Introduction

Gallstone disease affects approximately 6% of the global population. Adequate knowledge about gallstone disease among the public can facilitate early medical consultation and enable them to navigate healthcare pathways effectively. In the digital age, patients increasingly turn to the internet for health-related information, with over half of the global population relying on it for access to knowledge.

Aims & Methods

This study aimed to evaluate the quality, readability, usability, and reliability of patient-oriented websites providing information on gallstone disease, using validated assessment tools. The three most widely used search engines, Google, Yahoo, and Bing were searched employing keywords related to gallstone disease. The first 50 search results per keyword per engine were screened. Applying the inclusion and exclusion criteria, 52 websites were selected for detailed analysis. The information was assessed for readability using the Flesch Reading Ease Score (FRES), for usability and reliability using the LIDA tool, and for overall quality using the DISCERN instrument. Statistical analysis was performed using SPSS (v27), with significance set at p < 0.05.

Results

Among the 52 websites analyzed, only sixteen (30.8%) sites had obtained Health on the Net (HON) code certification. The median FRES score of the included websites was 60.5 out of 100 (range: 33-79.6), indicating readability appropriate for readers aged 13–15 years. The median LIDA usability and reliability scores were 40 out of 54 (range: 31–54) and 24.5 out of 51 (range: 10–51), respectively. The median DISCERN score was 69.8 out of 80 (range: 30-80) with 5.8% (n=3) of websites scoring below 50%. A low DISCERN score (≤ 50%) was found in three (5.8%) websites. The DISCERN score was found to be significantly associated with LIDA reliability and LIDA overall scores (p < 0.001), government run websites (p= 0.028) and HON code certification (p = 0.01). However, no significant association was found between DISCERN scores and LIDA usability or FRES. Most websites (86.5%) provided accurate clinical information, but only 76.9% discussed treatment complications.

Conclusion

The quality of online patient information on gallstone disease varied considerably, with only a minority meeting optimal standards for readability and certification. While clinical accuracy was generally satisfactory, gaps remain in presenting treatment risks and maintaining content currency. These findings emphasize the need for improved oversight and standardization of online health content to support patient education and informed decision-making.

References

1. Internet World Stats. Internet world stats: Usage and population statistics, http://www.internetworldstats.com/stats.htm (2013, accessed 16 June 2023).
2. Lee JS, Seo HS, Hong TH. YouTube as a source of patient information on gallstone disease. World J Gastroenterol 2014; 20: 4066–4070.
3. Raptis DA, Sinanyan M, Ghani S, et al. Quality assessment of patient information on the management of gallstone disease in the internet. HPB 2019; 21: 1632–1640.
4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol 2016; 65: 146–181.

Disclosure

There is no conflict of interest

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

Demographic Data	n =72 (%)
Male Female	36 (50) 36 (50)
Age:	mean 38 [SD 11.12] years
UC Crohn's	19 (26) 53 (74)
Disease Duration:	mean 13.2 [SD 10.39] years
Stoma	24 (33)
IBS	6 (8)
Smokers Ex smokers Non smokers	7 (15) 14 (31) 22 (49) n=45
No. of biologics used 0 1 2 3 4+	14 (19) 19 (26) 16 (22) 11(15) 12 (16)
Steroid use	25 (35)

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

Clinical Case Summary

We report a case of Intrahepatic Cholestasis of Pregnancy (ICP) leading to a rejections of a living, related donor liver two years after the liver transplantation (LT). The 36yo patient underwent LT in November 2021 in Mongolia due to a HBV/HDV related liver cirrhosis. Until August 2024, she had normal test results when she presented with severe pruritus and jaundice at 16-17th week of her second pregnancy. The ICP was diagnosed after elevated total bile acids were detected. A medical pregnancy termination was induced with subsequent three sessions of plasmapheresis. The patient's condition deteriorated further before she received her second living, unrelated donor LT in December 2024.
.

