Sessile serrated polyp detection rates after fecal immunochemical test or multitarget stool DNA test: Systematic review and meta-analysis.

Background and study aims Published studies report a higher adenoma detection rate (ADR) for FIT-DNA as compared with FIT. Data are less replete about the performance of stool-based tests for sessile serrated polyp (SSP) detection. We performed a meta-analysis to evaluate the performance of FIT and FIT-DNA testing for SSP detection rate (SSPDR) in patients undergoing colonoscopy for follow up of positive noninvasive tests. Methods A comprehensive literature search of multiple databases (until September 2022) was performed to identify studies reporting SSPDR in patients with positive FIT or FIT-DNA tests. The outcome was overall colonoscopy detection of any SSPs and advanced serrated polyps (ASP: SSP ≥ 10 mm and/or dysplasia). Results Included were 482,405 patients (52.4% females) with a mean age of 62.3 ± 4.4 years from 23 studies. The pooled SSPDR for all positive stool-based tests was 5.3% and higher for FIT-DNA (15.0%, 95% confidence interval [CI] 8.3-25.7) versus FIT (4.1%, 95% CI 3.0-5.6; P = 0.0002). The overall pooled ASP detection rate was 1.4% (95% CI 0.81-2.3) and higher for FIT-DNA (3.8 %, 95% CI 1.7-8.6) compared with FIT (0.71%, 95% CI 0.36-1.4; P <0.01). SSPDR with FIT-DNA was also significantly higher than FIT when the FIT cutoff was >10 ug/g and in FIT-positive patients in studies conducted in North America ( P <0.05). Conclusions FIT-DNA outperformed FIT in both SSP and ASP detection including FIT with a lower threshold cutoff of >10 ug/g. Further comparative studies are needed to assess the impact of our findings on colorectal cancer reduction.

Survival of Patients With Gastroenteropancreatic Neuroendocrine Tumors and Diabetes Mellitus.

OBJECTIVES: Diabetes mellitus (DM) is associated with an increased risk of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the association between DM and GEP-NET survival is unknown. We evaluated disease characteristics and survival in individuals with DM and GEP-NETs. METHODS: Using the Surveillance, Epidemiology, and End Results registry linked to Medicare (SEER-Medicare) claims database, we examined sociodemographics, GEP-NET characteristics, and treatment in patients with and without DM before GEP-NET diagnosis. We compared survival using univariate and multivariate analyses. RESULTS: We identified 1858 individuals with GEP-NETs: 478 (25.7%) with DM and 1380 (74.3%) without. Significant differences in race (P = 0.002) were found between the DM and non-DM groups. Compared with individuals without DM, those with DM had more gastric (9.7% vs 14.9%), duodenal (6.5% vs 10.0%), and pancreatic (17.0% vs 21.8%), and less jejunal/ileal (18.1% vs 12.8%) NETs (P < 0.0001). Patients with DM had earlier stages (stage I, 37.0%; stage IV, 30.8%) than those without (stage I, 30.6%; stage IV, 36.4%; P = 0.0012). We found no difference in survival (multivariate hazard ratio, 0.97; 95% confidence interval, 0.76-1.23) between groups. CONCLUSIONS: Among patients with and without DM before GEP-NET diagnosis, we found differences in tumor location and stage, but not survival.

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.

Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results-Medicare analysis of 5235 patients.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly common malignancies and tend to have favorable long-term prognoses. Somatostatin analogues (SSA) are a first-line treatment for many NETs. Short-term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. AIM: In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. METHODS AND RESULTS: Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991-2016), we identified patients age 65+ with no prior DM diagnosis and a GEP-NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ2 tests to compare SSA-treated and SSA-untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP-NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95-1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. CONCLUSION: DM was very common in GEP-NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA-treated and SSA-untreated GEP-NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

Gender-Specific Factors Influencing Gastroenterologists to Pursue Careers in Advanced Endoscopy: Perceptions vs Reality.

