Introduction

Diagnosis of noncalcific chronic pancreatitis (CP) remains a clinical challenge. Together with morphological changes, evaluation of pancreatic microvascularization could be useful in these patients, since the pancreatic inflammatory process could alter it. The development of techniques allowing the evaluation of microvascularization (Detective Flow Imaging, DFI) guided by endoscopic ultrasound (EUS) opens a new area of interest in this setting. EUS-DFI allows the evaluation of microvascularization and low-velocity blood flow without the need of contrast agents. There are no data on the potential usefulness of this technique in the evaluation of CP.

Aims & Methods

Aim of our study was to evaluate the findings of EUS-DFI in patients with clinically suspected CP.
Methods: A prospective, single-centre, observational study was designed. Patients undergoing EUS with advanced imaging for the evaluation of CP were included. Procedures were performed with a linear echoendoscope (Fujifilm 740UT) attached to the ultrasound system Arietta 850. EUS criteria of CP according to Rosemont classification were evaluated. EUS-DFI findings were classified into 4 grades (grade 0- absence of microvascularization; grade 1- reticular pattern with minimal microvascularization; grade 2- reticular pattern with moderate microvascularization; grade 3- reticular pattern with marked microvascularization. Correlation between EUS-DFI grades and the different groups of the Rosemont classification was analysed by chi-squared test.

Results

81 patients were included (mean age 54 years, range 21-85, 40 males). Eighteen patients (22.2%) presented a normal pancreas, 14 (17.3%) indeterminate findings for CP, 45 (55.6%) suggestive of CP and 4 (3.6%) consistent with CP. A EUS-DFI grade 0 (n=18) was just seen in normal pancreas. A EUS-DFI grade 1 (n=15) was associated with indeterminate findings of CP in 86.6% of the cases. A grade 2 (n=40) was associated with suggestive findings of CP in 97.5% of the cases, whereas a grade 3 (n=8) was seen in patients with suggestive (n=4) and consistent (n=4) findings of CP (p<0.001).

Conclusion

The evaluation of pancreatic microvascularization by EUS-DFI can be a useful tool for the evaluation of the inflammatory process in CP. Further studies are needed to evaluate the accuracy of this new technology for the diagnosis and activity evaluation of CP.

Disclosure

Julio Iglesias-Garcia: Advisor: Pemtax, FujiFilm, Mediglobe

Introduction

Splanchnic vein thrombosis (SVT) presents as a common complication of cirrhosis due to modification in hemodynamics and hemostatic balance, and it also frequently associated with solid cancers, myeloproliferative neoplasms and less often with pregnancy, abdominal infections, pancreatitis, or surgery.

Aims & Methods

The SVT registry is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for SVT at our Center since January 2005. Baseline and follow-up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of SVT, and treatment were collected during hospitalization, and at scheduled outpatient visits. The aim of this study was to describe patients with SVT and management in a single center, with focus on the differences between cirrhotic and non-cirrhotic patients.

Results

From January 2005 to December 2022, 320 patients were eligible SVT-registry, including 228 patients (71.2 %) with liver disease. Among the latter, 126 (55.3%) had isolated portal thrombosis, 18 (7.9%) isolated mesenteric thrombosis and the remaining multiple site venous thrombosis. Among isolated portal thrombosis, 61 (48.4 %) of patients experienced a complete thrombosis, 47 (37.3 %) a partial thrombosis. Therefore, there is a difference in the site of thrombosis and the extent of portal thrombosis between the two groups (p = 0.046 and p = 0.001, respectively). Ninety-three patients (40.7 %) experienced solid cancer and 45 (19.7 %) had HCC. Patients with liver disease developed a higher rate of portal hypertension-related complications, such as ascites and esophageal varices, than the other population (p < 0.0001). Most patients (77.6%) received an anticoagulation therapy and those with cirrhosis were preferably treated with low molecular weight heparin/heparin related agents (64.5%; p < 0.0001). Only patients treated with anticoagulants experienced a major complication such as bleeding (n=23, 10.1%), which in no case led to the patient’s death. Seventy-seven patients (33.8 %) experienced resolution of SVT with a median time of 8.4 months and no differences were found between the two groups, with 20.8% spontaneous resolution-rate. A lower rate of recanalization is shown in patients presenting with portal hypertension complications (p = 0.0431) such as esophageal varices (p = 0.0299) at the time of SVT diagnosis, regardless of therapeutic approach. Following recanalization, 7 patients with liver disease (9.1%) had a recurrence of venous thromboembolism earlier than the other group. Presence of HCC diagnosis and not long-term use of VKA have been found to be associated with an increased risk of SVT recurrence (p= 0.0099 and p= 0.037, respectively).

