Introduction

Bowel urgency (BU) is the sudden or immediate need to have a bowel movement. Although it is a common symptom in ulcerative colitis (UC), its burden is poorly known. We aimed to assess the overall burden of UC patients with BU.

Aims & Methods

The THEFAR study is a non-interventional, cross-sectional and multicenter study carried out in France between July and December 2022 including adult patients with UC treated with biologics/targeted-synthetic drugs. Clinical and therapeutic management data were collected by gastroenterologists using a e-CRF. Quality of life, disability and work impairment (WPAI:UC) were collected using patient-self completion questionnaires. BU was defined as a UNRS (0-10 Urgency Numeric Rating Scale) >1, BU remission as a URNS ≤1 and incontinence as a Wexner score ≥5. Descriptive statistics and bivariate analyses were performed. Continuous variables were summarized with mean values and SDs using the Student’s t-test or Wilcoxon test. Categorical variables were expressed as proportions and compared using the Pearson's Chi-Squared test or Fischer's exact test.

Results

Of the 293 patients enrolled at 41 sites, the median (IQR) age was 42.0 (31.0-55.0) years with a median (IQR) disease duration of 6.0 (3.0-11.0) years. 64.2% were employed. Respectively, 45 (15,4%), 117 (39.9%) and 131 (44.7%) had proctitis, left-side colitis and pancolitis. 38.9% had active disease (partial Mayo score ≥2) and 53.6% experienced flares over the past year. Overall, 144 (49.1%) of patients were treated with TNF-inhibitors, 99 (33.8%) with vedolizumab, 35 (11.9%) with ustekinumab, and 13 (4.4%) with tofacitinib with a median treatment duration of 1.0 year (0.0 - 3.0). Of the 291 patients who answered patient-self completion questionnaires, 57.0% had BU [median (IQR) UNRS: 2 (0.0-6.0)] and 78.3% had fecal incontinence [median (IQR) Wexner score: 8.0 (5.0-11.0)] with 14.7% wearing pads at least once a month. Overall, half of patients (52.3%) had both BU and fecal incontinence. A significantly higher proportion of patients had active disease with BU (57.2%) compared to those with BU remission (15.2%) (p<0.0001). Patients with BU had twice more months flaring over the past year (2.3 vs 1.0 month, p<0.0001) and a significantly higher proportion of patients with BU (45.8% vs 14.4%, p<0.0001) received steroids over the past year. Rates of BU were similar regardless of disease location (p=0.74), UC treatment (all UC treatments p>0.05) or line of therapy (p=0.27). Median (IQR) Wexner score was almost twice higher in patients with BU [10.0 (8.0-13.0) vs 6.0 (0.0-8.0), p<0.0001]. QoL was significantly impacted in patients with BU with lower mean (SD) EQ-5D-5L utility [0.846 (0.186) vs 0.943 (0.099), p<0.0001] and Visual Analogue Scale (VAS) scores [66.2 (18.2) vs 82.1 (14.5), p<0.0001]. There was a significantly higher proportion of patients with moderate to severe disability (IBD-DISK score ≥40) in patients with BU (53.7% vs 16.9%, p<0.0001) and BU was significantly associated with the IBD-DISK (r=0.52447, p<0.0001). Mean (SD) absenteeism [11.5% (25.4) vs 3.9% (12.5), p=0.0013], overall work impairment [35.7% (29.4) vs 11.3% (18.9), p<0.0001] and activity impairment [33.0% (27.0) vs 7.9% (13.7), p<0.0001] were significantly higher in patients with BU.

Conclusion

Despite advances in UC therapies, more than one in two patients treated with biologics/targeted-synthetic drugs experience BU. Patients with BU have a high symptom burden, disability and impaired quality of life and work productivity. These findings highlight that the control of BU remains an unmet medical need in UC patients.

