Epidemiology of Gastric Malignancies 2000-2018 According to Histology: A Population-Based Analysis of Incidence and Temporal Trends.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of cancer and cancer-related mortality. Recent reports suggest noncardia GC is increasing in certain U.S. POPULATIONS: However, whether these trends are driven by gastric adenocarcinoma (GA) or other histologies, including neuroendocrine tumors (NETs), lymphoma, or gastrointestinal stromal tumors (GISTs), is unclear. METHODS: We analyzed the Surveillance, Epidemiology and End Results-18 cancer registry (2000-2018) to determine age-standardized incidence rates (ASIR) and annual percentage change (APC) trends for histologically-confirmed GCs, stratified by anatomic location (noncardia vs cardia), age group (20-49 vs 50+ years), sex, race, and ethnicity. Joinpoint regression modeling estimated the statistical significance of trend comparisons. RESULTS: Of 74,520 individuals with noncardia GC, most (66.2%) were GA, with the next largest categories being non-mucosa-associated lymphoid tissue (non-MALT) lymphomas (6.9%), GIST (6.7%), NET (6.4%), and MALT lymphoma (5.6%). Noncardia GA ASIR was significantly higher than other histologies and demonstrated the greatest differences by race and ethnicity. APCs for GA and MALT, both Helicobacter pylori-associated cancers, declined significantly over time, which was driven primarily by trends among individuals ≥50 years-old. NET and GIST APCs significantly increased irrespective of age group, with the highest APCs observed among non-Hispanic white individuals. Cardia GC was rarer than noncardia GC and comprised primarily by GA (87.9%). Cardia GC incidence fell during the study period, which was primarily driven by decline in cardia GA. CONCLUSIONS: GA was the most common histology. On the basis of our findings, the rise in noncardia GC among certain U.S. populations appears predominantly driven by NET and GIST, not GA. Further studies are needed to clarify underlying etiologies for these findings.

Short and long-term outcomes of prophylactic total gastrectomy in 54 consecutive individuals with germline pathogenic mutations in the CDH1 gene.

BACKGROUND: Germline mutation of CDH1 is rare and leads to hereditary diffuse gastric cancer (DGC). METHODS: Patients (pts) with CDH1 mutation who underwent multidisciplinary counseling followed by open prophylactic total gastrectomy (PTG) by a single surgeon were reviewed. RESULTS: Fifty-four pts with a median age of 41 years (16-70 years) underwent PTG between 2006 and 2021. Median operative time was 161 min, and median hospital stay was 7 days (range 6-12). There were 5 complications (9.2%) within 30 days, and two complications (pulmonary embolism and pancreatitis) required readmission. There were no anastomotic leaks. The pathologic analysis of the first 10 pts included the entire gastric mucosa, revealing a median of 15 foci of DGC (range 5-136). The subsequent 44 pts with more limited analysis had a median of 2 foci (range 0-5), and two pts (3.7%) had no foci identified. Median maximum weight loss was 19%. In long-term follow-up (median 4.6 years) of 20 pts, median global QOL was 2.0 (very good), the majority had persistent difficulty with certain foods or liquids, and all stated they would again elect PTG over surveillance endoscopy. CONCLUSIONS: PTG can be performed safely at high-volume referral centers with very good QOL but nutritional sequelae persist.

Initiation of Somatostatin analogues for neuroendocrine tumor patients: a cost-effectiveness analysis.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous neoplasms. Although some have a relatively benign and indolent natural history, others can be aggressive and ultimately fatal. Somatostatin analogues (SSAs) improve both quality of life and survival for these patients once they develop metastatic disease. However, these drugs are costly and their cost-effectiveness is not known. METHODS: A decision-analytic model was developed and analyzed to compare two treatment strategies for patients with Stage IV GEP-NETs. The first strategy had all patients start SSA immediately while the second strategy waited, reserving SSA initiation until the patient showed signs of progression. Sensitivity analysis was performed to explore model parameter uncertainty. RESULTS: Our model of patients age 60 with metastatic GEP-NETs suggests empiric initiation of SSA led to an increase 0.62 unadjusted life-years and incremental increase in quality-adjusted life years (QALYs) of 0.44. The incremental costs were $388,966 per QALY and not cost-effective at a willingness-to-pay threshold of $100,000. Death was attributed to GEP-NETs for 94.1% of patients in the SSA arm vs. 94.9% of patients in the DELAY SSA arm. Sensitivity analysis found that the model was most sensitive to costs of SSAs. Using probabilistic sensitivity analysis, the SSA strategy was only cost-effective 1.4% of the time at a WTP threshold of $100,000 per QALY. CONCLUSIONS: Our modeling study finds it is not cost-effective to initiate SSAs at time of presentation for patients with metastatic GEP-NETs. Further clinical studies are needed to identify the optimal timing to initiate these drugs.

