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Introduction

Despite advances in treatment, overall survival for pancreatic cancer has not improved beyond a 5-year survival of 10%. Reasons for resistance to chemotherapy include a dense stroma, immunosuppressive environment, and poor vascularity within the primary pancreatic tumors. Vascularity within pancreatic tumors has been shown not to increase on contrast-enhanced harmonic EUS (CH-EUS) following 2 months of chemotherapy (Gemcitabine/Nab-Paclitaxel). Preliminary data has suggested that endoscopic ultrasound (EUS) guided intra-tumoral injection of phosphorus-32 (³²P) microparticles in addition to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess vascularity changes within pancreatic tumors (via CH-EUS) following implantation of ³²P microparticles in combination with standard chemotherapy.

Aims & Methods

We performed a prospective single-center trial of patients with unresectable, non-metastatic locally advanced pancreatic cancer (LAPC) undergoing standard chemotherapy (FOLFIRINOX) and ³²P implantation after 2 or 3 cycles of chemotherapy. We perform EUS with contrast-enhanced harmonic EUS (CH-EUS) after 2 cycles of chemotherapy and at 4 weeks and 12 weeks after implantation of ³²P microparticles. Time intensity curve (TIC) analysis was performed over 90 seconds from IV contrast bolus with baseline intensity (prior to contrast bolus) and peak intensity obtained. Intensity gain was defined as median peak intensity – median baseline intensity.

Results

Twenty patients (45% male, median age: 65) have been enrolled in the trial with 15 patients completing 12-week follow-up (3 withdrawals, 1 death, 1 proceeded to surgery prior). Technical success of ³²P implantation was 100% with no procedural complications. Median longest primary tumor size reduced from 32mm (IQR 27.5-38.75) pre-implantation to 24mm (IQR 16-26) 12 weeks post-implantation (p<0.001). Five patients (25%) thus far, have had tumor downstaging, with 3 resections (R1) and one pending. One patient refused surgical treatment. All tumors demonstrated hypoenhancement (lower intensity of enhancement relative to surrounding normal pancreatic tissue suggestive of hypovascularity) at baseline. Median intensity gain of contrast enhancement within the tumor pre-implantation post median 2 cycles of chemotherapy, was 32.15 (IQR 18.08-54.35). Median intensity gain increased to 46.85 (IQR 35.05-76.6; p=0.007) and 66.3 (IQR 54.7-76.3; p=0.001) at 4 weeks and 12 weeks post implantation respectively. Over a median follow-up period of 7.4 months (IQR 5.1-14.6), 16/20 (80%) remain alive (estimated median survival time of 16.0 months) with 3/20 (15%) demonstrating both local and distant disease progression, whilst 3/20 (15%) have had distant progression only.

Conclusion

This is the first study to demonstrate increased vascularity within pancreatic primary tumors in response to ³²P implantation in addition to standard chemotherapy with FOLFIRINOX, whilst historical data has not supported vascularity changes in response to chemotherapy alone. The result of this current study forms a platform to understand further, the potential benefits of chemoradiotherapy over chemotherapy alone in patients with LAPC. Larger comparative trials are warranted.

Disclosure

32P provided by OncoSil Medical

THE IMPACT OF COMBINED CHEMOTHERAPY AND INTRA-TUMORAL INJECTION OF PHOSPHORUS-32 MICROPARTICLES ON VASCULARITY IN LOCALLY ADVANCED PANCREATIC CARCINOMA

Amanda Lim 1, Joshua Zobel 2, Madison Bills 2, William Hsieh 2, Benjamin Crouch 2, Rohit Joshi 3, John-Edwin Thomson 2, EuLing Neo 2, Lilian Kuan 4, Romina Safaeian 2, Edmund Tse 5, Christopher K. Rayner 1, Andrew Ruszkiewicz 6, Nimit Singhal 2, Dylan Bartholomeusz 5, Nam Quoc Nguyen 5

