Interventions for Pancreatitis-New Approaches, Knowledge Gaps, and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

ABSTRACT: There exists no cure for acute, recurrent acute or chronic pancreatitis and treatments to date have been focused on managing symptoms. A recent workshop held by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) focused on interventions that might disrupt or perhaps even reverse the natural course of this heterogenous disease, aiming to identify knowledge gaps and research opportunities that might inform future funding initiatives for NIDDK. The breadth and variety of identified active or planned clinical trials traverses the spectrum of the disease and was conceptually grouped for the workshop into behavioral, nutritional, pharmacologic and biologic, and mechanical interventions. Cognitive and other behavioral therapies are proven interventions for pain and addiction, but barriers exist to their use. Whilst a disease specific instrument quantifying pain is now validated, an equivalent is lacking for nutrition - and both face challenges in ease and frequency of administration. Multiple pharmacologic agents hold promise. Ongoing development of Patient Reported Outcome (PRO) measurements can satisfy Investigative New Drug (IND) regulatory assessments. Despite multiple randomized clinical trials demonstrating benefit, great uncertainty remains regarding patient selection, timing of intervention, and type of mechanical intervention (endoscopic versus surgery). Challenges and opportunities to establish beneficial interventions for patients were identified.

Pancreatic quantitative sensory testing to predict treatment response of endoscopic therapy or surgery for painful chronic pancreatitis with pancreatic duct obstruction: study protocol for an observational clinical trial.

INTRODUCTION: Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP. METHODS AND ANALYSIS: This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction. PRIMARY OUTCOME: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment. ETHICS AND DISSEMINATION: The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies. TRIAL REGISTRATION NUMBER: NCT04996628.

Pancreatic Malakoplakia: A Rare Pathology Associated With Acute Pancreatitis.

Malakoplakia is a rare granulomatous tumor-like inflammatory condition, most frequently involving the genitourinary system and occurring in immunosuppressed patients. The gastrointestinal tract is the second most common site, where it is usually seen involving the colon. We report a case of malakoplakia presenting as a pancreatic mass. Imaging showed soft tissue along the pancreatic tail/greater curvature concerning for infiltrating tumor, but endoscopic ultrasound with biopsy showed malakoplakia. Our case discusses malakoplakia at an uncommon site, which was appropriately treated with antibiotics.

Characterizing mechanism-based pain phenotypes in patients with chronic pancreatitis: a cross-sectional analysis of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies.

ABSTRACT: Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.

Pancreatic Enzyme Replacement Therapy in Patients with Non-pancreatic Digestive Conditions: A Nationwide Claims Analysis.

BACKGROUND AND AIMS: Pancreatic enzyme replacement therapy (PERT) is most commonly used to treat exocrine insufficiency related to pancreatic diseases, but can be used for non-pancreatic digestive conditions (NPDC). We aimed to determine the prevalence of PERT use and describe prescription patterns in individuals with NPDC. METHODS: A nationally representative claims database of 48.6 million enrollees was used to identify individuals who received PERT prescription(s) in the absence of any pancreas-related diagnosis. Data on demographics, enrolment, comorbidities, exocrine function testing, treatment and potential indications for PERT were retrieved, and compared with individuals who received PERT for primary diagnosis of chronic pancreatitis (CP). RESULTS: A total of 29,234 individuals (64.1% female, mean age 52.4 ± 16.5 years) received PERT for NPDC. The overall estimated US population prevalence rate for PERT use for NDPC was 60.2/100,000 persons. Rates increased significantly with age and were higher in women in all age groups except 1-20 years old. When compared with CP, individuals with NPDC receiving PERT were more likely to be older (52.4 vs. 50.1 years), female (64.1% vs. 51.0%), have lower prevalence of alcoholism (3.6% vs. 25.0%), tobacco abuse (8.4% vs. 30.1%), and received PERT for shorter mean duration (5.3 vs. 8.2 months) (all p < 0.001). Median dose of PERT in individuals with NPDC was 2880 lipase units/day. CONCLUSIONS: Although proportionally low, a sizable population receives PERT for NPDC. PERT for NPDC is usually prescribed at a low dose and for shorter duration, suggesting it is used mostly as a trial for or until resolution of symptoms.

External nasal dilator decreases N95 respirator-related respiratory effort and symptoms in gastrointestinal endoscopy unit staff.

