Introduction

MAESTRO-NASH (NCT03900429) is an ongoing 54-month, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and fibrosis. 966 patients with biopsy confirmed NASH were randomized 1:1:1 to resmetirom 80 mg, resmetirom 100 mg, or placebo administered once daily. Histologic endpoints were assessed after 52 weeks. Dual primary endpoints at Week 52 were achieved with both resmetirom 80 mg and 100 mg: NASH resolution with no worsening of fibrosis (NR) or ≥1-stage reduction in fibrosis with no worsening of NAS (FI). Body weight is the major factor influencing exposure to resmetirom in patients with NASH/MASH.

Aims & Methods

This post-hoc analysis was performed to provide additional evidence of a relationship between resmetirom dose, baseline body weight and body mass index (BMI) and to assess the impact of baseline body weight and BMI on resmetirom response, we
stratified resmetirom efficacy data on the dual endpoints based on baseline patient body weight (≤100 and >100 kg) and BMI (≥35 and <35 kg/m2).

Results

For patients treated with resmetirom 80 mg who weighed ≤100 kg, the 30% PDFF response was 66.9%; and in patients with a Week 52 biopsy, 35.4% showed fibrosis improvement (FI) compared with 32% who showed no worsening of fibrosis (NR). In patients >100 kg, the 30% PDFF response was 56.7%; FI=22.5%; and NR=27%. For patients who received resmetirom 100 mg who were ≤100 kg, the 30% PDFF response was 71.7%; FI was 33.6% and NR was 35.8%; for patients >100 kg, PDFF=72.5%; FI=32.5%; NR=35.8%. Increases in FI were noted relative to placebo for patients who received resmetirom 80 mg (mITT population) who had BMI <35: 13.0% (5.2, 20.8); NR=33.4% (14.2, 30.6); and in patients with BMI ≥35: FI=7.0% (-0.7, 14.7); NR=9.8% (3.1, 16.6). Increases were also noted relative to placebo for patients who received 100 mg of resmetirom (mITT population) who had a BMI <35: FI=11.8% (4.2, 19.4) NR=21.0% (13.4, 28.7); for patients with BMI ≥35: FI=11.1% (3.4, 18.9); NR=20.0% (12.3, 27.7).

Conclusion

As shown in these stratified data, resmetirom 100 mg was consistently more effective than 80 mg in achievement of the dual primary endpoints in the sample of patients who had higher baseline body weight and BMI. In patients with a lower BMI, there was no observed difference in efficacy between the 80 and 100 mg resmetirom doses.

Disclosure

Authors are investigators in the MAESTRO-NASH trial or employees of Madrigal Pharmaceuticals. ​

Introduction

Watch-and-Wait is an increasingly recognized non-surgical management option for rectal cancer patients achieving a clinical complete response (cCR) following neoadjuvant therapy. This approach aims to preserve organ function by avoiding surgery, but necessitates vigilant endoscopic surveillance, to detect local tumor regrowth¹ (LTR). The specific endoscopic features associated with regrowth remain incompletely defined.

Aims & Methods

We performed a retrospective analysis of patients monitored under the Watch-and-Wait program at Karolinska University Hospital², focusing on the endoscopic characteristics of LTR. As of December 2023, 145 patients who met the criteria for clinical complete response (cCR) were included.
The neoadjuvant treatment consisted of chemoradiotherapy (CRT) in 16 patients (11%), short course radiotherapy (SCRT) + chemotherapy in 69 patients (47.6%) and SCRT alone (5 x 5 Gy) in 60 patients (41.4%). The median age of the patients was 66 years (range 29-94), with 61.4% being male. The initial tumor stage was T1/T2 in 42 patients (29%) and T3/T4 in 103 patients (71%). The nodal stage was N0 in 35 patients (24%) and N+ in 110 patients (75.9%). The median follow-up period was 29 months (range 3-102 months).
Patients were monitored with rectal digital exams, flexible endoscopy, CEA measurements, and MRI every 3 months for 2 years, and then every 6 months thereafter. During endoscopy, narrow-band imaging (NBI) and NICE classification³ was utilized.

