Clinical Case Summary

Acute severe ulcerative colitis (ASUC) is a medical emergency with significant morbidity and mortality. Current guidelines recommend infliximab or cyclosporin salvage therapy for corticosteroid-refractory ASUC. Other available medical therapies, albeit effective in other settings, are still not validated in ASUC.

We report the case of a 20-year-old male with left-sided ulcerative colitis (UC), previously treated with mesalamine, who had been started on oral prednisolone for a disease flare. Due to lack of response, the patient visited the emergency department two weeks later with worsening symptoms, presenting with 10 bloody stools/day, faecal urgency, tenesmus, and weight loss. Physical examination was significant for tachycardia and diffuse abdominal tenderness. Blood tests revealed anaemia (haemoglobin 7.3 g/dL), thrombocytosis, and CRP of 31 mg/L. Stool examination was negative for C. difficile. Sigmoidoscopy showed continuous erythema, friability, erosions, and scattered ulcers. Mucosal biopsy PCR was positive for cytomegalovirus. The patient was admitted and started on intravenous corticoids and ganciclovir. On the 3rd day, failure of initial therapy was evident and an infusion of infliximab 10 mg/kg was given, producing a partial and transient response. Surgical consultation agreed to maintaining medical treatment. The decision was made to try a second dose of infliximab, again with partial and even shorter response. No anti-infliximab antibodies were detected. A third off-label infusion yielded no response whatsoever. Since the patient preferred to avoid surgery, a trial of upadacitinib 45mg/day was proposed. Complete response was achieved within 24 hours, with 3 soft non-bloody stools/day. On 1-month follow-up, the patient maintains clinical remission.

As in this case, there have been other reports of the efficacy of upadacitinib in ASUC. Upon further validation, this drug might become an invaluable addition to current treatment algorithms.

References

1. Nakase H. Acute Severe Ulcerative Colitis: Optimal Strategies for Drug Therapy. Gut and Liver. 2023 Jan 15;17(1):49–57.

2. Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019 Dec;68(Suppl 3):s1–106.

3. Gilmore R, Tan WL, Fernandes R, An YK, Begun J. Upadacitinib Salvage Therapy for Infliximab-Experienced Patients with Acute Severe Ulcerative Colitis. Journal of Crohn’s and Colitis. 2023 Dec 30;17(12):2033–6.

4. Ali NM, Shehab MA. Upadacitinib as a Rescue Therapy in Acute Severe Ulcerative Colitis: A Case Report and Review of the Literature. Am J Case Rep [Internet]. 2023 Sep 26 [cited 2024 Mar 18];24. Available from: https://www.amjcaserep.com/abstract/index/idArt/940966

Introduction

Colorectal cancer associated to chronic colitis (CAC) has a different pathogenesis compared to sporadic or familial colorectal cancer (CRC) and represents the major complication of inflammatory bowel disease (IBD). It is now well-established that IL-33 and its receptor, ST2, are important factors in the pathogenesis of IBD. Emerging evidence also suggests its critical role in epithelial proliferation and the potential contribution to inflammation-driven tumorigenesis that can lead to CRC.

Aims & Methods

The aim of our study was to characterize the precise contribution of IL-33/ST2 axis in the azoxymethane (AOM)/dextran sodium sulfate (DSS) model of colitis-associated CRC. C57/BL6 wild-type (WT), Il33^-/-, T1/St2^-/- and Nt5e^-/- mice were given a single dose of AOM (10 mg/kg) followed by two cycles of 3% DSS for 7d in drinking water. Vehicle-treated WT mice served as controls and were sacrificed at the same time points. Another group of WT followed the same protocol and received CD73 inhibitor i.p. treatment or vehicle. Disease Activity Index (DAI), as well as endoscopic, stereomicroscopic and histological evaluations of colons were performed. IHC, immunofluorescence (IF), qPCR, and ELISA were done on full-thickness colons of WT for IL-33 and ST2 localization and identification, as well as mRNA and protein expression, respectively. RNA-Seq was performed on whole tissues from AOM/DSS treated WT, Il33^-/- and T1/St2^-/-. qPCR analysis was done on isolated polyps from WT, Il33^-/- and T1/St2^-/- for Nt5e (CD73) and adenosine pathway targets.

