Introduction

Multidisciplinary team meetings (MTM) have been adopted widely to ensure that oncological patients receive an optimal diagnosis, staging and treatment, especially in tertiary referral centers. The relevance of MTM on acute and chronic pancreatitis is unexplored.

Aims & Methods

The aim of this study is to describe the experience of a tertiary referral center MTM for pancreatic diseases in the management of patients with acute and chronic pancreatitis (AP/CP). A prospectively maintained database of patients with AP/CP discussed in MTM from 10/2020 to 01/2023 was queried and patients analyzed according with the subsequent clinical problems: etiology of AP (EAP), treatment of AP complications (TAP), etiology of chronic pancreatitis (ECP) and treatment of chronic pancreatitis complications (TCP).

Results

Globally 143 patients were included for a total of 201 discussions. 94 were AP and 49 CP (median/IQR age 55/43-68 years; males 58.3%). According with the established clinical questions:

• EAP (67 patients): the hypothesized etiology before MTM discussion was in most cases autoimmune (64%) or idiopathic (18%). Imaging revision alone at the MTM changed the suspicious etiology in 28%. After performing further investigations suggested by the MTM the final diagnosis was changed in additional 39% (3 overlooked cancers diagnosed).
• TAP (27 patients): mostly referred for pseudocysts (37%), management of complications in anatomical variants (17%), walled-off necrosis (13%). The problem was solved in 100% of cases, mostly by surgical (33%) or endoscopic (48%) treatments.
• ECP (14 patients): MTM changed the initial suspicion in 50% of cases, with previously unexplored genetic etiology in 64% of cases. 50% of initially idiopathic CP cases had a definite etiology.
• TCP (35 patients): mostly referred for appearance of focal lesion in CP (22%), pancreatic duct obstruction/stenosis (28%) or abdominal pain (28%) with resolution of the problem in 98% of cases by surgical (53%) or endoscopic (17%) treatments. Three malignant lesions were diagnosed.

Conclusion

Our observational study shows that a MTM conducted in tertiary referral center for pancreatic diseases allows to correctly establish etiology and treat complications in AP and CP. A high rate of previously overlooked malignancies were diagnosed and genetic defects identified.

Introduction

Angiodysplasias (AD) are the most common source of gastrointestinal (GI) bleeding of obscure origin in the elderly. In this population, GI AD often leads to red blood cell (RBC) transfusion-dependent anemia, resulting in high rate of hospitalizations and overuse of healthcare resources. Argon plasma coagulation (APC) is the standard treatment option, but it is an invasive procedure, with possible serious complications in the presence of significant comorbidities, and frequently ineffective in preventing recurrence of GI bleeding. Octreotide has been studied in this context, but currently it is not a widely recommended drug.

Aims & Methods

Aim: To evaluate the usefulness and safety of long-acting release-octreotide (LAR-OCT) in the control of bleeding from GI AD in elderly.
Methods: Retrospective study of patients diagnosed with chronic GI bleeding due to AD and treated with intramuscular LAR-OCT between January 2010 and December 2022 in a tertiary hospital was performed. Demographic and clinical data were collected. Exclusion criteria: LAR-OCT suspension before completing 6 months of treatment. Primary outcome: the presence of a normal Hb value (≥ 12g/dl) in the absence of any blood transfusions at 6 months(m) of therapy. Secondary outcomes: increase in Hb value, reduction of transfusional requirements and adverse events. Statistical analysis was performed with SPSS vs 25.0 (significance level of 0.05).

Results

Nineteen out of 23 patients completed at least 6m of LAR-OCT therapy. The mean age at diagnosis of AD was 74.2 years (62 to 89 years); 63.2% were female. The mean value of Charlson Comorbidity Index was 6.37 (estimated 10-year survival around 2%). Before starting LAR-OCT, 13 patients (68.4%) were under endovenous iron supplementation and 7 patients (36.8%) had undergone APC; 31.6% required at least 4 RBC units in the last month.
Primary outcome was achieved in 5 (21.7%) patients. There was a statistically significant increase in the Hb values in the first 6m of therapy (p=0.000). Three patients (15.8%) required RBC transfusions in this period, but only one presented with overt GI bleeding.
Only 8 patients achieved 24m of therapy, showing a statistically significant increase from initial to 24-m Hb values (p=0.012).
Twelve (52.2%) patients were under antithrombotic agents; there was a statistically significant difference between initial Hb and 6-m Hb value in this subgroup (p=0.002); between initial and 24-m values, there was an increase in the Hb value but not statistically significant (p=0.068).
Concomitant iron supplementation was performed in 13 and APC in 3 patients.
Adverse events were registered in 2 patients, leading to drug suspension in only 1 (dysrhythmia).