Conclusion

SVT-registry is a relatively large ongoing population-based registry of SVT patients, with high-quality data representing a valuable source of real-world data on the management and outcomes of SVT.
Our data show that there are differences in the presentation and course of SVTs between patients with and without liver disease, which may therefore require specific management.

Introduction

Insulinomas are rare, functioning neuroendocrine neoplasms that cause non-ketotic hypoglycemia due to hyperinsulinism. Surgery is considered the gold-standard treatment, although endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been recently described as a less invasive, efficient therapeutic option for these tumors. In this study, we aim to compare post-procedural outcomes of surgical resection versus EUS-RFA for pancreatic insulinomas.

Aims & Methods

All patients who underwent surgical resection or EUS-RFA for pancreatic insulinoma in our Institution were included in the study, and data from all procedures were retrospectively recorded and statistically analyzed. EUS-RFA was indicated for all subjects either unfit for surgery or unwilling to undergo surgical treatment. Patients’ baseline characteristics, location, size of insulinomas, procedural time, and intra- and postoperative outcomes were compared.

Results

From April 2012 to July 2022, 11 and 10 patients with pancreatic insulinoma underwent surgical resection and EUS-RFA, respectively. The median age was 65.5 (51-84) and 37 years (28-72, p<0.001) for the EUS-RFA and surgery cohorts, respectively. As a whole, 15 (71.4%) out of 21 were female. The median tumor size was 15mm (8-30) for the surgical group and 11mm (8-19) for the EUS-RFA group (p=0.17). The majority of the insulinomas were located in the pancreatic body (28.6%) and tail (28.6%), with no statistical difference between the two groups (p=0.16). Operative time was significantly longer in the surgical population (280min, 120-372) as compared to the endoscopic one (28min,18-40, p<0.001). Clinical success, defined as the normalization of glucose blood levels, was reached in all cases. The complication rate was significantly higher in the surgical group compared to the endoscopic group (7-63.6% vs 1-10%, p=0.01). Specifically, 7 patients in the surgical cohort developed a pancreatic fistula while one patient in the EUS-RFA population had self-limiting bleeding after the procedure. One patient of the surgical cohort underwent reoperation for an infected abdominal fluid collection.

Table 1. Characteristics of patients classified by treatments.

Conclusion

As compared to surgical resection, EUS-RFA for pancreatic insulinomas may be considered a safe and efficient treatment option with a shorter operative time and a lower rate of related complications. Prospective comparative studies are needed to ascertain the role of EUS-RFA as a treatment of choice for selected patients with pancreatic insulinoma.

References

Fahmawi Y, Mehta A, Abdalhadi H et al. Efficacy and safety of endoscopic ultrasound-guided radiofrequency ablation for management of pancreatic lesions: a systematic review and meta-analysis. Transl Gastroenterol Hepatol. 2022 Jul 25;7:30.
Zhao YP, Zhan HX, Zhang TP et al. Surgical management of patients with insulinomas: Result of 292 cases in a single institution. J Surg Oncol. 2011 Feb;103(2):169-74.

Introduction

Ozanimod (OZA) is approved for the treatment of moderately to severely active ulcerative colitis and relapsing multiple sclerosis. A previous phase 1 study of single dose OZA 0.23 mg showed a 31%–33% reduction of CC112273, the predominant active metabolite (MET) of OZA, in mild or moderate hepatic impaired participants (ppts) vs healthy ppts. That study was designed prior to identification of the 2 major METs of OZA (CC112273; CC1084037). Due to their slow accumulation and elimination, a new multiple dose study was designed with a long sampling schedule.

Aims & Methods

This multicenter, open-label phase 1 study (NCT04639115) evaluated the effect of mild (Child-Pugh [C-P] score 5–6) or moderate (C-P score 7–9) hepatic impairment on the multiple-dose pharmacokinetics (PK) of OZA and its 2 major active METs. Eligible ppts with hepatic impairment without active hepatitis were enrolled into the mild or moderate hepatic impairment groups (8 ppts each) based on their C-P scores. Ppts with normal hepatic function were matched to hepatic-impaired ppts by sex, age, weight, and smoking status. All ppts received once-daily OZA for 8 d in accordance with dose titration: 0.23 mg on Days (D) 1–4, 0.46 mg on D5–7, and 0.92 mg thereafter. Serial PK samples were collected on D1, D5, and D8, and additionally on D10, D12, and D15, and up to D72. Analysis of variance (ANOVA) fitted to the natural log-transformed PK parameters with hepatic function group as the fixed effect and the matching pair as a random effect was used to compare PK parameters between groups. Safety was assessed.

