Introduction

A significant proportion of patients with inflammatory bowel diseases (IBD) have extraintestinal manifestations (EIM), which may be very disabling. The presence of EIM and immunomediated diseases (IMIDs) may influence the selection of the biologic agent. On the other hand, biologic agents have been associated with the onset of IMIDs.

Aims & Methods

Aim: To evaluate the impact of ustekinumab on EIMs and IMIDs in a cohort of ulcerative colitis (UC) patients in real life.
Methods: Retrospective, multicenter study including UC patients who had received the first ustekinumab dose at least 16 weeks before the inclusion. Patients were followed-up from the first ustekinumab dose to treatment discontinuation or last visit, whichever came first. The evolution of previous EIMs and IMIDs was evaluated based on clinicians’ judgment. The onset of new EIMs and IMIDs under ustekinumab treatment was recorded.

Results

376 patients have been included so far (91% had PMS >2 at ustekinumab initiation, 96% had been previously exposed to biologics, and 25% had failed to anti-TNF, vedolizumab and tofacitinib). Median follow-up was 12 months (m). A total of 122 patients (32%) had previous EIM and/or IMIDs at ustekinumab start. A total of 80 patients (21%) had at least one EIM and/or IMIDs inactive at ustekinumab start, being the most frequent ones peripheral arthropathy (5%), axial spondyloarthropathy (3%) and psoriasis (3%). Some patients worsened from these conditions: a patient (6%) with peripheral arthropathy (partial response of UC), 2 (15%) patients with axial spondyloarthropathy (one in remission and one non-responder), a patient (33%) with rheumatoid arthritis (non-responder) and a patient (20%) with uveitis (non-responder). A total of 65 patients (17%) had active EIM and/or IMIDs at ustekinumab start; the outcomes of these patients are summarized in table 1. A total of 15 patients (4%) developed EIM and/or IMIDs after ustekinumab start: 6 (1.6%) patients developed peripheral arthropathy, 2 (0.5%) patients erythema nodosum, a patient (0.3%) was diagnosed with primary sclerosing cholangitis, a patient (0.3%) was diagnosed with vasculitis, and 6 (1.6%) patients developed other conditions.

Conclusion

In patients with active EIM at the start of ustekinumab treatment, improvement of those related to disease (UC) activity was observed. Other EIM and IMIDs not related to disease activity (axial spondyloarthropathy, uveitis, or rheumatoid arthritis) worsened. Treatment with ustekinumab does not appear to be associated with an increased risk of developing EIM or IMIDs.

Disclosure

This is an investigator-initiated study with financial support from Janssen (CNTO1275UCO4008).

Clinical Case Summary

A 57- year- old female with past medical history of NF1 and diverticulitis presented with one day history of left lower quadrant abdominal pain, nausea, and vomiting. CT Abdomen and Pelvis demonstrated sigmoid diverticulitis without abscess, and an incidental mesenteric mass 4.4 x 3.1 x 3.7 cm in the left lower quadrant. She was medically managed with intravenous antibiotics and discharged five days later. She was scheduled for a 1 month follow up with general surgery, who recommended resection of the mass. She underwent a small bowel resection of the mass and was discharged on postoperative day three. Pathology was consistent with gastrointestinal stromal tumor with two foci, 5.4 cm, and 0.6 cm in size with negative margins. The overall mitotic index was low (2/50 HPF) with Ki-67 staining of 5%. Tumor cells were positive for CD117, DOG1, SMA and negative for CD 31, CD 34, MSA, S100 and Desmin. Onkosight NGS KIT sequencing revealed no clinically relevant mutations in KIT exons 2, 9, 10, 11, 13, 14, 15, 17 and 18. Oncology recommended CT surveillance scans every 6 months without adjuvant therapy since the tumor developed in the setting of NF1. Our patient unfortunately deferred routine screening due to loss of insurance and inability to afford the out-of-pocket costs of CT imaging. In summary, our case illustrates the rare occurrence of GIST in a patient with NF1. Since NF1-associated GISTs typically present in female patients in their fourth decade of life, our case highlights the importance of early screening. Surgical resection is the mainstay of treatment for this condition as seen in our patient while tyrosine kinase inhibitors are typically reserved for sporadic cases or those with high-risk features [1,2]. Thus, further research into cost effective diagnostic surveillance and non-surgical treatment modalities for those with NF1 associated GIST is warranted.

