Introduction

5-aminosalicylates (5-ASAs) are commonly used in patients with Crohn’s disease (CD), especially in mild-to-moderate disease. Over half of patients receive 5-ASA during their disease course, with up to 30% continuing long-term therapy for either active (induction of remission) or quiescent (maintenance of remission) disease. However, the evidence regarding their efficacy is mixed, with conflicting findings in systematic reviews (SRs). In preparation for the results of the STATIC trial (NCT 03261206)¹, we conducted an umbrella review to consolidate existing knowledge by identifying, evaluating, and synthesizing findings from published SRs on the use of 5-ASA in patients with active or quiescent CD.

Aims & Methods

Following Cochrane guidelines for "Overviews of Reviews" and adhering to the Preferred Reporting Items for Overviews of Reviews (PRIOR), we systematically searched major databases for relevant SRs published in English until February 28, 2024, summarizing data on 5-ASA use in induction, maintenance, or withdrawal trials of CD. We excluded SRs focusing solely on post-surgical patients or studying the chemoprevention effects of 5-ASA. Two independent reviewers screened articles, extracted data, and assessed quality using AMSTAR 2.

Results

Of 795 screened references, 8 SRs met our inclusion criteria, with the number of included RCTs ranging from 2 to 22 (Table). Most SRs included RCTs of patients with mild-to-moderate ileo-colonic CD. Three SRs focused on induction of remission, two on maintenance of medically induced remission, and three included both, while none investigated withdrawal of therapy. Two SRs were network meta-analyses (NMA) comparing 5-ASAs with other active treatments or placebo; four were Cochrane systematic reviews comparing 5-ASAs with placebo, corticosteroids, or thiopurines (AZA or 6-MP). One SR, published in 2017,used the outdated Jadad scale to assess the risk of bias of RCTs; only Cochrane reviews assessed the level of certainty of evidence. The latest NMA in 2017, including 22 RCTs for induction of remission, suggested that high-dose mesalamine was more effective than placebo, ranking higher than low-dose budesonide and sulfasalazine, though lower than systemic corticosteroid and high-dose budesonide. Conversely, the latest Cochrane review in 2016, including 12 RCTs for maintenance of remission, found no evidence of benefit for oral 5-ASAs over placebo for maintaining medically induced remission. No SRs performed subgroup analysis for duration of remission upon enrollment. Only the NMA conducted a sensitivity analysis to evaluate baseline disease activity, indicating that high-dose mesalamine was superior to placebo when restricted to RCTs with an enrollment CDAI between 150 to 450.

Conclusion

The results of this umbrella review of SRs suggest that high-dose mesalamine may be considered for inducing remission in mild-to-moderate CD. However, evidence does not support the role of 5-ASA for maintaining medically induced remission. Updating SRs with new evidence is imperative to provide guidance on patient subsets who may benefit from 5-ASA use and these results will be updated with the STATIC trial ¹.

References

1. NCT03261206. Stopping Aminosalicylate Therapy in Inactive Crohn's Disease (STATIC) https://classic.clinicaltrials.gov/ct2/show/NCT03261206

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone in the diagnosis and treatment of pancreatobiliary diseases. However, it carries the risk of complications including potentially fatal post-ERCP pancreatitis (PEP). Despite ongoing efforts, effective strategies for managing PEP remain unestablished. Current guidelines define PEP based on symptoms and findings occurring within 24 hours after ERCP; however, early diagnosis and intervention may prevent its incidence and severity. Recently, urinary trypsinogen-2 (UT2) has emerged as a potential biomarker for early acute pancreatitis, but its role and the optimal timing for PEP remain unclear. Therefore, we aimed to evaluate the diagnostic performance of UT2 at multiple time points following ERCP.

Aims & Methods

This is a single-center prospective observational study conducted at The University of Tokyo Hospital. Patients who underwent their initial ERCP at our institution between February 2022 and June 2024 were enrolled. Patients with choledochojejunostomy, biliary pancreatitis, or those undergoing hemodialysis were excluded. UT2 levels were measured using a rapid dipstick test before ERCP, immediately after, and at 1 and 3 hours post-procedure. Serum amylase (AMY) levels were measured 3 hours after ERCP. We evaluated the diagnostic performance (sensitivity, specificity, and accuracy) of UT2 at multiple time points, for the diagnosis of PEP. PEP was defined as an elevation in pancreatic enzyme >3x upper limit of normal with abdominal pain at 24 hours post-pocedure.