Conclusion

In the setting of “difficult-to-treat” patients with GI bleeding due to AD, octreotide has been proposed as an alternative therapeutic strategy. In this cohort of older patients, with a relatively low estimated 10-year survival due to its comorbidities, LAR-OCT appears to be effective in increasing Hb values while reducing the need of RBC transfusions and, therefore, the number of hospital admissions. This is particularly important in elderly patients, having a potential impact on their quality of life and on the healthcare costs associated with recurrent GI bleeding. Limitations of this study are the retrospective design, the small number of enrolled patients and the inability of analyzing the individual effect of LAR-OCT. Further studies are needed.

Introduction

Plummer-Vinson syndrome is a rare entity that associates dysphagia, iron deficiency anemia, and cervical esophageal membrane. Our work aimed to describe the clinical profile and to specify the predictive factors of degeneration in patients with Plummer-Vinson syndrome associated with esophageal cancer and to show interest in endoscopic surveillance.

Aims & Methods

It was a retrospective descriptive and analytical study over 30 years (1993-2023) including all patients treated and followed up for Plummer-Vinson syndrome and who presented esophageal cancer. Data collection and statistical analysis were performed by SPSS version 20.0 software.

Results

Out of the 160 patients treated for Plummer-Vinson syndrome, 15 patients had associated esophageal cancer resulting in a prevalence of 9.37%. The median age was 50.6 years with extremes of 28 and 74 years, with a sex ratio of M/F = 2/13. The interval between the diagnosis of Plummer-Vinson syndrome and the appearance of cancer was 8 years +/- 7.4.
All our patients with associated cancer had dysphagia with weight loss, odynophagia in 92.9% (n=13), clinical anemia syndrome in 59 %(n=8), and upper gastrointestinal bleeding in 10%(n=1). All patients had hypoferritinemia with a median value of ferritin 6.2μg/l.
The location of the Plummer-Vinson ring was at the level of the Killian triangle at 46%(n=7) and the upper third of the esophagus at 54%(n=8).
The location of the cancerous process at the level of Killian's triangle was in 46% of cases (n=7), and the location at the level of the upper third of the esophagus was in 19.7%(n=3). In 33.3% of cases (n=5) in the middle third. It was squamous cell carcinoma in all cases. Surgical treatment was initiated in 14% of cases (n=2), radio-chemotherapy in 72% (n=11) and refusal of treatment in 14% of cases (n=2). Two patients progressed well with the disappearance of dysphagia, 10 patients died between 5 months and 5 years of cancer progression, and the rest of the patients could not be followed up.
In multivariate analysis, the statistically significant predictive factors for the degeneration of Plummer-Vinson syndrome were: Age>50.6 years (OR= 2.37, p=0.003 CI=1.875-4.236), Ferritinemia <6.2 μg/l (OR=3.02, p=0.001 CI=0.977-12. 516) and location of the ring at the level of the Killian triangle (OR=1.140, p=0.001 CI=1.057-1.229). Gender and dysphagia did not appear to be associated with degeneration with (p=0.26) and (p=0.35) respectively.

Conclusion

Plummer-Vinson syndrome is a precancerous lesion requiring endoscopic surveillance. In our series, the prevalence was 9.37%. Malignant transformation of this ring at the level of the triangle of Killian was present in 46% of cases. The predictive factors of degeneration were advanced age, low ferritinemia, and the location of the ring in the mouth of Killian.

Introduction

In adults with primary sclerosing cholangitis (PSC), dominant stricture (DS) develops in up to 50% of the patients (1) and is associated with an impaired long-term prognosis (2). The impact of dominant stricture (DS) on the outcomes of paediatric-onset primary sclerosing cholangitis (PSC) is unknown.