References

1. von Mehren M, Joensuu H. Gastrointestinal Stromal Tumors. J Clin Oncol. 2018 Jan 10;36(2):136-143. doi: 10.1200/JCO.2017.74.9705. Epub 2017 Dec 8. PMID: 29220298; PMCID: PMC6553810.
2. Rutkowski P, Skoczylas J, Wisniewski P. Is the Surgical Margin in Gastrointestinal Stromal Tumors Different? Visc Med. 2018 Oct;34(5):347-352. doi: 10.1159/000491649. Epub 2018 Aug 24. PMID: 30498701; PMCID: PMC6257087.

Clinical Case Summary

A 22-year-old female without comorbidities presented with epigastric and lower retroesternal chest pain, nausea and vomiting since 3 days that didn't response to oral medication. Patient denied dysphagia or odinophagia. Assessed in the emergency, treated with intravenous (IV) medications and discharged with prescription. Next day, the pain increased and vomited 15 times. Patient was admitted as a case of acute gastritis on intravenous proton pump inhibitors (PPIs) and metoclopramide. Routine laboratory and upper abdominal ultrasound done without significant findings only remarkable mild hyponatremia 134 (135-145).
Physical examination looked unwell. Vitally stable 105/75 mmHg. Afebrile (36.2). Malnourished. Weight 28.7 Height 145cms BMI 14.2. Mild epigastric tenderness.
Due to refractory symptoms despite IV medication. Endoscopy was done and showed round and serpiginous ulcers in the lower third of the esophagus with yellowish exudate suggestive of infectious esophagitis Cytomegalovirus vs Herpes. Normal aspect of stomach and duodenum. Histopathology confirmed herpes simplex esophagitis.
Under the suspicion of infectious esophagitis HIV serology came negative, CMV antibodies IgM negative IgG positive. Normal immunoelectrophoresis. No previous herpes viral infection. The only risk factor identified for the patient was the malnutrition, nevertheless vitamins and proteins were normal.
With histological confirmation after 48 hours of the endoscopy she was started on Acyclovir IV 5mg/kg every 8 hours with significant improvement in the next 48 hours. Patient discharged in stable condition after re-starting oral intake and completing the oral acyclovir 400 mg every 8 hours for 10 days. Patient responded well was assessed 7 days after discharge, free of symptoms and a weight gain of 1.3 kg.
Infectious esophagitis needs to be considered in immunocompetent host. Odynophagia/dysphagia can be absent. Endoscopy findings alone isn't sufficient to make a definitive diagnosis.

References

Endoscopy and histopathology.

Clinical Case Summary

A 45-year-old woman was founded with a raised serum alpha-fetoprotein (AFP) level of 89 ng/ml ( normal range < 8ug/L ) when taking a routine physical examination. During the following year, the serum AFP concentration level was gradually rising, up to 6353 ng/ml. There was no significant loss of weight or loss of appetite, and she denied having any feeling of bloating or abdominal pain.
Although the serum AFP concentration level was abnormally high, the cancer antigen (CA)125, cancer antigen (CA)199, carcinoembryonic antigen (CEA), PIVKA-II, AFP-L3, β-HCG levels were all within normal limits at each check. There was no abnormal findings in the hepatobiliary systems except the modest increased bilirubin (within 2 times). Hepatitis A, hepatitis C, hepatitis E antibody screen was negative. The result of HBV markers were: HBsAg(-), HBsAb(+), HBeAb(-), HBeAb(-), HBcAb(+), While HBV DNA quantification was less than 5.00E+2 IU/ml. Moreover, there was no significant abnormality concerning autoimmune liver disease. During the one-year follow up, several imaging examinations were performed,including abdominal ultrasonography, enhanced computer tomography (CT) , magnetic resonance imaging (MRI) and PET-CT. However, there was no evidence of liver lesion or tumour on all of them, even the PET scan.To check for hepatoid adenocarcinoma, gastroscopy, colonscopy, enhanced chest CT enhanced abdomen CT, and thyroid ultrasound were performed. Nevertheless, no suspicious lesion was found.
One year later, a 2.8×2.6 cm mass was detected in the left lobe of liver in a surveillance ultrasound scan. She underwent laparoscopic hepatocarcinoma resection, and the mass was confirmed moderately differentiated hepatocellular carcinoma by pathology. After surgery, AFP levels took 3 months to normalize.
From this case, we found that a gradual rise elevation in AFP were positive predictors for tumor development, especially hepatocellular carcinoma.