Results

All dosed ppts (N=26) completed the study. Each hepatic impairment group had 8 ppts; 10 ppts were in the normal hepatic function group, of whom 6 matched both mild and moderate hepatic-impaired ppts. Of the 16 hepatic-impaired ppts, 13 had documented hepatic cirrhosis. No clinically meaningful differences in total and unbound PK parameters for OZA and its major METs were observed between healthy and hepatic-impaired ppts on D1, D5, or D8 (dose titration) (Table). The unbound area under the plasma concentration-time curve from D8, time 0 to the time of last quantifiable concentration (AUC_0-last) (up to 64 d after the D8 dose) of both METs increased ~2-fold in both mild and moderate hepatic-impaired ppts (Table). Although steady state for both METs was not achieved by D8, AUC_0-last is a reasonable predictor of exposure at steady state. No correlation was observed between PK parameters for OZA or its major METs and measures of hepatic function (C-P score, serum albumin, and prothrombin time). No laboratory results (ie, absolute lymphocyte count), vital signs, physical examination, or 12-lead ECG results were reported as treatment-emergent adverse events.

Conclusion

Due to the lack of OZA PK differences between hepatic-impaired and healthy ppts during dose titration and the 2-fold increase of AUC_0-last of both METs in hepatic-impaired ppts, a dose adjustment of OZA 0.92 mg once every other day is recommended in patients with mild or moderate hepatic impairment after completing the standard 1-week dose titration.

Disclosure

This study was funded by Bristol Myers Squibb, Princeton, NJ, USA.
PZ, FH, KY, SW, MS, GT, BM, and DT: employees and/or shareholders of Bristol Myers Squibb.

Introduction

Fatigue is commonly reported by Crohn's Disease patients even in the absence of disease activity.
Other possible causative factors need to be determined in order to successfully address this problem, which significantly affects patients' lives even when treatment targets have been achieved.
Sarcopenia and Depression are also common in Crohn's Disease and possibly related to fatigue.

Aims & Methods

Consecutive patients with Crohn's Disease who came to the infusion center to receive maintenance intravenous infliximab treatment were included. All participants had to be in full clinical (HBI <5), biological (C-RP < 0.5 mg/dL and/or fecal calprotectin <100 μg/mg) , endoscopic (SES-CD 0-2), or enterographic remission in the past 6 months. Anthropometric measurements (Weight, Height, Body Mass Index, Circumcenter waist, hips, gastrocnemius, Waist to Hip Ratio), Body Composition Measurements (Body Fat, Total Body Water, Body Fat Mass Index, Lean Body Mass), Physical Activity Tests (Handgrip Strength test, 6-meter Walk Test, One Leg Standing test, 30-second Chair Stand test) and Questionnaires related to Sarcopenia ( Lawton Instrumental Activities of Daily Living Scale-LIADLS, Activities Daily Living Scale-ADLS, Dixon's Diet Score-DASH, Mini Nutritional Assessment-MNA, Mediterranean Diet Serving Score MDSS, the Mind Diet Score-MDS) were conducted. We used the Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) to measure fatigue. We used the Hamilton Depression Rating Scale (HAM-D) to assess for depression. Linear regression analysis was used to assess the impact of sarcopenia and depression on fatigue.

Results

A total of 39 patients were included: mean age 38.6 years, mean body weight 80 Kg, median disease duration 9 years, female 22 (56,%), male 17 (44%).
We included patients with ileal disease (48%), perianal disease (28%), stomas (8%), extraintestinal manifestations (12%), on second or third biologic therapy (56%), smokers (10%).
Median C-RP was 0.13 mg/dL and median albumin was 4.5 g/dL.
Sarcopenia was almost non existent by all measures: Indicatively, Median Max Hand Grip was 25.7 (range 10.8-57.4).
Median FACIT-F was 45 (range 7-52).
Median HAM-D was 4 (range 0-25).
There was no correlation between FACIT-F and Sarcopenia (Max Hand Grip): p=0,280, β coefficient = 0,159.
There was a correlation between FACIT-F and HAM-D: p<0,001, β coefficient = -1,576.
Interestingly there was also a correlation between HAM-D and max Hand Grip: p=0,029, β coefficient = -0,804.

Conclusion

We found expectantly low (though not in all patients) estimates of sarcopenia, fatigue and depression in this selected group of Crohn's Disease patients in complete remission receiving intravenous infliximab.
Fatigue could not be attributed to sarcopenia. On the contrary depression seemed to be one of the main determinants of fatigue.
Multidisciplinary care of fatigue should include psychological evaluation and possible intervention.
Further research in the field of fatigue related to Inflammatory Bowel Disease is needed.