Results

Out of the 145 patients, 28 (19.3%) experienced LTR as of December 2023. The median time from the completion of radiotherapy to regrowth was 9 months (range 3-20 months). Regrowth was detected intraluminally by endoscopy in 23 patients (82.1%), while in 5 patients (17.9%), regrowth was detected on MRI but was not visible intraluminally.
The most common endoscopic features of regrowth included a NICE 3 pattern (n=16) and contact bleeding (n=16). Additional findings included polypoid tissue (n=13), ulceration (n=10), irregular surface (n=9), fibrin cover (n=9), stenosis (n=6), and submucosal nodules (n=5).

Conclusion

As regrowth occurs in at least one of five patients and most commonly with intraluminal findings, this study highlights the importance of meticulous endoscopic follow-up. Contact bleeding and NICE type 3 lesions observed with narrow-band imaging (NBI) were key endoscopic findings in patients with tumor regrowth, while polypoid lesions were observed in less than 50%. Combining endoscopic assessment with other modalities, such as MRI, is essential, as regrowth may be undetectable endoscopically in a proportion of patients.

References

1. Cerdan-Santacruz C, Vailati BB, Sao Juliao GP, Habr-Gama A, Perez RO. Local tumor regrowth after clinical complete response following neoadjuvant therapy for rectal cancer: what happens when organ preservation falls short. Tech Coloproctol 2023;27(1):1-9. DOI: 10.1007/s10151-022-02654-5.
2. Nilsson PJ, Ahlberg M, Kordnejad S, Holm T, Martling A. Organ preservation following short-course radiotherapy for rectal cancer. BJS Open 2021;5(5). DOI: 10.1093/bjsopen/zrab093.
3. Hamada Y, Tanaka K, Katsurahara M, et al. Utility of the narrow-band imaging international colorectal endoscopic classification for optical diagnosis of colorectal polyp histology in clinical practice: a retrospective study. BMC Gastroenterol 2021;21(1):336. DOI: 10.1186/s12876-021-01898-z.

Disclosure

Stephan Haas (SLH) has received speaker's honoraria from Santax Medico, Tillotts Pharma, Lilly, Mediahuset, and Johnson & Johnson.

Introduction

Interleukin (IL) inhibitors are monoclonal antibodies that have been shown to be effective in inducing and maintaining remission in moderate to severe ulcerative colitis (UC).
Ustekinumab (UST) was approved in the EU for the treatment of UC in 2019 and binds specifically to the p40 protein subunit of IL-12 and IL-23. Mirikizumab (MIRI) was approved 4 years later and selectively binds to the p19 subunit of the IL-23 cytokine. By binding to the IL subunits, the interaction with the IL-23 receptor is inhibited.
In this study, we compared the response rate to induction therapy with UST and MIRI in patients with moderately to severe UC.

Aims & Methods

All patients with active UC who began induction therapy with UST or MIRI at our outpatient clinic between 2019 and 2024 were analyzed retrospectively with a follow-up period until April 2025. Patients who received the IL-23 inhibitor due to a disease other than UC or following a prednisolone therapy exceeding 20 mg and patients with pouchitis were excluded from the study.
We determined the response to IL-23 therapy 8 to 24 weeks after the start of treatment and documented this either as clinical remission (Mayo-Score ≤1), improvement (Mayo-Score reduction by at least 3 points), inadequate response (Mayo-Score reduction between 0 and 2) or no response (lack of benefit, switch to another medical class or colectomy).
We examined the levels of calprotectin in the stool 0 to 24 weeks before the start of IL-23 therapy up to 24 weeks after initial administration.
Our study included 40 patients treated with UST and 23 patients treated with MIRI, in the latter group 26% have previously been treated with UST. Patients in both groups were similar in age (mean age, 47.75 vs. 44.59 y; P 0.28), gender, disease duration (mean duration, 11 vs. 9 y; P 0.32), and extent of disease (pancolitis, 40% vs. 48%).

Results

After completion of induction, 25% in the UST group and 57% in the MIRI group reached clinical remission. MIRI after UST achieved clinical remission in 67%. Improvement was shown in 20% vs. 30%, UST vs. MIRI. For UST, 5% were non-responder. For MIRI, no non-responder was noted. In general, the difference between the pre- and post-induction Mayo-Score is significantly higher for MIRI, indicating a better response to the newly started drug (mean Mayo-Score difference, UST vs. MIRI, 2.95 vs 4.5; P 0.0003)
The mean calprotectin level before treatment was not significantly different (mean calprotectin, UST vs. MIRI, 1652 vs. 2452 mg/kg; P 0.17). The post-treatment calprotectin level was significantly higher for UST vs. MIRI (mean calprotectin, 1092 vs. 278 mg/kg; P 0.0083).