1 University of Adelaide, Adelaide, Australia|||Royal Adelaide Hospital, Adelaide, Australia

2 Royal Adelaide Hospital, Adelaide, Australia

3 Lyell McEwin Hospital, Elizabeth Vale, Australia

4 Queen Elizabeth Hospital, Woodville, Australia

5 Royal Adelaide Hospital, Adelaide, Australia|||University of Adelaide, Adelaide, Australia

6 SA Pathology, Adelaide, Australia|||University of South Australia, Adelaide, Australia

Conference

UEG Week Vienna 2024

Topics

Pancreas

Submission format

Abstract

Session

Overview of pancreatic diseases (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

UEG Presentation

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ONE-YEAR CHANGES IN ALT AND LSM, BUT NOT IN CAP, PREDICT LONG-TERM LIVER OUTCOMES IN PATIENTS WITH MASLD

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Introduction

The availability of new drugs for the treatment of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) underlines the need of early predictors of response to such therapies. This study evaluated the impact of 1-year changes in liver stiffness measurement by Vibration-Controlled Transient Elastography (LSM by VCTE), controlled attenuation parameters (CAP), and serum alanine aminotransferase (ALT) on liver outcomes in patients with MASLD.

Aims & Methods

A large multicenter cohort of MASLD patients with LSM≥8kPa and prospective follow-up was enrolled. Liver-related events (LRE), including hepatocellular carcinoma (HCC) and liver decompensation (LD), were evaluated during follow-up. LSM, CAP, and ALT were assessed at baseline and at 1-year follow-up. Cumulative incidence functions and cause-specific Cox regression analyses were performed to correlate 1-year reduction in LSM, CAP, and ALT with the risk of developing LRE, LD and HCC.

Results

In 2443 patients with MASLD and LSM≥8kPa, a 1-year reduction in ALT of 17 IU/L (HR 0.62; 95% CI 0.41-0.95; p=0.02) and a 20% reduction in LSM (HR 0.44; 95% CI 0.29-0.67; p<0.001) were both independently associated with a lower risk of LRE. Similarly, in 1412 patients with MASLD and LSM≥10kPa, a 1-year reduction in ALT of at least 17 IU/L (HR 0.62; 95% CI 0.39-0.98; p=0.04) and a 20% reduction in LSM (HR 0.42; 95% CI 0.27-0.66; p<0.001) were independently associated with a decreased risk of LRE. Comparable results were observed when considering LD separately, but not for HCC. One-year changes in CAP did not predict liver outcomes. When combining 1-year reduction in ALT of 17 IU/L and a 1-year 20% reduction in LSM, the 5-year probabilities of LRE ranged from 2.1% in the best profile to 5% in the worst profile in patients with LSM≥8kPa, and from 3.3% to 8.1% in those with LSM≥10kPa.

Conclusion

One-year reductions in ALT of 17 IU/L and in LSM by 20%, but not changes in CAP, reduce long-term liver outcomes in patients with MASLD, providing suggestion on monitoring therapy effectiveness.

ONE-YEAR CHANGES IN ALT AND LSM, BUT NOT IN CAP, PREDICT LONG-TERM LIVER OUTCOMES IN PATIENTS WITH MASLD

Grazia Pennisi 1, Giuseppe Infantino 2, Gabriele Di Maria 2, Emmanuel Tsochatzis 3, Elisabetta Bugianesi 4, Masato Yoneda 5, Ming-Hua Zheng 6, Hannes Hagström 7, Jérôme Boursier 8, Jose Luis Calleja 9, George Boon-Bee Goh 10, Wah-Kheong Chan 11, Rocio Gallego-Durán 12, Arun J Sanyal 13, Victor De Ledinghen 14, Philip Newsome 15, Jian-Gao Fan 16, Laurent Castera 17, Michelle Lai 18, Céline Fournier-Poizat 14, Grace Lai-Hung Wong 5, Angelo Armandi 19, Atsushi Nakajima 20, Wen-Yue Liu 6, Ying Shang 21, Marc de Saint-Loup 22, Elba Llop 23, Kevin Kim Jun Teh 24, Carmen Lara-Romero 25, Amon Asgharpour 26, Sara Mahgoub 15, Mandy Sau-Wai Chan 27, Manuel Romero-Gomez 28, Huapeng Lin 29, Seung Up Kim 30, Terry Cheuk-Fung Yip 5, Adele Tulone 2, Che To Jimmy Lai 5, Boyu Yang 5, Hye-Won Lee 31, Abraham Aregay Desta 32, Giacinta Ciancimino 2, Marco Enea 2, Calogero Camma 33, Vincent Wai Sun Wong 5, Salvatore Petta 34

