Barriers to Community-Based Eradication of Helicobacter pylori Infection.

Helicobacter pylori (HP) is a causative agent in gastric cancer (GC).1 In the United States, HP is more prevalent in racial and ethnic minorities, including African Americans, Asian Americans, Latinos, and immigrants, the same groups that are more likely to develop and die from GC.2 Although screening for HP is not presently performed in the United States, there are plausible benefits to doing so, because HP is considered a group 1 carcinogen by the World Health Organization, and its link to GC parallels that of human papilloma virus and cervical cancer.1 HP eradication as a means of preventing GC also fulfils the Wilson and Jungner criteria for a successful screening program, and literature has consistently demonstrated that HP eradication reduces GC risk and death from GC.3 In fact, in countries with a high burden of GC, HP eradication is considered primary prevention for GC. As such, targeted HP testing in the United States may reduce GC burden in high-risk groups.4 We evaluate the results of community-based HP testing in an at-risk, underserved population.

Demographics, distance to gastrointestinal specialists, and social deprivation are associated with advanced stage of gastrointestinal cancer diagnosis.

Background: Gastrointestinal (GI) luminal cancers can be detected at early stages by endoscopic procedures. Place-based factors, such as social deprivation and distance to specialist care, are under-investigated with regard to the stage of diagnosis. Methods: This was a retrospective cohort study among persons ≥18 years of age in the Florida Cancer Data System, a population-based cancer incidence registry. We included persons diagnosed with esophageal cancer, gastric canceror colorectal cancer, with at least 1 measure of geographic location during the period January 1, 1981, to December 31, 2016. Multivariate multinomial logistic regression was used to identify factors associated with the stage of diagnosis, including social deprivation and proximity to GI care. Results: Among 379,054 persons, the median age was 71 years, and 54% were male. Distant stage disease was significantly less likely than local stage in those of non-Hispanic/Latino ethnicity (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.89-0.94, P<0.001). Distant disease was more likely in African Americans (OR 1.30, 95%CI 1.26-1.34) and Asians (OR 1.41, 95%CI 1.27-1.56, P<0.001), with each 5-min increase in travel time to specialists, (OR 1.02, 95%CI 1.01-1.02, P<0.001), and with each 10-point increase in Social Deprivation Index (OR 1.01, 95%CI 1.01-1.02, P<0.001). Conclusions: A greater distance from care and living in areas with increased deprivation are associated with an advanced stage of diagnosis and should be recipients of policy-driven efforts to improve access to care. That the strongest risk factors include minority race and ethnicity underlines the complexity of healthcare disparities.

Association between country of birth and gastric intestinal metaplasia: a retrospective cohort study.

Background: As a precursor to gastric cancer, gastric intestinal metaplasia (GIM) represents a target for surveillance. US-based guidelines recommend surveillance of racial/ethnic minorities and immigrants from high incidence gastric cancer regions, yet there is marked variability in prevalence amongst these subgroups and within groups from high incidence regions. There is a paucity of information regarding country of birth as a risk factor for GIM and we sought to determine the association between country of birth and GIM in an ethnically and racially diverse US population. Methods: This was a retrospective cohort study of persons who underwent esophagogastroduodenoscopy (EGD) with gastric biopsy at University of Miami Hospital between 2011 and 2021. A natural language processing (NLP) algorithm was developed and implemented to extract diagnoses of GIM and Helicobacter pylori (HP) infection from endoscopic pathology reports. Multivariable logistic regression was performed to evaluate risk factors for GIM, accounting for important covariates, including country of birth. Findings: A total of 21,108 persons from 130 varying countries of birth were included in the study. A total of 1699 cases of GIM were identified yielding a prevalence of 8.0% (95% CI: 7.7-8.4%). Multivariable analysis was restricted to countries with at least 100 persons in the cohort, yielding 15 countries with 1208 cases of GIM. Country of birth (p < 0.0001), race/ethnicity (p = 0.026), active HP infection (p < 0.0001), and increasing age (p < 0.0001) were significantly associated with increased odds of GIM. Highest odds for GIM were among persons born in Ecuador (OR 2.34, 95% CI 1.56-3.50), Honduras (OR 2.34, 95% CI 1.65-3.34), and Peru (OR 2.17, 95% CI 1.58-2.99). Interpretation: We demonstrate that country of birth is a key risk factor for GIM. Not all countries that are thought to be in "high-risk" regions are associated with higher rates of GIM, underlining the importance of studying the under-investigated risk factor of country of birth. Guidelines should account for country of birth, in addition to other risk factors, to tailor screening/surveillance appropriately. Funding: Shida Haghighat, MD, MPH is supported by an NIH training grant T32 DK 11667805.

