Introduction

Patients with new onset diabetes (NODM) have a higher risk of pancreatic cancer (PAC) development. We aimed to (1) compare the incidence of PAC among NODM and non-DM patients and (2) develop a risk prediction model for incident PAC within 1 year after diagnosis of DM.

Aims & Methods

We included adult patients who were newly diagnosed with type 2 DM (i.e. NODM group) or had any clinical consultation without a diagnosis of DM (i.e. non-DM group) between 2008 and 2015 from a territory-wide electronic healthcare database in Asia. Patients with type 1 DM or prior history of PAC were excluded. Each patient was followed from the diagnosis date of DM (or first consultation in non-DM group) till PAC development, death or 1 year. The incidence rate of PAC was calculated under Poisson distribution and compared between NODM and non-DM groups. The NODM cohort with complete data was further randomly split in a ratio of 7:3 into a training set (to develop the prediction model) and a validation set, respectively. Logistic regression with forward stepwise selection was conducted to identify the potential predictors of PAC. Model performance against the validation set was assessed by the area under receiver operating characteristic curve (AUC).

Results

Among 4,002,826 patients identified, 261,046 (6.5%) of whom had NODM. The incidence of PAC at 1 year was 11.68 per 10,000 persons (95% CI: 10.41-13.07) for NODM group and 1.82 per 10,000 persons (95% CI: 1.68-1.96) for non-DM group, with an incidence rate ratio of 6.43 (95% CI: 5.60-7.37). To develop a prediction model for PAC at 1 year, 19,210 NODM patients (28 PAC cases) were included, of whom 13,447 (18 PAC cases) were in the training set and 5,763 (10 PAC cases) in the validation set. After forward stepwise selection, the final prediction model included age, baseline body mass index (BMI), BMI change in 1 year, baseline blood glucose, prescription of anti-diabetic medications (oral drugs or insulin) and high-density lipoprotein cholesterol (HDL-C) change in previous 1 year. NODM patients who were older (OR: 1.06, 95% CI: 1.01, 1.11), had higher baseline blood glucose (OR: 1.01, 95% CI: 1.00, 1.01), were prescribed anti-diabetic medications at baseline (OR: 3.40, 95% CI: 1.92, 9.70), had larger drop in BMI (OR: 1.24, 95% CI: 1.05, 1.45) and HDL-C (OR: 3.28, 95% CI: 1.33, 8.09) in previous year were more likely to be diagnosed with PAC (Table 1). Using the validation set, the model showed an AUC of 0.89 (95% CI:0.81-0.96) with a sensitivity of 90.0% and specificity of 72.3%. The number-needed-to-screen (NNS) to identify one PAC case among all NODM and high-risk NODM patients was 763 and 234, respectively.
Table 1: The final model for 1-year risk prediction of pancreatic cancer using logistic regression with forward stepwise.

Conclusion

Patients with NODM had 6.4-times higher risk of developing PAC within 1 year than patients without DM, and our new prediction model may help to identify high risk patients.

Introduction

Therapeutic management of acute biliary pancreatitis (ABP) includes endoscopic sphincterotomy and cholecystectomy. However, the optimal feeding strategy prior to cholecystectomy—early oral intake or exclusive enteral nutrition—remains debated, particularly given the risk of recurrent biliary events (BEs) before surgery, especially when surgery is delayed.

Aims & Methods

The primary objective was to evaluate the likehood of BEs (biliary colic/migration, stone impaction, cholangitis, recurrent acute pancreatitis, and acute cholecystitis) prior to cholecystectomy, comparing feeding methods: oral vs. exclusive enteral nutrition. The secondary objective was to evaluate cholecystectomy rates during the initial hospitalization and the reasons for non-performance. Data were collected during hospitalization, at 3 months, and at 6 months if surgery had not been performed by month 3. BEs and feeding modalities at those times were documented. Analyses included Cox models and Chi-square tests.

Results

From October 2022 to December 2023, 1,172 patients with ABP were prospectively enrolled by 60 French hospitals, with 1,167 included in the final analysis. Sixty patients (5%) were lost to follow-up, and 34 deaths (3%) were reported. Severe ABP was observed in 27.2% (n=317) of patients. After 48–72 hours, oral feeding was resumed in 62% (n=724), enteral feeding in 16% (n=192), and fasting/parenteral feeding in 21% (n=249). During follow-up, 236 BEs occurred in 172 patients, meaning 15.5% experienced at least one event, with a median onset time of 26 days (range: 9–57 days). Specifically, 6% had at least one episode of biliary colic/migration, 2.1% experienced stone impaction, 2.3% developed cholangitis, 6.1% had recurrent AP (9% of which were severe), and 1.6% developed acute cholecystitis.
Univariate analysis identified several factors associated with a higher risk of BE recurrence (p < 0.10): age ≥52 years (p=0.093), obesity (BMI ≥30, p=0.032), ASA score >2 (p=0.097), total bilirubin ≥60 µmol/L (p=0.010), CRP >150 mg/L, diagnostic delay ≥21 days (p=0.009), and prior sphincterotomy (p=0.136). No difference in BE incidence was observed between severe and non-severe ABP (p=0.497) when analyzing the first 172 BEs.
Over the full follow-up period, despite the 87 BEs analyzed and potential biases, there remained no significant association between nutrition type (oral vs. exclusive enteral nutrition ) and the likelihood of BE occurrence (p=0.447).
In patients with non-severe ABP, cholecystectomy was performed during the initial hospitalization in only 33% of cases. The main reasons for non-performance were structural (e.g., lack of availability or surgeon refusal), accounting for 45% of cases.

