Introduction

The standard treatment for pT1 colorectal cancer classified as high risk (poor differentiation, deep submucosal invasion, intense tumor budding, resection margins that are positive or lymphovascular invasion) is surgery [1]. However, some studies have revealed that patients who undergo surgery and endoscopic treatment have similar disease progression outcomes, and it is also controversial which histological factors influence disease progression [2,3].

Aims & Methods

The aim of this study was to analyze the characteristics and evolution of patients undergoing surgery or endoscopic treatment after the resection of pT1 colorectal adenocarcinoma with histological findings considered high risk for lymph node metastasis.
We conducted an observational study of historical cohorts. We included patients with pT1 Adenocarcinoma and histological criteria of poor prognosis with at least six months of follow-up, and who were diagnosed between 2018 and 2024. The therapeutic approach was determined by a multidisciplinary committee.

Results

We included 54 patients (74.1% male) with a mean age of 65.3 years and mean follow-up time of 3.07 years; no significant differences in both groups. The indications for colonoscopy were screening (42.6%), alarm symptoms (38.9%), radiological findings (3.7%), prior polypectomy (9.3%), history of colorectal cancer (1.9%), and family history (3.7%). The rate of patients with endoscopic complications was 2.9% intraprocedural bleeding and 2.9% delayed bleeding.
The mean lesion size was 23.48 mm, and the most common location was the rectum.
Regarding the therapeutic approach, 63.0% of patients underwent surgery and 29.6% underwent endoscopic surveillance. Among the surgical patients, complications included suture dehiscence (6%), and hemorrhage (2%). In the surgical specimen analysis, residual lesion was found in 6 patients, and metastatic lymph nodes in 2. 5.55% required adjuvant therapy due to lymph node involvement, and 1.85% were stage IV at diagnosis, excluded from the comparative analysis.
Comparing both study groups, the surgical group had a significantly higher rate of submucosal invasion, with no differences in the remaining characteristics studied. During the study period, progression with lymph node involvement was observed in one patient who underwent surgery and two patients who underwent endoscopy treatment (average time 11 and 24.5 months, respectively). No patient has developed distant metastases to date.

	Surgery treatment (n =34)	Endoscopic therapy (n = 16)	p-value
Piecemeal resection (n, %)	16 (47.05%)	8 (50%)	p > 0.05
Poor differentiation (n, %)	1 (2.9%)	0	p > 0.05
Deep submucosal invasion (n, %)	33 (97%)	11 (68.75%)	P = 0.016
Margins affected or not precise (n, %)	14 (41.17%)	6 (37.5%)	p > 0.05
Lymphovascular invasion (n, %)	6 (18.18%)	0	P = 0.06
Perineural invasion (n, %)	2 (6.66%)	0	p > 0.05
Intense tumor budding (n, %)	0	0
Total number of poor prognostic factors (media, SD)	2,59 (1,076)	1,93 (1,03)	P = 0.043
Disease progression (n, %)	1 (2,9%)	2 (1,25%)	p > 0.05

Conclusion

In our study, patients who underwent endoscopic treatment did not present significant differences with respect to those who received surgery in terms of long-term tumor progression, despite having a higher rate of submucosal invasion. Further studies with larger sample sizes are needed to determine which factors and to what extent influence lymphatic and distant dissemination of pT1 adenocarcinoma.

References

1. Hassan C, Wysocki PT, Fuccio L, Seufferlein T, Dinis-Ribeiro M, Brandão C, et al. Endoscopic surveillance after surgical or endoscopic resection for colorectal cancer: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Digestive Oncology (ESDO) Guideline. Endoscopy 2019;51:266–77. https://doi.org/10.1055/a-0831-2522.
2. Ozeki T, Shimura T, Ozeki T, Ebi M, Iwasaki H, Kato H, et al. The risk analyses of lymph node metastasis and recurrence for submucosal invasive colorectal cancer: Novel criteria to skip completion surgery. Cancers (Basel) 2022;14:822. https://doi.org/10.3390/cancers14030822.
3. Zwager LW, Bastiaansen BAJ, Montazeri NSM, Hompes R, Barresi V, Ichimasa K, et al. Deep submucosal invasion is not an independent risk factor for lymph node metastasis in T1 colorectal cancer: A meta-analysis. Gastroenterology 2022;163:174–89. https://doi.org/10.1053/j.gastro.2022.04.010.