Urgent need to mitigate disparities in federal funding for cancer research.

We evaluate National Cancer Institute (NCI) funding distribution to the most common cancers, considering their respective public health burdens, and explore associations between funding and racial and ethnic burden of disease. The NCI's Surveillance, Epidemiology and End Results, US Cancer Statistics database, and Funding Statistics were used to calculate funding-to-lethality (FTL) scores. Breast and prostate cancer had the first (179.65) and second (128.90) highest FTL scores, and esophagus and stomach cancer ranked 18th (2.12) and 19th (1.78). We evaluated whether there were differences between the FTL and cancer incidence and/or mortality within individual racial and ethnic groups. NCI funding correlated highly with cancers afflicting a higher proportion of non-Hispanic White individuals (Spearman correlation coefficient = 0.84; P < .001). Correlation was stronger for incidence than mortality. These data reveal that funding across cancer sites is not concordant with lethality and that cancers with high incidence among racial and ethnic minorities receive lower funding.

No difference in outcomes with 15 mm vs. 20 mm lumen-apposing metal stents for endoscopic ultrasound-guided gastroenterostomy for gastric outlet obstruction: a meta-analysis.

BACKGROUND/AIMS: We compared outcomes between use of 15 vs. 20 mm lumen-apposing metal stents (LAMSs) in endoscopic ultrasound-guided gastroenterostomy (EUS-GE) for gastric outlet obstruction. METHODS: Databases were queried for studies that used LAMS for EUS-GE to relieve gastric outlet obstruction, and a proportional meta-analysis was performed. RESULTS: Thirteen studies were included. The 15 mm and 20 mm LAMS had pooled technical success rates of 93.2% (95% confidence interval [CI], 90.5%-95.2%) and 92.1% (95% CI, 68.4%-98.4%), clinical success rates of 88.6% (95% CI, 85.4%-91.1%) and 89.6% (95% CI, 79.0%-95.1%), adverse event rates of 11.4% (95% CI, 8.1%-15.9%) and 14.7% (95% CI, 4.4%-39.1%), and reintervention rates of 10.3% (95% CI, 6.7%-15.4%) and 3.5% (95% CI, 1.6%-7.6%), respectively. Subgroup analysis revealed no significant differences in technical success, clinical success, or adverse event rates. An increased need for reintervention was noted in the 15 mm stent group (pooled odds ratio, 3.59; 95% CI, 1.40-9.18; p=0.008). CONCLUSION: No differences were observed in the technical, clinical, or adverse event rates between 15 and 20 mm LAMS use in EUS-GE. An increased need for reintervention is possible when using a 15 mm stent compared to when using a 20 mm stent.

Intragastric Balloon Significantly Improves Metabolic Parameters at 6 Months: a Meta-Analysis.

INTRODUCTION: It is estimated that by 2030, 38% of the world population will be overweight, and another 20% will be people with obesity. Intragastric balloons (IGBs) are an option in conjunction with lifestyle modification for the treatment of obesity. We sought to investigate the effects of IGB therapy on hemoglobin A1c (A1c), systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs). METHODS: PubMed, Embase, and Google Scholar were queried through November 2021 to identify studies that evaluated the effects of IGB therapy on selected variables at 6 months. A total of 17 studies and 1198 patients met inclusion criteria. Results were pooled using a random-effects model. RESULTS: At 6-month post-IGB insertion, patients had a significant reduction in A1c (mean difference (MD): - 0.62, 95% confidence interval (CI): - 0.884 to - 0.355, p < 0.001), SBP (MD: - 8.39, 95% CI: - 11.39 to - 5.386, p < 0.001), DBP (MD: - 5.807, 95% CI: - 8.852 to - 2.76, p < 0.001), TC (MD: - 9.189, 95% CI: - 15.763 to - 2.616, p = 0.006), LDL (MD: - 5.20, 95% CI: - 9.05 to - 1.35, p = 0.008), and TGs (MD: - 25.35, 95% CI: - 40.30 to - 10.10, p = 0.001). There was no significant difference in HDL (MD: 1.245, 95% CI: - 0.11 to 2.60, p = 0.071). CONCLUSIONS: Our meta-analysis suggests that IGB therapy is associated with improvements in insulin resistance, blood pressure, and dyslipidemia at 6 months. The results of this analysis suggest that IGB placement can be a viable treatment option to improve important metabolic parameters beyond weight loss alone.