Results

A total of 521 patients underwent initial ERCP during the study period, and 337 were included in the final analysis. The median age was 74 years, and 64% were male. A naïve papilla was present in 89% of patients. The indications for ERCP included bile duct stones (39%), malignant biliary obstruction due to pancreatic cancer (13%) or non-pancreatic cancer (18%), benign biliary stricture (5%), diagnostic pancreatogram (24%), and others (1.2%). EST, EPBD, and EPLBD were performed in 37%, 6.5%, and 4.5%, respectively. Prophylactic pancreatic stent placement and rectal NSAIDs administration were performed in 29% and 20%, respectively. PEP occurred in 10% (mild 8.6%, moderate 1.2%, and severe 0.3%) of patients. UT2 demonstrated a trend toward higher sensitivity compared to AMY (AMY: 52.9% vs. UT2 at 0 h: 52.9%, 1 h: 64.7%, 3 h: 64.7%), while AMY exhibited significantly higher specificity (AMY: 92.7% vs. UT2 at 0 h: 65.3%, 1 h: 64.7%, 3 h: 65.0%) and accuracy (AMY: 88.7% vs. UT2 at 0 h: 64.1%, 1 h: 64.7%, 3 h: 65.0%). Notably, 28.5% of patients were positive for UT2 prior to undergoing ERCP. These patients were significantly older (79 vs. 71 years, P < 0.01), more likely to have pancreatic cancer (19.8% vs. 9.5%, P = 0.02), and less likely to have chronic pancreatitis (3.1% vs. 12.9%, P = 0.01). After excluding 96 cases (28.5%) who were UT2-positive before ERCP, we further evaluated the diagnostic performance of UT2 and AMY. UT2 at 0 h had lower sensitivity compared to AMY (AMY: 54.2% vs. UT2 at 0 h: 37.5%, 1 h: 54.2%, 3 h: 54.2%). In contrast, specificity was similarly high across all markers (AMY: 91.7% vs. UT2 at 0 h: 88.9%, 1 h: 87.1%, 3 h: 87.1%). Diagnostic accuracy was comparable between AMY and UT2 (AMY: 88.0% vs. UT2 at 0 h: 83.8%, 1 h: 83.8%, 3 h: 83.8%).

Conclusion

UT2 showed slightly lower predictive performance for PEP compared to AMY. However, excluding UT2-positive pre-ERCP improved the diagnostic accuracy. The diagnostic performance plateaued at 1 hour after ERCP, suggesting its potential utility in predicting PEP earlier.

Disclosure

The author is affiliated with Nipro Corporation through a labor-related arrangement, but has received no financial support or remuneration related to this study.

Introduction

Pancreatic cancer (PC) screening can improve survival in high-risk patients by detecting preneoplastic lesions or early-stage tumors.
Surveillances is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). However, little has been described regarding the possibility of finding other morphological changes that may be also important.

Aims & Methods

The aim of the study is to evaluate all the findings described in screening test and to analyze the correlation between these two screening techniques.
Descriptive observational single-center study that includes high-risk PC patients either due to family history (familial pancreatic cancer) or because they belong to hereditary syndromes, who have been undergone pancreatic cancer screening at our center from 2015 to 2023. Demographic variables and findings described in the EUS or MRI were collected.