1 Policlinico Paolo Giaccone, Palermo, Italy

2 University of Palermo, Palermo, Italy

3 UCL Institute of Liver and Digestive Health, London, United Kingdom

4 AOU Città della Salute e della Scienza University of Torino, Torino, Italy, Torino, Italy

5 University of Hong Kong, Hong Kong, China

6 Wenzhou Medical University, Wenzhou, China

7 Department of Upper GI Diseases, Karolinska university hospital Huddinge, Stockholm, Sweden

8 Centre Hospitalier Universitaire, Angers, France

9 University of Madrid, Madrid, Spain

10 University of Singapore, Singapore, Malaysia

11 University of Malaya, Kuala Lumpur, Malaysia

12 University of Seville, Seville, Spain

13 Virginia Commonwealth University School of Medicine, Richmond, United States

14 Echosense, Paris, France

15 University of Birmingham, Birmingham, United Kingdom

16 Shanghai Jiaotong University School of Medicine, Shanghai, China

17 Hôpital Beaujon - Service d’Hépatologie, Hôpital Beaujon; Clichy/FR, Clichy, France

18 Harvard Medical School, Boston, United States

19 University of Turin, Torino, Italy

20 Yokohama City University Hosp. Dept. of Gastroenterology, Yokohama, Japan

21 Karolinska Institutet, Stockholm, Sweden

22 Angers University, Angers, France

23 Gastroenterology, Hospital Puerta de Hierro, Madrid, Spain, Madrid, Spain

24 Changi General Hospital, Singhealth, Singapore, Singapore

25 Punta Europa Hospital, Algeciras, Spain

26 VCU School of Medicine, Richmond, United States

27 Echosens, Paris, France

28 Valme University Hospital University of Seville, Sevilla, Spain

29 University of Shanghai, Shanghai, China

30 Yonsei University College of Medicine, Seoul, Korea, Republic of

31 Yonsei University College Dept. of Internal Medicine, Seoul, Korea, Republic of

32 University of Florence, Florence, Italy

33 UOC Gastroenterologia Ed Epatologia, Palermo, Italy

34 University of Palermo Italy 48.37, Palermo, Italy

Event

UEG Week Berlin 2025

Topics

Hepatobiliary IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

Predicting and understanding early stages of advanced liver disease

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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The management of enterocutaneous fistulae

Philip Allan 1

1 Oxford University Hospitals Nhs Ft, Oxford, United Kingdom

Event

UEG Week Berlin 2025

Topics

Endoscopy Nurses Small Intestine & Nutrition Oesophagus Surgery

Session

Mistakes in…: Upper GI

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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DECREASED RISK OF OESOPHAGEAL AND GASTRIC CANCER AMONG USERS OF MENOPAUSAL HORMONE THERAPY IN A POPULATION-BASED STUDY FROM THE FIVE NORDIC COUNTRIES

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Introduction

The incidence of oesophago-gastric cancer has an age-dependent male predominance mirroring physiological changes in sex hormonal levels. Some previous studies suggest that menopausal hormone therapy (MHT) counteracts the occurrence of these tumours, but larger studies with longer follow-up and adjustment for confounders are needed, which prompted the present study.