Trends in the Incidence of Upper Gastrointestinal Cancers Show Changing Dynamics.

Over the last 50 years, there have been shifts in the incidence of gastric and esophageal cancers in the United States, including a decline in noncardia gastric adenocarcinoma (NCGC), and increases in cardia gastric adenocarcinoma (CGC) and esophageal adenocarcinoma (EAC).1,2 Hypotheses for the changing incidences include eradication of Helicobacter pylori, the main causative agent of NCGC, and rising rates of reflux, obesity, and diet, which are risk factors associated with EAC and CGC.1,3.

The Approach to Performance of Quality Upper Endoscopy in Lynch Syndrome (QUELS): An International Expert Statement.

Strong evidence demonstrates the protective benefit of frequent colonoscopy surveillance for colorectal cancer prevention in Lynch Syndrome (LS) and is endorsed by many guidelines. Until recently, the evidence supporting the utility of upper endoscopy [esophagogastroduodenoscopy (EGD)] for upper gastrointestinal (UGI) cancer surveillance was limited. Over the last 3 years, multiple studies have demonstrated that EGD surveillance in LS is associated with the detection of both precancerous lesions and early-stage UGI cancers. On the basis of the emerging favorable evidence derived from EGD surveillance programs, the 2022 National Comprehensive Cancer Network (NCCN) Guidelines for LS recommend UGI surveillance with EGD starting between age 30 and 40 years with repeat EGDs every 2 to 4 years, preferably in conjunction with colonoscopy, in all patients with a germline pathogenic variant (PV) in MLH1, MSH2, EPCAM, and MSH6 and, because of the lack of data, consideration in PMS2. Standardization of the approach to performing EGD surveillance in LS and reporting clinically actionable findings is requisite for both improving quality and understanding the cost efficiency and outcomes of patients undergoing EGD as a surveillance tool. Accordingly, the primary objective of this Quality of Upper Endoscopy in Lynch Syndrome (QUELS) statement is to articulate a framework for standardizing the approach to performing and reporting EGD findings in patients with LS by introducing emerging quality metrics. The recommendations presented herein were developed from available evidence and consensus-based expert opinion and provide a practical approach for clinicians applying EGD surveillance in accordance with the most recent and existing LS guidelines.

Outcomes of upper endoscopy screening in Lynch syndrome: a meta-analysis.

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes affected individuals to a high lifetime risk of malignancies, including colorectal, endometrial, gastric, and duodenal cancers. The role of upper GI (UGI) cancer screening in LS has been uncertain, but recent studies have evaluated its utility. METHODS: Databases were queried through December 2021 to identify studies that examined upper endoscopy screening in LS using EGD. Mantel-Haenszel pooled odds ratios and 95% confidence intervals (CIs) for outcomes were constructed using a random-effects model to identify pooled odds of endoscopic findings in persons with LS. Event rates for detection of gastric and duodenal cancers, high-risk lesions, and clinically actionable findings were calculated. Statistical heterogeneity was assessed using the I2 statistic. RESULTS: Nine studies were identified with 2356 LS patients undergoing approximately 7838 EGDs. In total, 47 LS-associated UGI cancers (18 gastric and 29 duodenal cancers), 237 high-risk lesions, and 335 clinically actionable findings were identified. The pooled event rate for detection of any UGI cancer, high-risk lesions, and clinically actionable findings during screening were .9% (95% CI, .3-2.1; I2 = 89%), 4.2% (95% CI, 1.6-10.9; I2 = 98%), and 6.2% (95% CI, 2.2-16.5; I2 = 99%), respectively. There was no difference between LS-associated gene and gastric or duodenal cancer detection. CONCLUSIONS: In LS, there is evidence that endoscopic screening detects UGI cancers, precancerous lesions, and other clinically actionable findings that favor its use as a part of cancer risk management in LS.