Introduction

After resection of a malignant colorectal polyp, patients may be proposed for surgical treatment or surveillance, depending on the presence of cure criteria.

Aims & Methods

The aim of this study was to compare the detection of metachronous lesions in patients with malignant polyps undergoing surgery versus surveillance.
Retrospective cohort study including patients with endoscopic removal of malignant polyps. Patients were divided into 2 groups, according to the strategy defined in the oncology group consultation: surveillance (group 1) and surgery (group 2). The diagnosis of metachronous lesions during the follow-up period was the main outcome studied. A metachronous lesion was defined as the detection of adenoma/adenocarcinoma, 6 or more months after index colonoscopy.

Results

77 patients were included, 55.8% in group 1, 44.2% in group 2. Mean age was 65.2±10.8 years, 45.5% were women.
In group 1, significantly more patients developed metachronous lesions compared to group 2 (66.7% vs 33.3%, p=0.036). The mean time to diagnosis of metachronous lesion was significantly shorter in group 1 (18.6±2.8 vs 36.0±5.6 months, p=0.004).
In group 1, 32.1% of patients developed metachronous lesions in the same colonic segment as the endoscopic resection of the malignant polyp.
In histological characterization, the two groups did not present statistically significant differences: low-grade dysplasia in 92.9% (group 1) and 85.7% (group 2); high-grade dysplasia in 7.1% (group 1) and 14.3% (group 2), p=0.457. No adenocarcinomas were detected during the follow-up period.

Conclusion

Surgical approach was associated with a lower incidence of metachronous lesions, suggesting that a significant proportion of the risk of metachronous lesion occurs in the segment of the index lesion.

Introduction

Laser therapy is a relatively recent technique that allows the treatment of anal fistulas (FIstula-tract LAser Closure: FilaC®), and anal fissure (Laser anal fissure: LSL) with the FilaC fibre, pilonidal sinuses with the SiLaC® fibre (Sinus Pilonidalis treatment), and haemorrhoids with the Laser Hemorrhoido Plasty fibre (LHP®).

Aims & Methods

Our study aims to report the preliminary results of a prospective bicentric study including all patients treated with laser therapy in two private hospitals.​
​This prospective descriptive study includes 141 patients treated with laser therapy for proctological pathology (anal fistulas, pilonidal sinuses, anal fissures, and hemorrhoids) performed in two proctology units. The majority of these procedures were performed under spinal anesthesia. Data were collected directly from the patients using an evaluation form. We studied their clinical data and the immediate and medium-term postoperative follow-up

Results

141 patients were included. The mean age was 44 years (18-76 years). 78% were male and 22% female (sex ratio = 3.5). The anal fistula was the main indication for laser therapy, with FilaC® performed in 105 patients (74.5%), followed by SiLaC® in 16 patients (11.3%), LHP® in 7 patients (5%) and 4 cases of LSL (2.8%). 9 patients benefited from combined treatment: 5 LHP®+ LSL patients (3.5%), 2 FilaC®+ LSL patients (1.4%), 1 FilaC®+ SiLaC® patient (0.7%), and 1 FilaC®+ LHP® case (0.7%). 79 patients (73.2%) benefited from initial drainage of the fistula with a loose seton for 1 to 5 months before FilaC®, while 29 patients (26.8%) with a short direct extrasphincteric fistula benefited from laser therapy.18 patients were lost to follow-up (12,8%). 104 patients (84,5%), all pathologies combined, progressed well with 19 cases of failure (15,5%) with a follow-up time of 1 to 50 months. Fistulas healed in 74 patients (80%). There were 18 confirmed failures. 15 of these were treated surgically with 4 FilaC. Failure was diagnosed within an average of 6 months and was manifested by persistent leakage with no healing of the external orifice. There were no continence problems after the procedure. 16 patients were lost to follow-up. In patients with LHP, 2 patients (15,4%) experienced early post-operative bleeding requiring surgical suturing. All patients treated with SiLaC® had a favorable outcome. The 4 patients treated for anal fissures were satisfied with the procedure.