Aims & Methods

To investigate the hypothesis that MHT decreases the risk of developing oesophago-gastric cancer, especially oesophageal adenocarcinoma.
This population-based case-control study included women aged ≥45 years in all five Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) between 1995-2020. Prospectively collected data came from national complete registries for medications, cancer, diagnoses, total populations, and death. The study included 19,518 case patients with oesophago-gastric cancer and 195,094 randomly identified control participants matched for age, country and calendar year. The participants were categorised into three equal-sized groups (tertiles) of defined daily doses (DDD) of MHT, with non-users as the reference group. MHT was also categorized as systemic or local, and oestrogen only or oestrogen combined with progesterone MHT. Oesophago-gastric cancer was divided into oesophageal or cardia adenocarcinoma, oesophageal squamous cell carcinoma, and gastric non-cardia adenocarcinoma as separate outcomes. Conditional logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, calendar year, country, obesity, gastroesophageal reflux disease, smoking, alcohol, Helicobacter pylori eradication, use of statins and non-steroidal anti-inflammatory drugs.

Results

Compared to non-users of MHT, the adjusted ORs of oesophageal or cardia adenocarcinoma were 0.74 (95% CI 0.67-0.81) for low MHT-use (<158 DDDs), 0.68 (95% CI 0.61-0.75) for intermediate MHT-use (158-848 DDDs), and 0.68 (95% CI 0.61-0.75) for high MHT-use (>848 DDDs). The corresponding ORs were 0.69 (95% CI 0.62-0.77), 0.70 (95% CI 0.62-0.77), and 0.71 (95% CI 0.64-0.79) for oesophageal squamous cell carcinoma, and 0.90 (95% CI 0.84-0.96), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86) for gastric non-cardia adenocarcinoma.

Table. Odds ratios (OR) and 95% confidence intervals (CI) of oesophago-gastric cancer by tertiles of defined daily doses (DDD) of menopausal hormone therapy (MHT), MHT hormonal constitution and administration of MHT.

	Oesophageal and cardia adenocarcinoma	Oesophageal sqamous cell carcinoma	Gastric adenocarcinoma
MHT DDD's
<158	0.74 (0.67-0.81)	0.69 (0.62-0.77)	0.90 (0.84-0.96)
158-848	0.68 (0.61-0.75)	0.70 (0.62-0.77)	0.85 (0.79-0-91)
>848	0.68 (0.61-0.75)	0.71 (0.64-0.79)	0.80 (0.74-0.86)
MHT formulation, type
Oestrogen	0.77 (0.69-0.87)	0.77 (0.68-0.87)	0.88 (0.81-0.97)
Combined	0.68 (0.63-0.73)	0.68 (0.63-0.73)	0.85 (0.80-0.89)
Systemic	0.67 (0.61-0.74)	0.71 (0.65-0.78)	0.82 (0.76-0.88)
Local	0.72 (0.66-0.78)	0.69 (0.63-0.75)	0.87 (0.83-0.92)

Conclusion

This study provides support for the hypothesis of an inverse association between MHT and risk of developing oesophago-gastric cancer, and particularly for oesophageal adenocarcinoma where the association was seemingly dose-dependent and stronger for combined oestrogen and progesterone MHT and for systemic MHT. A limitation to the study was the inability to adjust for socioeconomic factors as confounders.

DECREASED RISK OF OESOPHAGEAL AND GASTRIC CANCER AMONG USERS OF MENOPAUSAL HORMONE THERAPY IN A POPULATION-BASED STUDY FROM THE FIVE NORDIC COUNTRIES

Victoria Wocalewski 1, Giola Santoni 1, Helgi Birgisson 2, My von Euler-Chelpin 3, Joonas Kauppila 4, Eivind Ness-Jensen 5, Shao-Hua Xie 1, Jesper Lagergren 6

1 Karolinska Institutet, Stockholm, Sweden

2 The Icelandic Cancer Registry, Reykjavik, Iceland

3 University of Copenhagen, Copenhagen, Denmark

4 Karolinska Institutet, Stockholm, Sweden|||Oulu University Hospital and University of Oulu, Oulu, Finland

5 Karolinska Institutet, Stockholm, Sweden|||Levanger Hospital, Levanger, Norway|||NTNU, Norwegian University of Science and Technology, Levanger, Norway