Impact of Medicaid Expansion on Incidence and Mortality from Gastric and Esophageal Cancer.

BACKGROUND AND AIMS: Individuals in Medicaid expanded states have increased access to treatment for medical conditions and other health care resources. Esophageal and gastric cancer are associated with several modifiable risk factors (e.g. smoking, drinking, Helicobacter pylori infection). The impact of Medicaid expansion on these cancers incidence and mortality remains uninvestigated. METHODS: We evaluated the association between Medicaid expansion and gastric and esophageal cancer incidence and mortality in adults aged 25-64. We employed an observational design using a difference-in-differences method with state level data, from 2010 to 2017. Annual, age-adjusted gastric and esophageal cancer incidence and mortality rates, from the CDC Wonder Database, were analyzed. Rates were adjusted for by several socio-demographic factors. RESULTS: Expansion and non-expansion states were similar in percent Hispanic ethnicity and female gender. The non-expansion states had significantly higher proportion of Black race, diabetics, obese persons, smokers, and those living below the federal poverty line. Adjusted analyses demonstrate that expansion states had significantly fewer new cases of gastric cancer: - 1.6 (95% CI 0.2-3.5; P = 0.08) per 1,000,000 persons per year. No significant association was seen between Medicaid expansion and gastric cancer mortality (0.46 [95% CI - 0.08 to 0.17; P = 0.46]) and esophageal cancer incidence (0.8 [95% CI - 0.08 to 0.24; P = 0.33]) and mortality (1.0 [95% CI - 0.06 to 0.26; P = 0.21]) in multivariable analyses. CONCLUSION: States that adopted Medicaid expansion saw a decrease in gastric cancer incidence when compared to states that did not expand Medicaid. Though several factors may influence gastric cancer incidence, this association is important to consider during health policy negotiations.

Sporadic Neurofibroma of the Peritoneal Cavity.

Neurofibromas are peripheral nerve sheath tumors that are typically seen in syndromic conditions such as neurofibromatosis 1. We present the case of a 26-year-old woman suffering from chronic abdominal pain for over 5 years. Prior workup showed a large retroperitoneal mass extending into the abdomen and encasing multiple major vessels. She underwent endoscopic ultrasound (EUS)-guided biopsy, which was histologically consistent with a solitary neurofibroma. There is no prior report of solitary neurofibroma of the abdomen diagnosed with the use of EUS-guided biopsy. This case highlights the utility of EUS-guided biopsy in the evaluation of intra-abdominal pathology.

Transjejunal drainage of an infected postsurgical fluid collection using a 6-mm lumen-apposing metal stent.

Video 1The successful placement of a 6-mm lumen-apposing metal stent for transjejunal drainage of an infected collection after recent surgery, with resolution of collection after removal of stents.

Full-thickness resection: troubleshooting, tips, and tricks for success in the colorectum.

Video 1Difficult scenarios encountered during colorectal full thickness resection and their management: (1) Inability to advance device to target lesion; (2) injury to extraluminal structures; (3) anal trauma; (4) anal stenosis; (5) luminal edema after resection; (6) difficulty in grasping lesion; (7) recommendation for "mini time-out"; (8) Summary.

Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome.

Lynch syndrome is a common hereditary cancer predisposition syndrome associated with increased digestive cancer risk including colorectal, gastric, and duodenal cancers. While colorectal cancer surveillance is widely accepted to be an important part of a comprehensive Lynch syndrome risk management plan, the use of upper gastrointestinal cancer surveillance in Lynch syndrome remains more controversial. Currently, upper gastrointestinal cancer surveillance guidelines for Lynch syndrome vary widely, and there is no consensus on who should undergo upper gastrointestinal cancer surveillance, how surveillance should be performed, the age at which to initiate surveillance, or how often individuals with Lynch syndrome should undergo upper gastrointestinal cancer surveillance. Fortunately, research groups around the world have been focusing on upper gastrointestinal cancer surveillance in Lynch syndrome, and recent evidence in this field has demonstrated that upper gastrointestinal cancer surveillance can be performed with identification of precancerous lesions as well as early-stage upper gastrointestinal cancers. In this manuscript, we review the upper gastrointestinal cancer risks in Lynch syndrome, differing guideline recommendations for surveillance, outcomes of upper gastrointestinal cancer surveillance, and controversies in the field, and we provide a framework based on our collective experience with which to incorporate upper gastrointestinal cancer surveillance into a risk management program for individuals with Lynch syndrome.

