Introduction

Early diagnosis of pancreatic cancer relies on detecting subtle, indirect signs of minute tumors. Endoscopic ultrasonography (EUS) is crucial for this purpose. However, EUS image construction is influenced not only by the density and structure of the target areas but also by the characteristics of the surrounding tissue. Directly correlating preoperative EUS images and precisely aligning the pathological images of the area of interest remains challenging, as comparisons often rely on approximate anatomical regions. To overcome this limitation and to gain a deeper understanding of EUS imaging capabilities at the microscopic level, the present study examined unfixed pancreatic resection specimens using EUS immediately after surgery.

Aims & Methods

The present study aimed to investigate the characteristics and limitations of EUS imaging by directly comparing EUS images with the corresponding pathological sections of resected pancreatic specimens. The samples derived from distal pancreatectomies for pancreatic ductal adenocarcinoma without chemotherapy (pT1b or less in the UICC classification, 8th edition) were obtained between January 2023 and November. Specimens from pancreatoduodenectomies were excluded to enable a precise, one-to-one comparison between the pathological specimens and EUS images. The resected specimens were immersed in saline and examined using a convex-type EUS scope (Olympus UCT260/ME-2, Tokyo, Japan). Areas of interest, including the main tumor site and any abnormal findings, were marked with nylon sutures. HE-stained pathological sections from these marked areas were then directly compared with the corresponding EUS images to evaluate the imaging characteristics of various pathological features.

Results

The present study included four male and three female patients with a mean age of 76.3 years. The tumor location included the pancreatic body (n = 5) and the tail (n = 2). According to the 8th edition of the UICC classification, the pathological T stage was Tis, T1a, and T1b in four, two, and one cases, respectively. The pathological findings of 24 samples were compared with the corresponding EUS images. The rate of detection of the specific pathological features using EUS was 0%, 33%, 64%, 47%, and 60% for PanIN lesions, invasive carcinoma, localized pancreatic atrophy (predominantly fatty), localized pancreatic atrophy (predominantly fibrotic), and pancreatic cysts ≤ 2 mm, respectively. Solitary cysts ≤ 2 mm were often identifiable, while multiple, clustered cysts appeared as faint, hypoechoic areas. Localized pancreatic atrophy with predominant fibrosis appeared as a faint, hypoechoic area, and atrophy with predominantly fatty replacement appeared as a high-intensity area within the parenchyma. However, complete fatty replacement obscured the boundary with surrounding fatty tissue, leading to its appearance as loss of the pancreatic parenchyma.

Conclusion

The present findings demonstrated that despite its high diagnostic accuracy for pancreatic diseases, EUS is limited in its ability to visualize tissue microarchitecture. Understanding the specific imaging features of localized pancreatic atrophy and small pancreatic cysts on EUS is crucial for improving the accuracy of early diagnoses of pancreatic cancer. The insights gained from this one-to-one comparison of the EUS findings and pathological specimens can contribute to enhancing the precision of the diagnosis and facilitate the earlier detection of pancreatic cancer.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a key procedure in managing biliary and pancreatic disorders. In cases of difficult cannulation (DC), when standard cannulation techniques (SCT) fail, precut sphincterotomy (PS) may be used as an alternative technique, often by experienced endoscopists. PS has been shown to improve cannulation success rates, but its use has been associated with an increased risk of adverse events, including post-ERCP pancreatitis (PEP), perforation, and bleeding. Despite this it is argued that it might be safer to proceed with PS early rather than to traumatise the papilla with continuous attempts with SCT. DC is defined as cannulation taking more than 5 minutes, more than 5 attempts or accidently entering the pancreatic duct with a guidewire more than once and is known to be associated with more complications than non-DC. The aim of this study was to compare outcomes of PS versus SCT in cases of DC, regarding complication rates and successful cannulation.

Aims & Methods

Data were retrieved from the Swedish National Register for Gallstone surgery and ERCP, GallRiks from September 2016 to December 2023. A total of 30,561 ERCPs, performed as index ERCPs without rendezvous technique, were identified and cross-checked. Logistic regression analyses were conducted, adjusting for endoscopist and clinic volume using generalized estimating equations.