Background and study aims N95-filtering facepiece respirators (FFR) use is associated with physiological changes and symptoms due to impaired nasal airflow and increased breathing resistance. We prospectively studied the effect of using an external nasal dilator (END) in gastroenterology laboratory (gastrointestinal lab) staff using N95FFR. Patients and methods N95FFR qualitative saccharine fit testing was performed on study participants with and without an END. Prospective data collection and comparisons included: 1) survey of perceived symptoms and difficulty of performing one day of gastrointestinal procedures with N95FFR and 1 day of gastrointestinal procedures with END plus N95FFR in random sequence; and 2) vitals and respiratory belt plethysmography in ten gastroenterologists performing simulated colonoscopy while wearing a surgical mask (SM), N95FFR plus SM, END plus N95FFR plus SM for 20 minutes each in random sequence and rapid succession. Results Twenty-nine of 31 participants passed the N95FFR and the END plus N95FFR fit test. Twenty-two participants (12 physicians; 11 males; mean age 44.1 years, range 31-61) performed 1 day of gastrointestinal procedures with an N95FFR and 1 day of gastrointestinal procedures with an END plus N95FFR. Significantly less difficulty with nasal breathing and severity of symptoms including breathing difficulty, headache, fatigue and frustration, occurred while using an END plus N95FFR. Respiratory plethysmography peak-to-trough measurement showed an increase during the N95FFR stage compared to the END plus N95FFR stage and the SM stage. Conclusions N95FFR related respiratory changes and symptom development may be mitigated by END use.

Acute physiologic effects of N95 respirator use on gastroenterologists performing simulated colonoscopy.

BACKGROUND AND AIMS: During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies. METHODS: Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence. RESULTS: Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%). CONCLUSIONS: N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms.

Groove pancreatitis has a spectrum of severity and can be managed conservatively.

BACKGROUND & AIMS: The natural history of groove pancreatitis is incompletely characterized. Published literature suggests a high rate of surgery. We describe the short- and long-term outcomes in a cohort of patients with groove pancreatitis treated at our institution. METHODS: Medical records of patients hospitalized in the University of Pittsburgh Medical Center system from 2000 to 2014 and diagnosed with groove pancreatitis based on imaging were retrospectively reviewed. Clinical presentation and outcomes during index admission and follow-up were recorded. RESULTS: Forty-eight patients with groove pancreatitis were identified (mean age 53.2 years, 79% male). Seventy-one percent were alcohol abusers and an equal number were cigarette smokers. Prior histories of acute and chronic pancreatitis were noted in 30 (62.5%) and 21 (43.8%), respectively. Forty-four (91.7%) met criteria for acute pancreatitis during their index admission. Alcohol was the most common etiology (68.8%). No patient experienced organ failure. The most frequent imaging findings were fat stranding in the groove (83.3%), duodenal wall thickening (52.1%), and soft tissue mass/thickening in the groove (50%). Over a mean follow-up of 5.0 years, seven (14.6%) required a pancreas-related surgery. Patients had a high burden of pancreatitis-related readmissions (68.8%, 69.4/100 patient-years). Incident diabetes and chronic pancreatitis were diagnosed in 5 (13.9% of patients at risk) and 8 (29.6% of patients at risk) respectively. CONCLUSIONS: Groove pancreatitis has a wide spectrum of severity; most patients have mild disease. These patients have a high burden of readmissions and progression to chronic pancreatitis. A small minority requires surgical intervention.

Prior History of Pancreatitis Accelerates the Development of Pancreatic Adenocarcinoma.

OBJECTIVES: Presentation of pancreatic adenocarcinoma (PC) as acute pancreatitis (AP), association of chronic pancreatitis (CP) with PC, and role of inflammation in PC carcinogenesis are well recognized. We hypothesized that inflammatory changes associated with remote history of AP (≥2 years before PC diagnosis) would result in earlier age of PC diagnosis. METHODS: We evaluated PC patients prospectively enrolled in the Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) study at the University of Pittsburgh for history of pancreatitis and reviewed relevant medical records and imaging studies. Univariate and multivariable linear regression analyses evaluated the relationship between PC and remote history of AP. RESULTS: Among 790 patients with histologically confirmed PC, 114 (14.4%) had a history of pancreatitis (AP within 2 years of PC diagnosis in 69 [8.7%], remote history of AP in 28 [3.5%], CP in 4 [0.5%], and unknown duration of pancreatitis in 13 [1.6%]). After controlling for age, sex, body mass index, smoking, alcohol history, and diabetic status at diagnosis, patients with a remote history of AP were diagnosed on average 4.7 years earlier with PC when compared with PC patients without history of AP (P < 0.035). CONCLUSIONS: Remote history of AP may accelerate carcinogenesis in PC.