	2023.07.03- prior to pregnancy	2024.08.18- during the pregnancy	2024.09.30- A month after termination	2024.11.04	2025.02.02- Two months after re-transplantation
Total bilirubin (mg/dL) /norm 0-1.2/	1.5 N	17.6 H	20.2 H	40.6 H	0.73 N
GOT/GPT (IU/mL) /norm 0-40/	11.3/18.3 N	265.3/196.1 H	79.5/77.1 H	262.5/113.1 H	6.2/7.6 N
Total bile acids (umol/mL) /norm 0-10/		170.2 H	332 H		7 N

The explant histology stated a massive hepatocellular necrosis (fulminant), total bile duct loss, massive cholestasis (canalicular and intracellular), allograft arteriopathy: Foamy histiocytes in the intimal artery, Arteriosclerosis and Lumen narrowing. No genetic test was performed , either prior or after the LTs. The final diagnosis: An Intrahepatic Cholestasis of Pregnancy leading to a liver graft rejection.
The ICP is a relatively common pregnancy related condition (0.2-2% of pregnancies in Europe and Americas¹) that presents with jaundice and pruritus. The condition usually improves after delivery/termination. In rare cases elevated serum bile acid levels lead to fetal abnormalities or loss of pregnancy. Since the patients condition did not improve after the pregnancy termination in September, 2024, Progressive Familial Intrahepatic Cholestasis (PFIC) was suspected when she admitted her first pregnancy was also complicated by ICP. Better history taking is needed to prevent graft rejection due to bile acid transport dysfunction.

References

1- Williamson, C. and V. Geenes, Intrahepatic cholestasis of pregnancy. Obstet Gynecol, 2014. 124(1): p. 120-133

Clinical Case Summary

MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a rare mitochondrial disorder characterized by multisystem involvement, particularly in the neurological, cardiovascular, and gastrointestinal (GI) systems. GI manifestations are less commonly discussed but can present significant clinical challenges, including dysmotility, bowel ischemia, and obstruction.
A 19-year-old male, with a family history of MELAS affecting multiple relatives, was admitted with status epilepticus and other associated neurological and cardiovascular symptoms. On admission, the patient exhibited severe metabolic acidosis and elevated lactate levels, raising suspicion for mitochondrial dysfunction. During his ICU stay, he was found to have significant GI symptoms, including a post-operative ileus likely secondary to dysmotility syndrome associated with MELAS. He was subsequently diagnosed with a faecal bezoar causing large bowel obstruction (LBO) in the sigmoid colon, requiring laparotomy with disimpaction of the faecal mass, and decompression of the small and large bowel. There was evidence of bowel ischemia during the surgical exploration, with friable mucosa and necrotic areas observed in the proximal rectum and descending colon. Fortunately, all bowel sections were viable after decompression, and no further ischemic damage was noted.
This case highlights the importance of considering gastrointestinal complications, such as fecal bezoars and bowel ischemia, in patients with MELAS syndrome. GI manifestations, though less commonly recognized, can lead to significant clinical issues such as bowel obstruction and ischemic damage. Early intervention, including surgical management and decompression, is crucial to preventing further complications. Awareness of these potential issues is essential for clinicians managing patients with MELAS, as prompt treatment can improve outcomes and mitigate the risk of severe long-term GI dysfunction.

References

1. Colonoscopy images of diffuse friable mucosa with necrosis in sigmod colon and descending colon

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

Diabetes mellitus (DM) is a risk factor of pancreatic cancer (PC), but the effect of glycemic control on PC development among patients with long-standing type 2 diabetes (T2D) is not well investigated.

