Introduction

Intraductal papillary mucinous neoplasms (IPMN) have a potential to evolve into pancreatic adenocarcinomas. While main-duct IPMN (MD-IPMN), involving the main pancreatic duct (MPD), are less common than side-branch IPMN (SB-IPMN) or mixed-type IPMN (mixed-IPMN), their malignant transformation potential is far greater. Current guidelines refer to worrisome radiological features and high-risk stigmata of IPMN in dictating recommended management strategies, whether surgical resection, endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) or long-term radiological follow-up. However, controversy exists between different guidelines in terms of recommended follow up duration.

Aims & Methods

To assess the utility of radiological follow up of MD-IPMN and mixed-IPMN, including prevalence of worrisome radiological findings and their correlation to development of progression or pancreatic adenocarcinoma.
​Eighty-four patients with MD-IPMN or mixed-IPMN who underwent at least one magnetic resonance cholangiopancreatography (MRCP) at our medical center were included. Clinical and laboratory data were obtained retrospectively from their medical records, and imaging tests were revised. A cross-sectional analysis was aimed to point clinical and laboratory parameters associated with development of pancreatic adenocarcinomas. A retrospective cohort study was performed on 44 patients of the study population, who had at least six months of follow up (mean follow up time 26.51±18.75 months), trying to point factors correlating with worrisome radiological features.

Results

Nine cases of pancreatic adenocarcinoma were recorded in the cohort (10.7%). These were diagnosed in 7 patients at presentation, whereas 2 patients developed them during follow up period. Factors associated with cyst progression greater than 5 mm during follow up were alanine aminotransferase (ALT) levels (p=0.007), maximal cyst size (p=0.02), MPD diameter (p=0.01) and the presence of jaundice (p=0.04) or a sense of abdominal fullness (p=0.008). The cross-sectional analysis indicated that pancreatic adenocarcinoma was associated with complaints of nausea (p=0.01), as well as elevation of aspartate aminotransferase (AST) (p=0.05), gamma glutamyl transpeptidase (GGT) (p=0.01) and alkaline phosphatase (ALP) (p=0.01).

Conclusion

This study demonstrates the association between clinical findings and elevated liver enzymes and the risk of IPMN malignant transformation. Although further studies are needed, these data may aid in risk stratifying patients when determining the duration and mode of follow up for IPMN.

Introduction

The need for endoscopic necrosectomy (EN) has increased dramatically, as endoscopic EUS-guided drainage has become gold standard for treatment of pancreatic walled-off-necrosis (WON)[1,2]. Although snares and baskets are commonly used in EN procedures, they can be ineffective and dedicated instruments specifically designed for EN are scarce. Recently, an innovative powered endoscopic debridement system (EndoRotor, Interscope Inc., Northbridge, MA, USA) designed to excise and remove necrotic tissue within the WON was introduced specifically for EN with promising results[3,4]. While the first generation EndoRotor catheter was limited to 3.2 mm diameter, a larger catheter that fits into a large-channel gastroscope with a working channel of 6.0 mm has now been introduced. This study evaluates the clinical outcomes, safety, and feasibility of the novel 6.0 catheter for EN of WON.

Aims & Methods

This retrospective study was performed using prospectively collected data from all patients who underwent EN with the 6.0 catheter between December 2021 and March 2023 at Gastro Unit, Copenhagen University Hospital Hvidovre, a tertiary referral center in Denmark. All patients with symptomatic WON and need for necrosectomy were considered eligible for this study. Technical feasibility, safety, and clinical outcomes were evaluated.