Preoperative Endoscopic Retrograde Cholangiopancreatography Is Not Associated With Increased Pancreatic Cancer Mortality.

BACKGROUND & AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) before surgery for pancreatic cancer has been associated with infectious complications after surgery. Little is known about the effects of preoperative ERCP on the survival of patients with pancreatic cancer. We investigated whether ERCP before surgery affects overall survival, after controlling for confounding factors. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) and linked Medicare claims data to identify patients older than 65 years with cancer localized to the head of the pancreas, from 2000 through 2011. We used inverse propensity-weighted Cox proportional hazard models to assess the effects of ERCP on the survival of patients who underwent surgery for pancreatic cancer. RESULTS: Among 16,670 patients with cancer of the head of the pancreas, 2890 (17.3%) underwent surgical resection; 1864 (64.5%) of these patients received preoperative ERCP. After we adjusted for confounders, we found that patients who received preoperative ERCP did not have an increased risk of death compared with patients who underwent resection alone (hazard ratio, 1.02; 95% CI, 0.96-1.08). CONCLUSIONS: Patients with pancreatic cancer who underwent ERCP before surgery did not have an increased risk of death compared with patients who proceeded directly to surgery. Studies are needed to identify subsets of patients who may benefit from this procedure.

Familial Predisposition and Genetic Risk Factors Associated with Pancreatic Cancer.

Pancreatic cancer (PC) is a highly lethal cancer and projected to be the second leading cause of cancer death by 2030. Multigene panel testing has facilitated the identification of germline variants associated with an increased risk of PC. Precision treatment has led to improved outcomes for patients with these findings. Because of these improved outcomes as well as the implications for at-risk family members who may benefit from additional cancer screening, the NCCN recommends universal genetic testing for newly diagnosed PC patients. This review describes the most common heritable conditions associated with PC and those who may benefit from screening.

Impact of COVID-19 pandemic on gastrointestinal cancer diagnosis and resection: An observational study.

BACKGROUND: The COVID-19 pandemic disrupted routine screening for and treatment of gastrointestinal (GI) cancers. We analyzed changes in GI cancer pathology specimens resulting from diagnostic and therapeutic procedures at a single academic center in an epicenter of the COVID-19 pandemic. Our aim was to determine which cancer types, procedures, and patients were impacted by the pandemic. METHODS: This was a retrospective, cohort study of patients identified based on carcinoma containing pathologic specimens reviewed in our institution resulting from diagnostic or resection procedures. Pathology and medical records of patients with GI and liver carcinoma and high-grade dysplasia were reviewed from February 1 to April 30 in 2018, 2019 and 2020. We used March 16, 2020 to delineate the pre-COVID-19 and COVID-19 period in 2020. Chi-squared or t-tests, as appropriate, were used to compare these time periods in each year. Mann Kendall test was used to test for trend in volume. ANCOVA was used to compare differences across years. RESULTS: A total of 1028 pathology samples from 949 unique patients were identified during the study period. There was a 57% drop in samples within 2020 (p = 0.01) that was not present in either 2018 or 2019 (p<0.01). In 2020, there were significantly fewer resections compared to biopsies overall in the COVID-19 period (p = 0.01). There were fewer colorectal cancer specimens (p = 0.04) which were procured from older patients (p<0.01) in the 2020 COVID-19 period compared to pre-COVID-19. CONCLUSIONS: In our institution, there was a significant drop in diagnostic and resection specimens of GI cancers during the COVID-19 pandemic, disproportionately affecting older colorectal cancer patients.