Conclusion

Laser proctology is a minimally invasive conservative procedure with significant postoperative pain reduction. In the literature, the success rate of this technique ranges from 65 to 80%. Our hospitals were the first in Morocco to introduce this procedure. Preliminary results from our pilot study showed satisfying healing in 84.5% of patients. However, long-term confirmation is required.

References

1- Adegbola SO, Sahnan K, Tozer P, Warusavitarne J. Emerging Data on Fistula Laser Closure (FiLaC) for the Treatment of Perianal Fistulas; Patient Selection and Outcomes. Clin Exp Gastroenterol. 2021 Dec 6;14:467-475. doi: 10.2147/CEG.S269464. PMID: 34908858; PMCID: PMC8664604.

Introduction

The incidence of elderly-onset ulcerative colitis (EO-UC) and Crohn’s disease (EO-CD) is increasing globally. However, whether the initial disease presentation of EO-UC and EO-CD differs from that in adult-onset (AO) is currently poorly investigated.

Aims & Methods

The aims of this study were to explore the initial presentation, severity, and disease course of newly diagnosed EO-UC and EO-CD (age ≥60 years) in comparison to AO-UC and AO-CD (18–59 years). The study was conducted as an ongoing prospective population-based inception cohort, IBD Prognosis Study, with enrollment between May 2021 and April 15^th, 2023, within a catchment population of 1.050.000 citizens (~20% of the Danish population). We defined severe disease course as requiring surgery or initiation of biological therapies within six months of diagnosis.

Results

The cohort comprised 501 patients, including 398 (79.4%) with AO disease (AO-UC: 223 (56.0%), AO-CD: 145 (36.4%), AO-IBDU: 30 (7.5%)), and 99 (19.8%) with EO disease (EO-UC: 64 (64.6%), EO-CD: 35 (35.4%), EO-IBDU: 5 (5.1%)). A comparison of the clinical presentation, severity, and initial disease course is presented in Table 1. As shown, EO-UC and EO-CD did not differ significantly from AO-UC and AO-CD in terms of demographic factors, disease phenotype, severity, and initial therapy. However, a significantly higher proportion of patients with EO-UC had left-sided UC, and tended to be treated less frequently with biological therapies and immunomodulators.
In a Cox multivariable regression model with Bonferroni correction adjusting for disease type and gender, patients with EO-UC (adjusted hazard ratio (aHR)=1.9 (95% confidence interval (CI) 0.5-7.3)) and EO-CD (aHR =4.1 (95% CI 0.3-12.3)) were not at different risk of requiring surgery or initiation of biological therapies within six months of diagnosis than patients with adult-onset IBD.
Table 1: Pairwise comparison of newly diagnosed elderly-onset and adult-onset inflammatory bowel diseases

Conclusion

In this population-based study, we found no difference between EO-IBD and AO-IBD in terms of initial disease presentation, severity, and course. However, patients with EO-IBD tended to be treated with less biological therapies and immunomodulators.

Disclosure

Mohamed Attauabi: None
Gorm Roager Madsen: None
Flemming Bendtsen: Tillotts, Ferring
Klaus Theede: Ferring, Janssen, Takeda, Pfizer, and Tillotts
Jakob Benedict Seidelin: has received research grants from Takeda, Janssen and is national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly, and Boehringer Ingelheim. None of these pertain to the research submitted here.
Johan Burisch: reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work.