Introduction

Radiation proctopathy (RP) is a common late complication of pelvic radiotherapy, affecting up to 20% of patients treated for pelvic malignancies. It manifests as rectal bleeding, anaemia, urgency, and diarrhoea, significantly reducing quality of life. Argon Plasma Coagulation (APC) remains the standard endoscopic therapy but has notable limitations, including high recurrence rates, the need for multiple sessions, and risks such as ulceration and perforation.
PuraStat, a synthetic self-assembling peptide hydrogel, offers an innovative alternative by creating a transparent matrix that promotes haemostasis and mucosal healing without thermal injury. While small series have shown benefit, robust real-world evidence is lacking.

Aims & Methods

We assessed real-world outcomes of PuraStat in RP at a UK tertiary centre (2023–2024). Consecutive patients with chronic radiation-induced rectal bleeding were included and treated by a single endoscopist. Patients were stratified into two cohorts:
1. De novo PuraStat – no prior APC (n=50)
2. APC→PuraStat – persistent or recurrent symptoms despite APC (n=50)
PuraStat was applied during flexible sigmoidoscopy, either as monotherapy or following APC. The primary outcome was resolution or improvement of rectal bleeding. Secondary outcomes included the number of repeat endoscopic interventions within 6 months and treatment-related adverse events.

Results

A total of 100 patients were included (median age: 74 years, range 64–85; 52% male). Most had prostate or gynaecological cancer treated with pelvic radiotherapy.
- De novo PuraStat (n=50): All achieved symptomatic relief, with marked bleeding reduction and endoscopic improvement. Follow-up sigmoidoscopy showed mucosal healing or mild residual proctitis in 92%. Mean repeat sessions: 1.3 (range 0–3) over 6 months.
- APC→PuraStat (n=50): These patients had undergone a median of 3 APC sessions with limited success. PuraStat led to complete symptom control in all cases, reducing the need for frequent interventions (mean: 1.5 sessions over 6 months).
No adverse events (e.g., perforation, infection, severe pain) were reported in either group. Patients with severe radiation-associated vascular ectasia (RAVE) and refractory bleeding demonstrated excellent response to PuraStat.

Conclusion

This large real-world series demonstrates that PuraStat is a safe, effective, and well-tolerated therapy for radiation proctopathy, whether used as first-line treatment or following APC failure. It provided rapid and sustained bleeding control, significantly reduced the need for repeat endoscopic interventions, and promoted mucosal healing without the risks associated with thermal therapies. Importantly, PuraStat showed consistent efficacy even in patients with severe radiation-associated vascular ectasia (RAVE) and those refractory to conventional modalities, highlighting its role as both a frontline and salvage option. These findings position PuraStat as a valuable addition to the therapeutic armamentarium for radiation-induced rectal bleeding. Larger prospective, multicentre studies and cost-effectiveness analyses are warranted to validate these results and define its optimal place in treatment algorithms.

Table 1: Treatment Outcomes by Group

Group	n	Symptom Relief	Mean Repeat Sessions
De novo PuraStat	50	100%	1.3
APC→PuraStat	50	100%	1.5

References

1- White K, Henson CC. Endoscopically delivered PuraStat for the treatment of severe haemorrhagic radiation proctopathy: Service evaluation of a new endoscopic treatment for a challenging condition. Frontline Gastroenterol. 2021;12(1):37–42. doi:10.1136/flgastro-2020-101735
2-Van de Wetering FT, Verleye L, Andreyev HJN, Maher J, Vlayen J, Pieters BR, et al. Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis. Cochrane Database Syst Rev. 2016;(4):CD003455. doi:10.1002/14651858.CD003455.pub2
3-Andreyev HJN, Davidson SE, Gillespie C, Allum WH, Swarbrick E. Practice guidance on the management of acute and chronic gastrointestinal problems arising as result of treatment for cancer. Gut. 2012;61:179–192. doi:10.1136/gutjnl-2011-300563
4-Dahiya DS, Kichloo A, Tuma F, Albosta M, Wani F. Radiation proctitis and management strategies. Clin Endosc. 2022;55(1):22–32. doi:10.5946/ce.2020.288
5-Rustagi T, Mashimo H. Endoscopic management of chronic radiation proctopathy. World J Gastroenterol. 2011;17(41):4554–4562. doi:10.3748/wjg.v17.i41.4554
6-Lenz L, Rohr R, Nakao F, Libera E, Ferrari A. Chronic radiation proctopathy: A practical review of endoscopic treatment. World J Gastrointest Surg. 2016;8(2):151–158. doi:10.4240/wjgs.v8.i2.151

Introduction

​​​​​Pancreatic cancer (PC) has one of the poorest prognoses among malignancies. Early detection, particularly of stage 0 or stage 1 disease, is crucial to improving survival outcomes. However, conventional screening strategies based solely on family history or symptoms—as commonly practiced in Western countries—have shown limited sensitivity for early-stage PC. In Japan, more comprehensive approaches are being developed.