Aims & Methods

We aimed to investigate the benefit effect of optimal glycemic control on PC development in patients with long-standing T2D. In this retrospective cohort study, adults with newly diagnosed T2D between 2001 and 2015 were identified from a territory-wide electronic healthcare database. T2D diagnosis was based on the American Diabetes Association criteria, ICD-9 codes, or use of anti-diabetic medications. Exclusion criteria were prior history of PC, immunoglobulin G4 disease, pancreatectomy and PC cases occurring within three years of T2D diagnosis (to address reverse causality). The primary outcome was PC, while secondary outcome was PC-related mortality. For primary exposure, optimal glycemic control was defined as time-weighted mean hemoglobin A1c (HbA1c) <7%, For secondary exposure, optimal glycemic control was defined as fasting glucose (FG) ≤7mmol/L. Adjusted hazard ratios (aHRs) were derived from propensity score (PS) regression adjustment for 28 covariates including age, sex, smoking, alcohol use, body mass index, diabetes complications, history of pancreatitis and cholangitis, comorbidities, and medications (aspirin, statins, anti-diabetic drugs).

Results

Among 458,331 T2D patients (mean age:60.0±12.1 years; 51.2% male), there were 257,659 and 200,672 patients with optimal and suboptimal glycemic control. Among them, 1,382 (0.3%) developed PC and 922 (0.2%) died from PC over a mean follow-up of 10.8±4.1 years. Optimal glycemic control was associated with lower PC risk – HbA1c <7% (aHR:0.43; 95%CI:0.37-0.48) and FG <7mmol/L (aHR:0.71; 95%CI:0.63-0.80). Optimal control of both HbA1c and FG conferred lowest PC risk (aHR:0.39; 95% CI:0.33-0.46). Optimal control was also associated with lower PC-related mortality – HbA1c <7% (aHR:0.35; 95%CI:0.30-0.41) and FG <7mmol/L (aHR:0.69; 95%CI:0.59-0.79). Every 1% rise in HbA1c and 1mmol/L rise in FG was associated with higher PC risk by 46% (95%:39-35%) and 14% (95% CI:11-17%), respectively. When compared with HbA1c <7.0%, higher HbA1c conferred stepwise increase in PC risk (P_trend<0.001), with aHRs being 1.85 (95% CI:1.59-2.16), 2.52 (95% CI:2.10-3.02), 3.47 (95%CI:2.81-4.29), 3.58 (95% CI:2.76-4.66) and 4.61 (95% CI:3.72-5.70) for HbA1c levels of <7%, 7.0 to <7.5%, 7.5 to <8.0%, 8.0 to <8.5%, 8.5 to <9.0% and ≥9.0%, respectively. When compared with FG <7.0%, higher FG also conferred stepwise increase in PC risk (P_trend<0.001), with aHRs being 1.36 (95% CI:1.20-1.54) and 2.53 (95% CI:1.99-3.22), respectively.

Conclusion

Optimal glycemic control was associated with lower risk of PC risk and PC-related mortality in T2D. Further multicenter cohort studies are warranted to confirm its oncopreventive strategy.

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

	EUS-guided 32P implantation	SBRT
Total number of patients	58	61
Median Age (IQR)	70 (62-79)	72 (65-76.5)
Female (no. %)	25 (43 %)	25 (41%)
ECOG (no. %) 0 1 2	32 (55%) 18 (31%) 8 (14%)	22 (37%) 29 (48%) 10 (15%)
Neoadjuvant chemotherapy (no. %) FOLFIRINOX Gemcitabine/Nab-Paclitaxel Gemcitabine Concurrent chemotherapy Capecitabine	47 ( 73.8%) 8 (19.0%) 3 (7.1%)	42 (71.2%) 13 (18.6%) 6 (10.2%) 19 (32.2%)
Location of tumour (no. %) Head/uncinated/neck Body/Tail	36 (62%) 22 (38%)	47 (78%) 14 (22%)
Median Tumour Volume (Cc) (IQR)	35.0 (20-47.5)	37.5 (20.6-56.2)
Median baseline Ca 19-9 (U/mL) (IQR)	120 (34.75-272.25)	135.5 (26.25-482.75)

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.