Results

Il33, Ilrl1(ST2L), and Ilrl1(sST2) mRNA transcripts, as well as IL-33 and total ST2 proteins were dramatically elevated in AOM/DSS-treated WT mice vs. controls. IHC and IF of treated WT mice revealed localization of IL-33 to the colonic epithelium and to cells within the polyp LP morphologically consistent with stromal and mast cells. Little to no staining for IL-33 was present in controls. Using IF, IL-33 co-localized with sub-epithelial myofibroblast markers Actin and Vimentin, or with mast cell markers Tryptase and MCPT1. AOM/DSS treatment in Il33^-/- and T1/St2^-/- mice resulted in a significant decreased polyp number and size vs. WT, with colonoscopy revealing the development of protruding lesions with abnormal vascular patterns, suggesting tumorous lesions in WT mice, while all deficient mice showed their absence with a more impressive mucosal inflammation, likely due to reduced epithelial proliferation and repair caused by the deficiency of IL-33 signaling. RNA-Seq identified a significant reduction of Nt5e and adenosine pathway targets in Il33^-/- and T1/St2^-/- vs. WT. qPCR on isolated polyps confirmed this observation. AOM/DSS-treated Nt5e^-/- showed a significant decreased polyp number and size vs. controls. Therapeutic inhibition of CD73 produced similar results.

Conclusion

Our results suggest that the IL-33/ST2 axis promotes tumorigenesis in colitis-associated CRC through the activation of CD73. Further studies are underway to determine mechanisms of action that support these findings.

Introduction

Endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) is one of the most challenging endoscopic procedures due to the high risk of bleeding and fibrosis caused by prior treatment of varices. However, due to the small number of such cases, the clinical outcomes of ESD for ESCC with EVs have been reported in only a limited number of cases at single centers^​1-3.

Aims & Methods

We conducted a multicenter, retrospective, cohort study to clarify the safety and efficacy of ESD for ESCC with EVs.Eleven institutions in the Tohoku region of Japan participated in this multicenter, collaborative, retrospective study. We performed endoscopic resection for 3619 patients with esophageal carcinoma at the participating institutions during the period from January 2010 to April 2022. Among those, 30 patients who underwent ESD for ESCC with EVs were recruited for the present study.
Rates of en bloc resection and R0 resection, procedure time and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD.

Results

Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 minutes. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC.

Conclusion

This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

References

1. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopic submucosal dissection for superficial esophageal cancer in patients with cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.
2. Choi YK, Noh JH, Kim DH, et al. Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis. Clin Endosc 2022;55:381-9.
3. Zhang S, Liu YD, Chai NL, et al. Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices: Ten-year experience from a large tertiary center in China. Gastrointest Endosc 2023 Online ahead of print.

Disclosure

The authors declare that they have no conflicts of interest.

Clinical Case Summary

Introduction: Sarcoidosis is a multi-systemic disorder of unknown etiology that primarily involves the pulmonary system. Nevertheless, a diagnosis can be challenging for clinicians because of the potential for almost any organ to be affected. Hepatic granulomas occur in 50-65% of patients with systemic sarcoidosis, while isolated hepatic sarcoidosis is rare.
Aims & Methods: A 50-year-old Montenegrin female patient was consulted by a gastroenterologist due to multiple focal lesions open etiology in the liver and spleen detected on routine ultrasound examination.
Results: Laboratory results showed normal complete blood count, total bilirubin 11.1 µmol/L, aspartate-aminotransferase 35 U/L, alanine-aminotransferase 25 U/L, gamma-glutamyl transferase 247 U/L, pancreatic amylase 40 U/L, and lipase 23 U/L. Tumor markers were in range: carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, alpha fetoprotein (AFP), CA 72-4, except CA 15-3, which was slightly elevated. Increased activity of serum angiotensin-converting enzyme was shown. Viral and serological tests for hepatotropic viruses and autoimmune liver diseases were negative. Imaging methods performed were: Multi-Slice Computer Tomography (MSCT) of the lungs, abdomen and pelvis, Nuclear Magnetic Resonance of the abdomen with Magnetic Resonance Cholangiopancreatography (MRCP), mammography, upper endoscopy and colonoscopy, but these did not provide an answer to the primary cause of the focal lesion. In the end, a liver biopsy was performed, where non–caseous granulomas were described and a diagnosis of sarcoidosis was established.
Conclusion: The patient had isolated sarcoidosis of the liver and spleen, as no granulomatous abnormalities were identified in other organs. The patient showed a remarkable clinical response to corticosteroid therapy. Isolated hepatic and splenic sarcoidosis should be considered in asymptomatic patients with hepatosplenomegaly and suspected metastatic disease.