INTRODUCTION: In 2020, only 19% of 63 matched advanced endoscopy (AE) fellows were women. This study evaluates the gender-specific factors that influence gastroenterologists to pursue careers in AE. METHODS: An anonymous survey was distributed to gastroenterology fellows and attendings through various gastroenterology society online forums. Data were collected on demographics, training, mentorship, current practice, family planning, and career satisfaction. RESULTS: Women comprised 71.1% of the 332 respondents. 24.7% of female fellows plan to pursue an AE career compared with 37.5% of male fellows (P = 0.195). The main motivating factor for both genders was interest in the subject area. Interest in another subspecialty was the main deterring factor for both genders. Women were more deterred by absence of same-sex mentors (P < 0.001), perception of gender-based bias in the workplace (P = 0.009), family planning (P = 0.018), fertility/pregnancy risks from radiation (P < 0.001), and lack of ergonomic equipment (P = 0.003). AE gastroenterologists of both genders were satisfied with their career decision and would recommend the field to any fellow. Most respondents (64%) believed that more female role models/mentors would improve representation of women in AE. DISCUSSION: There are multiple gender-specific factors that deter women from pursuing AE. Increasing the number of female role models is strongly perceived to improve representation of women in AE. Most AE attendings are satisfied with their career and would recommend it to fellows of any gender. Thus, early targeted mentorship of female trainees has potential to improve recruitment of women to the field.

The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors.

This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.

Analysis of Real-World Treatment Patterns, Healthcare Resource Utilization, and Costs Between Octreotide and Lanreotide Among Patients With Neuroendocrine Tumors.

OBJECTIVE: The aim of the study was to assess treatment patterns, healthcare resource utilization, and healthcare costs among patients with neuroendocrine tumors (NETs) receiving long-acting octreotide versus lanreotide, overall and in patients with carcinoid syndrome (CS). METHODS: A provider-based claims database was used to identify NET patients who first initiated long-acting octreotide or lanreotide (index date) from January 2015 to November 2017. Propensity-score matching 1:1 was used. Patients with CS were identified from the previously mentioned matched cohorts. Time-to-treatment discontinuation (TTD) was estimated using Kaplan-Meier analyses. Per-patient-per-month rates of healthcare resource utilization were compared using rate ratios from multivariable Poisson regression models. Multivariable linear regression models were used to compare mean monthly cost differences. RESULTS: The median TTD was similar between the 2 matched cohorts (N = 543 each; long-acting octreotide = 19.2 months, lanreotide = 17.5 months, P = 0.58). Significantly fewer NET-related outpatient visits (rate ratio = 0.95, P = 0.005) and significantly lower total healthcare costs (mean monthly cost difference: all-cause = US -$3701, NET-related = US -$3752, Ps < 0.001) were observed in the long-acting octreotide cohort than lanreotide. Similar results were found in CS patients. CONCLUSIONS: Patients on first-line long-acting octreotide and lanreotide had similar TTD. Long-acting octreotide was associated with significantly lower total healthcare costs than lanreotide.

Impact of Mesenteric Mass in Patients With Midgut Neuroendocrine Tumors.

OBJECTIVES: In this study, we used the institutional pathological and clinical databases from The Mount Sinai Hospital to investigate the impact of mesenteric mass on clinical and staging features in small intestinal neuroendocrine tumors. METHODS: Demographic, clinical, and staging data were collected. Tumor-node-metastasis stage was assigned according to the American Joint Committee on Cancer eighth edition staging manual. We used a χ-square test to evaluate the association between mesenteric mass and presenting symptoms, as well as the association between mesenteric mass and tumor characteristics, type of surgical resection, and use of somatostatin analogues. RESULTS: Presence of mesenteric mass was strongly associated with highly symptomatic clinical presentation (P < 0.0001). Patients with a mesenteric mass were more likely to have more advanced tumor status (T3 and T4; P = 0.005). The presence of a mesenteric mass was also more strongly associated with metastatic disease (P = 0.002). Patients with a mesenteric mass were more likely to undergo extensive surgical resection (P < 0.0001) and be treated with somatostatin analogues (P < 0.003). CONCLUSIONS: The data confirm our clinical observations that mesenteric involvement represents more extensive disease and is also associated with more aggressive treatment.

