Introduction

Pancreatic cancer (PC) presents as a highly aggressive malignancy characterized by limited treatment modalities and a poor prognosis. Its prevalence is steadily increasing, with projections indicating that it will rank as the second most common cause of cancer-related mortality by the year 2030, reflecting a substantial escalation in the global burden ^[1]. Due to the early metastasis of PC and the limited efficacy of current treatment for advanced stages, the overall five-year survival rate remains below 9% ^[2-3]. Therefore, the development of novel therapeutic approaches is crucial.
In recent years, there has been a surge of interest in natural products due to their perceived potential as anti-cancer agents. Our initial findings suggest that the co-administratin of Formononetin (FMN, a compound derived from Astragalus mongholicus) combined with Salvianolic Acid B (SalB, one of the major water-soluble components of Salvia miltiorrhiza), referred to as "FcS" in subsequent sections of this study, effectively suppresses the proliferation, metastasis, and promotes apoptosis of Panc-1 cells in a zebrafish embryo xenograft model. While FMN and SalB individually inhibited the PC cell viability, their combined treatment exhibited a stronger and significant suppressive effect. However, the mechanism of this combined treatment suppressing the malignant progression of PC remains unclear.

Aims & Methods

This study aims to assess the potential therapeutic effectiveness of FcS therapy for PC, with a focus on investigating the impact of this treatment strategy on PC cell survival, proliferation, and migration capabilities through a series of experiments conducted in vitro and in vivo. Additionally, our study investigated the expression of MBOAT2 in PC and its correlation with prognosis and tumor invasion.
The proliferation of PC cells was evaluated through the utilization of CCK-8 and EdU assay in vitro experiments to investigate the effects of FcS. Wound healing assay and transwell assay were conducted to assess the impact of FcS on the migration and invasion of PC cells. Through molecular docking and analysis of the Cancer Genome Atlas (TCGA) database, the potential regulatory factor MBOAT2 was identified. A Mboat2 knockdown cell line was established and treated with FcS to investigate the interaction between MBOAT2 and FcS. In vivo experiments were conducted using the LSL-Kras (G12D/+), LSL-Trp53 (R172H/+), and Pdx-1-Cre (KPC) transgenic mouse model, with tumor weight serving as a measure of the effects of FcS. Immunohistochemistry was utilized to assess protein expression levels from mice tumor tissues.

Results

Experiments conducted on three PC cell lines revealed that treatment with FcS resulted in reduced cell viability, inhibited proliferation, and decreased cell migration and invasion. Furthermore, analysis of TCGA data was utilized to investigate the impact of FcS on MBOAT2 expression in pancreatic cancer cells, demonstrating a down-regulation of MBOAT2 and subsequent reductions in viability, proliferation, and invasion. Additionally, the study identified the JAK/STAT signaling pathway as a potential regulatory mechanism. In vivo administration of FcS also exhibited tumor growth suppression in a KPC transgenic mouse model.

Conclusion

FcS treatment may be effective in suppressing the growth and invasion of PC cells through the downregulation of MBOAT2. The unique contribution of this research lies in the therapeutic impact of combining natural compounds and identifying MBOAT2 as a potential target, along with the involvement of the JAK/STAT signaling pathway.

References

1. Wungki, Park,Akhil, Chawla,Eileen M, O'Reilly,Pancreatic Cancer: A Review [J]. JAMA, 2021, 851-862. https://doi.org/10.1001/jama.2021.13027
2. Rebecca L, Siegel,Kimberly D, Miller,Ahmedin, Jemal,Cancer statistics [J]. CA Cancer J Clin. 2020, 7-30. https://doi.org/10.3322/caac.21590
3. Ahmedin, Jemal,Rebecca, Siegel,Elizabeth, Ward et al. Cancer statistics [J]. CA Cancer J Clin, 2006,106-130. https://doi.org/10.3322/canjclin.56.2.106

Clinical Case Summary

Intragastric balloons (IGBs) have emerged as a treatment option for obesity, bridging the gap between lifestyle modification/pharmacotherapy and bariatric surgery. The Allurion IGB is a swallowable balloon that spontaneously degrades after residing in the stomach for 4 months, allowing the balloon to be naturally excreted. Here we present a novel strategy for removing an Allurion intragastric balloon at a non-specialist centre using standard endoscopic accessories.

A 57-year-old female presented 4 weeks following insertion of an Allurion IGB abroad with severe abdominal pain and emesis after every meal since balloon placement. Contrast CT showed the IGB inflated within the fundus but no evidence of intestinal obstruction or perforation. Following consultation with other centres, we proceeded with endoscopic removal under general anaesthetic and with surgical support. On gastroscopy, 1L of food residue was aspirated and the IGB was seen in the stomach. An endoscopic ultrasound (EUS) 19Fr aspiration needle was used to puncture the balloon. 200ml was aspirated with a 50ml syringe. The remaining fluid was released with a further puncture performed using grasper forceps. The balloon was then successfully retrieved with grasper forceps. The patient’s symptoms resolved and she was discharged two days later.