Increasing Rates of Pancreatic and Hepatocellular Cancers Parallel Increasing Obesity Rates.

OBJECTIVES: Gastrointestinal (GI) cancers are now the second leading cause of cancer death in the United States, and six are convincingly associated with obesity. We interrogate the association of a state's obesity prevalence with cancer incidence. METHODS: We use data from US Cancer Statistics for each of the 6 cancers of interest from 2011 to 2018. Age-adjusted incidences were calculated, and the Behavioral Risk Factor Surveillance System was used to identify prevalence of obesity in each state. A generalized estimating equation model was used to relate the rate of cancer with the rate of obesity. RESULTS: Increased state-level prevalence of obesity was significantly associated with increasing state-level incidence of pancreatic and hepatocellular cancers. The rate of colorectal cancer was not associated with increasing obesity in 2011-2014 but from 2015 to 2018 was inversely associated with increasing rates of obesity. State-level prevalence of obesity was not associated with esophageal, gastric, or gallbladder cancers. CONCLUSIONS: Weight management interventions may reduce risk of pancreatic and hepatocellular cancers.

Ranitidine Use and Gastric Cancer Among Persons with Helicobacter pylori.

BACKGROUND: The Food and Drug Administration requested withdrawal of ranitidine formulations, due to a potentially carcinogenic contaminant, N-nitrosodimethylamine. AIMS: We evaluate whether ranitidine use is associated with gastric cancer. METHODS: This is a retrospective multicenter, nationwide cohort study within the Veterans Health Administration, among patients with Helicobacter pylori (HP) prescribed long-term acid suppression with either: (1) ranitidine, (2) other histamine type 2 receptor blocker (H2RB), or (3) proton pump inhibitor (PPI)) between May 1, 1998, and December 31, 2018. Covariates included race, ethnicity, smoking, age, HP treatment, HP eradication. Primary outcome was non-proximal gastric adenocarcinomas, using multivariable Cox proportional hazards analysis. RESULTS: We identified 279,505 patients with HP prescribed long-term acid suppression (median 53.4 years; 92.9% male). Compared to ranitidine, non-ranitidine H2RB users were more likely to develop cancer (HR 1.83, 95%CI 1.36-2.48); PPI users had no significant difference in future cancer risk (HR 0.92, 95% CI 0.82-1.04), p < 0.001. Demographics associated with future cancer included increasing age (HR 1.18, 95% CI 1.15-1.20, p < 0.001), Hispanic/Latino ethnicity (HR 1.46, 95% CI 1.21-1.75, p < 0.001), Black race (HR 1.89, 95% CI 1.68-2.14) or Asian race (HR 2.03, 95% CI 1.17-3.52), p < 0.001, and gender (female gender HR 0.64, 95% CI 0.48-0.85, p = 0.02). Smoking was associated with future cancer (HR 1.38, 95% CI 1.23-1.54, p < 0.001). Secondary analysis demonstrated decreased cancer risk in those with confirmed HP eradication (HR 0.24, 95% CI 0.14-0.40). No association between ranitidine and increased gastric cancer was found. CONCLUSION: There is no demonstrable association between ranitidine use and future gastric cancer among individuals with HP on long-term acid suppression.

How much progress have we made?: a 20-year experience regarding esophageal stents for the palliation of malignant dysphagia.