Conclusion

Mirikizumab is an effective induction treatment for patients with active ulcerative colitis, including those who previously did not respond adequately to Ustekinumab therapy.

Introduction

Intestinal point-of-care ultrasound, as standardized by the International Bowel Ultrasound Group (IBUS), has emerged as a valuable tool for diagnosing, monitoring, and managing patients with Inflammatory Bowel Disease (IBD). While IBUS emphasizes a structured intestinal assessment, some European centers adopt a more comprehensive approach, combining intestinal ultrasound with a complete abdominal examination.
The Karolinska Centre for Digestive Health, a tertiary referral institution providing specialized care to approximately 4,500 patients with IBD, established a dedicated Gastrointestinal Ultrasound Unit in October 2023. This unit offers advanced diagnostic services to both hospitalized patients and those treated on an outpatient basis.

Aims & Methods

This retrospective study aimed to assess the prevalence of secondary extraintestinal findings in IBD patients undergoing comprehensive abdominal ultrasound between October 4, 2023, and March 4, 2025. All patients underwent ultrasound assessments that included both intestinal and abdominal imaging. Patients referred for indications unrelated to intestinal ultrasound (IUS), as well as those undergoing repeat examinations, were excluded from the analysis to ensure data consistency.
All examinations were performed by a single gastroenterologist with 25 years of ultrasound experience. In cases where secondary extraintestinal findings were identified, patients’ electronic medical records were reviewed to determine whether these findings represented new diagnoses or previously known conditions.

Results

The study included 348 patients with IBD, 201 (58%) females and 147 (42%) males, with a mean age of 42.4 years. Among these, 260 (75%) were referred internally by our IBD Outpatient Clinic, 47 (13%) by the Gastroenterology Ward, 33 (10%) by private outpatient clinics, and the remainder from other healthcare sites. IUS revealed evidence of intestinal inflammation in 144 patients (42%), while findings were normal in 204 patients (58%).
Furthermore, 150 patients presented with a total of 195 secondary extraintestinal findings, of which 113 (58%) represented newly identified pathologies. Among all secondary findings, the majority, 104 (53%), were related to the hepatobiliary system, including 33 newly diagnosed cases of hepatic steatosis and 17 new cases of cholecystolithiasis. One patient demonstrated ultrasound features suggestive of primary sclerosing cholangitis (PSC) and is currently undergoing further evaluation. Additional findings involved the reproductive system (29/15%), urinary system (15/7%), spleen (32/16%), and pancreas (5/2%). Various other intra-abdominal findings were also identified (37/18%). Notably, one patient presented with a suspicious mass in the right iliac fossa, and another demonstrated ultrasound findings suggestive of a prostatic tumor; both cases were referred for further oncologic evaluation. Additionally, three patients were newly diagnosed with intraductal papillary mucinous neoplasm (IPMN), which was subsequently confirmed via magnetic resonance imaging, and all were enrolled in the national IPMN surveillance protocol.

Conclusion

A considerable proportion of patients with IBD were found to have previously unknown extraintestinal abdominal pathologies, underscoring the essential role of comprehensive ultrasound examination that combines both intestinal and abdominal assessment. Fortunately, only a minority of these findings resulted in changes to patient management.

Disclosure

Francesca Bresso has acted as national and/or local principal investigator for clinical trials for Janssen, Ferring, and AbbVie. Charlotte Hedin served as a speaker and/or advisory board member for AstraZeneca, AbbVie, Dr. Falk Pharma and the Falk Foundation, Galapagos, Janssen, Pfizer, Ferring, Takeda, and Tillotts Pharma and received grant support from Tillotts Pharma and Takeda. Stephan L. Haas has served as a speaker for Takeda, Santax Medico, Tillotts Pharma, Johnson & Johnson, and Mediahuset. The rest of the authors have nothing to declare.