The technique described here allows for safe retrieval of an Allurion IGB using endoscopic accessories available at hospitals without a dedicated bariatric service. Nausea and pain are often encountered following IGB insertion and occasionally necessitate endoscopic balloon retrieval. Although general anaesthetic for IGB removal remains contentious, we felt this represented the safest strategy given the documented risks of aspiration as well as the lack of prior experience at our centre. With increasing numbers of patients undergoing weight-loss interventions, familiarity with strategies for addressing their complications is crucial, even at non-specialist centres.

References

Bazerbachi F, Vargas EJ, Abu Dayyeh BK. Endoscopic Bariatric Therapy: A Guide to the Intragastric Balloon. American Journal of Gastroenterology. 2019;114(9):1421-1431. doi:10.14309/ajg.0000000000000239

National Institute for Health and Care Excellence. Swallowable gastric balloon capsule for weight loss: interventional procedures guidance [IPG684]. Published 18 November 2020.

Introduction

According to the ROME IV criteria, functional dyspepsia (FD) can be subdivided into PDS (postprandial distress syndrome) with meal-related symptoms such as early satiation and postprandial fullness and EPS (epigastric pain syndrome) with meal-unrelated complaints such as epigastric pain or burning. Nausea can also co-exist in FD but the literature is poor in reporting whether this symptom is mainly triggered by meal ingestion. A recent global epidemiology study of gastroparesis-like symptoms showed that the prevalence of nausea or vomiting, in combination with postprandial fullness or early satiation varies between continents.¹

Aims & Methods

This study aims to compare the difference in prevalence rates of nausea within each FD subgroup between western and eastern secondary and tertiary care centers. Adult patients with disorders of gut-brain interaction (DGBI) recruited in 9 western and 7 eastern secondary and tertiary care facilities between the ages of 18 and 70 years completed the Enhanced Asian Rome IV questionnaire (Asian European Gastrointestinal Symptoms cohort or AEGIS). The western centers were located in Belgium, Bulgaria, France, Israel, Italy (2x), Slovakia, Sweden and The United Kingdom while the eastern centers were located in Australia, China, Iran, Japan, Malaysia and Singapore (2x). FD patients were divided into PDS, EPS and PDS-EPS overlap (OVP) subgroups. Patients were furthermore classified as having nausea when this symptom was reported at least once per week. The questionnaire EARQ4 questionnaire was also used to address the relationship between nausea and food intake. Patients were asked how often they experienced nausea, whether nausea was triggered or worsened by meal intake, how often nausea occurred after a meal and if so, how soon after a meal nausea started. A comparison of the prevalence of nausea and meal-related nausea was made between eastern and western patients and among FD subgroups. Continuous variables are reported as median (IQR) and compared with a Kruskal-Wallis test. Categorical variables were compared using a Pearson Chi-square test.

Results

Of the 1074 DGBI patients that completed the survey, 483 were classified as having FD (59.4% PDS, 27.5% EPS, 13.0% PDS-EPS overlap). FD patients from eastern (N=202) and western sites (N=281) had a similar body mass index (22.5 (19.6-25.7) vs. 21.3 (19.7-25.4)kg/m²) and age (39.0 (29.0-55.0) vs. 38.0 (26.0-54.0) years). Eastern sites included significantly more female patients than western sites (43 % vs. 17.5%, p<0.001). PDS and EPS patients from eastern sites had significantly less nausea than PDS and EPS patients from western sites (17.9% vs. 46.3% and 6.8% vs. vs 40.5% respectively, both p<0.001). The majority of FD patients with nausea experienced meal-related nausea with no difference between eastern and western sites (63.9% vs. 73.7%). In PDS patients with nausea, nausea was significantly more triggered or worsened by a meal (72.4%) than in PDS-EPS overlap and EPS (48.6% and 35.3% respectively; p<0.001). All groups reported that meal-related nausea started mostly (> 85%) within 60 minutes after the meal.

Conclusion

In contrast to previous literature, we found that western PDS and EPS patients report nausea more frequently than eastern PDS and EPS patients. In both eastern and western patients nausea was mostly meal-related. Meal-related nausea is more common in PDS than in PDS-EPS overlap and EPS patients. Further research is needed to investigate the role of ethnic factors in the pathophysiology of nausea in functional dyspepsia.

References

Huang IH, Schol J, Khatun R, et al. Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United Eur Gastroenterol J. 2022;10(8):888-897.

Disclosure

Bert Broeders received lecture fees from the Rome Foundation.

