the 2 primary types (intestinal and diffuse) of gastric carcinomas from 1973 through 2000. DESIGN: Trends in age-adjusted rates were determined for gastric carcinomas through the SEER statistical program (SEER*Stat), which is available on the Internet to the public. RESULTS: During the period studied, the intestinal type continued to decline in males, females, African Americans, and whites. The intestinal type was more common in males than in females and more common in African Americans than in whites. In contrast, a consistent increase in the rate of the diffuse type of gastric carcinoma was seen during this period. The rate increased from 0.3 cases per 100 000 persons in 1973 to 1.8 cases per 100 000 persons in 2000. This increase was seen in males, females, African Americans, and whites. The predominant increase occurred in the signet ring type. CONCLUSIONS: The results indicate a progressive decrease in the incidence of the intestinal type of gastric cancer and an increase in the diffuse type of gastric carcinoma, especially the signet ring cell type. The clinical implications of the increase are considered.