Clinical Case Summary

Introduction: Inflammatory bowel disease (IBD) is linked to cutaneous manifestations in 10% of cases. Neutrophilic dermatoses represent a diagnostic and management challenge, as it requires a dual-targeted treatment approach.
Clinical Case: We present a 67-year-old man with A3L1B1 Crohn’s disease (CD) followed in our IBD consultation. His medical history included previous tobacco abuse, hypertension, type 2 diabetes and ischemic cardiopathy with heart failure. He was medicated for his comorbidities and had been treated with budesonide.
Due to evidence of disease progression, increased fecal calprotectin (FC) at 751ug/g and a history of invasive pulmonary aspergillosis, vedolizumab was initiated.
The patient presented with recurrent erythematous, tender, nodular lesions on the abdomen, limbs and face. Dermatological consultation and cutaneous biopsies led to an initial misdiagnosis of infectious panniculitis, as methicillin sensitive Staphylococcus aureus (MSSA) was isolated and the lesions regressed with antibiotics.
Two months later, cutaneous lesions reappeared and histopathology confirmed IBD-associated erythema nodosum-like neutrophilic dermatosis with MSSA isolation. A 10-week doxycycline course induced their regression. However, recurrence transpired 5 months later, associated with an increased FC (816ug/g).
A swap for ustekinumab (UST) resulted only in transient clinical and biochemical improvement (FC 324ug/g). Despite dose escalation to every 4 weeks, nodular/papular lesions with central postulation recently reappeared, prompting initiation of daptomycin with a potential swap to another drug class.
Conclusions: IBD can be associated with neutrophilic dermatoses and its diagnosis can be challenging. This case reports an CD-associated erythema nodosum-like neutrophilic dermatosis, underscoring its complex approach and management.
Note: We are submitting this case with iconography as it underscores a rare IBD manifestation.

References

Photographs of cutaneous lesions (3-4)

Clinical Case Summary

Autoimmune gastritis (AIG) is an immune-mediated disease characterized by destruction of gastric parietal cells, which leads to the loss of internal factor Casl and decreased production of hydrochloric acid. When conducting endoscopic examination, it is possible to visualize a specific picture of the gastric body mucosa: diffuse atrophy, revealing changes occurring on the background of long-term hypergastrinemia.
Female patient, 45 years old, complaining of increased gas formation, burning sensation and heaviness in the epigastrium after eating, air burping. Chronic diseases: chronic iron deficiency anemia, B12 deficiency, autoimmune thyroiditis. Notes restriction of eating red meat, which causes heaviness in the abdomen. Heredity for cancer is not aggravated. Esophagogastroduodenoscopy revealed pallor of the mucous membrane of the stomach body, single islets of preserved mucous membrane of the stomach body, presence of multiple point whitish inclusions (WGA - white globe appearance) on all walls, forming the effect of “stardust”.
The diagnosis of autoimmune atrophic gastritis was confirmed by laboratory tests: Gastrin dated 01/20/2024 - 746 pg/mL, Chromogranin A CgA dated 01/2024 - 150.4 ng/mL, antibodies to gastric parietal cells -2560. Gastropanel from 20.01.2024 - gastrin-17 baseline > 30.6 pmol/l; pepsinogen I 21.89 µg/l; pepsinogen II 11.80 µg/l, pepsinogen I/II ratio - 1.9. 13C-urease breath test for HP dated 01.2024 - 1.3. Antibodies to Helicobacter, IgG < 13. Histologic conclusion: Moderate atrophy of the gastric body mucosa with the presence of cystic-expanded glands filled with opaque content.
The “stardust” phenomenon was first described in a case of long-term administration of potassium-competitive hydrochloric acid blockers. Given that elevated gastrin levels always accompany AIG, detection of this phenomenon is also possible in cases of AIG.The present case is the first description of the "stardust" phenomenon in a patient with autoimmune gastritis.