Age, socioeconomic features, and clinical factors predict receipt of endoscopic retrograde cholangiopancreatography in pancreatic cancer.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the recommended technique for biliary decompression in pancreatic cancer. Previous studies have suggested racial, socioeconomic and geographic differences in diagnosis, treatment and outcomes of pancreatic cancer patients. AIM: To examine geographic, racial, socioeconomic and clinical factors associated with utilization of ERCP. METHODS: Surveillance, Epidemiology and End Results and linked Medicare claims data were used to identify pancreatic cancer patients between 2000-2011. Claims data were used to identify patients who had ERCP and other treatments. The primary outcome was receipt of ERCP. Chi-squared analyses were used to compare demographic information. Trends in use of ERCP over time were assessed using Cochran Armitage test. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for receipt ERCP were calculated using logistic regression, controlling for other characteristics. RESULTS: Among 32510 pancreatic cancer patients, 14704 (45.2%) underwent ERCP. Patients who had cancer located in the head of the pancreas (aOR 3.27, 95%CI: 2.99-3.57), had jaundice (aOR 7.59, 95%CI: 7.06-8.17), cholangitis (aOR 4.22, 95%CI: 3.71-4.81) or pruritus (aOR 1.42, 95%CI: 1.22-1.66) and lived in lower education zip codes (aOR 1.14, 95%CI: 1.04-1.24) were more likely to receive ERCP. In contrast, patients who were older (aOR 0.88, 95%CI: 0.83, 0.94), not married (aOR 0.92, 95%CI: 0.86, 0.98), and lived in a non-metropolitan area (aOR 0.89, 95%CI: 0.82, 0.98) were less likely to receive ERCP. Compared to white patients, non-white/non-black patients (aOR 0.83, 95%CI: 0.70-0.97) were less likely to receive ERCP. Patients diagnosed later in the study period were less likely to receive ERCP (aOR 2004-2007 0.85, 95%CI: 0.78-0.92; aOR 2008-2011 0.76, 95%CI: 0.70-0.83). After stratifying by indications for ERCP including jaundice, racial differences persisted (aOR black patients 0.80, 95%CI: 0.67-0.95, nonwhite/nonblack patients 0.73, 95%CI: 0.58-0.91). Among patients with jaundice, those who underwent surgery were less likely to undergo ERCP (aOR 0.60, 95%CI: 0.52, 0.69). CONCLUSION: ERCP utilization in pancreatic cancer varies based on patient age, marital status, and factors related to where the patient lives. Further studies are needed to guide appropriate biliary intervention for these patients.

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.

Risk of Primary Neuroendocrine Pancreatic Tumor After a First Primary Cancer: A US Population-Based Study.

OBJECTIVE: This study aimed to describe the relative and excess risk of pancreatic neuroendocrine tumor (NET) at least 6 months after the first primary cancer (FPC) among the US population. METHODS: Surveillance, Epidemiology, and End-Results Program data were analyzed for patients diagnosed as having FPC from 2000 to 2015 (n = 4,008,092). Standardized incidence ratios, excess risk, and average time to diagnosis of a second primary pancreatic NET were reported by FPC site, stratified by sex and receipt of radiotherapy and chemotherapy. RESULTS: Risk of pancreatic NET was significantly higher after FPC at any site, any solid tumor (standardized incidence ratios, 1.3; 95% confidence interval, 1.2-1.5), pancreas, thymus, small intestine, liver, stomach, kidney, lung, and female breast. Excess incidence of pancreatic NET was highest among those with FPC (especially NET) of the pancreas, bladder, thymus, and female breast; those who received radiotherapy/chemotherapy for bladder, melanoma, and stomach cancers; and those who received chemotherapy for uterine, cervical, prostate, and other genital cancers. Time to diagnosis was shortest after pancreatic, liver, lung, and stomach cancer. CONCLUSIONS: Cancer survivors have increased risk and excess incidence of primary pancreatic NET compared with the population, particularly for certain primary sites. High-risk patients should receive regular follow-up screenings, counseling to reduce carcinogen exposure, and lifestyle interventions.

