Glycemic Changes and Weight Loss Precede Pancreatic Ductal Adenocarcinoma by up to 3 Years in a Diverse Population.

BACKGROUND & AIMS: Elevations in fasting blood glucose are observed prior to the development of pancreatic ductal adenocarcinoma (PDAC). Our aim was to describe glycemic and weight changes that occur prior to PDAC diagnosis in a diverse population. METHODS: We conducted a case-control study comparing patients with PDAC with matched controls between January 2011 and November 2019 at a tertiary care institution. Normally distributed variables were compared using t tests, and the Wilcoxon rank sum test was used for non-normally distributed variables; logistic regression was used to estimate odds of PDAC based on changes over time in hemoglobin A1c (HbA1c) and body mass index (BMI), controlling for appropriate confounders. RESULTS: A total of 4626 patients met inclusion criteria: 1542 cases and 3084 controls; the median age was 69.3 years, and 2487 (53.8%) were male; 751 cases (48.7%) were non-Hispanic white. In the 3 years prior to diagnosis, HbA1c was higher in patients with PDAC compared with controls (P ≤ .02 for all); a similar trend was seen for glucose values. BMI was greater for patients with PDAC for all study periods, except 0 to 6 months prior to cancer diagnosis when BMI was lower (P < .01 for all). The change in BMI (ΔBMI) of cases at 1 year and 6 months before diagnosis was -0.59 and -1.21 when compared with -0.08 and 0.03 for controls (P < .01 for both). Multivariable logistic regression demonstrated that HbA1c slope (adjusted odds ratio, 1.33; 95% confidence interval, 1.01-1.76) and BMI slope (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87) were predictors of PDAC. CONCLUSION: Glycemic elevations and weight loss predate PDAC diagnosis. These metabolic changes may suggest an underlying PDAC.

Design of and outcomes in a student-run free mental health clinic serving the uninsured in East Harlem.

BACKGROUND: Safety-net clinics are an important source of low-cost or free mental healthcare to those with limited financial resources. Such clinics are often staffed by trainees in early stages of their career. Only limited data exist on best practices in treatment-implementation and on clinical outcomes attained in such clinics. The primary purpose of this article is to describe the design of an outpatient psychiatry student-run free clinic (SRFC) serving uninsured individuals in New York City's East Harlem neighborhood and to analyze the quality of services provided and the clinical outcomes attained. METHODS: The authors conducted a retrospective chart review of n = 69 patients treated in the EHHOP Mental Health Clinic (E-MHC) to describe the demographic and clinical characteristics of the study population. Utilizing Health Effectiveness Data and Information Set metrics, they estimated the likelihoods of patients meeting metric quality criteria compared to those in other New York State (NYS) insurance groups. The authors derived linear mixed effect and logistic regression models to ascertain factors associated with clinical outcomes. Finally, the authors collected patient feedback on the clinical services received using a customized survey. RESULTS: Almost all patients were of Hispanic ethnicity, and about half of patients had more than one psychiatric disorder. The clinical service performance of the E-MHC was non-inferior on most measures examined. Factors associated with symptom improvement were the number of treatment sessions and certain demographic and clinical variables. Patients provided highly positive feedback on the mental healthcare services they received. CONCLUSIONS: SRFCs can provide quality care to vulnerable patients that leads to clinically meaningful reductions in psychiatric symptoms and is well-received by patients.

Elevated hemoglobin A1c is associated with the presence of pancreatic cysts in a high-risk pancreatic surveillance program.

