Introduction

In recent years, both the incidence and early-stage diagnosis of pancreatic neuroendocrine tumors (pNETs) have increased, likely due to advancements in cross-sectional imaging techniques (1). Management strategies are size-dependent, with observation generally preferred for lesions <10 mm and surgical resection for those >20 mm. However, there is no consensus regarding the optimal approach for tumors between 10 and 20 mm, highlighting the need for multidisciplinary decision-making (2). In this setting, endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) or fine-needle biopsy (FNB) plays a crucial role not only in diagnosis but also in tumor grading (3). However, samples obtained through EUS-FNA or FNB may not provide sufficient histological material to determine tumor grade in pNETs smaller than 20 mm. This study aims to summarize the current evidence regarding the adequacy of histological samples obtained via EUS-FNA/FNB for tumor grading.

Aims & Methods

This study followed the PRISMA guidelines for Systematic Reviews and Meta-Analyses. MEDLINE, EMBASE, and SCOPUS databases were searched up to December 2024 for studies reporting on the sample adequacy of EUS-FNA or FNB for grading pNETs ≤ 20 mm. Sample adequacy was defined as the proportion of samples in which the Ki-67 index was successfully obtained for tumor grading among all samples collected. Pooled estimates were calculated using random-effects models. Heterogeneity was assessed using the I² statistic. Subgroup analyses were conducted based on needle type (FNA vs. FNB).

Results

17 studies were included, analyzing a total of 1414 patients. The pooled adequacy rate was 71.6% (95% CI: 0.592–0.841), with substantial heterogeneity across studies (I² = 98.69%). The risk of publication bias was considered low based on Egger’s test (p = 0.162). When considering only studies that used FNA, adequacy rates were lower, with a pooled estimate of 52.5% (95% CI: 0.302–0.748; I² = 97.99%). In contrast, studies employing FNB showed higher adequacy rates, with a pooled estimate of 79.8% (95% CI: 0.605–0.991), although heterogeneity remained high (I² = 87.32%). In this subgroup, there was also evidence of publication bias, as suggested by Egger’s test (p = 0.017) and visual asymmetry in the funnel plot.

Conclusion

Our study found that EUS-FNA/FNB provides adequate histological specimens for tumor grading in pNETs < 20 mm, although significant heterogeneity was observed. As expected, FNB demonstrated considerably better performance than FNA in establishing tumor grade, suggesting it should be preferred for pNET sampling. However, even with FNB, tumor grade could not be determined in up to 20% of cases, indicating that it remains a suboptimal tool for grading and may offer limited additional value beyond diagnostic confirmation in some patients. Notably, our study did not distinguish between first-, second-, and third-generation FNB needles; therefore, results from newer-generation FNBs may show improved sample adequacy rates. Furthermore, the observed heterogeneity highlights the need for studies specifically evaluating the ability of EUS-FNB to obtain high-quality tissue for grading, thereby supporting the role of EUS in clinical decision-making for these small tumors.

References

1. Souche R, Hobeika C, Hain E, et al. Surgical Management of Neuroendocrine Tumours of the Pancreas. J Clin Med 2020;9.
2. Mansour JC, Chavin K, Morris-Stiff G, et al. Management of asymptomatic, well-differentiated PNETs: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association. HPB (Oxford) 2019;21:515-523.
3. Franchellucci G, Andreozzi M, Carrara S, et al. Contrast Enhanced EUS for Predicting Solid Pancreatic Neuroendocrine Tumor Grade and Aggressiveness. Diagnostics (Basel) 2023;13.

Introduction

Fatigue is highly prevalent in patients with Inflammatory bowel disease (IBD)and associated with reduced quality of life. However, effective treatments for IBD fatigue are lacking.

Aims & Methods

We aimed to assess the real-world efficacy of modafinil – a stimulant medication – on fatigue in IBD patients. The was a prospective evaluation in a tertiary IBD centre in the UK. Adults with a confirmed diagnosis of IBD, who were fatigued for at least 6 months, were referred for fatigue evaluation using the Inflammatory Bowel Disease Fatigue Self-Assessment Scale (IBD-F). The IBD-F includes 5 questions scored 0-4 using a Likert scale to identify fatigue. Scores range from 0-20 and scores ≥11 denote severe fatigue.
After treating organic causes of fatigue (anaemia, B12 deficiency, hypothyroidism, mucosal inflammation) and excluding contraindications, patients with a baseline IBD-F score ≥11 were offered modafinil. Modafinil was started at 100mg daily and titrated in 100mg increments to a maximum of 400mg daily if needed. If unable to tolerate 100mg, dosage was reduced to 50mg.
Patients were followed up until week 12 or drug withdrawal. IBD-F scores were reviewed at 12 weeks and compared to baseline. A clinically significant fatigue improvement was a reduction in the IBD-F score ≥3¹. Any patient who withdrew drug before 12 weeks was regarded as having severe fatigue at follow up.
Descriptive statistics were presented as means with standard deviation [SD]. A paired t-test was used to assess change in IBD-F scores from baseline with 5% significance level used.