Clinical Case Summary

Introduction: PSC is closely associated with IBD and affects up to 3.6% of Crohn's disease patients, while AIH is also more prevalent in IBD patients, in up to 16% of patients.
Case report: We report a female patient who, at the age of 14, presented with right hypochondrial pain and abnormal liver biochemistry (SGOT: 44 U/l, SGPT: 145 U/l, γ-GT: 300 U/l, ALP: 421 U/l, TBL: 1 mg/dL). The patient underwent MRCP (Figure A) which revealed local strictures with prostenotic dilatation in both intrahepatic and extrahepatic bile ducts, suggestive of PSC. One year later the patient presented with severe abdominal pain and bloody diarrhea. Ileocolonoscopy showed terminal ileitis (Figure B) and segmental colitis. Histological evaluation (Figure C) showed disruption of the architecture, focal erosions of the epithelium, mild mucopenia, inflammatory infiltrate in the dermis, sites of cryptitis and focal formation of crypt abscesses with extension of inflammation to the muscularis mucosae, suggestive of Crohn’s Disease. Two years later, in a regular laboratory test, the patient had abnormal liver function tests (SGOT: 211 U/l, SGPT: 603 U/l, γ-GT: 54 U/l, ALP: 105 U/l, TBL: 0.9 mg/dl). Further evaluation with immunoassay revealed ANA (+) 1/80, AMA (-), SMA (+) 1/160, + F-actin, anti-LKM (-), anti-LC (-), anti-LM (-), p ANCA (+) 1/80, so the patient underwent percutaneous liver biopsy with findings of portal spaces with presence of waxy-containing macrophages, thin fibrous septa, parenchyma with centrolobular necrosis with aggregates of inflammatory cells and waxy macrophages, suggestive of Autoimmune Hepatitis. Today, the patient is in clinical remission under treatment with Ursodeoxycholic acid, Ustekinumab and Mycophenolate Mofetil.
Conclusion: The association of IBD with PSC, AIH and variant forms is now known, however the complexity of the diseases presents a challenge for the clinician and the provision of individualized care.

References

1. Ballotin VR, Bigarella LG, Riva F, Onzi G, Balbinot RA, Balbinot SS, Soldera J. Primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome associated with inflammatory bowel disease: A case report and systematic review. World J Clin Cases. 2020 Sep 26;8(18):4075-4093.
2. Saich R, Chapman R. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease. World J Gastroenterol. 2008 Jan 21;14(3):331-7.
3. Rocha HC, Vilela EG. Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases. Gastroenterol Hepatol. 2022 Feb;45(2):83-90. English, Spanish.
4. Malik T, A, Gutierrez A, M, McGuire B, Zarzour J, G, Mukhtar F, Bloomer J: Autoimmune Hepatitis-Primary Sclerosing Cholangitis Overlap Syndrome Complicated by Crohn’s Disease. Digestion 2010;82:24-26.

Clinical Case Summary

Splenic granulomas are a rare extraintestinal manifestation of Crohn’s disease (CD). In previously reported cases, the diagnosis was confirmed by biopsy. However, due to the increased risk of complications associated with biopsy, confirmation by imaging is desirable.
52-year-old male patient presented with a previously diagnosed, currently untreated CD.
Symptoms:

• Abdominal pain in the right lower quadrant for several weeks, postprandial
• Bowel movements: 4-6 times/day for a few weeks, liquid consistency
• No fever or weight loss
• Palpation: tenderness in the lower right abdomen

Findings:

• C-reactive protein and leukocytes: not elevated
• Calprotectin: 184ug/g. Stool culture and intestinal cytomegaly virus PCR biopsy negative
• Tuberculosis interferon-g release assay: negative
• Colonoscopy and magnetic resonance enterography (MRE): ileitis of terminal Ileum (Fig. 1)
• MRE: multiple T2w-hyperintense splenic lesions, increased in number since last imaging 2024 (Fig. 2)
• B-mode ultrasound: splenomegaly, round nodules of mixed echogenicity (Fig. 3)
• Contrast-enhanced ultrasound (CEUS): 1,5ml contrasting agent (sulphur hexafluoride microbubbles): arterial isoenhancement and late phase hypoenhancement of nodules (Fig. 3), atypical for haemangiomas
• 18-Fluorodeoxyglucose positron emission tomography with computed tomography: no uptake in the spleen (Fig. 4)