Clinical Case Summary

We present a case of the extremely rare Sarcina Ventriculi infection in a 75-year-old female, adhering to a predominantly vegetarian diet, suffering with chronic dyspepsia, abdominal pain, vomiting and weight loss over a period of six months. Blood tests were consistent with iron deficiency anaemia. Imaging studies initially showed distended stomach with possible gastroparesis and later revealed significant gastric outlet obstruction (GOO) secondary to a suspected duodenal mass. Several gastroscopies were performed which initially showed gastric stasis and later revealed a strictured, oedematous duodenal wall with a duodenal ulcer. Biopsies from the duodenum showed chronic inflammation and bacterial colonies consistent with Sarcina Ventriculi. Biopsies were negative for Helicobacter pylori and there was no evidence of dysplasia or invasive malignancy on multiple levels examined. Although there are no treatment guidelines for Sarcina Ventriculi infection we tried a combination of Ciprofloxacin, Metronidazole and Omeprazole based on the results of the limited case reports^[1] of patients diagnosed with this infection. After completion of the 1-week antibiotic course, the stricture had significantly improved and Sarcina Ventriculi bacteria were not detected on repeat biopsy. Unfortunately, despite the treatment, our patient developed life-threatening complications of a bleeding duodenal ulcer and perforation requiring exploratory laparotomy. The incidence of Sarcina Ventriculi infection appears to be rising. This case highlights the urgent need for research to identify the most effective management for Sarcina Ventriculi infection and to create standardised treatment guidelines for its management. Clinicians managing patients with Sarcina Ventriculi infection should be vigilant about the potential complications ranging from gastroparesis and gastrointestinal ulcers to life threating presentations such as GOO, emphysematous gastritis and gastrointestinal perforation.

References

Figure 1 - Endoscopic view before treatment showing gastric food residue with pyloric obstruction secondary to distal duodenal stricture.
Figure 2 - Endoscopic view before treatment showing tight stricture with mucosal oedema at D2 causing complete gastric outlet obstruction.
Figure 3 - Histopathology slide of duodenal biopsy of the patient, showing Sarcina Ventriculi bacteria seen as the characteristic cuboidal and tetrahedral structures, on a background of chronic inflammation.
Figure 4 - Endoscopic view of duodenum after treatment with antibiotics showing improvement of the duodenal stricture and mucosal oedema, allowing a clearer view of the duodenum, and revealing a distal stricture bleeding duodenal ulcer.

[1] Tartaglia D, Coccolini F, Mazzoni A, Strambi S, Cicuttin E, Cremonini C, et al. Sarcina Ventriculi infection: a rare but fearsome event. A Systematic Review of the Literature. International Journal of Infectious Diseases. 2021;115: 48-61.
https://doi.org/10.1016/j.ijid.2021.11.027

Introduction

Heyde syndrome is the co-occurrence of aortic stenosis and gastrointestinal bleeding secondary to vascular lesions, including angiodysplasias. Several studies have demonstrated cessation of gastrointestinal bleeding after transcatheter aortic valve implantation (TAVI), but the etiology and effects on vascular lesions are largely unknown.

Aims & Methods

We aimed to establish the effects of TAVI on gastrointestinal vascular lesions and identify the factors associated with recovery. In this prospective, single-center cohort study, patients with iron-deficiency anemia on the TAVI waitlist from September 2020 to February 2022 were assessed by capsule endoscopy. Those with vascular lesions were reassessed six months after TAVI. Endoscopic images were anonymized and evaluated by two independent researchers.

Results

Twenty-four patients underwent capsule endoscopy, and vascular lesions were present in 18 (prevalence 75%). TAVI was performed in 15/18 patients with vascular lesions, of which 11 agreed to a second capsule endoscopy. The mean number of vascular lesions across the gastrointestinal tract decreased from 6.4 (SD 5.6) to 2.0 (SD 2.1) (P = .036). The number of vascular lesions decreased in 9/11 (82%) patients, including 6/11 (55%) who no longer had typical angiodysplasias. Cessation of angiodysplasias was less frequent in patients who had multiple valvular heart disease before TAVI (0/3 [0%] vs 6/8 [75%]) and patients with significant paravalvular leakage after TAVI (2/5 [40%] vs 4/6 [67%]).

Conclusion

Angiodysplasias are present in 75% of anemic patients with severe aortic stenosis. TAVI effectively reduces the size and number of angiodysplasias in these patients.

Disclosure

Lia Goltstein, Maxim Rooijakkers, Naomi Thierens, Selene Schoormans, Charles Houdeville, Marlijn Hoeks, and Sanna Rijpma do not have potential conflicts of interest or disclosures to report. Hanneke Beaumont has received speaker fees from Medtronic. Erwin van Geenen has received research funding from Viatris, Boston Scientific, and Olympus and serves as a consultant for MTW-Endoskopie and Microtech. Xavier Dray is cofounder and shareholder of Augmented Endoscopy, has served as a consultant for Norgine and Provepharma, and received speaker fees from Bouchara Recordati, Fujifilm, Medtronic, Norgine, and Sandoz. Niels van Royen has received research funding from Abbott, Philips, Medtronic, and Biotronik, has served as a consultant for RainMed, Castor, and Medtronic, and received speaker fees from Abbott. The Radboudumc, on behalf of Joost Drenth, has received research funding from Gilead to support Hepatitis C elimination in The Netherlands.