Results

Sixteen patients underwent a total of 25 EN procedures with the 6.0 catheter. The mean age of the patients was 51.8 years (SD 17.7 years) and 11 (68.8%) were male. The etiology of the acute necrotizing pancreatitis was alcohol in 4 patients (25.0%), gall stones in 7 patients (43.8%), post-endoscopic retrograde cholangiopancreatography (ERCP) in 3 patients (18.8%), and idiopathic in 2 patients (12.5%). The mean size of the WON was 27.5 cm (SD 10.5 cm). The median computed tomography severity index (CTSI) was 8.5 (P25-P75: 6.0-9.0) and median modified CTSI (mCTSI) was 9.0 (P25-P75: 8.0-10). Two patients did not achieve clinical resolution (12.5%), as they died from multisystem organ failure before resolution of the WON was achieved. The median length of stay in hospital for the patients who achieved clinical resolution was 56.0 days (P25-P75: 36.5-96.0 days) and the median number of necrosectomy procedures performed to achieve clinical resolution was 5.0 (P25-P75: 2.0-8.5). All patients had EN procedures performed with snares in addition to the procedures with the powered debridement system. Five patients had necrosectomy performed with the 3.2 catheter (31.0%) as well as the 6.0 catheter. The median duration of EN with the 6.0 catheter was 60.0 minutes (P25-P75: 45.0-100 minutes) per procedure.
A device-related adverse event was noted in one instance (4.0%). The patient exhibited symptoms of peritoneal reaction in the hours following the procedure, which may have been caused by perforation of the WON into the peritoneal cavity. The patient was treated with laparoscopic peritoneal lavage and drainage and recovered without further interventions. No other procedure-related adverse events were identified. Malfunction of the catheter was observed in 7 procedures (28.0%).

Conclusion

To perform necrosectomy procedures optimally, dedicated endoscopic instruments designed for debridement of pancreatic WON are required. This study suggests that EN with the novel EndoRotor 6.0 catheter is safe and feasible with promising clinical results for EN of pancreatic WON. To assess the efficacy relative to standard techniques, comparative studies are warranted.

References

[1] Karstensen JG, Novovic S, Hansen EF, et al. EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: A single-centre randomised controlled trial. Gut 2022; 0: 1–7. doi:10.1136/gutjnl-2022-328225
[2] Ebrahim M, Werge MP, Hadi A, et al. Clinical outcomes following endoscopic or video-assisted retroperitoneal management of acute pancreatitis with large (>15 cm) walled-off pancreatic necrosis: Retrospective, single tertiary center cohort study. Dig Endosc 2022; 34: 1245–1252. doi:10.1111/den.14295
[3] Stassen PMC, de Jonge PJF, Bruno MJ, et al. Safety and efficacy of a novel resection system for direct endoscopic necrosectomy of walled-off pancreas necrosis: a prospective, international, multicenter trial. Gastrointest Endosc 2022; 95: 471–479. doi:10.1016/J.GIE.2021.09.025
[4] Wiel SE van der, May A, Poley JW, et al. Preliminary report on the safety and utility of a novel automated mechanical endoscopic tissue resection tool for endoscopic necrosectomy: a case series. Endosc Int Open 2020; 08: E274–E280. doi:10.1055/A-1079-5015

Introduction

In recent years, evidence shows that long non-coding RNAs (lncRNAs) are key regulators of gene transcription and play important roles in the pathogenesis of inflammatory bowel diseases. LncRNAs are involved in the regulation of intestinal epithelial cell apoptosis, cell-cell interactions, and enhancing inflammation, among others. Biological therapies, which are considered the most potent for disease control, only benefit one-third of patients. For this reason, a deeper understanding of the mechanisms by which biological drugs elicit their effect on intestinal mucosal is needed. Hence, we aimed to unravel the ex vivo modulator effect of infliximab on the lncRNAs expression in intestinal biopsies from patients with Crohn´s Disease (CD).

Aims & Methods

We performed an unbiased transcriptomic analysis of intestinal biopsies from the ileum and colon from 30 patients [active CD = 10, quiescent CD = 10, healthy controls (HC) = 10] to identify lncRNA differentially expressed in the setting of infliximab modulation. Endoscopic biopsies were cultured with or without infliximab and the transcriptome was determined by Illumina gene expression array. We used different databases (Ensembl Biomart, RNAcentral and ToppGene) to search for non-annotated lncRNA information and data on the location (cellular component), biological process and molecular function of differentially expressed lncRNAs.