6 Karolinska Institutet, Stockholm, Sweden|||Kings College London, London, United Kingdom

Event

UEG Week Berlin 2025

Topics

Digestive Oncology Endoscopy Stomach & H. Pylori Oesophagus

Submission format

Abstract

Session

Targeting gastric cancer: How to proceed

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

UEG Presentation

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ORGANISATIONAL FACTORS ASSOCIATED WITH POST ENDOSCOPY UPPER GASTROINTESTINAL CANCER (PEUGIC): RESULTS OF THE ENGLISH NATIONAL PEUGIC PROJECT

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Introduction

Post endoscopy upper gastrointestinal cancers (PEUGIC) are often missed opportunities to diagnose earlier or even prevent cancer. A national process for identifying all PEUGIC in the English National Health Service (NHS) and performing root cause analysis was developed. In parallel, a survey of NHS endoscopy providers diagnostic and surveillance UGI endoscopy practices was undertaken to investigate organisational factors which may contribute to endoscopy quality and PEUGIC.

Aims & Methods

PEUGIC occurring 3-36 months after an index endoscopy without a cancer diagnosis between 2017 and 2023 were identified from National Cancer Registration and Hospital Episode Statistics datasets. Data from local root cause analysis were uploaded onto a secure portal for national analysis. Endoscopy providers taking part in the project were asked to complete an online organisational survey, covering diagnostic and surveillance endoscopic practices, equipment and the management of dysplasia and early cancer.

Results

3151 PEUGIC were examined by local reviewers in 144 hospitals in England. 635 (20%) were excluded on local review. Data were available for 2516 PEUGIC. 1897 PEUGIC (75.4%) were following diagnostic endoscopy and 618 (24.6%) were undergoing surveillance. 80% of endoscopy providers responded to the survey.
For diagnostic PEUGIC, less than 20 minutes being allocated to UGI endoscopy was associated with no abnormalities detected in the PEUGIC segment at index endoscopy OR 1.25 (95% CI 1.04-1.50). Oesophageal squamous cell PEUGIC were associated with less time allocated per endoscopy OR 1.28 (95% CI 1.03-1.59). Endoscopy providers with lower number of procedures during an endoscopy session were associated more frequently with adequate management of lesions OR 2.6 (95% CI 1.03-6.87). Patient harm and adverse treatment outcomes were associated with an inadequate index endoscopy OR 1.56 (95% CI 1.28-1.91). The most common reason for inadequate endoscopy was inadequate management of lesions identified, which were most likely to be cancer associated lesions OR 1.43 (95% CI 1.11-1.69), specifically oesophageal strictures (24%) and gastric ulcers (23%).
For surveillance PEUGIC, organisational factors associated with increased detection of stage 1 (success of surveillance) PEUGIC compared with stage ≥2 were: dedicated surveillance sessions OR 2.08 (95% CI 1.46-2.98), >20 minutes allocated per endoscopy OR 2.05 (95% CI 1.48-2.84) and surveillance in an endoscopic resection centre OR 3.50 (95% CI 1.99-6.13).
Booking delays and errors were noted in 12% of PEUGIC, patient factors (e.g. non-attendance) were noted in 11% and clinical error in 11.7% (inappropriate decision 7.5% and histology not actioned in 4.2%). Surveillance was delayed in 27% of PEUGIC and associated with adverse treatment outcomes OR 1.79 (95%CI 1.72-2.73).

Conclusion

A survey of endoscopy providers’ organisational structure has revealed factors which contribute to PEUGIC not captured during individual root cause analysis. Less time allocated for endoscopy was associated with no abnormalities being found during endoscopies that lead to PEUGIC. Surveillance outcomes were better in patients who had their endoscopies in dedicated surveillance sessions, with more time allocated and undertaken in endoscopic resection centres. Surveillance delays are common and associated with worse outcomes.