Cost-effectiveness of screening with polymerase chain reaction for Helicobacter pylori to prevent gastric cancer and peptic ulcers.

Background: Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer. Screening and treatment of H. pylori may reduce the risk of gastric cancer and peptic ulcer disease (PUD). Polymerase chain reaction (PCR) of gastric biopsies provides superior sensitivity and specificity for the detection of H. pylori. This study explores whether population-based H. pylori screening with PCR is cost-effective in the US. Methods: A Markov cohort state-transition model was developed to compare three strategies: no screening with opportunistic eradication, 13C-UBT population screening and treating of H. pylori, and PCR population screening and treating of H. pylori. Estimates of risks and costs were obtained from published literature. Since the efficacy of H. pylori therapy in gastric cancer prevention is not certain, we broadly varied the benefit 30-100% in sensitivity analysis. Results: PCR screening was cost-effective and had an incremental-cost effectiveness ratio per quality adjusted life-year (QALY) of $38,591.89 when compared to 13C-UBT strategy with an ICER of $2,373.43 per QALY. When compared to no screening, PCR population screening reduced cumulative gastric cancer incidence from 0.84% to 0.74% and reduced PUD risk from 14.8% to 6.0%. The cost-effectiveness of PCR screening was robust to most parameters in the model. Conclusions: Our modeling study finds PCR screening and treating of H. pylori to be cost-effective in the prevention of gastric cancer and PUD. However, the potential negative consequences of H. pylori eradication such as antibiotic resistance could change the balance of benefits of population screening.

Opioid Prescription Is Associated With Increased Survival in Older Adult Patients With Pancreatic Cancer in the United States: A Propensity Score Analysis.

PURPOSE: Few studies have assessed the interaction between pain treatment and mortality in pancreatic cancer. The aim of this study was to investigate the association between receipt of opioid prescriptions and survival in adults with pancreatic cancer. METHODS: The SEER-Medicare linked database was used to identify patients diagnosed with late-stage pancreatic cancer between 2007 and 2015. Kaplan-Meier models were used to assess the association between opioid prescriptions in the year after cancer diagnosis and survival. Cox proportional hazard models were used to determine the association between opioid receipt and survival, adjusting for propensity score and other relevant confounders including cancer-directed therapies and palliative care referral. RESULTS: A total of 5,770 older adults with pancreatic cancer were identified; 1,678 (29.1%) were prescribed opioids for at least 60 days. Median survival was increased in those with opioid prescriptions (6.0 months) compared with those without (4.0 months, P < .0001). After adjustment for confounders, opioid prescriptions were still associated with improved survival (hazard ratio 0.80; 95% CI, 0.75 to 0.86). On multivariable analysis, opioid prescriptions were associated with older age, female sex, residing in nonmetro areas, and treatment with celiac plexus neurolysis, chemotherapy, and radiation. CONCLUSION: Receipt of opioid prescriptions is associated with longer survival in patients with pancreatic cancer. This may be due to the impact of cancer-related pain, although further studies are needed to better understand the interaction between pain management, cancer-directed therapies, and systemic factors, such as palliative care, availability of opioids, and clinical practice culture.

Use of endoscopic ultrasound for pancreatic cancer from 2000 to 2016.