Results

Transcriptomic results revealed a widespread dysregulation of lncRNAs in ileum biopsies from patients with active CD, quiescent CD and HC compared to the colon at baseline and after infliximab culture. These differentially expressed lncRNAs were enriched in such pathways as proliferation, apoptosis, migration, inflammatory response of fibroblasts, response to wounding, posttranscriptional regulation of inflammatory genes and activation of the mitogen-activated protein kinase signaling pathways. Regarding the effect of infliximab according to intestinal location, presence of disease and activity, no significant lncRNAs were identified in the different study comparatives.

Conclusion

We have characterized the basal transcriptomic landscape of lncRNAs in patients with CD (active and quiescent) and HC both in ileum and left colon. However, we have not found differential lncRNA expression due to the effect of infliximab, suggesting that the location (ileum or colon) is more relevant when analyzing differences in lncRNA expression in the intestinal tissue.

Introduction

Gastroenterology (GE) is a medical discipline that studies all diseases of the digestive system. It comprises several areas of study and offers a large variety of sub-specializations: proctology, interventional endoscopy or even digestive oncology. The decisive elements in the choice of this specialty vary among interns. The aim of our study is to determine the various factors influencing the choice of gastroenterology as a specialty among medical interns.

Aims & Methods

This is a cross-sectional, multicentric, survey-type study, conducted from September 1 to 30, 2023, involving 7 national medical faculties. All medical interns, regardless of sex or age, participated in our study.
An electronic survey with 29 items was created using Google Forms®. It was divided into two parts: the first part contained 13 questions on socio-demographic characteristics and exposure to GE during the academic curriculum, while the second part concerned the factors motivating the choice or not of GE as a specialty.
A statistical analysis using the Fisher’s exact test was performed. P values of <0.05 were considered statistically significant. Data were analyzed using Jamovi (Version 2.3).

Results

A total of 329 responses were collected: the majority were women 208 (63.2) with a F/M sex ratio of 1.7 and a median age of 27 [25; 28] years. The majority had already completed a GE rotation during their training course n=205 (62.3), of which 90 (44.1) had found it "satisfactory". More than half of the participants n= 178 (54.1) had already considered GE as a future specialty, and this choice was mostly made during GE lectures given in medical school n= 66 (36.9). Among those who had never considered GE, the main reasons were lack of interest in the specialty, the fact that it is a medical specialty, lack of information about GE, potential remuneration, and dissatisfaction with GE rotation during the training course (59.2%, 28.9%, 13.9%, 10.4% and 10% respectively).
Among those who finally opted for GE, the majority were women (70.2% vs. 29.8%, p=0.004). Satisfaction with the GE rotation during the training course had an impact on the final choice: "satisfactory" vs. "mediocre" (43.8% vs. 6.3% p=0.009).
Multivariate analysis showed that early interest in fields such as endoscopy (OR= 4.46, CI95%: 1.44-13.78, p=0.009) or proctology (OR= 4.26, CI95%: 1.01-18.01, p=0.05) increased the chance of choosing GE.

Conclusion

This study showed that there is a gender disparity in the choice of GE as a specialty. The fact that it is a medical discipline may lead men to choose another path. Our study also highlighted the importance of GE training courses during the medical curriculum to motivate interns to join our specialty, as well as the need to spotlight certain areas such as endoscopy or proctology.

Introduction

Patients with ulcerative colitis (UC) report that UC negatively affects their quality of life (QoL), including sexual functioning, satisfaction, and drive.^1,2 These effects are rarely discussed with or by gastroenterologists in clinical practice. The CONFIDE study aims to elucidate the impact of symptoms on the lives of patients with moderate to severe UC in the United States (US), Europe (EU5; France, Germany, Italy, Spain, and UK), and Japan. Data presented here are from the US and EU5.