Aims & Methods

This study was aimed at investigating the impact of DS on the clinical course and prognosis of patients with paediatric-onset PSC.
We identified patients with paediatric-onset PSC diagnosed between January 1993 and May 2017 from Helsinki University Hospital records or our PSC registry. The diagnosis of PSC was made according to the EASL Clinical Practice Guidelines (3). DS was defined as a stricture with a diameter less than 1.5 mm in the common bile duct or less than 1 mm in the hepatic duct within 2 cm from the bifurcation (4). Data including clinical (i.e., presence of inflammatory bowel disease (IBD), autoimmune hepatitis (AIH) and other autoimmune diseases), laboratory markers (i.e., bilirubin, alanine aminotransferase (ALT), gamma glutamyl-transferase (GGT), carbohydrate antigen 19-9, Ca 19-9) were collected. Endoscopic retrograde-cholangiography (ERC) images were scored for severity with the modified Amsterdam PSC-score). Therapeutic interventions (i.e., need of dilatation and stenting), and cytology (i.e., biliary dysplasia andaneuploidy) were collected. The following outcomes were evaluated: biliary dysplasia, cirrhosis, liver transplantation (LT) (for all indications: decompensated cirrhosis, repeatedly confirmed biliary dysplasia and hepatocellular carcinoma), cholangiocarcinoma (CC), and/or PSC-related-death. Fisher´s exact, Wilcoxon (Mann-Whitney) tests and the fitted univariate or multiple Cox regression models to calculate hazard ratios (HR) and 95% confidence intervals (CI), for selected variables were used. In these analyses, DS was treated as a time-varying variable.

Results

We traced 68 patients (42 males) with paediatric-onset PSC (median age at diagnosis 15 years). The median follow-up was 13 years and the median age at the last follow-up was 27 years. In total 35 (51%) had concomitant AIH. DS was diagnosed in 33 patients (48%): in eight at the time of PSC diagnosis (12%) and in 25 (37%) by the end of follow-up. DS appeared on a median of 3 years after PSC diagnosis; 20/33 patients (61%) were still < 18 years at the last follow-up. Out of 33 patients with DS, 21 (64%) needed dilatations and 11 (33%) stenting. In patients with DS, two developed cirrhosis, seven were transplanted and one patient was operated on for a biliary mass with low-grade dysplasia. In patients without a DS, two developed cirrhosis, and four were transplanted; one female was excluded from survival analysis because she already had cirrhosis at the time of PSC diagnosis. Cirrhosis or biliary dysplasia or needing LT for these indications were more frequent after the development of DS (10/33, adjusted HR 4.26, 95%CI: 1.26-14.4). Also, one unit increase of log-GGT at the time of PSC diagnosis was associated with these outcomes (13/54 adjusted HR 1.78 for one unit increase of log-GGT, 95%CI: 1.04-3.05). Sex or age at PSC diagnosis, overlap with AIH, association with another autoimmune disease or IBD, bilirubin, ALT, Ca 19-9, and modified Amsterdam PSC-score at PSC diagnosis were not associated with outcomes. No CC or death occurred during the follow-up.

Conclusion

DS was present at diagnosis or developed during follow-up in about half of the patients with paediatric-onset PSC and was associated with impaired outcomes.

References

1. Björnsson E, Olsson R. Dominant strictures in patients with primary sclerosing cholangitis-revisited. Am J Gastroenterol. 2004;99(11):2281.
2. Stiehl A, Rudolph G, Klöters-Plachky P, Sauer P, Walker S. Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment. J Hepatol. 2002;36(2):151-6.
3. easloffice@easloffice.eu EAftSotLEa, Liver EAftSot. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol. 2022;77(3):761-806.
4. Chapman MH, Webster GJ, Bannoo S, Johnson GJ, Wittmann J, Pereira SP. Cholangiocarcinoma and dominant strictures in patients with primary sclerosing cholangitis: a 25-year single-centre experience. Eur J Gastroenterol Hepatol. 2012;24(9):1051-8.