References

1. Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J. Sarcoidosis. Nat Rev Dis Primers. 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. Erratum in: Nat Rev Dis Primers. 2019;5(1):49
2. Franzen DP, Brutsche M, Nilsson J, Böni C, Daccord C, Distler O, Elsener D, Funke-Chambour M, Gruner C, Hayward-Könnecke H, Hostettler KE, Kündig T, Ribi C, Seebach JD, Seeger H, Vrugt B, Kolios AGA. Sarcoidosis - a multisystem disease. Swiss Med Wkly. 2022;152:w30049

Disclosure

This abstract was presented at the 11^th Congress of North Macedonian Society of Gastroenterohepatology with international participation held from June 9-11, 2023 in Ohrid, North Macedonia.

Introduction

Pancreatic adenocarcinoma has a poor prognosis with an overall 5-year survival rate of 10% as most patients present with unresectable or metastatic disease. Evaluation of microsatellite instability (MSI) or deficient DNA mismatch repair (dMMR) status can tailor treatment to increase the efficacy of systematic therapy. However, the adequacy of tissue samples obtained by routine endoscopic ultrasound-guided fine needle biopsy (EUSFNB) of pancreatic adenocarcinoma for MSI/dMMR assessment remains unclear. This study evaluated the role of EUSFNB using the Procore (Cook Medical) biopsy needles for MSI/dMMR assessment. In recent years, a new 20G Procore needle has been developed to overcome the limitations of tissue acquisition of the smaller needles (22G,25G) and the rigidity of the larger one (19G). We also aimed to study the performance assessment between Procore 20G vs 22G needles in tissue acquisition for MSI/dMMR assessment.

Aims & Methods

This was a single-centre study reviewed patients with suspected pancreatic adenocarcinoma who underwent diagnostic EUSFNB in a tertiary referral centre using either 20G or 22G Procore needles from January 2022 to March 2023. The newer 20G Procore needle was designed with a forward side-bevel, whereas the 22G needle had a reverse side-bevel, for tissue core acquisition. Clinical data and characteristics of lesions in all patients undergoing EUSFNB in the participating site are prospectively maintained in a registry for quality control and audit purposes. All cases of adenocarcinoma were tested for MSI/dMMR status by immunochemistry (MLH1, MSH2, MSH6 & PMS2). The primary study outcome measure was the adequacy of tissue samples for MSI/dMMR testing. Secondary outcomes were the rate of histological core tissue acquisition, the difference in the adequacy of tissue for MSI/dMMR testing between 20G and 22G Procore needles and the rate of MSI-high pancreatic adenocarcinoma. The impact of the use of these needles in obtaining adequate tissue on patient management was also evaluated.

Results

A total of 31 patients (mean age 68.2 SD± 8.17; 51% male) with pancreatic adenocarcinoma were included in the study. The mean size for the pancreatic mass was 33.17 SD±20.4 with most of the pancreatic mass located at the pancreatic head, uncinate, and neck region 70% (21/31). The histological yield of EUSFNB was 100%. Overall tissue adequacy rate for MSI/dMMR assessment was 80% (25/31), which was higher with 20G compared to 22G Procore needles (88.8%;16/18 vs 69.2%;9/13, p-value = 0.207). Two of the 23 patients with successful MSI/dMMR testing (8.7%) had MSI-high status. One received second-line treatment with pembrolizumab, and the other received the best supportive care due to worsening liver function and poor functional status.

Conclusion

This study affirmed the feasibility of routine MSI testing from specimens acquired by EUSFNB using the Procore EUSFNB needles. Our results also suggested that the larger 20G Procore needle with forward side-bevel had a higher yield for MSI testing than the 22G needle with reverse side-bevel, even though both needle types could obtain tissue cores for histology, and this should be reassessed by a further study with larger sample size that is adequately powered.

Disclosure

None