BACKGROUND: Emerging evidence demonstrates that surveillance of individuals at high-risk (HRIs) of developing pancreatic adenocarcinoma allows for identification and treatment of resectable tumors with improved survival. Population-based data suggest that hyperglycemia may be present up to three years before the development of pancreatic cancer. We investigated whether elevated hemoglobin A1c (HbA1c) is associated with the development of pancreatic cysts in a pancreatic surveillance program. METHODS: We performed a retrospective study of HRIs who underwent pancreatic surveillance at a single institution between May 2013 and March 2019, according to published criteria. We collected demographic information, clinical data including HbA1c, and imaging results. We compared data using univariable and multivariable analyses. Our primary outcome was the presence of pancreatic cysts on initial surveillance in patients with elevated HbA1c. RESULTS: Ninety-eight patients underwent surveillance imaging via EUS or MRCP and seventy-four patients met inclusion criteria. Thirty patients were found to have cysts on initial imaging. Older age (p < 0.01) and HbA1c in the prediabetic range or higher (p = 0.01) were associated with the presence of cysts or solid lesions on univariable analysis. After controlling for confounders, age (aOR 9.08, 95% CI 2.29-36.10), and HbA1c > 5.7% (aOR 5.82, 95% CI 1.50-22.54) remained associated with presence of cysts and solid lesions in HRIs. In patients with cysts or solid lesions there was a strong association between increased age and elevated HbA1c (p < 0.01). CONCLUSION: HRIs with elevated HbA1c were more likely to have pancreatic cysts compared to individuals with lower HbA1c on initial imaging in a pancreatic surveillance program. These findings may help tailor the surveillance protocols for those at increased risk of developing pancreatic adenocarcinoma.

Incidence Trends of Gastroenteropancreatic Neuroendocrine Tumors in the United States.

BACKGROUND & AIMS: Although multiple studies have reported an increasing incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) over the past decades, there are limited national data on recent trends. Using a population-based registry, we evaluated GEP-NET incidence trends in the United States population from 1975 through 2012, based on age, calendar year at diagnosis, and year of birth. METHODS: GEP-NET cases from 1975 through 2012 were identified from the most recent version of the Surveillance, Epidemiology, and End Results registry using histologic and site codes. We calculated overall annual incidence, age-adjusted incidence (number of cases per 100,000), annual percent change (APC), and average APC by 5-year age intervals. We also evaluated the incidence rates by age, period, and birth year cohorts. RESULTS: We identified 22,744 patients with GEP-NETs. In adults 25-39 years old, GEP-NET incidence rates decreased from the mid-1970s to the early 1980s, then increased until 2012. In adults ages 40 years and older or young adults ages 15-24 years, incidence rates generally increased continuously from 1975 through 2012. Adults ages 40-69 years had the most rapid increases in average APC (approximately 4%-6% per year). Overall incidence rates were highest in adults 70-84 years old. Since the inception of the Surveillance, Epidemiology, and End Results registry, GEP-NET incidence has increased in consecutive birth cohorts. CONCLUSION: The incidence of GEP-NET continues to increase-particularly in older adults. More recent generations have had higher GEP-NET incidence rates than more distant generations.

Association of Antibiotic Receipt With Survival Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Receiving Chemotherapy.

Importance: The prognosis for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is dismal, due in part to chemoresistance. Bacteria-mediated mechanisms of chemoresistance suggest a potential role for antibiotics in modulating response to chemotherapy. Objective: To evaluate whether use of peritreatment antibiotics is associated with survival among patients with metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Design, Setting, and Participants: Using the population-based Surveillance, Epidemiology, and End Results-Medicare linked database, this retrospective cohort study analyzed data for patients diagnosed with PDAC between January 1, 2007, and December 31, 2017. Data analysis was conducted between September 1, 2021, and January 15, 2023. The population-based sample included 3850 patients with primary metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Patients who received antibiotics were matched based on propensity scores to patients who did not receive antibiotics. Exposures: Receipt of 5 or more days of oral antibiotics or 1 injectable antibiotic in the month before or after beginning first-line chemotherapy. Main Outcomes and Measures: Overall survival and cancer-specific survival. The end of follow-up was December 31, 2019, for overall survival and December 31, 2018, for cancer-specific survival. Results: Of the 3850 patients treated with first-line gemcitabine (3150 [81.8%]) or fluorouracil (700 [18.2%]), 2178 (56.6%) received antibiotics. The mean (SD) age at diagnosis was 74.2 (5.8) years and patients were predominantly women (2102 [54.6%]), White (3396 [88.2%]), and from metropolitan areas (3393 [88.1%]) in the northeastern or western US (2952 [76.7%]). In total, 1672 propensity-matched pairs were analyzed. Antibiotic receipt was associated with an 11% improvement in overall survival (hazard ratio [HR], 0.89; 95% CI, 0.83-0.96; P = .003) and a 16% improvement in cancer-specific survival (HR, 0.84; 95% CI, 0.77-0.92; P < .001) among patients treated with gemcitabine. In contrast, there was no association between antibiotic receipt and overall survival (HR, 1.08; 95% CI, 0.90-1.29; P = .41) or cancer-specific survival (HR, 1.12; 95% CI, 0.90-1.36; P = .29) among patients treated with fluorouracil. In a subgroup of gemcitabine-treated patients who received antibiotics, nonpenicillin ß-lactams were associated with an 11% survival benefit (HR, 0.89; 95% CI, 0.81-0.97; P = .01). Conclusions and Relevance: In this cohort study, receipt of perichemotherapy antibiotics was associated with improved survival among patients treated with gemcitabine, but not fluorouracil, suggesting that antibiotics may modulate bacteria-mediated gemcitabine resistance and have the potential to improve PDAC outcomes.