Introduction

Mirikizumab (miri), an anti-IL-23p19 antibody, demonstrated efficacy and safety in patients with moderately-to-severely active ulcerative colitis (UC) in the Phase 3 LUCENT-1 induction¹ (NCT03518086) and LUCENT-2 maintenance² (NCT03524092) trials. Bowel urgency (BU) remission and clinically meaningful improvement (CMI) are associated with clinical response and remission.³ This analysis evaluated if the addition of BU improvement to the achievement of clinical response or remission was associated with better quality of life (QoL).

Aims & Methods

In LUCENT-1, patients were randomized 3:1 to miri 300mg intravenous or placebo every four weeks. Miri-treated patients achieving clinical response to miri at week 12 (W12) were re-randomized 2:1 to subcutaneous miri 200mg or placebo Q4W for 40 weeks in LUCENT-2 (continuous treatment up to W52). Clinical remission is based on the modified Mayo Score (MMS) and was defined as: stool frequency subscore = 0 or 1 with a ≥1-point decrease from baseline; rectal bleeding (RB) subscore = 0; endoscopic subscore = 0 or 1. Clinical response was defined as ≥2-point and ≥30% decrease in the MMS from baseline, and RB = 0 or 1, or ≥1-point decrease from baseline. Patients’ QoL was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ): IBDQ response (≥16-point improvement from baseline in IBDQ total score) and IBDQ remission (IBDQ total score ≥ 170; higher scores indicating better disease specific QoL).^4,5 BU was assessed using the Urgency Numeric Rating Scale (UNRS), an 11-point scale ranging from 0 (“no urgency”) to 10 (“worst possible urgency”), with both BU CMI (≥3-point change) and BU remission (UNRS score of 0 or 1), measured in patients with a baseline UNRS of ≥3.⁶ The association between BU improvement (CMI or remission) and IBDQ (response or remission) was evaluated using the chi-square test of association among patients with baseline UNRS ≥3 who achieved clinical response. This analysis was repeated among patients who achieved clinical remission.

Results

Among patients achieving clinical response, a significantly higher proportion achieved IBDQ response and IBDQ remission when they also achieved BU CMI or BU remission compared with those who did not both at W12 and W52 (p<0.005) (Table 1). Among patients who achieved clinical remission, achievement of BU CMI was significantly associated with IBDQ response (p<0.005) but not IBDQ remission, and achievement of BU remission was significantly associated with IBDQ remission (p<0.005) but not IBDQ response at W12; achieving BU remission was significantly associated with better IBDQ response and IBDQ remission at week 52 (p<0.05).

Table 1. Association of Clinical Remission and Response with achievement of Bowel Urgency Remission and CMI on IBDQ Response/Remission in patients with UC at W12 and W52 of Continuous Treatment

Conclusion

Among patients with UC from miri phase 3 trials, the additional improvement of BU (CMI or remission) to the achievement of clinical response or remission was associated with greater QoL assessed by IBDQ response and remission.

References

1. D’Haens, G., et al. "OP26 Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study." Journal of Crohn's and Colitis 16. Supplement_1 (2022): i028-i029.
2. Dubinsky, M. C., et al. "867e: Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study." Gastroenterology 162.7 (2022): S-1393.
3. Dubinsky, M.C., et al. “Clinical Effect of Mirikizumab Treatment on Bowel Urgency in Patients with Moderately to Severely Active Ulcerative Colitis and the Clinical Relevance of Bowel Urgency Improvement for Disease Remission.” Crohn’s & Colitis 360, Volume 5, Issue 1, January 2023, otac044.
4. Irvine EJ. Quality of life of patients with ulcerative colitis: past, present, and future. Inflamm Bowel Dis. 2008;14: 554-565.
5. Irvine EJ. Development and subsequent refinement of the inflammatory bowel disease questionnaire: a quality-of-life instrument for adult patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1999;28: S23-S27.
6. Dubinsky, M. C., et al. "P138 Psychometric validation and interpretation of a patient-reported outcomes instrument to assess bowel urgency among adults with moderate to severe Ulcerative Colitis." Journal of Crohn's and Colitis 16. Supplement_1 (2022): i220-i222.

Disclosure

David T. Rubin receives grants or contracts from Takeda, and discloses consultancy fees with Abbvie, Altrubio, Allergan, Inc., American College of Gastroenterology, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd., 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 Pharmaceuticals, Eli Lilly and Company, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda and Techlab, Inc. Jianmin Wu, Simin K Baygani, Nathan Morris, Theresa Hunter Gibble are employees of Eli Lilly and Company. Stefan Schreiber receives consultancy and/or personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, HIKMA, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Prometheus, Takeda, and Theravance.