Results

Altogether 9,909 procedures were classified as DC among which 3,005 (30%) were performed with PS, compared to 434 (2%) of 20,218 in the non-DC group. In DC the rate of pancreatitis was 9.4%, cholangitis 2.3%, bleeding 1.4%, bile leakage 1.9% and perforation 0.7%. PS was not associated with increased risk of procedure related complications in DC. The rate of successful cannulation in DC was 87.9% when SCT were used and 70.4% when PS was performed.

Conclusion

PS is a safe technique in ERCP when cannulation is difficult and is not associated with an increased risk of complications compared to SCT.

Introduction

Tumour necrosis factor-like ligand 1A (TL1A) is a novel therapeutic target for inflammatory bowel disease. Patients (pts) with moderately to severely active ulcerative colitis (UC) treated with the anti-TL1A antibody, RO7790121 (formerly PF-06480605 and RVT-3101), showed significant endoscopic improvement and adequate safety in the phase 2a TUSCANY trial.¹ Here, we report data from the global, randomised, double-blind, placebo-controlled, dose-ranging phase 2b TUSCANY-2 (NCT04090411) trial evaluating the efficacy and safety of subcutaneous (SQ) doses of RO7790121 in adult pts with moderately to severely active UC (total Mayo Score [tMS] ≥6, endoscopic subscore ≥2) who had previously failed conventional/advanced therapy.

Aims & Methods

Pts were randomised to receive RO7790121 SQ 50mg, 150mg, 450mg or placebo (PBO) monthly during the 12-week induction period and RO7790121 SQ 50mg, 150mg or 450mg monthly during the treat-through 40-week maintenance period. Efficacy endpoints were assessed at weeks 14 and 56 in the induction and maintenance intent-to-treat analysis sets, respectively. The primary efficacy endpoint was clinical remission at week 14 by tMS. Safety was assessed throughout the induction and maintenance periods. The secondary endpoint of clinical remission using modified Mayo Score (mMS) is aligned to updated FDA guidance. Other secondary endpoints included clinical remission (by tMS and mMS) at week 56 and endoscopic improvement at weeks 14 and 56. Efficacy analysis by pre-defined biomarker subgroups was also performed.

Results

Overall, 245 pts were randomised and treated; 228 completed the induction and 224 entered the maintenance period of the study. At week 14, 25.5%, 23.3% and 23.9% of pts in the RO7790121 50mg, 150mg, 450mg arms, respectively vs 11.6% in PBO experienced clinical remission by tMS (p>0.05 [Table]). The proportion of pts achieving clinical remission using mMS at week 14 was 29.8%, 35.0% and 31.8% in the RO7790121 50mg, 150mg, 450mg arms, respectively vs 11.6% in PBO (nominal p<0.05). Improvements in clinical remission were sustained throughout the maintenance period (Table). A greater proportion of pts demonstrated endoscopic improvement across all doses of RO7790121 vs PBO at week 14 and week 56. Numerically greater treatment effects were observed in biomarker-positive pts relative to all-comer pts. During the induction period, 47.8% (117/245) of pts reported ≥1 treatment-emergent adverse event (TEAE). The most common TEAEs (occurring in ≥5% pts overall) were anaemia (5.3%) and headache (5.3%). In the induction period, 10 pts experienced serious TEAEs (PBO=4; 50mg=3; 450mg=3); 2 treatment-related (PBO=1; 450mg=1). No pts discontinued the study due to TEAEs. A generally similar safety profile was observed during the maintenance period.

Conclusion

Data from the phase 2b TUSCANY-2 dose-ranging study suggests that RO7790121 has a favourable benefit/risk profile with clinically meaningful improvements in pts with moderately to severely active UC. A phase 3 study will be conducted to confirm these results.