References

"Propensity score matching analysis: incidence and risk factors for "stardust" gastric mucosa, a novel gastric finding potentially induced by vonoprazan" Tetsuya Yoshizaki et al. DOI: 10.1111/apt.16151
https://pubmed.ncbi.nlm.nih.gov/33159407/

Disclosure

Yes

Introduction

Accepted oncological principles advise enbloc, R0, excision of cancer to provide a cure. In Barrett’s neoplasia, this includes T1a and T1b disease, where histology is favorable. While treatment options include endoscopic mucosal resection (EMR) and submucosal endoscopic dissection (ESD), a mechanism for appropriate technique selection has not been described.

Aims & Methods

We conducted a prospective observational study to evaluate the performance of a selective resection algorithm for Barrett’s neoplasia (SRAB). To achieve an enbloc resection, ESD was selected if there was a suspicion for ≥T1a disease and the lesion was >15 mm (January 2017 to April 2023). This was compared with a conventional EMR predominant approach (CEA), where ESD was only performed in cases suspicious for deep submucosal invasion or T1b disease (February 2013 to December 2016). The primary outcome was curative oncologic resection (R0 resection with favorable histologic features).

Results

A total of 298 resections were performed in 298 patients (68 UEA, 230 SRAB). Median lesion size was 20 mm (IQR 15-30). T1a adenocarcinoma was identified in 83 (27.9%) and T1b in 58 (19.5%), of which 31 (10.4%) were SM1. Comparing T1a and T1b disease, the rate of enbloc resection (CEA 12 [46.2%] vs SRAB 103 [90.4%]; P<0.001), R0 excision (CEA 7 [26.9%] vs SRAB 86 [74.8%]; P<0.001) and curative resection (CEA 6 [23.1%] vs SRAB 58 [50.4%]; P=0.011) was higher in the SRAB group. Among all T1a and T1b-SM1 cases with favorable histology, which underwent ESD, 39/46 (84.8%) were R0 excisions and are likely cured. There were no significant differences in adverse events (P>0.788 for all).

Conclusion

A selective resection algorithm optimizes oncologic outcomes for Barrett’s adenocarcinoma and mitigates the risk of piecemeal resection of cancers.

Disclosure

Michael J. Bourke: Research Support: Olympus, Cook Medical, Boston Scientific.

Introduction

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders characterized by alterations of acute relapses and remission. The past decades have brought substantial advances in the pharmacological management of IBD by a wide range of medicines. However, the sustained efficacy of the currently available anti-inflammatory therapies is still far from optimal. Therefore, the development of novel therapies represents a major unmet clinical need in this field. Recently, the enrichment of the coagulation pathway genes and among these, Plasminogen activator inhibitor 1 (PAI-1) was described in IBD, whereas PAI-1 emerged as a link between the epithelium and inflammation. Moreover, the genetic deletion of PAI-1 prevented the severity of experimental colitis in mice.

Aims & Methods

Based on these, we aimed to develop and test novel PAI-1 inhibitors for the treatment of IBD.
The novel, amino acid-based PAI-1 inhibitor, LDN-071 was synthesized by the A³SMO^® platform. The inhibitory potential and cytotoxicity effects of the peptide were determined by in vitro assays. Acute and chronic colitis was induced in mice with DSS and 10 mg/bwkg LDN-071 was administered per os. The changes of body weight, spleen weight, and colon length were measured. Haematoxylin eosin (HE) and Periodic acid-Schiff (PAS) staining were performed for histology. ELISA and qRT-PCR measurements were applied to analyze the cytokine expressions. Hydroxyproline assay was used to quantify the mucosal collagen deposition. In vivo, the toxicity of LDN-071 was determined in mice. Human colon organoid and fibroblast (FB) cell cultures were generated from IBD patients and the effects of LDN-071 were observed.