Results

Seventy-two patients (50% male) were included with a mean age of 38 (SD 11.1) years . Of these, 53 (74%) had Crohn’s and 19 (27%) had UC with a mean disease duration of 13.2 (10.4) years (Table 1). The cohort showed refractory disease with 23 (32%) of patients having used at least 3 biologics, 24 (33%) had a stoma and 41(57%) had at least one bowel resection. The most common total modafinil dose was 200mg. Dosages ranged from 50mg to 400mg per day.
Both UC (15.9 [SD 2.58]) and Crohn’s (15.0 [2.31]) had similar mean (SD) baseline IBD-F scores. After treatment with modafinil, there was a statistically significant improvement in mean IBD-F score from baseline 15.3 [SD 2.38] to 10.4 [SD 3.83] (p<0.0001). There was no difference in the score improvement between UC and Crohn’s p=0.29. No difference was observed between those with and without irritable bowel syndrome (p=0.35). At follow up, 53 (74%) had a clinically significant improvement in fatigue and 38 (53%) were no longer severely fatigued.
Nine patients (13%) reported side effects: headache (n=5), and anxiety, mood changes, nausea, and visual issues (n=1 each). Three patients withdrew before the 12 week follow up. No serious adverse events were recorded.

Table1

Conclusion

In this real-world evaluation, modafinil was associated with a statistically significant improvement in fatigue in patients with mostly refractory IBD. Modafinil was generally well tolerated. Randomised, placebo-controlled trials of modafinil for IBD fatigue are now warranted.

References

1 Nocerino A, Nguyen A, Agrawal M, Mone A, Lakhani K, Swaminath A. Fatigue in Inflammatory Bowel Diseases: Etiologies and Management. Adv Ther. 2020;37(1):97-112. doi:10.1007/s12325-019-01151-w

Introduction

Radioactive phosphorus (³²P) is an innovative therapy for locally advanced pancreatic cancer that is implanted through endoscopic ultrasound (EUS). Pancreatic cancer is the fourth cause of death and is responsible for 7% of all deaths caused by cancer. Nowadays the improvement of chemotherapy and the usage of combination therapies led to a better prognosis and studies showed an improvement of the survival parameters (OS, Free Progression Survival). One of the most innovative therapies is the implantation of radioactive phosphorus-32 which is a type of brachytherapy. It is indicated for the treatment of patients with Locally Advanced Pancreatic Cancer (LAPC) in combination with gemcitabine-based chemotherapy.

Aims & Methods

The primary goal of this study is to determine the safety of the intra-tumoral implantation of radioactive phosphorus (³²P) through EUS and the complications of the procedure of implantation. The secondary goals are to determine the Local Disease Control Rate (LDCR) at 16 weeks and the effectiveness of the implantation of radioactive phosphorus by measuring Overall Survival (OS), Progression Free Survival (PFS) and Local Progression Free Survival (LPFS). We currently have made the implantation in eight patients with similar clinical and demographic features who suffer from locally advanced pancreatic cancer. They receive gemcitabine-based chemotherapy in combination with an intra-tumoral therapy with radioactive phosphorus (³²P) through a 22-gauge FNA needle guided by EUS. The adverse events of the implantation are evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The LDCR is evaluated at 16 weeks and the alteration of Tumor Volume every two months for the first year after implantation and every three months the second year after implantation according to RECIST 1.1.

Results

The eight procedures (median age of patients: 68,5 years) were unremarkable and no complication during the procedure was noted. The patients did not have any major adverse events during the day of the procedure. Five out of eight patients (62,5%) revealed mild abdominal pain on the second day which recovered with typical pain killers. The LDCR, for all patients, at 16 weeks, was 100%. Two of the patients had a major reduction in the tumor so it was resectable. The operations were without any complications and the pathology test showed R0 resection. Two patients died after 12 months of follow up (one patient showed progression disease after 10 months from implantation and one patient had stable disease until death) and one patient revealed progression of disease after 12 months and is still alive after 15 months of follow up. Three patients have stable disease after 6 months of follow up, even though a slight reduction of the tumor has been noted. The six patients (including the two that died and not including the two that underwent surgery) have been followed up for 6 to 15 months, depending on time of implantation. The median Progression Free Survival for these six patients is 7 months (max 12 months – min 6 months) and the median Local Progression Free Survival is 6 months (max 12 months – min 6 months).

Conclusion

We must include more patients to conduct more useful results, but the initial results look promising.

References

1.Wungki P, Akhil C, Eileen M. Pancreatic Cancer: A Review. JAMA. 2021 September 07;326(9):851-862.
2.OncoSil System: Instruction for Use
3.Audrey V, Joseph H, Rich S, et al. Pancreatic cancer. Lancet. 2011 August 13; 378(9791): 607-620. doi: 10.1016/S0140-6736(10)62307-0.

Disclosure

​None to report

Introduction

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated metabolic and cardiovascular benefits in patients with type 2 diabetes (T2D). However, their potential effect on pancreatic cancer (PC) risk remains unclear.