Table. Summary of efficacy outcomes at week 14 and week 56

References

1. Danese S, et al. Clin Gastroenterol Hepatol 2021;19:2324–32.e6.

Disclosure

This study was sponsored by Pfizer Inc and Roivant Sciences Ltd. Medical writing support, under the direction of the authors, was provided by Margarita Gkrava, MSc, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.
SD, consultancy/advisory role/board: AbbVie, Alimentiv, Allergan, Amgen, AMT, AstraZeneca, Athos Therapeutics, Biogen, Boehringer, BMS, Celgene, Celltrion, Dr Falk Pharma, Enthera, Ferring, Gilead, Hospira, Inotrem, Janssen, J&J, Lilly, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc, TiGenix, UCB, Vial, Vifor. Lecture fees: Abbvie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda.
JRA, consulting/advisory role/board: Abbvie, Adiso, BMS, Ferring, Finch Therapeutics, GSK, Janssen, Merck, Pfizer, Roivant, Seres Therapeutics. Speakers’ bureau: Abbvie, BMS, Janssen. Research funding: Janssen, Merck, Pfizer.
SS, consulting/advisory role/board: AbbVie, Amgen, Arena Pharmaceuticals, Biogen, BMS, Celgene, Celltrion, Dr Falk Pharma, Ferring, Fresenius Kabi, Galapagos/Gilead Sciences, Hikma Pharmaceuticals, I-Mab, Janssen, Lilly, Morphic Therapeutic, MSD, Mylan, Pfizer, Protagonist Therapeutics, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma, and Ventyx Biosciences.
LP-B, consulting/advisory role/board : Abbvie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, AMT, Arena, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer, GSK, Hac Pharma, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par' Immune, Pfizer, Prometheus, Protagonist, Roche, Roivant, Samsung, Sandoz, Sanofi, Takeda, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vifor, Vectivbio, Ventyx, Ysopia. Speakers’ Bureau: Abbvie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Lilly, Medac, MSD, Pfizer, Sandoz, Takeda, Tillots, Viatris, Vifor. Research funding: Celltrion, Fresenius Kabi, Takeda. Support travel: Abbvie, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, Tillots.
VJ, employment: Western University, London Health Sciences Centre, Alimentiv. Consulting or advisory role/board : AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei, Asieris, AstraZeneca, Avoro Capital, BMS, Celltrion, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GSK, Genentech, Gilead, Innomar, JAMP, Janssen, Lilly, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion. Speakers’ bureau: AbbVie, Ferring, BMS, Galapagos, Janssen, Pfizer, Shire, Takeda, Fresenius Kabi.
GRD, consulting/advisory role/board: Alimentiv, Abbvie, BMS, Boehringer, Celltrion, GSK, Immunic, Index, J&J, Lilly, Polpharm, Takeda, Tillotts, Ventyx, Pfizer. Speakers’ bureau: Lilly, Pfizer, Takeda. Research funding: Cellitron, Lilly, Pfizer, Takeda.
JK, no COI.
RWL, consulting/advisory role/board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus, Takeda. Research funding: Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, McKusker Charitable Foundation.
AJY, consulting/advisory role/board: Abbvie, Takeda, Celltrion, BMS, J&J, Abivax.
JMM, employment/stock/other ownership interests: Roche/Genentech.
DB, employment: F. Hoffmann-La Roche.
KL, employment: Roche/Genentech.
CS, employment/stock/other ownership interests: Roche/Genentech.
KEH, employment/stock/other ownership: Pfizer.
BGF, stock/other ownership interests: Connect Biopharm, EnGene. Honoraria/consulting/advisory role/board: AbbVie, Abivax, Adiso, Agomab, Allianthera, Amgen, AnaptysBio, Arena Pharma, Avoro Capital, Atomwise, BioJamp, Biora Therapeutics, Blackbird Laboratories, Boehringer, Boxer Capital, Celsius Therapeutics, Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Equillium, Ermium, First Wave, Forbion, Galapagos, Galen Atlantica, Roche/Genentech, Gilead, Gossamer, GSK, Hinge Bio, Index Pharma, Imhotex, Immunic Therapeutics, Intercept, JAKAcademy, Janssen, Japan Tobacco, Kaleido, Klick Health, Landos Biopharma, Lenczner Slaght, LifeSci Capital, Lilly, Lument, Mage Biologics, Mestag, Millennium, MiroBio, Monte Rosa, Morgan Lewis, Morphic Therapeutics, Mylan, Nexys Therapeutics, Nimbus Therapeutics, OM Pharma, OrbiMed, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Roivant/Televant, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Sobi, Spyre Therapeutics, Surrozen, Synedgen, Takeda, Teva, Thelium, Tigenix, Tillotts, Triastek, Ventyx Biosciences, Zagbio, Zealand Pharma. Speakers’ Bureau: Takeda, Janssen, Abbvie.