Disclosure

AbbVie, Ferring, Janssen, MSD, Takeda, Pfizer, Celgene, Biogen, Amgen, Boehringer Ingelheim, Lilly, Hospira et Celltrion

Clinical Case Summary

A 72 years old caucasian women with no relevant medical history presented to the emergency department with two weeks history of abdominal pain in the upper quadrants associated with fullness, vomiting and a significant weight loss and nighttime hypersweating. On physical examination, abdomen was painful on epigastric and periumbilical region. Analytically, hemoglobin 11.1g/dL, leukocytes 9200/mm3, platelet count 315000/μL, CRP 8.22mg/dL. Tests for HIV and EBV were negative. Computed Tomography (CT) of the abdomen and pelvis revealed stomach with thickened walls, densification of adjacent fat and heterogeneous adenopathies. She was admitted to the department of Gastroenterology for investigation. The upper gastrointestinal endoscopy revealed extensive neoplasia of the body and gastric antrum. Biopsies revealed gastric mucosa with infiltration by atypical lymphoid proliferation with a "starry sky" pattern suggestive of high-grade B-cell non-Hodgkin's lymphoma (NHL). FISH analysis revealed t(8;14) c-myc positive. Once morphological and immunohistochemistry feature favors Burkitt’s lymphoma, she was transferred to the department of Hematology. Patient was treated with a full dose CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) and 3 cycles of dose adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab). Complete remission was documented on positron emission tomography (PET).
Sporadic Burkitt's lymphoma is rare (1-2% of all lymphomas in adults), being one of the most aggressive forms of B-cell NHL. Primary gastric involvement is extremely rare. With the advancement of medicine and greater survival, we must consider this diagnosis, even in the absence of risk factors, atypical location and age group. This case emphasizes the importance of clinicopathological correlation and the importance of early diagnosis for immediate and aggressive intervention, fundamental in reducing morbidity and mortality.

References

1. Zhimin Bai, Yong Zhou. A systematic review of primary gastric diffuse large B-cell lymphoma: Clinical diagnosis, staging, treatment and prognostic factors, Leukemia Research,
Volume 111, 2021, 106716, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2021.106716.
2. Čubranić A, Golčić M, Fučkar-Čupić D, Brozović B, Gajski D, Brumini I. BURKITT LYMPHOMA IN GASTROINTESTINAL TRACT: A REPORT OF TWO CASES. Acta Clin Croat. 2019 Jun;58(2):386-390. doi: 10.20471/acc.2019.58.02.25. PMID: 31819338; PMCID: PMC6884372.
3. Usman A. Pirzada, Kishore Kumar, Hassan Tariq, Masooma Niazi, Jasbir Makker; Case of Gastric Diffuse Large B-Cell Lymphoma. Case Rep Oncol 6 May 2019; 12 (1): 39–46. https://doi.org/10.1159/000496332
4. Khan A, Khan S, Arshad U. Primary Gastric Burkitt's lymphoma. Pak J Med Sci. 2017 Sep-Oct;33(5):1294-1297. doi: 10.12669/pjms.335.13002. PMID: 29142583; PMCID: PMC5673752.

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

A 62 y/o male complaining from epigastric pain, constipation, vomiting and eructation for two months and CT abd revealed irresectable pancreatic head mass 4.5x4.5 cm encasing PV and SMV with duodenal invasion. Ryle decompression was done before EGD, duodenal obstruction was noted and biopsy showed duodenitis (stasis induced). EUS-FNB confirmed well differentiated AC. Duodenal stenting was successfully performed with improving symptoms.
After one week patient complained from weakness and abnormal gait, examination showed normal vital signs, bilateral lower limb edema and patient was lethargic. Three days after, the patient became confused (GCS 12), so he was admitted to ICU.
CT brain was unremarkable. Lab investigations showed the following:
Na 130, K 4.1, Ca 7.8, Phos 2.8, Mg 2.6, Alb 2.9
Refeeding injury was suspected and TPN was started by the ICU team. No improvement of the consciousness was achieved and patient caught chest infection, developed sepsis and died.
Discussion: Refeeding syndrome is a serious complication that can be easily missed [1] in upper GI malignant obstructions with prolonged decreased oral intake along with the malignancy cachexia status. These obstructions may need surgery or stenting to regain patency and without cautious monitoring of the nutrients repletion rate either enteral or parenteral this will lead to fluid and electrolyte disturbance (Fluid balance abnormalities, Abnormal glucose metabolism, Vitamin deficiency, e.g., vitamin B1 (thiamine), Hypophosphatemia, Hypomagnesaemia and/or Hypokalemia) [2] with symptoms ranging from vague up to life threatening conditions like disturbed conscious level and heart failure. Our patient had high risk of developing refeeding syndrome due to caloric deprivation secondary to duodenal obstruction with development of the symptoms after stenting and restarting oral intake.
Conclusion: Nutritionist counseling after GI stenting of upper GI malignant obstructions is needed to avoid refeeding syndrome.

