Study of the gastrointestinal bioavailability of a pancreatic extract product (Zenpep) in chronic pancreatitis patients with exocrine pancreatic insufficiency.

INTRODUCTION: The Food and Drug Administration in 2006 required that all pancreatic enzyme products demonstrate bioavailability of lipase, amylase, and protease in the proximal small intestine. METHODS: In this phase I open-label, randomized, crossover trial, 17 adult chronic pancreatitis (CP) patients with severe exocrine pancreatic insufficiency (EPI) underwent two separate gastroduodenal perfusion procedures (Dreiling tube suctioning and [14C]-PEG instillation by an attached Dobhoff tube in the duodenal bulb). Patients received Ensure Plus® alone and Ensure Plus with Zenpep (75,000 USP lipase units) in random order. The bioavailability of Zenpep was estimated by comparing the recovery of lipase, amylase, chymotrypsin activity in two treatment conditions. 14C-PEG was used to correct duodenal aspirates volume. The primary efficacy endpoint was lipase delivery in the duodenum after Zenpep administration under fed conditions. Secondary efficacy endpoints included chymotrypsin and amylase delivery, serum CCK levels, and measuring duodenal and gastric pH. RESULTS: Zenpep administration with a test meal was associated with significant increase in duodenal aspiration of lipase (p = 0.046), chymotrypsin (p = 0.008), and amylase (p = 0.001), compared to the test meal alone, indicating release of enzymes to the duodenum. Lipase delivery was higher in the pH subpopulation (the efficacy population with acid hypersecretors excluded) (p = 0.01). Recovery of [14C]-PEG was 61%. Zenpep was generally well tolerated. All adverse events were mild and transient. CONCLUSIONS: In CP patients with severe EPI, lipase, chymotrypsin and amylase were released rapidly into the duodenum after ingestion of Zenpep plus meal compared to meals alone. Results also reflected the known pH threshold for enzyme release from enteric coated products.

Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions.

Hematogenous dissemination is thought to be a late event in cancer progression. We recently showed in a genetic model of pancreatic ductal adenocarcinoma that pancreas cells can be detected in the bloodstream before tumor formation. To confirm these findings in humans, we used microfluidic geometrically enhanced differential immunocapture to detect circulating pancreas epithelial cells in patient blood samples. We captured more than 3 circulating pancreas epithelial cells/mL in 7 of 21 (33%) patients with cystic lesions and no clinical diagnosis of cancer (Sendai criteria negative), 8 of 11 (73%) with pancreatic ductal adenocarcinoma, and in 0 of 19 patients without cysts or cancer (controls). These findings indicate that cancer cells are present in the circulation of patients before tumors are detected, which might be used in risk assessment.

A pilot retrospective study of the relationship between estrogen use and pancreatitis/pancreatic function in women with chronic abdominal pain.

CONTEXT: Estrogens are thought to cause pancreatitis by raising triglyceride levels but whether there are other effects on the pancreas is debatable. OBJECTIVE: To better elucidate the relationship between estrogens and pancreatitis and pancreatic function in a pilot study. DESIGN/SETTING/PATIENTS: Our retrospectively collected database of 224 patients who had undergone secretin stimulation testing was queried for females with available medication histories, who were then divided into two groups: those taking estrogens (E) and those not on estrogens (N). Mann Whitney U and Fisher's exact tests were used. RESULTS: Seventy of the patients in the database were females with available medication histories. Thirty-five (50.0%) were taking estrogens. Twenty-nine (82.9%) of the E patients experienced any type of pancreatitis (i.e., acute pancreatitis, acute relapsing pancreatitis, chronic pancreatitis) while only 19 (54.3%) of the N patients did (P=0.019). During secretin stimulation testing, the peak bicarbonate levels for E and N patients were 80±18 and 90±23 mEq/L, respectively (P=0.058). When patients with any type of pancreatitis were excluded, E patients still displayed decreased peak bicarbonate levels in response to secretin (90±18 vs. 104±19 mEq/L; P=0.021). Weight, age, triglyceride levels, frequency of patients with cholecystectomy and biliary stones did not significantly differ between the two groups (E and N respectively). CONCLUSIONS: These pilot data suggest exogenous estrogens may be related to the development of acute pancreatitis and acute relapsing pancreatitis, and probably to a lesser degree chronic pancreatitis, perhaps through a triglyceride independent mechanism. During secretin stimulation testing, peak bicarbonate production may be diminished in women on estrogens (even in those who have never had pancreatitis). Further study is necessary to better define the relationship between estrogen use, pancreatitis, and pancreatic function.

Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Minimal Change Patients Versus Obvious Chronic Pancreatitis: A Comparison of Classical Secretin Stimulation Testing Results.

OBJECTIVES: The objective was to assess if the peak bicarbonate level during secretin stimulation testing (SST) differs between patients with minimal change (or small duct) chronic pancreatitis (CP) versus those with obvious CP (or large duct) versus those without CP. METHODS: Two hundred nineteen patient records at the University of Florida who had been referred for SST were analyzed for peak bicarbonate, total volume of juice collected, age, sex, and clinical presentation. RESULTS: Fifty-one patients with minimal change CP were identified. Thirty-three patients were felt to have advanced CP, and 135 patients did not have CP by clinical criteria. The peak bicarbonate and total volume of pancreatic juice collected was significantly different (P < 0.001) between all 3 groups by multiple comparison testing. The peak bicarbonate of advanced CP and minimal change groups was less than controls (P < 0.001). There was a significant difference (P < 0.05) on direct testing between peak bicarbonate in advanced CP and minimal change CP. CONCLUSIONS: The peak bicarbonate and volume measured during SST differs among patients with minimal change CP, advanced CP and in disease controls. These results could be useful in diagnosing minimal change/early CP.

A pilot study of Octreotide LAR vs. octreotide tid for pain and quality of life in chronic pancreatitis.

CONTEXT: Chronic abdominal pain is the most difficult management issue in patients with chronic pancreatitis. Recently, a long-acting depo-formulated version of octreotide has been developed that can be given as a once monthly intramuscular injection, Octreotide LAR(R) (O-LAR) rather than as a thrice daily subcutaneous injection (octreotide short-acting, O-SA). OBJECTIVE: To see if O-LAR is similar in efficacy to O-SA in the treatment of painful chronic pancreatitis in a small open-label, unblinded pilot study. PATIENTS: Seven advanced chronic pancreatitis patients with daily, severe abdominal pain who had previously responded to O-SA were recruited from the pancreas clinics of the University of Florida and monitored for one month on O-SA and for four months while on O-LAR. Each patient served as his/her own control as this was a paired data set. MAIN OUTCOME MEASURES: 1) Daily VAS scores; 2) daily morphine equivalents; 3) monthly health related quality of life chronic pancreatitis surveys; 4) daily diaries of work/pleasurable activities missed or hospitalization/Emergency Department visits. RESULTS: Average daily VAS scores for patients during O-SA therapy were 4.50+/-2.28 and during the fourth month of O-LAR therapy, 3.86+/-2.11, difference -0.64+/-0.80 (P=0.078). Average daily morphine equivalents were not dissimilar at 124.3+/-177.3 mg during O-SA therapy and 131.6+/-194.3 mg during O-LAR therapy; difference 7.3+/-17.5 mg P=0.310. Health related quality of life chronic pancreatitis scores were not significantly changed when moving from O-SA to O-LAR. Adverse events were rare. CONCLUSIONS: Octreotide LAR(R) may be a reasonable substitute for tid octreotide in treating chronic pancreatitis pain. Further, larger studies would be useful to better characterize the role of Octreotide LAR(R) in the management of chronic pancreatitis pain.

Pancreatic function testing: here to stay for the 21st century.

The diagnosis of Chronic Pancreatitis (CP) is based on the detection of abnormal structure or function of the diseased pancreas. The pancreatic function tests more accurately determine the presence of CP than tests of structure, especially for early stage disease. The function tests can be divided into two categories: non-invasive and invasive. The invasive "tube" tests can reliably detect mild, early CP, but are only available at a few referral centers and tend to be poorly tolerated by patients. The non-invasive tests are easy to obtain, but tend to perform poorly in patients with early, mild disease. Therefore, no one test is useful in all clinical situations, and a detailed understanding of the rational, pathophysiologic basis, strengths, and limitations of various tests is needed. This review highlights the role of various pancreatic function tests in the diagnosis of CP including fecal fat analysis, fecal elastase, fecal chymotrypsin, serum trypsin, the secretin stimulation test, the cholecystokinin (CCK) stimulation test, the combined secretin-CCK stimulation test, the intraductal and endoscopic secretin stimulation tests, and the functional magnetic resonance imaging of the pancreas after secretin stimulation.