Aims & Methods

Low-grade relevant (LGR) factor	High-grade relevant (HGR) factor
・sporadic family history ・diabetes mellitus ・diabetes mellitus worsening ・stomach/back symptoms ・weight loss ・elevated serum pancreatic enzyme ・heavy alcohol consumption ・smoking history ・obesity	・familial PC ・hereditary PC syndrome/pancreatitis ・new-onset diabetes mellitus ・jaundice ・elevated serum tumor biomarkers ・chronic pancreatitis ・pancreatic cyst ・main pancreatic duct dilation
Score positive; 3 points or more	Score positive; 1 point or more

This nationwide, multicenter prospective study aimed to evaluate the utility of a novel scoring system for early PC detection among hospital outpatients. From August 2019 to May 2024, all outpatients presenting with symptoms, risk factors, subtle imaging abnormalities of the pancreas, or requesting pancreatobiliary screening at the Department of Gastroenterology in hospitals participating in the Early Pancreatic Cancer Screening Study (EPSS) were considered for inclusion. Consecutive patients who had no pancreatic tumors suspected by any imaging modalities were examined, no prior history of endoscopic ultrasound (EUS) examination for pancreatic disease, and/or no referrals from other hospitals specifically for PC diagnosis were prospectively enrolled. The system comprised low- and high-grade relevant (LGR/HGR) factors referring to both risk factors and diagnostic indicators, including symptoms and subtle imaging abnormalities associated with PC. Patients were classified as score-positive if they had ≥3 LGR or ≥1 HGR factor(s). Diagnostic yield for stage 0/1 and all-stage PC was compared between score-positive and score-negative groups. Diagnostic performance was also evaluated against previous large-scale Japanese data and Western screening methods based on family/genetic risk or symptoms. The sample size was determined based on a previous large-scale PC screening study in Japan.

Results

Of 3,287 patients, 2,531 were score-positive and 756 were score-negative. PC was diagnosed in 283 patients (8.6%), including 67 with stage 0/1 disease. The detection rate of stage 0/1 PC was significantly higher in score-positive than in score-negative patients (2.6% vs. 0.7%, P=.001). Compared to a previous Japanese study (0.78%), this study showed a significantly higher detection rate (P<.001). The sensitivity of the scoring system for stage 0/1 PC was 93.1%, significantly outperforming Western-style approaches (12.5% for family/genetic risk and 50.0% for symptom-based screening; both P<.001), while maintaining comparable accuracy. Even combining family/genetic risk and symptoms, sensitivity remained lower than that of the scoring system (56.9%, P<.001). For all-stage PC, both the accuracy and sensitivity of the diagnosis based on the scoring system were significantly higher than those based on family/genetic risk, symptom, or the combination of symptom and family/genetic risk (P = .030, .004, .002 for accuracy; and all P <.001 for sensitivity, respectively). Among the 283 PC cases, 23.7% were stage 0/1, 15.9% were ≤10 mm, and 45.6% underwent surgical resection. Multivariate logistic analysis identified older age, worsening diabetes, and MPD dilation as significant independent predictors of stage 0/1 PC.

Conclusion

The scoring system demonstrated superior sensitivity and comparable accuracy to traditional screening strategies for detecting early-stage PC. Its use in outpatient settings may facilitate earlier diagnosis and intervention, thereby improving resectability and prognosis.

References

Klein AP. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol 2021;18:493-502.
Hanada K, Okazaki A, Hirano N, et al. Diagnostic strategies for early pancreatic cancer. J Gastroenterol 2015;50:147-54.
Sagami R, Hayasaka K, Ujihara T, et al. Role of EUS combined with a newly modified scoring system to detect pancreatic high-grade precancerous lesions. Endosc Ultrasound 2022.

Introduction

Acute pancreatitis (AP) is an acute inflammatory autodigestive disorder triggered by dysfunction of pancreatic exocrine activity and represents the most common gastrointestinal emergency in clinical practice. Global data indicate an annual incidence rate of 33.74 per 100,000 population and a mortality rate of 1.16 per 100,000. Despite ongoing optimization of therapeutic strategies, current clinical management primarily relies on supportive care and surgery. Hypertriglyceridemia (HTG) is the second leading etiological factor for AP, accounting for 10.36% of cases. Compared to other causes, HTG-associated acute pancreatitis (HTG-AP) exhibits higher recurrence rates and more severe complications (e.g., pancreatic necrosis and renal insufficiency). With the rising prevalence of HTG, the disease burden of HTG-AP is increasing, yet its specific pathogenic mechanisms remain unclear.

Aims & Methods

This study integrated whole-genome sequencing (WGS) and next-generation sequencing (NGS) to screen for shared mutations in the exonic regions of 5 HTG-AP family members. Candidate genes were identified based on MutationTaster classification and CADD scores. A mouse model carrying the PDLIM2 gene rs145349678 mutation was constructed using CRISPR/Cas9 technology, and an HTG-AP animal model was established. Pancreatic and hepatic histopathology (HE staining) and serological markers (TG, lipase, amylase, IL-6) were analyzed to evaluate the impact of the mutation on pancreatitis severity and hepatic lipid deposition.

Results

A clinical HTG-AP family was identified, with all 5 members exhibiting hypertriglyceridemia, including 2 cases of recurrent pancreatitis. WGS revealed 278 mutation sites across 10 chromosomes (involving 23 genes) in the family, and NGS validation narrowed these to 7 candidate loci. The PDLIM2 rs145349678 mutation (NM_001368120.1:exon9:c.C1055T:p.A352V), located within the LIM domain (which mediates protein localization and signaling transduction), was selected as the target due to cross-species conservation. Experimental results demonstrated that HTG-AP mice with the PDLIM2 mutation exhibited significantly aggravated pancreatic pathological damage (edema, hemorrhage, and inflammatory cell infiltration; *P* < 0.05), elevated serological markers (TG: 2.3 ± 0.4 vs. 1.5 ± 0.3 mmol/L; lipase: 520 ± 68 vs. 320 ± 45 U/L; IL-6: 48.2 ± 6.1 vs. 28.5 ± 4.3 pg/mL; *P* < 0.01 for all), and a 2.3-fold increase in hepatic lipid deposition (*P* < 0.001) compared to controls.

Conclusion

The PDLIM2 rs145349678 mutation exacerbates inflammatory responses and hepatic lipid accumulation in HTG-AP by modulating lipid metabolism. This finding provides new insights into the pathogenesis of HTG-AP and potential therapeutic targets.