A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors.

We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.

Long-term Outcomes of Gastroenteropancreatic Neuroendocrine Tumors.

OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare but have been increasing in incidence. Limited data on the long-term outcomes of patients with these tumors are available. METHODS: In this study, we used population-based data from the National Cancer Institute to assess long-term disease-specific survival (DSS) of patients who have undergone surgery for nonmetastatic disease. All patients with NETs of the stomach, small intestine, colon, rectum, appendix, and pancreas diagnosed between 1988 and 2009 were identified from the Surveillance, Epidemiology and End Results registry. Staging was derived from Surveillance, Epidemiology and End Results data using the European Neuroendocrine Tumor Society guidelines. Cases with incomplete staging data were excluded, along with those with stage IV disease, or those who did not undergo surgical resection. RESULTS: Kaplan-Meier analyses were constructed to determine DSS. Analyses were further stratified according to tumor site, stage at diagnosis, and tumor grade. Overall, 13,348 patients with GEP-NETs meeting the inclusion criteria were identified. CONCLUSIONS: There were excellent outcomes for most GEP-NET patients, with a 20-year DSS of greater than 75% across all sites and stages. Pancreatic tumors had the worst outcomes, but DSS remains greater than 50% at 20 years.

Comparison of Endoscopic Ultrasound-Fine-Needle Aspiration and Endoscopic Ultrasound-Fine-Needle Biopsy for Solid Lesions in a Multicenter, Randomized Trial.

BACKGROUND & AIMS: Endoscopic ultrasound with fine-needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the gastrointestinal tract. Fine-needle biopsy (FNB) may provide higher diagnostic yield with fewer needle passes. The aim of this study was to assess the difference in diagnostic yield between FNA and FNB. METHODS: This is a multicenter, prospective randomized clinical trial from 6 large tertiary care centers. Patients referred for tissue sampling of solid lesions were randomized to either FNA or FNB of the target lesion. Demographics, size, location, number of needle passes, and final diagnosis were recorded. RESULTS: After enrollment, 135 patients were randomized to FNA (49.3%), and 139 patients were randomized to FNB (50.7%).The following lesions were sampled: mass (n = 210, 76.6%), lymph nodes (n = 46, 16.8%), and submucosal tumors (n = 18, 6.6%). Final diagnosis was malignancy (n = 192, 70.1%), reactive lymphadenopathy (n = 30, 11.0%), and spindle cell tumors (n = 24, 8.8%). FNA had a diagnostic yield of 91.1% compared with 88.5% for FNB (P = .48). There was no difference between FNA and FNB when stratified by the presence of on-site cytopathology or by type of lesion sampled. A median of 1 needle pass was needed to obtain a diagnostic sample for both needles. CONCLUSIONS: FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. On the basis of these results, there is no significant difference in the performance of FNA compared with FNB in the cytologic diagnosis of solid lesions adjacent to the gastrointestinal tract. ClinicalTrials.gov identifier: NCT01698190.

The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society.

Small bowel neuroendocrine tumors (SBNETs) have been increasing in frequency over the past decades, and are now the most common type of small bowel tumor. Consequently, general surgeons and surgical oncologists are seeing more patients with SBNETs in their practices than ever before. The management of these patients is often complex, owing to their secretion of hormones, frequent presentation with advanced disease, and difficulties with making the diagnosis of SBNETs. Despite these issues, even patients with advanced disease can have long-term survival. There are a number of scenarios which commonly arise in SBNET patients where it is difficult to determine the optimal management from the published data. To address these challenges for clinicians, a consensus conference was held assembling experts in the field to review and discuss the available literature and patterns of practice pertaining to specific management issues. This paper summarizes the important elements from these studies and the recommendations of the group for these questions regarding the management of SBNET patients.