References

[1] Reber, E., Friedli, N., Vasiloglou, M.F., Schuetz, P. and Stanga, Z., 2019. Management of refeeding syndrome in medical inpatients. Journal of clinical medicine, 8(12), p.2202.
[2] Crook, M.A., Hally, V. and Panteli, J.V., 2001. The importance of the refeeding syndrome. Nutrition, 17(7-8), pp.632-637.

Introduction

The enhancement of the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has become a major therapeutic target in the management of this disease. Sexuality is one of its main determinants. However, in Tunisia, there is little data on sexual dysfunction (SD) and fertility among IBD patients.

Aims & Methods

The aim of this study was to determine the incidence and the factors associated with SD during IBD. We conducted a cross-sectional study including patients with IBD followed at the Gastroenterology Department of Charles Nicole Hospital between July and December 2020. Sexual function was assessed by the Female Sexual Function Index (FSFI) score in women and by the International Index of Erectile Function (IIEF) in men. Scores assessing patients ‘overall QoL were calculated: Hospital anxiety and depression scale (HADS), Fatigue Severity Scale (FSS), and Short Inflammatory Bowel Disease Questionnaire (S-IBDQ). All patients gave oral informed consent before answering the questionnaires.

Results

A total of 65 patients were included of whom 72.3% had CD and 27.7% had UC, with a mean age of 47.58±10.18 years and sex ratio (M/F) of 0.44.
SD was found in 73.3% of women according to the FSFI and in 15% of men according to the IIEF-15. Erectile dysfunction (ED) was observed in 40% of patients based on the IIEF-5.
Female gender was a significant factor of SD (p<0.001; OR 15.6; CI [3.9-62.8]).
An analytical statistical study was conducted, showing factors associated with SD in the female patient group only.
Our study showed that the factors associated with the presence of female SD were age (p=0.018), absence of professional activity (p=0.034), length of marriage (p=0.022), presence of probable or overt depression (p=0.01), fatigue (p=0.042), impaired QoL judged by the S-IBDQ (p=0, 042), the four domains of the S-IBDQ (bowel symptoms (p=0.04), general signs (p=0.011), emotional domain (p=0.004), social domain (p=0.013)), IBD-disk score (p=0.007), and IBD-disk domains (sexual activity (p<0.001), emotion (p=0.001), energy (p=0.016), and joint pain (p=0.015)).
There were no factors that appeared to be associated with male SD. Meanwhile, we found a statistically significant association between men's perception of impaired sexuality due to IBD and the presence of ED (p=0.004; OR=33; CI [2.4-443.6]).
In multivariate analysis, the factors independently associated with female SD were the duration of marriage (p=0.018; OR 3.58; CI [1.43-7.83]), the presence of suspected or overt depression (p<0.001; OR 12.6; CI [1.82-72.52]) and fatigue (p=0.032; OR 11.8; CI [1.61-96.7]).

Conclusion

Our study shows that sexual disorders are frequent in IBD patients, especially in women. A multidisciplinary management involving gastroenterologists, psychologists, and sexologists is sometimes necessary in these young patients, in order to improve their QoL.

Introduction

Biological therapy in IBD patients is one of the cornerstones of treatment. For patients with loss of response while on maintenance therapy, options for dose escalation with the same agent are used to avoid switching targets, and this is done through a reinduction and dose intensification. While dose escalation is standard treatment with anti-TNF agents, current data on the efficacy of dose optimisation with ustekinumab in real life is limited.