Background and study aims Pancreatic cancer (PC) is the fourth most common cause of cancer death in the United States. Previous studies have suggested a survival benefit for endoscopic ultrasound (EUS), an important tool for diagnosis and staging of PC. This study aims to describe EUS use over time and identify factors associated with EUS use and its impact on survival. Patients and methods This was a retrospective review of the Surveillance, Epidemiology and End Results (SEER) database linked with Medicare claims. EUS use, clinical and demographic characteristics were evaluated. Chi-squared analysis, Cochran-Armitage test for trend, and logistic regression were used to identify associations between sociodemographic and clinical factors and EUS. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. Results EUS use rose during the time period, from 7.4 % of patients in 2000 to 32.4 % in 2015. Patient diversity increased, with a rising share of older, non-White patients with higher Charlson comorbidity scores. Both clinical (receipt of other therapies, PC stage) and nonclinical factors (region of country, year of diagnosis) were associated with receipt of EUS. While EUS was associated with a survival improvement early in the study period, this effect did not persist for PC patients diagnosed in 2012 to 2015 (median survival 3 month ± standard deviation [SD] 9.8 months without vs. 4 months ± SD 8 months with EUS). Conclusions Our data support previous studies, which suggest a survival benefit for EUS when it was infrequently used, but finds that benefit was attenuated as EUS became more widely available.

Celiac Plexus Neurolysis Is Associated With Decreased Survival in Patients With Pancreatic Cancer: A Propensity Score Analysis.

OBJECTIVE: The aim of this study was to investigate survival in patients who received celiac plexus neurolysis (CPN) compared with patients who received opioids. METHODS: The Surveillance, Epidemiology and End Results-Medicare database was used to identify patients older than 65 years diagnosed with pancreatic cancer between 2007 and 2015. We used claims data to identify patients with a history of CPN and opioid use within 1 year of diagnosis, and other demographic, clinical, and treatment variables. Kaplan-Meier analyses and inverse propensity-weighted adjusted Cox proportional hazard ratios were used to evaluate survival. RESULTS: We identified 648 patients who underwent CPN (19.0%) compared with 2769 patients who received opioids (81.0%). The median survival and interquartile range for patients who received CPN was 4.0 months (2.0-8.0 months) compared with 7.0 months (3.0-12.0 months) for opioid users (P < 0.0001). After adjusting for confounders and propensity score, the patients who received CPN showed worsened survival (hazard ratio, 1.69; 95% confidence interval, 1.59-1.79). CONCLUSIONS: Pancreatic cancer patients who underwent CPN had decreased survival compared with opioid users. This suggests that opioid sparing methods to reduce pancreatic cancer pain may actually be harmful. Future prospective studies should investigate whether other opioid sparing therapies impact pancreatic cancer survival.

Inherited predisposition to pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer death in the US by 2030. There are multiple germline pathogenic variants and cancer syndromes associated with an increased risk of PDAC. Precision treatment, informed by germline genetic testing and molecular tumor analysis, can optimize therapeutic regimens and outcomes for those diagnosed with PDAC. As a result, the National Comprehensive Cancer Network currently recommends genetic testing for all newly diagnosed PDAC patients given the clinical implications for treatment but also for the identification of at-risk family members who can benefit from pancreatic cancer screening and other cancer prevention strategies. This article reviews inherited risk factors for the development of PDAC and current screening strategies for the early detection of PDAC in high-risk populations.

Inherited Predisposition to Gastric Cancer.

Approximately 10% of patients with gastric cancer show familial aggregation and up to 3% are related to an inherited cancer syndrome. There are multiple germline pathogenic variants and cancer syndromes associated with an increased risk of gastric cancer. Appropriate assessment of familial and genetic risk may allow a personalized approach to gastric cancer prevention through screening and risk-reducing surgeries. The ability to better identify carriers with pathogenic genetic variants associated with gastric cancer before a diagnosis of cancer requires effective genetic risk assessment and testing, followed by optimal screening and surveillance recommendations to further reduce the morbidity and mortality.

Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management.

Autoimmune gastritis (AIG) is a chronic immune-mediated, inflammatory condition that involves the destruction of the gastric oxyntic mucosa through the autoimmune-mediated loss of parietal cells, with replacement by atrophic and metaplastic tissue. Diagnosing AIG is important, given the need for ongoing clinical management and vigilance with respect to downstream complications, the most serious of which is gastric adenocarcinoma. Other clinical consequences include gastric neuroendocrine tumors, consequences related to decreased gastric acid and decreased intrinsic factor due to parietal cell destruction and antibodies against intrinsic factor (e.g. micronutrient deficiencies), as well as concomitant autoimmune disorders. Considering the prevalence of AIG and the potential for severe clinical outcomes, it is important to engage in efforts to reduce practice pattern variability related to diagnosis and management. Accordingly, herein, we review of the epidemiology, pathogenesis, clinical presentation of AIG, including both gastric and extragastric manifestations, and provide an overview of clinical management.