Screening and Surveillance for Pancreatic Adenocarcinoma in High-Risk Individuals.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high mortality, largely due to late stage at diagnosis. Approximately 10% to 15% are hereditary, and detection of early stage PDAC or precursor lesions through pancreatic surveillance programs may improve outcomes. Current surveillance is annual, typically with endoscopic ultrasound and/or magnetic resonance imaging.

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.

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.

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.

Psychological distress in the face of a pandemic: An observational study characterizing the impact of COVID-19 on immigrant outpatient mental health.

Undocumented immigrants have disproportionately suffered during the novel coronavirus disease 2019 (COVID-19) pandemic due to factors including limited medical access and financial insecurity, which can exacerbate pandemic-associated distress. Psychological outcomes for immigrant outpatients were assessed after transition to telepsychiatry in March 2020. Mental health was assessed with Patient Health Questionnaire (PHQ-2) and Generalized Anxiety Disorder (GAD-2) inventories, a novel coronavirus-specific survey, and the Kessler Psychological Distress Scale (K10+). Feedback on telepsychiatry sessions and access to non-clinical resources were also gathered, after which multivariable linear regression modeling identified psychosocial factors underlying changes in distress levels. 48.57% and 45.71% of participants reported worsened anxiety and depression levels due to the pandemic, respectively. From March to April, PHQ-2 and GAD-2 scores significantly increased by 0.81 and 0.63 points, respectively. The average total psychological distress score was 23.8, with 60% of scores reflecting serious mental illness. Factors that most influenced K10+ scores included a pre-existing depressive disorder, food insecurity, and comfort during telepsychiatry visits. 93.75% of participants believed access to remote psychiatry helped their mental health during COVID-19. The negative impact of COVID-19 on mental health in vulnerable populations stems from medical and psychosocial factors such as pre-existing psychiatric conditions and unmet essential needs.

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.

Lymph Node Metastasis in the Prognosis of Gastroenteropancreatic Neuroendocrine Tumors.

OBJECTIVES: This study aimed to determine the prognostic use of the extent of lymph node (LN) involvement in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) by analyzing population-based data. METHODS: Patients in the Surveillance, Epidemiology, and End Results registry were identified with histologically confirmed, surgically resected GEP-NETs. We divided patients into 3 lymph node ratio (LNR) groups based on the ratio of positive LNs to total LNs examined: 0.2 or less, greater than 0.2 to 0.5, and greater than 0.5. Disease-specific survival was compared according to LNR group. RESULTS: We identified 3133 patients with surgically resected GEP-NETs. Primary sites included the stomach (11% of the total), pancreas (30%), colon (32%), appendix (20%), and rectum (7%). Survival was worse in patients with LNRs of 0.2 or less (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.2-2.0), greater than 0.2 to 0.5 (HR, 2.0; 95% CI, 1.6-2.5), and greater than 0.5 (HR, 3.1; 95% CI, 2.5-3.9) compared with N0 patients. Ten-year disease-specific survival decreased as LNR increased from N0 (81%) to 0.2 or less (69%), greater than 0.2 to 0.5 (55%), and greater than 0.5 (50%). Results were consistent for patients with both low- and high-grade tumors from most primary sites. CONCLUSIONS: Degree of LN involvement is a prognostic factor at the most common GEP-NET sites. Higher LNR is associated with decreased survival.