Aims & Methods

The aim of the study is to assess the efficacy of dose optimisation (reinduction and intensification) therapy with Ustekinumab and to identify prognostic factors associated with clinical response. We performed a retrospective cohort study of patients that received dose optimisation with ustekinumab between January 2016 to July 2022. Demographic and clinical characteristics were obtained from the medical records. To assess for prognostic factors, responders and non-responders were compared using logistic regression analysis.

Results

A total of 94 patients were on ustekinumab treatment, and from these, 32 (30%) patients required dose optimisation during follow-up. The characteristics of patients included are summarized in Table 1. In 16 (50%) patients dose optimization was performed due to lack of response during the induction with Ustekinumab, the other 16 patients (50%) were intensified due to secondary failure. There were 15 (46.9%) patients in whom intravenous reinduction was performed prior to intensification. Three types of intensification were performed: 90mg subcutaneous every 4 weeks, 90mg subcutaneous every 6 weeks or 130mg intravenous every 4 weeks.
In 23 (72%) patients clinical remission was obtained after dose optimisation and were considered responders for logistic regression analysis. Extraintestinal manifestations (p=0.03) and secondary failure to Ustekinumab (p=0.049) were associated with a better response. No significant differences were observed between the type of intensification, the fact that they received prior reinduction or other demographic characteristics.

Conclusion

Dose optimization with ustekinumab is useful in clinical practice with a good response rate, specially in patients with secondary failure.

Introduction

Pancreatic acinar cystic transformation (ACT) was first described in 2000. Its initially supposed pre-neoplastic nature was reconsidered in the WHO Classification 2019. Its current management prone to a non-surgical approach, and so rare cases of histopathological diagnosis have been obtained since. Radiological diagnostic criteria have been proposed to differentiate ACT from Branch-duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN) (Delavaud et al., 2014): 1) ≥ 5 cysts, 2) clustered peripheral small cysts, 3) cyst calcifications and 4) no communication with the main pancreatic duct.

Aims & Methods

The aims of this study were to describe the clinical and radiological characteristics of patients with a presumed diagnosis of ACT in imaging and to assess the role of these known radiological criteria in case of possible differential diagnoses. In this single-centre retrospective study (2003-2021), consecutive patients with a presumed diagnosis of ACT in the coding database were included. Patients without an available imaging (CT or MRI) for expert radiological centralized review were excluded. A group of “typical” diagnosis of ACT was defined as the absence of differential diagnosis to be evoked. A group of “uncertain” diagnosis of ACT was defined as other possible differential diagnoses.

Results

A total of 64 patients were included (35 male patients [55%]). Median age of diagnosis was of 60 (IQR 47-67) years. ACT diagnosis was “typical” for 35 (55%) patients and was “uncertain” for 29 (45%) patients. In the “typical” group, 91.4% of patients presented ≥3 radiological criteria versus 96.6% in the “uncertain” group (p=0.61). There were more calcifications and <10 cysts in the “uncertain” group compared to the “typical” group (86% versus 66%, p = 0.041 et 24% versus 6%, p = 0.06, respectively). In the “uncertain” group, the main differential diagnoses suggested were: 16 (55%) BD-IPMN and 7 (24%) calcified chronic pancreatitis (CCP). A pathological confirmation of ACT was obtained for three patients from which two were in the “uncertain” group.

Conclusion

ACT displays an heterogenous morphological imaging presentation reflecting a challenge for accurate non-invasive diagnosis. The published diagnostic radiological criteria seem not to be sufficient, especially in case of calcifications or/and <10 cysts.

References

Delavaud C, d’Assignies G, Cros J, et al. CT and MR imaging of multilocular acinar cell cystadenoma: comparison with branch duct intraductal papillary mucinous neoplasia (IPMNs). Eur Radiol 2014; 24: 2128–2136

Disclosure

No conflict of interest to be disclosed