Results

LDN-071 significantly inhibited PAI-1 in vitro without decreasing the cell viability in a concentration range of 1µM-1mM. In the acute mice model, the administration of 10 mg/bwkg LDN-071 in the DSS-treated mice prevented the body weight loss, the development of bloody diarrhea, the decrease of colon length, and the increase of the spleen weight, which were displayed by the DSS+vehicle-treated animals. The histological analysis of the colon revealed that DSS treatment induced severe transmural inflammation, ulceration, loss of crypt structures, and goblet cell depletion. Importantly, all these parameters were significantly ameliorated by the administration of 10 mg/bwkg LDN-071 in the acute and chronic models as well. Additionally, mucosal gene and protein expressions of TNF-α, IL-1β, and IL-6 were significantly decreased by PAI-1 inhibition in the acute phase. Besides, the LDN-071 treatment significantly reduced the inflammation, epithelial erosion, and fibrosis caused by chronic administration of DSS. However, the collagen deposition was significantly lower in the PAI-1-inhibited DSS mice. Importantly, no signs of toxicity were observed in mice exposed to 100 mg/bwkg LDN-071 for 7 days. In our in vitro models, the PAI-1 inhibition reduced the protein level and gene expression of pro-inflammatory cytokines in human colon organoid of IBD patient. Moreover, the gene expression of fibrosis-related genes significantly decreased after the LDN-071 treatment in IBD patients-derived human FB cell culture.

Conclusion

Our results showed that LDN-071, a novel amino acid-based inhibitor of PAI-1, significantly ameliorated the severity of acute and chronic colitis in mice. However, the LDN-071 reduced the expression of inflammation- and fibrosis-related genes and proteins in vitro human models. We propose that the inhibition of PAI-1 could be a potential novel therapeutic strategy in IBD.

Disclosure

LDN-071 PAI-1 inhibitor is owned by Ladon Therapeutics Ltd.

Clinical Case Summary

Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by remitting and relapsing patterns, necessitating multifaceted therapeutic interventions, among which mesalazine, or 5-aminosalicylic acid (5-ASA), is prominently utilized. Despite its typically favorable tolerability profile, mesalazine may occasionally precipitate severe adverse events, such as myocarditis.
Case presentation: A 46-year-old male recently diagnosed with UC presented with a moderate UC flare-up and was initiated on 5-ASA therapy upon admission.
Within a span of two days following initiation of oral therapy, he developed acute chest pain, palpitations, dyspnea, and desaturation, necessitating intensive care due to cardiogenic shock.
Paraclinical assessments revealed elevated troponin levels, along with electrocardiographic and echocardiographic abnormalities, including left ventricular dysfunction and reduced ejection fraction.
Discontinuation of mesalazine resulted in symptom improvement and reduction of cardiac markers. Subsequent evaluations demonstrated a recovery in cardiac function, establishing a causal relationship between myocarditis and the administration of 5-ASA. Consequently, a therapeutic switch to mercaptopurine was instituted.
Conclusion: This case underscores the infrequent yet significant hazard of mesalazine-triggered myocarditis, emphasizing the critical necessity for vigilant patient monitoring during this therapy and prompt consideration of alternative therapeutic options in the presence of severe cardiac complications.

Introduction

Post colonoscopy colorectal cancer (PCCRC) is colorectal cancer diagnosed after a normal colonoscopy with no cancer found. In England, the rate of PCCRCs has been decreasing but remains around 6.5% for colonoscopies performed from 2011-2013¹. English study suggested that 80% of PCCRCs are avoidable². We aim to analyse PCCRC cases using the local data and determine the demographics, nature of cancer and the cause of PCCRC.

Aims & Methods

The PCCRCS are identified following the linkage of Hospital Episode Statistics, Bowel cancer screening programme (BCSP) and cancer registry datasets. As new colorectal cancers are registered with the National Cancer Registration and Analysis Service (NCRAS), PCCRC cases will be identified. Each colorectal cancer (ICD-10 code C18-20) provisionally registered within the Hospital Episode Statistics dataset will be identified and determined whether a colonoscopy was performed within 6- 48 months before the diagnosis which failed to identify the cancer.
This audit includes patients diagnosed with PCCRC 6-48 months after a colonoscopy was performed in a single medical centre in England.
Once the cases had been confirmed, we reviewed the clinical, pathology and radiological findings of each case. We also looked at interval cancer which the World Endoscopy Organisation (WEO) defines as one diagnosed before the next recommended interval. Important to note that all interval cancers are PCCRCs but not all PCCRCs are interval cancer.