Results

Thirty-five patients were included, with a mean age of 57.3 ± 8.2 years and a predominance of females (65.7%). Four patients (11.4%) were smokers, two were diabetic (5.7%), and one had a history of chronic pancreatitis (2.9%). The median follow-up time was 23 months (interquartile range 8-59 months).
The most frequent hereditary syndrome was hereditary breast and ovarian cancer syndrome (n=19, 54.3%), followed by familial atypical multiple mole melanoma syndrome (n=4; 11.4%). The BRCA2 mutation was the most common identifiable genetic factor (34.8%).
Regarding screening test findings, solid tumors were detected in three patients (8.6%) (Two stage I and IV adenocarcinomas and one stage I neuroendocrine tumor). In two individuals (5.7%) branch-duct intraductal papillary mucinous neoplasm were observed. Other pancreatic abnormalities were detected in 18 patients (51.4%) that include chronic pancreatitis-like parenchymal changes (34.3%), peripancreatic lymph nodes and fatty pancreas (5.7%). Finally, in 12 patients (34.3%) the screening tests were normal.
In relation to the concordance between MRI and EUS, in ten patients (28.6%) there was no agreement between these two techniques. EUS detected more parenchymal changes (n=5), pancreatic steatosis (n=2) and one neuroendocrine tumor that were not described on MRI. In contrast, MRI detected a cystic lesion and a pseudonodular enhancement that were not found on EUS.

Conclusion

Pancreatic cancer screening in high-risk individuals, detects neoplastic and preneoplastic lesions at a high rate.
Other findings, such as chronic pancreatitis-like parenchymal changes, peripancreatic lymph nodes or fatty pancreas, were also common in these patients
MRI and EUS have a good correlation, but EUS detects more parenchymal changes.

References

1. Goggins M, Overbeek KA, Brand R et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut 2020; 69 (1): 7-17
2. Bogdanski AM, van Hooft JE, Boekestijn B, Bonsing BA, Wasser MNJM, Klatte DCF, van Leerdam ME. Aspects and outcomes of surveillance for individuals at high‑risk of pancreatic cancer. Fam Cancer 2024; 23(3):323-339.
3. Blackford AL, Canto MI, Dbouk M, Hruban RH, Katona BW, Chak A et al. Pancreatic Cancer Surveillance and Survival of High-Risk Individuals. JAMA Oncol. 2024;10(8):1087-1096.
4. Maurer E, Lehman B, Matthäi E, Denzer U, Figiel J, Jseinghaus M et al. Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant‐negative familial pancreatic cancer families. United European Gastroenterol J 2024; 12 (9): 1211-1221

Introduction

Hormonal exposure influences cancer initiation and progression in several organs, including the pancreas. The association between gynecological factors and the onset of pancreatic adenocarcinoma (PDAC) is conflicting, with some studies showing a reduced risk of PDAC with the use of hormonal replacement therapy (HRT) or with having had a late-onset menopause. Nonetheless, the association between gynecological factors and disease prognosis has not yet been investigated. Our objective was to evaluate whether gynecological/reproductive factors affect PDAC prognosis.

Aims & Methods

This was a single-center retrospective analysis of a prospectively maintained database of PDAC patients. Risk factors were assessed via questionnaires regarding gynecologic/reproductive factors (age at menarche, menopause, years of fertility, breastfeeding, pregnancy, miscarriages, use of oral contraceptives (OC) or HRT), medical history, and prognosis were evaluated with follow-up visits and/or telephonic calls. Continuous variables were investigated using the Mann–Whitney test, and factors associated with survival probability were evaluated using Cox's proportional hazards model, adjusting for potential confounders.

Results

228 PDAC women were analyzed, with mean age at diagnosis being 68. The most frequent stages were borderline resectable (35.9%) and locally advanced (25.4%), with a median overall survival (OS) of 14 months. The age of PDAC onset for patients with previous use of OC was significantly lower than that of non-users (63 years vs. 72; p<0.0001), and OC use was associated with a trend toward increased survival (HR 0.6; 95%CI: 0.35-1.03; p=0.06). In addition, previous use of HRT was associated with a reduced risk of recurrence or progression (HR, 0.4; 95%CI: 0.26-0.99; p=0.001). No differences in survival or progression-free probability were observed with the other factors.

Conclusion

This is the first study to evaluate whether gynecological/reproductive factors are associated with the prognosis of PDAC patients, with the use of OC and HRT being the most relevant factors. Previous OC users had a significantly lower onset age for PDAC and a borderline significant association was seen with increased survival. Additionally, HRT use is associated with a reduced risk of tumor recurrence or progression. These data need to be confirmed, and the potential mechanisms need to be elucidated.