Conclusion

BEs are frequent and clinically relevant: 15.5% of patients experienced at least one before surgery, with 6% developing recurrent ABP (9% of which were severe). Cholecystectomy remains underutilized; only one-third of patients with non-severe ABP underwent it during their initial stay, often due to modifiable reasons. Neither ABP severity nor nutritional type-oral vs enteral nutrition (despite potential biases, missing data, and ongoing analysis)-appeared to be associated with the occurrence of BEs prior to surgery. Early cholecystectomy, when possible, remains the only reliable strategy for preventing BEs.

Disclosure

This study received a research grant from Fresenius Kabi.

Introduction

Gastric dysplasia is a pre-malignant lesion that can progress to gastric cancer (GC), however the factors that influence its progression is still poorly understood. Here, we aim to identify molecular factors that promote the development of GC from gastric dysplasia.

Aims & Methods

We performed whole exome sequencing on 110 gastric dysplasia or GC samples from 82 patients, with an average exome coverage of 154X including the germline normal comparison. The samples were obtained from 2017 to 2019 and included (a) dysplastic samples from 34 patients without GC (b) GC samples from 20 patients without dysplasia (c) concurrent dysplasia and GC samples from 28 patients.

Results

Classification based on TCGA GC subtypes showed CIN (chromosomal unstable) GC to be more prevalent in GC without concurrent dysplasia (60% vs 21.4%; Fisher test p-value 0.030) whereas MSI (microsatellite unstable) GC tend to be concurrent with dysplasia (21.4% vs 5.0%; Fisher test p-value 0.21), suggesting acquisition of copy number alterations to be associated with rapid progression into GC. Consistent with this hypothesis, we also identified a significant increase in copy number alterations in GC samples compared to dysplasia (Wilcoxon test; p=5.1x10^-3), while somatic mutation rate was more modestly increased (Wilcoxon test; p=0.12). CIN samples were enriched with GC samples, TP53 mutations, 17q12 (ERBB2) amplification and 9p21 (CDKN2A) deletion whereas non-CIN samples showed high APC mutations, 5q23 (APC) deletion and is associated with gastric dysplasia.

Conclusion

The molecular data presented in this study is the most comprehensive to date for gastric dysplasia and early GC. Our results suggest copy number alterations may be the key driver of GC progression in dysplastic samples and molecular profiling may be used to identify patients at higher risk of developing GC.

Introduction

Up to 50% of patients (pts) with inflammatory bowel disease have one or more extraintestinal manifestations (EIMs), which are independent risk factors for poor quality of life and greater disability.¹ Here, we evaluated EIM resolution in patients (pts) with moderate to severe Crohn’s disease (CD) who received risankizumab (RZB), an anti-IL-23p19 monoclonal antibody, versus (vs) placebo (PBO) during the ADVANCE and MOTIVATE induction and FORTIFY maintenance studies.^2,3

Aims & Methods

In this post-hoc analysis of pooled data from ADVANCE and MOTIVATE, data collected from an EIM form, used by investigators to record the presence of 16 pre-specified EIMs (yes/no), were examined. EIM presence at induction baseline (BL), resolution (see Table footnote for definition) at wk 12 with intravenous (IV) RZB 600 mg vs PBO in ADVANCE+MOTIVATE, and maintained resolution at FORTIFY wk 52 among pts treated with subcutaneous (SC) RZB 180 mg or 360 mg vs PBO (withdrew RZB) were assessed.³ Statistical analysis methods are provided in Table footnotes. Nominal P-values for pairwise treatment comparisons are shown.