Aims & Methods

We aimed to examine the association between SGLT-2i use and PC risk in T2D patients prescribed metformin. We conducted a retrospective cohort study using a territory-wide electronic healthcare database, retrieving adult patients (≥18 years) with T2D who initiated metformin between 2015 and 2022. The index date was the first metformin prescription during the study period. Patients were observed until PC, pancreatectomy, death, or study end date (December 31, 2022). Exclusion criteria included prior history of PC, IgG4 disease, pancreatectomy, or fewer than two HbA1c measurements during follow-up. The outcome and exposure of interest was PC and SGLT-2i use (including dapagliflozin, empagliflozin, canagliflozin and ertugliflozin), respectively. SGLT-2i exposure was defined as continuous use during 90-day entry period following the index date. Cox proportional hazards model with propensity score (PS) matching (1:2) on 28 covariates – age, sex, smoking, alcohol use, body mass index (BMI), diabetes duration and complications, glycemic control (in terms of time-weighted mean HbA1c), history of pancreatitis and cholangitis, comorbidities, and concomitant medication use (aspirin, statins, and other antidiabetic medications) – were used to estimate hazard ratios (HRs). Sensitivity analysis by treating medication use as time-varying variable was conducted to address immortal time bias.

Results

Among 144,468 matched patients (mean age:59.3±11.2 years; male:58.3%; 48,156 SGLT-2i users and 96,312 SGLT-2i non-users), 441 (0.31%) developed PC during a mean follow-up of 6.6±2.0years. The mean duration of SGLT-2i use was 2.1±1.6 years. SGLT-2i use was associated with lowered PC risk (aHR:0.43; 95% CI:0.34-0.55), irrespective of empagliflozin (aHR0.43; 95%CI: 0.33-0.57) or dapagliflozin use (aHR:0.33; 95% CI:0.22-0.49). When drug use was modelled as time-varying variables, the protective effect remained significant (aHR:0.35; 95% CI:0.15-0.78). Furthermore, a dose- and duration-dependent relationship was observed. The aHR was 0.88 (95% CI:0.84-0.92) per 100-cumulative defined daily dose (cDDD) increase in use, and 0.66 (95% CI:0.59-0.75) per 1-year increase in use. Subgroup analysis showed beneficial effects persistent regardless of age (cutoff of 65 years), sex, BMI (cutoff of 25 kg/m²), diabetes complications, usage of other medications (aspirin, statins, and insulin).

Conclusion

SGLT-2i use was associated with a lower risk of PC in a dose- and duration-dependent manner, which was independent of glycemic control, among T2D patients treated with metformin. These findings provide insights into informing the choice of second-line anti-diabetic drug in lowering PC risk in T2D metformin users.

Introduction

Although the role of radiotherapy in locally advanced pancreatic cancer (LAPC) is still debated, data has demonstrated encouraging results for more precise methods of radiotherapy delivery, including stereotactic body radiation therapy (SBRT) and endoscopic ultrasound (EUS) guided intra-tumoural phosphorus-32 (³²P) microparticle implantation. We compare survival and safety outcomes of patients with SBRT versus EUS-guided ³²P implantation in combination with chemotherapy in patients with LAPC.

Aims & Methods

This is a single-centre retrospective study from March 2015 – April 2025 including all patients with LAPC who underwent combination neoadjuvant chemotherapy with either EUS-guided ³²P microparticle implantation or SBRT. The primary outcome was overall survival from chemotherapy commencement. Secondary outcomes include progression-free survival (PFS), resection rate and rate of adverse effects including grade 3 (CTCAE v. 5) or above adverse effects.

Results

A total of 119 patients (58 ³²P vs. 61 SBRT) were included. Demographics and tumour characteristics were comparable between the groups (Table 1). All ³²P microparticle implantation was successful, with an average volume of 1.6+0.1mL and an estimated 100Gy activity applied to the tumour. The median highest dose of SBRT therapy was 35Gy (IQR 35-40Gy) delivered over 5 fractions. Median overall survival from the date of chemotherapy commencement was significant better with ³²P implantation than SBRT (hazard ratio [HR] 1.98; p=0.004). Compared to SBRT, ³²P implantation was associated with superior local and distant PFS (HR 1.61; p=0.034 and HR 1.71; p=0.019 respectively). Both therapies resulted in significant reduction in serum Ca19.9. Tumour downstaging (15/58 vs. 5/61, P<0.001) and surgery (13/58 vs. 0/61, P<0.001) rates after the therapy were significant higher with ³²P implantation than SBRT. The rate of R0 resection was 77% (10/13) in the ³²P group. The rate of grade 3 adverse events was not significantly different between the groups (6/58 vs. 5/61).

Table 1. Demographics and tumour characteristics

Conclusion

When radiotherapy is used in combined with chemotherapy for LACP, EUS guided intra-tumour ³²P implantation is associated with better clinical outcomes than SBRT, including overall and progression free survival, tumour downstaging and surgical resection. Both forms of radiotherapy have demonstrated a good safety profile. These findings warrant further evaluation with a larger randomized controlled trial.