Aims & Methods

Online, quantitative, cross-sectional surveys were conducted (July–September 2021). Criteria based on previous treatment, steroid use, and/or hospitalization were used to define moderate-to-severe UC. Data collected included patient perspectives on the impact of UC on sexual activity. Sexual activity was not limited to intercourse and included activities such as masturbation.

Results

Surveys were completed by 200 US patients (male [M]=62%, mean age 40 years) and 556 EU5 patients (M=57%, mean age 39 years). Of these, 77% US and 54% EU5 patients were receiving advanced therapy (biologic/novel oral) and 52% and 73% were receiving steroids at the time of survey completion, respectively. Overall, 63% US patients (M=55%, female [F]=77%) and 53% EU5 patients (M=47%, F=60%) reported avoiding or decreasing sexual activity due to UC in the 3 months prior to the survey. Among these patients (US: N=126; EU5: N=292), most frequently reported reasons for avoidance of sexual activity were bowel urgency (BU; 41%), decreased sexual desire (37%), and fear of BU-related accidents (34%) in the US and fear of faecal seepage (37%), fear of BU-related accidents (36%), and BU itself (31%) in EU5. Although reasons for avoiding sexual activity were broadly similar between sexes, higher percentage of male patients from both US and EU5 (US: M=33%, F=24%; EU5: M=42%, F=33%) reported fear of faecal seepage as a factor affecting sexual activity. Conversely, higher percentages of female patients reported perianal pain (M=13%, F=19%) and self-consciousness (M=13%, F=24%) as reasons for avoiding sexual activity in the US and decreased sexual desire (M=16%, F=26%), BU (M=26%, F=36%) and fatigue (M=14%, F=22%) in EU5.

Conclusion

In both US and EU5 populations, >50% patients with moderate-to-severe UC reported avoiding or decreasing sexual activity due to UC, with bowel urgency and bowel urgency-related accidents being among the top three reasons. In addition to other QoL parameters, impact of UC on patients’ sexual health needs to be assessed in routine clinical practice.

References

¹Bulut AE, et al. Turk J Gastroenterol. 2019;30:33-39.
²Jedel S, et al. Inflamm Bowel Dis. 2015;21:923-38.

Disclosure

Simon Travis, Grants: Ferring Pharmaceuticals, AbbVie, Schering-Plough, MSD, Procter & Gamble, Warner Chilcott, International Organization for the Study of IBD, ECCO, UCB, Vifor Pharma, Normal Collision Foundation, Buhlmann, Takeda, Janssen, Pfizer, and Eli Lilly and Company.
Marla C. Dubinsky, Consultancy fees: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Celgene Corporation, Eli Lilly and Company, F. Hoffman-La Roche Ltd, Genentech Inc., Gilead Sciences, Janssen, LLC, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals USA, Inc., and UCB; Stockholder: Trellus Health Inc.; Research support: AbbVie, Janssen, LLC, Pfizer, and Prometheus Biosciences.
Toshifumi Hibi, Consultancy fees/grant/research support/speaker: AbbVie GK, ActivAid, Alfresa Pharma Corporation, Apo Plus Station, Aspen Japan K.K, Bristol-Myers Squibb, Celltrion, EA Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, JMDC Inc., Kyorin, Mitsubishi-Tanabe Pharma Corporation, Mochida Pharmaceutical, Nichi-Iko Pharmaceutical, Nippon Kayaku Co. Pfizer, Takeda Pharmaceutical, Zeria Pharmaceutical, and MIYARISAN Pharmaceutical.
David T. Rubin, Grants/contracts: Takeda; Consultancy fees: AbbVie, Altrubio Inc., Allergan, Inc., American College of Gastroenterology, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Celgene Corp/Syneos, Cornerstones Health, Inc. (non-profit), GalenPharma/Atlantica, Genentech/Roche, Gilead Sciences, GODURN, LLC, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen, Eli Lilly and Company, Materia Prima, Pfizer, Prometheus Biosciences, Reistone Biopharma, Takeda, and Techlab Inc; Stockholder: Altrubio and Datos Health.
Remo Panaccione, Consultancy/speaker fees and/or advisory board member: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; Consultancy fees and/or advisory board member: Alimentiv, AstraZeneca, Biogen, Boehringer Ingelheim, Genentech, Glaxo-Smith Kline, JAMP Bio, Mylan, Novartis, Oppilan Pharma, Pandion Pharma, Progenity, Protagonist Therapeutics, Sublimity Therapeutics; Consultancy fees: Abbott, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Galapagos, JAMP Bio, Pendopharm, Satisfai Health, Theravance Biopharma, Trellus, Viatris, and UCB.
Stefan Schreiber, Consultancy and lecture fees: AbbVie, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Falk, Ferring Pharmaceuticals, Galapagos/Gilead, Genentech/Roche, Eli Lilly and Company, Janssen, MSD, Pfizer, and Takeda.
Christian Atkinson, Employee: Adelphi Real World; Consultancy: Eli Lilly and Company in connection with this study.
Alison P. Bleakman, Cem Kayhan, Theresa H. Gibble, Christophe Sapin, and Eoin J. Flynn are employees and stockholders of Eli Lilly and Company.