Results

Previously, EIM resolution at wk 12 in pts with EIMs at BL was evaluated as a ranked secondary endpoint in ADVANCE and MOTIVATE.² A greater proportion of pts achieved EIM resolution at wk 12 with IV RZB 600 mg vs PBO in ADVANCE (38.1% vs 20.5%, nominal P-value = 0.02), but not MOTIVATE (29.5% vs 23.7%, nominal P-value = 0.38). In this pooled analysis, at BL, 323 EIMs were reported for 240 pts in the IV RZB 600 mg arm, and 221 EIMs were reported for 161 pts in the PBO arm; approximately 45% of pts in each arm had ≥1 EIM at BL. The most frequently reported EIMs at BL were peripheral arthropathy (IV RZB 600 mg, 64% [103/161]; PBO, 70.4% [169/240]), anaemia (IV RZB 600 mg, 36% [58/161]; PBO, 28.8% [69/240]), and axial arthropathy (IV RZB 600 mg, 16.1% [26/161]; PBO, 19.2% [46/240]). Together, these EIMs accounted for most reported EIMs across the IV RZB 600 mg (87.9% [284/323]) and PBO (84.6% [187/221]) arms; the incidence of other EIMs were too low for clinically meaningful interpretation (see Table footnotes). A greater proportion of pts achieved resolution of any EIM at wk 12 vs PBO (P = 0.031) with IV RZB 600 mg (Table). A significantly greater proportion of pts with anaemia or axial arthropathy, but not peripheral arthropathy, at BL achieved resolution of the respective EIM at wk 12 with IV RZB 600 mg vs PBO (anaemia: RZB 600 mg, 26/69 [37.4%]; PBO, 13/58 [22.4%]; adjusted (adj) difference 14.4%, P = 0.049; axial arthropathy: RZB 600 mg, 23/46 [50%]; PBO, 8/26 [30.8%]; adj difference 22.6%, P = 0.042; peripheral arthropathy: RZB 600 mg, 67/169 [39.8%]; PBO, 32/103 [31.2%]; adj difference 6.8%, P = 0.236). With SC RZB 360 mg compared to PBO, a greater proportion of pts with EIMs at BL achieved resolution of EIMs at wk 52 (P = 0.005), and a greater proportion of pts who achieved resolution of any EIM at wk 12 maintained resolution at wk 52 (P=0.014) (Table).

Conclusion

References

1. Marinelli C, et al. Gastroenterology Research and Practice. 2019 Aug 21;2019:1–10.
2. D’Haens G, et al. The Lancet. 2022 May;399(10340):2015–30.
3. Ferrante M, et al. The Lancet. 2022 May;399(10340):2031–46.

Disclosure

Subrata Ghosh: SG has received consulting fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Gilead, Galapagos, Janssen, Pfizer, and Receptos; speaker fees from AbbVie, Falk Pharma, Pfizer, Ferring, Janssen, Shield, and Takeda
Marc Ferrante: Research grants from: AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda and Viatris; Consultancy fees from: AbbVie, Agomab Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Medtronic, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda and ThermoFisher; Speakers’ fees from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare and Viatris
Britta Siegmund: Consultant for AbbVie, Arena, BI, BMS, Celgene, Falk, Galapagos, Janssen, Lilly, Pfizer, Prometheus, and Takeda; and received speaker’s fees from AbbVie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, Pfizer, and Takeda
Takehiro Arai: Nothing to disclose
Walter Reinisch WR has served as a speaker for AbbVie, Celltrion, Falk Pharma GmbH, Ferring, Janssen, Galapagos Medice, MSD, Roche, Pfizer, Pharmacosmos, Shire, Takeda, Therakos, as a consultant for AbbVie, Amgen, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Bioclinica, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celgene, Celltrion, Eli Lilly, Falk Pharma GmbH, Ferring, Galapagos, Gatehouse Bio Inc., Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Landos Biopharma, Medahead, MedImmune, Microbiotica, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, OMass, Otsuka, Parexel, Periconsulting, Pharmacosmos, Pfizer, Protagonist, Provention, Quell Therapeutics, Sandoz, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Teva Pharma, Therakos, Theravance, Zealand, as an advisory board member for AbbVie, Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Galapagos, Janssen, Mitsubishi Tanabe Pharma Corporation, MSD, Pharmacosmos, Pfizer, Sandoz, Takeda, and has received research funding from AbbVie, Janssen, MSD, Sandoz, Sanofi, Takeda.
David Hudesman Consultant: AbbVie, BMS, Fresenius Kabi, Janssen, Pfizer, Prometheus, Takeda, UCB
Research Support: Janssen and Pfizer
Edouard Louis: Research grant: Janssen, Pfizer, Ferring, Falk, AbbVie and Takeda; educational grant: AbbVie, Janssen, Fresenius-Kabi and Takeda; speaker fees: AbbVie, Falk, Ferring, Janssen, Pfizer, Galapagos, BMS and Takeda; advisory board: Abbvie, Celgene, Ferring, Janssen, BMS, Pfizer, and Takeda, Galapagos, Gilead, Arena, Eli Lilly; consultant: Abbvie
Naomi Martin, Joanne Rizzo,Kristina Kligys, Yafei Zhang, Javier Zambrano, and Jasmina Kalabic are AbbVie employees and may own AbbVie stock and/or options.