After excluding malignancy, abscesses, sarcoidosis, and infectious causes, the splenic granulomatous lesions represented an extraintestinal manifestation of CD. The patient was started on prednisolone, 60mg/day, resulting in marked clinical improvement in 4 days; with reduced abdominal pain and decreased stool frequency. Patient declined recommended maintenance therapy with ustekinumab.
This CEUS pattern is novel to CD and resembles previously reported enhancement patterns of inflammatory lesions. This is a rare reported case of splenic granulomas as an extraintestinal manifestation of CD diagnosed non-invasively by CEUS.

References

Figure 1: Colonoscopy shows 2-4mm aphthous ulcers in the terminal Ileum
Figure 2: (A)T2-Haste and (B)T2-STIR MRE depicting multiple hyperintense splenic lesions
Figure 3: B-mode (left) and CEUS (right) of the splenic lesions. (A) Nodules appear mixed in echogenicity, nodules show isoenhancement during the arterial phase. (B) Nodules exhibit hypoenhancement in the late phase
Figure 4: 18F-Fluorodeoxyglucose (FDG) positron emission tomography with computed tomography shows no uptake of FDG in the spleen
1. Castellani L, Sartini A, Marocchi M, Balbi T, Belluzzi A. Splenic granulomas in a patient with severe Crohn's disease associated with multiple extraintestinal manifestations. Inflamm Bowel Dis. 2011 Jun;17(6):E35-7. doi: 10.1002/ibd.21665. Epub 2011 Feb 11. PMID: 21319276.
2. Schulz C, von Arnim U, Kuester D, Fischbach F, Malfertheiner P. Milzbefall - seltene extraintestinale Manifestation bei Morbus Crohn [Splenic granulomas - rare extraintestinal manifestation of Crohn's disease]. Z Gastroenterol. 2010 Dec;48(12):1367-70. German. doi: 10.1055/s-0029-1245562. Epub 2010 Dec 1. PMID: 21125512
3. Safai Zadeh E, Prosch H, Ba-Ssalamah A, Findeisen H, Alhyari A, Raab N, Görg C. Contrast-enhanced ultrasound of the liver: basics and interpretation of common focal lesions. Rofo. 2024 Aug;196(8):807-818. English, German. doi: 10.1055/a-2219-4726. Epub 2024 Jan 4. PMID: 38176437

Disclosure

Travel grant from Johnson & Johnson

Clinical Case Summary

27-year-old male with penetrating Crohn's disease (CD; A1, L2, pB3), diagnosed at the age of 9, with multiple hospitalizations. The patient was treated with infliximab + azathioprine for three years. Colonoscopy at 16 years showed pancolitis and was complicated with perforation, being submitted to total colectomy with rectal preservation and ileostomy. Therapy was switched to adalimumab+methotrexate, with partial clinical response. After seven years, due to severe complex fistulizing perianal disease, adalimumab was switched to ustekinumab. After 2 years of Ustekinumab monotherapy, he presented disabling symptoms and developed an enterocutaneous fistula peri-ileostomy. Combination therapy with ustekinumab+vedolizumab was started. The patient still maintained discharge from the enterocutaneous and perianal fistulas. After 1 year, a painful circumferential penile ulcer with swelling and seropurulent discharge was noted. Other causes, namely infections were excluded. Biopsies were performed and revealed non-caseous granulomatous inflammation with lymphocytic and eosinophilic infiltrates, compatible with CD. Topical therapy with tacrolimus ointment was applied, with no response. Ustekinumab+vedolizumab was switched to upadacitinib. There was a substantial improvement of the penile lesion, the enterocutaneous fistula discharge reduced, and perianal symptoms resolved on maintenance therapy with Upadacitinib.
Genital metastatic CD is uncommon and mainly occurs in the setting of colonic involvement and perianal disease. Treatment options for MCD remain underwhelming due to the limited available evidence and varying responses of reported therapeutic methods. Optimization of biologic therapy is mandatory.

References

For this case we'll include:
- Pictures ​of the penile ulcers before and during maintenance therapy with upadacitinib
- Endoscopic evaluation during follow-up
- Histological specimen of colectomy and from multiple endoscopic evaluations performed
- Radiological evidence of perianal and peri-ileostomy enterocutaneous fistula