Clinical Case Summary

Neurological manifestations in Hepatitis E Virus (HEV) infection are rare. Even so, they constitute the most frequent extrahepatic involvement (55%). The most frequent neurological presentations are amyotrophic neuralgia, Guillain-Barré Syndrome (GBS) and meningoencephalitis.
A 58-year-old presents 2 week's progressive weakness of the lower limbs and jaundice. Blood tests show elevated liver enzymes and hyperbilirubinemia; with no signs of liver insufficiency. Serologies show positivity for HEV IgG and IgM. The patient confesses game meat (deer) consume in the prior 5 weeks.
The neurological examination reveals a general decrease in symmetrical strength, with abolished musculoskeletal reflexes. After normal CT, cerebrospinal fluid discloses albumin-cytological dissociation. The electromyogram is compatible with motor radiculopathy. Diagnosis of GBS is stablished and so, immediate iv immunoglobulins 0.4g/kg are administered for 5 days, with progressive analytical and clinical improvement.
HEV is the main cause of acute viral hepatitis in humans. Infection in endemic areas is generally related to the consumption of contaminated water. In contrast, in developed countries, sporadic cases are frequently described and linked to the consumption of animal meat (pigs, wild boars and deer). Thus, HEV is currently considered an emerging zoonosis.
Most cases are asymptomatic, with spontaneous clearance in most healthy subjects. As with any hepatitis, it frequently presents as painless jaundice and asthenia.
The association with GBS is well established. An immune-mediated mechanism has been postulated as the immediate cause. Supportive treatment with immunoglobulins, plasmapheresis, steroids and physical therapy are generally used. The use of ribavirin is reserved for acute fulminant hepatitis or chronic hepatitis cases.
The course is usually satisfactory with complete recovery around 60% of patients.

Introduction

The use of infliximab (IFX) is limited by low treatment persistence. Proactive therapeutic drug monitoring (pTDM) has been shown to increase the treatment persistence in inflammatory bowel disease (IBD) patients but the real-life data evaluating effectiveness, safety and costs of this approach are scarce.

Aims & Methods

The aim of this study was to assess survival on treatment, safety and costs of pTDM of IFX in the treatment IBD.
IBD patients who started IFX in a referral centre using pTDM between January 2018 and March 2021 were included. The main outcomes were treatment persistence, adverse events and incremental costs of pTDM.
IFX trough levels were assessed in the week 14 and subsequently every six months by commercially available ELISA kit (Ridascreen R-Biopharm) and the intensification of treatment the cut-off of 3μg/ml was used.
Costs related to the measurements of levels and the costs of intensified treatment were calculated. The costs of pTDM were compared costs of a modelled cohort using reactive TDM (rTDM) based on the data from the same cohort. The model used arbitrarily determined intensification regimen to 5mg/kg of IFX every 4 weeks in pharmacokinetically determined clinical or endoscopic loss of response. The calculation was performed for the first year of treatment.

Results

Overall, 99 patients with IBD were included (58 men – 59%; mean age 39,96 years, minimum-maximum, 20-73 years; 64% patients with Crohn´disease; mean disease duration 103 months, minimum – maximum, 8-402 months).
The treatment was intensified in 57 patients (58%). Overall treatment survival with pTDM was 87% at 6 months, 77% at one year, 66% at two years and 60% at both, the third and fourth year of treatment. There were no differences between patients on conventional regimen vs. intensified regimen with regards to adverse events.
The costs related to pTDM in this cohort of 99 patients were € 90 306,56 while the costs of the modelled cohort using rTDM were € 24 846,30. The overall incremental costs were thus € 65 460,26 with mean costs per patient for the first year of treatment of € 661,21.

Conclusion

Proactive TDM of IFX results in a steady 60% treatment persistence beyond the second year of treatment with no impact on the safety.
In the context of this solid treatment persistence, the incremental costs related to proactive TDM seem negligible when considering the costs of alternative biologicals used in case of loss of response to IFX.

Disclosure

nothing to disclose