Bisphosphonate Use Does Not Impact Survival in Patients with Pancreatic Cancer: A Propensity Score Matching Analysis.

Background/Aims: : Bisphosphonates are increasingly recognized for their anti-neoplastic properties, which are the result of their action on the mevalonate pathway. Our primary aim was to investigate the association between bisphosphonate use and survival in patients with pancreatic cancer. Since statins also act on the mevalonate pathway, we also investigated the effect of the combined use of bisphosphonates and statins on survival. Methods: The Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database was used to identify patients with pancreatic ductal adenocarcinoma (PDAC) between 2007 and 2015. Kaplan-Meier models were used to examine the association between survival with bisphosphonate use alone and in combination with statins within 1 year prior to the diagnosis of PDAC. Propensity score matching analysis and Cox-proportional hazard models were used to determine the association between overall survival with bisphosphonate use alone and combined with statins, after adjusting for relevant confounders, such as the Charlson comorbidity index score, stage, treatment, sociodemographic characteristics, and propensity score. Results: In total, 13,639 patients with PDAC were identified, and 1,203 (8.82%) used bisphosphonates. There was no difference in the mean survival duration between bisphosphonate users (7.27 months) and nonusers (7.25 months, p=0.61). After adjustment for confounders, bisphosphonate use was still not associated with improved survival (hazard ratio, 1.00; 95% confidence interval, 0.93 to 1.08; p=0.96). Combined bisphosphonate and statin use was also not associated with improved survival (hazard ratio, 0.97; 95% confidence interval, 0.87 to 1.07; p=0.48) after adjustment for confounders. Conclusions: Our findings suggest that the use of bisphosphonates, whether alone or in combination with statins, does not confer a survival advantage in patients with PDAC.

Beta-blockers have no impact on survival in pancreatic ductal adenocarcinoma prior to cancer diagnosis.

Previous studies have suggested that ß-adrenergic signaling may regulate the growth of various cancers. The aim of our study is to investigate the association between the incidental use of beta-blockers for various conditions on the overall survival of patients with pancreatic ductal adenocarcinoma (PDAC). Patients with histologically-confirmed PDAC between 2007 and 2011 were extracted from Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database. Kaplan Meier and multivariable Cox Proportional-Hazard models were used to examine the association between beta-blocker usage before diagnosis and overall survival adjusting for appropriate confounders. As an additional analysis we also examined continuous beta-blocker use before and after diagnosis. From 2007 to 2011, 13,731 patients were diagnosed with PDAC. Of these, 7130 patients had Medicare Part D coverage in the 6-month period before diagnosis, with 2564 (36%) of these patients using beta-blockers in this period. Patients receiving beta-blockers had a mean survival time of 5.1 months compared to 6 months for non-users (p < 0.01). In multivariable analysis, beta-blockers usage was not associated with improved survival (Hazard Ratio (HR) 1.04, 95%, Confidence Interval (CI) 0.98-1.1, p = 0.2). When patients were stratified by conditions with indications for beta-blocker usage, such as hypertension, coronary artery disease and cardiac arrhythmia, differences in survival were insignificant compared to non-users in all groups (p > 0.05). After stratification by receptor selectivity, this lack of association with survival persisted (p > 0.05 for all). As a subgroup analysis, looking at patients with continuous Medicare Part D coverage who used beta-blockers in the 6-month period before and after cancer diagnosis, we identified 7085 patients, of which 1750 (24.7%) had continuous beta blocker use. In multivariable analysis, continuous beta-blockers usage was associated with improved survival (Hazard Ratio (HR) 0.86, 95%, Confidence Interval (CI) 0.8-0.9, p < 0.01). Beta-blocker usage before diagnosis does not confer a survival advantage in patients with PDAC, though continuous use before and after diagnosis did confer a survival advantage. Prospective studies into the mechanism for this advantage are needed.