Introduction

Screening by fecal immunochemical test (FIT) reduces colon cancer (CC) mortality and incidence, yet its efficiency may vary depending upon tumor location and recipient demographics. We addressed the modifications of left and right CC epidemiology following screening adoption.

Aims & Methods

To address the differences between left and right CC, we analyzed by Joinpoint, robust and logistic regression models the data of Parma County tumor registry, comprising 6697 incident cases above 50 years of age in the period 1994-2018 and recording screening adherence since the start in 2005.

Results

Adjusted standardized rates of left-CC declined significantly within screening age (50-69 years) (male annual percent changes [APC] -8.38; p<.001; female APC -13.1; p=.007), as well above it (male APC-4.97; p=.001; female APC -3.96; p=.003). The incidence of right-CC did not decline in screening age and increased above (male APC, 1.91%; p=0.001; female APC, 2.23%; p<0.001). Robust regression confirmed that left-CC decreased irrespectively of sex and age (all p<.001, but for elder males, p=.03), pointing to significant increase of right-CC across sexes and ages (all p£.006).
In multivariable regression models, as compared left-CC the risk of right-CC almost doubled in the 7^thdecade (Odds Ratio 1.89, 95%CI 1.43-2.44; p=.001), was higher for females (OR 1.40; 95%CI 1.27-1.54; p<.001) and after screening adoption (OR 1.44, 95%CI 1.27-1.54; p<.001).
In sex specific models, the probability of right-CC in females increased from 65 years of age (OR 1.80, 95%CI 1.18-2.75; p=.007) and in males from 75 years (OR 1.58, 95% CI 1.09-2.27; p=.015).
Due to the unequal distribution of right-CC, the rate of interval cancers over screen detected ones was significantly different between males (78/315; 25%) and females (93/200; 46.5%; p=.0004).
Independently from screening participation, right-CC in females brought an increased risk only of stage II (OR 1.43, 95%CI 1.06-1.92; p=.017) while in males it also enhanced the risks of stage III (OR 1.54, 95%CI 1.17-2.02; p=0.002), and IV (OR 1.47, 95%CI 1.06-2.03; p=.02) cancers.
At Cox modeling, right-CC carried a lower risk of death in females than in males (HR 0.77, 95%CI 0.67-0.89; p<.001), independently from tumor stage and screening status.

Conclusion

The screening reduced only the incidence of left-CC, while that of right-CC raised with aging, primarily and earlier in females. Right-CC progression in males carried a higher risk of death. Unimodal administration of FIT was followed by increasing burden of right-CC, advocating awareness on its specific development and progression by sex and age.