Results

39 cases were included and 29 were confirmed to be true PCCRC which fulfilled the above criteria. 7 did not meet the criteria. (2 index colonoscopies performed at other trusts, 3 missing data, 2 other types of cancers such as Neuroendocrine tumour and appendiceal tumour, 1 has <6 months to cancer diagnosis from index colonoscopy, 2 flexible sigmoidoscopy was performed as index colonoscopy to investigate per rectal bleeding but subsequent cancer was found in ascending colons).
52% (n=15) of patients were male with a median age of cancer diagnosis at 74 years old (range 22-84). In terms of PCCRC, 24% (n=7) presented via the National Bowel Screening Programme (BCSP), 14%(n=4) presented with per rectal bleeding, 7% (n=2) presented with abnormal imaging and the same proportion of patients presented due to anaemia, non-specific change in bowel habit, weight loss, diarrhoea, abdominal pain and surveillance for family history of gene mutation. 3% (n=1) were diagnosed after presenting for polypectomy and 3% (n=1) presented with intestinal obstruction.
In terms of investigations that led to PCCRC, 45% (n=13) were via 2-weeks-wait colonoscopy, 24% (n=7) were via National Bowel Screening Programme, 17% (n=5) were diagnosed by Computed Tomography (CT) imaging, 7% (n=2) via flexible sigmoidoscopy and 7% (n=2) was via surgically resected sample. Upon diagnosis of PCCRC, 7% (n=2) tested positive for Lynch syndrome, 24% (n=7) was tested but no marker was found and 69% (n=20) was not tested. In terms of size of PCCRC, 66% (n=19) had tumour size >2cm. 66% (n=17) of tumour size was determined by histopathological sample, 21 (n=6) via endoscopy, 3% (n=1) via CT imaging and 17% (n=6) was not known.
In terms of PCCRC staging, 48% (n=14) was Dukes’ A staging, 21% (n=6) was Dukes’ B, 7% (n=2) was Dukes’ C and 24% (n=7) was Dukes’ D. 83% (n=24) was planned for curative treatment and 17% (n=5) was planned for palliative treatment. 52% (n=16) had surgical resection only, 17% (n=29) had surgical resection and chemotherapy, 3% (n=11) had surgical resection and radiotherapy, 3% (n=1) had surgical resection, chemotherapy and radiotherapy, 7% (n=2) had chemotherapy and radiotherapy, 3% (n=1) had chemotherapy only, 3% (n=1) had endoscopic resection only and 7% (n=2) had no treatment.
In terms of the type of interval cancer, 14% (n=4) was non-interval A, 7% (n=2) was non-interval B, 66% (n=19) was non-interval C and 21% (n=4) was interval cancer. Important to note was 66% (n=19) had no further follow-up or test arranged due to adequate examination on the index endoscopy. 90% of index endoscopies report no difficulties. 75% (n=22) was due to clinician factors, 10% (n=3) was due to administrative errors such as booking delay and 10% (n=3) was due to patient factors such as patient’s decision and intercurrent illness.

Conclusion

The majority of the PCCRC had treatment with curative intent. Most PCCRC cases are due to clinician factors and measures needed to improve this. The high percentage of non-interval type C PCCRC would be explained by either a fast-growing cancer or a missed lesion since up to 90% of the index procedures reported no difficulty.

References

1. Burr NE, Derbyshire E, Taylor J, et al. Variation in post-colonoscopy colorectal cancer across colonoscopy providers in English National Health Service: population-based cohort study. BMJ 2019;367:l6090. doi:10.1136/bmj.l6090
2. Anderson R, Burr NE, Valori R. Causes of Post-colonoscopy Colorectal Cancers Based on World Endoscopy Organization System of Analysis. Gastroenterology Published Online First: January 2020. doi:10.1053/j.gastro.2019.12.03