Clinical Case Summary

Background: Hepatic artery aneurysm (HAA) is a rare and often asymptomatic pathology with a high risk of rupture [1]. HAA is mostly asymptomatic, and 60-80% of the patients are diagnosed when the aneurysm has complications [2]. HAA is a rare cause of jaundice, the most common causes are cholelithiasis, cholangitis, pancreatic head cancer and cholangiocarcinoma [3]. True aneurysms involve all layers of the wall, while pseudoaneurysms result from a tear in the vessel wall with subsequent periarterial hematoma formation.
Case Report: A 45-year-old male presented to the hospital with painless jaundice and fever. Patient is known to have chronic hepatitis B virus, with no treatment. Magnetic resonance cholangiopancreatography (MRCP) was done revealing dilated biliary radicles down to long common bile duct (CBD) stricture by mostly external compression.
Endoscopic retrograde cholangiopancreatography (ERCP) was done, opacification of biliary tree showed dilated biliary radicles on both sides down to tight long CBD stricture about 5 cm in length. Placement of plastic biliary stent was done with adequate biliary drainage.
Computed tomography (CT) done showed evidence of contrast extravasation of common hepatic artery (CHA), forming a large pseudoaneurysm 7x4 cm, compressing the CBD.
After discussion with the patient about treatment options, interventional radiology consultation was done, angiography with occlusion of aneurysm using mixture of lipiodol and histoacryl successfully. Follow-up CT showed reduction size of the aneurysm with no flow inside.
Discussion: Management of HAA is highly variable and depends on clinical presentation and anatomic location. Biliary stenting provides temporary relief for patients with obstructive jaundice. Definitive options include open aneurysmal repair versus endovascular therapy. Hepatic artery aneurysms represent a significant risk for hemorrhage and therefore must be addressed promptly once discovered [4].

References

1- Jana M, Gamanagatti S, Mukund A, Paul S, Gupta P, Garg P, Chattopadhyay TK, Sahni P. Endovascular management in abdominal visceral arterial aneurysms: A pictorial essay. World J Radiol 2011;3:182-7.
2- Sheldon DM, Crawford M, Mihrshahi S, Gallagher J, Storey D. Therapeutic considerations in obstructive jaundice due to hepatic artery aneurysm. HPB (Oxford) 2006;8:74.
3- Hama Y, Chakiri A, Azzaoui F, Dahmane H, Lafrouji S, et al. (2019) Hepatic Artery Aneurysm: A Rare Presentation as Painless Obstructive Jaundice. Med Rep Case Stud 4: 173.
4- Schick C, Ritter RG, Balzer JO, et al. Hepatic artery aneurysms: treatment options. Eur Radiol. 2004;14:157–159.

Introduction

Lateral lymph node dissection (LLND) is considered for patients with advanced lower rectal cancer because of possibility of metastasis. The standard surgical procedure for ulcerative colitis (UC)-associated cancer is total colectomy; however, the significance of LLND in UC-associated rectal cancer remains unclear.

Aims & Methods

The aim of this study is to clarify the outcomes of LLND for UC-associated rectal cancer. Of 1,249 patients treated for UC-associated colorectal neoplasms between 1983 and 2020 at 43 Japanese institutions, we retrospectively analyzed 415 patients with rectal cancer.

Results

LLND was performed in 45 (10.8%) patients with UC-associated rectal cancer: 33 of 139 (23.7%) patients with pT3–4 cancer and 12 of 276 (4.3%) patients with pTis–T2. Of the 45 patients with LLND, 11 (24.4%) had lateral lymph node metastasis (LLNM). LLNM-positive group (n = 11) had a significantly higher proportion of patients with pT3-4 cancer (100% vs. 64.7%, P < 0.0046) and poorly differentiated adenocarcinoma/ signet-ring cell carcinoma/ mucinous adenocarcinoma (por/sig/muc) (70% vs. 17.7%, P = 0.002) than LLNM-negative group (n = 34). There was no significant difference in R0 resection rate between the LLND and non-LLND groups (81.8% vs. 91.2%, P = 0.41). The LLNM-positive group showed significantly worse 5-year overall (30.8% vs. 82.8%, P = 0.0005) and 5-year disease-free (0% vs. 72.4%, P < 0.001) survival rates than the LLNM-negative group. There was no significant difference in the administration of adjuvant chemotherapy between the two groups (54.6% vs. 40.6%, P = 0.42).

Conclusion

The LLND rate for UC-related rectal cancer was 23% in patients with T3-4 cancer in Japan. The LLNM-positive group had more advanced disease, more por/sig/muc histology, and showed poor prognostic outcomes even after LLND.