Esophageal stents are widely used for the palliation of malignant esophageal obstruction. Advances in technology have made esophageal stenting technically feasible and widespread for such obstruction, but complications remain frequent. We present outcomes of a large cohort undergoing esophageal stent placement for malignant esophageal obstruction at a tertiary care cancer center. Patients who underwent placement of esophageal stents for malignancy-related esophageal obstruction between 1 January 2001 and 31 July 2020 were identified. Exclusion criteria included stents placed for benign stricture, fistulae, obstruction of proximal esophagus (proximal to 24 cm from incisors), or post-surgical indications. Patient charts were reviewed for demographics, procedure and stent characteristics, complications, and follow-up. A total of 242 patients underwent stent placement (median age: 64 years, 79.8% male). The majority, 204 (84.3%), had esophageal cancer. During the last two decades, there has been an increasing trend in the number of esophageal stents placed. Though plastic stents were previously used, these are no longer utilized. Complications are frequent and include early complications of pain in 68 (28.1%) and migration in 21 (8.7%) and delayed complications of recurrent symptoms of dysphagia in 46 (19.0%) and migration in 26 (10.7%). Over the study period, there has not been a significant improvement in the rate of complications. During follow-up, 92 (38%) patients required other enteral nutrition modalities after esophageal stent placement. No patient, treatment, or stent characteristics were significantly associated with stent complication or outcome. Esophageal stent placement is an increasingly popular method for palliation of malignant dysphagia. However, complications, particularly pain, migration, and recurrent symptoms of dysphagia are common. Almost 40% of patients may also require other methods of enteral access after esophageal stent placement. Given the high complication rates and suboptimal outcomes, removable stents should be considered as first-line in the case of poor palliative response.

Eastern European and Asian-born populations are prone to gastric cancer: an epidemiologic analysis of foreign-born populations and gastric cancer.

BACKGROUND: The highest incidence of gastric cancer is in East Asia, corresponding to a high prevalence of Helicobacter pylori (H. pylori), yet other regions with a similarly high prevalence of H. pylori have lower cancer rates. Foreign-born persons who immigrate to the United States are thought to remain at high-risk for gastric cancer, but this has not been confirmed by large population-based studies. METHODS: We evaluated total and foreign-born populations in metropolitan statistical areas (MSAs). Cardia and non-cardia gastric adenocarcinomas diagnosed between 2006 and 2016 were identified using the Surveillance, Epidemiology, and End Results Program. Generalized linear regression models determined whether the incidence of gastric cancer in each MSA was associated with specific foreign-born populations. RESULTS: Among 32 MSAs, we identified 55,937 patients with gastric adenocarcinoma. A greater percentage of Eastern European-born individuals in an MSA was associated with a higher incidence of cardia cancers (coefficient 1.32, P=0.02). Evaluating Asian-born populations alone, a greater percentage of Japanese-born individuals was associated with a higher incidence of non-cardia cancers (coefficient 2.48, P=0.03), whereas Korean or Chinese origin was not associated with a significantly higher risk. CONCLUSIONS: On a population level, a greater percentage of Eastern European-born individuals is associated with a higher incidence of cardia gastric adenocarcinomas. Among Asian-born individuals, Korean or Chinese origin was not associated with a significantly higher risk, but a greater percent of persons born in other Asian countries, including Japan, was associated with a higher incidence of non-cardia gastric adenocarcinomas in an MSA.

Threshold Analysis of the Cost-effectiveness of Endoscopic Ultrasound in Patients at High Risk for Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Data from the International Cancer of the Pancreas Screening Consortium studies have demonstrated that screening for pancreatic ductal adenocarcinoma can be effective and that surveillance improves survival in high-risk individuals. Endoscopic ultrasound (EUS) and cross-sectional imaging are both used, although there is some suggestion that EUS is superior. Demonstration of the cost-effectiveness of screening is important to implement screening in high-risk groups. METHODS: Results from centers with EUS-predominant screening were pooled to evaluate efficacy of index EUS in screening. A decision analysis model simulated the outcome of high-risk patients who undergo screening and evaluated the parameters that would make screening cost-effective at a US $100,000 per quality-adjusted life-year willingness to pay. RESULTS: One-time index EUS has a sensitivity of 71.25% and specificity of 99.82% to detection to detect high-risk lesions. Screening with index EUS was cost-effective, particularly at lifetime pancreatic cancer probabilities of greater than 10.8%, or at lower probabilities if life expectancy after resection of a lesion that was at least 16 years, and if missed, lesion rates on index EUS are 5% or less. CONCLUSIONS: Pancreatic cancer screening can be cost-effective through index EUS, particularly for those individuals at high-lifetime risk of cancer.