Clinical Case Summary

An hemoperitoneum may be the initial presentation of a liver tumour. A good differential diagnosis is critical, including trauma, vascular rupture and tumours.
A 79-year-old male, retired welder and painter, consulted for weight loss, abdominal pain and distension of 3 months of evolution. Ascitic semiology led to do a paracentesis with hematic debit. An urgent computerized tomography (CT) reported hemoperitoneum secondary to multicentric liver tumor with active bleeding (Figure 1) and intratumoral pseudoaneurysms compatible with angiosarcoma, performing an urgent transarterial embolization (Figure 2). Extension CT ruled out distant disease, magnetic resonance imaging (MRI) was realized (Figure 3) and fine needle aspiration (FNA) showed atypical cellular with CD31 expression (Figure 4), consistent with primary hepatic angiosarcoma (PHA). Given the bilobar involvement, surgery was dismissed and he was treated with chemotherapy (CTX), dying at 10 months of diagnosis.
PHA is a rare entity (2% of primary liver tumor) with an annual prevalence of 200 worldwide cases and a male predominance (3:1) at 60 years. It has been associated to exposure to vinyl chloride, arsenic or thoracotrast, but currently 75% of diagnoses have unknown aetiology.
Diagnosis is based on anatomopathology and inmunohistochemistry, including atypical cellularity in FNA and expression of vascular markers as ERG (100%), CD34 (87%) and CD31 (79%). Imaging tests are non-specific, with hypodense lesions in CT and T2-weighted hyperintense sequence in MRI.
Due to its aggressiveness, around 60% of PHA presents lymph nodes or lung, bones or spleen metastases at diagnosis. Liver resection is the only potentially curative treatment because it is a radioresistent tumour. Transplantation is not recommended due to its high recurrence rate. PHA has less than 6 months of overall survival (OS) without treatment. Otherwise, patients with CTX treatment has a OS of 3% at 2 years of diagnosis.

Introduction

Hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of activated immature myeloid cells that are characterized by different specific surface molecules, they express each of CD11b+CD33+ and lack expression of HLA-DR. MDSC are immunosuppressive cells that decrease immune cell activation and induce immunological tolerance in inflammation and cancer. Under normal conditions, MDSC remain in the bone marrow until differentiation; however, under pathological conditions these cells arrest at various stages of development, migrate out of the bone marrow in an immature state and, accumulate in circulation and peripheral lymphoid organs, causing negative regulation of immune responses via various mechanisms, primarily T cell suppression. MDSC are known to increase in patients with chronic hepatitis C virus infection. But it is not clear till now if eradication of HCV using directly acting antivirals can restore normal levels of MDSC on long term or not.

Aims & Methods

This study aimed to assess the levels of MDSC in patients with previous chronic hepatitis C after achieving sustained virologic response (SVR) for at least 2 years using sofosbuvir containing regimens.
This study was a case-control one. Fifty five subjects were involved in the study. All patients had completed DAAs therapy 2-3 years before involvement. Estimation of (CD33+ HLA-DR– CD11b+) expressing cells by flow cytometry was done and levels were compared between HCV patients achieved SVR for 2-3 years and healthy control without any current or previous chronic disease.

Results

MDSC were significantly higher among patients with eradicated HCV for 2-3 years than in healthy controls (4.98% (IQR=3.3 – 7.7) vs 3.09% (1.4 – 3.9), p = 0.001)

Conclusion

Normal MDSC levels are not restored after eradication of HCV using directly acting antivirals even after passage of 2 years on viral eradication. Clinical implications and consequences of these findings should be further investigated.

Introduction

Large non-pedunculated colorectal polyps (LNPCP's) are significant precursors of colorectal cancer, commonly treated by piecemeal endoscopic mucosal resection (pEMR). When histology reveals a focus of adenocarcinoma invading the sub-mucosa, the resection is often considered non curative and salvage surgery is performed. Recent evidence shows that the risk of residual cancer in the bowel wall or lymph nodes of the surgical specimen are uncommon and that in some cases surgery may be avoided even when a focus of invasive cancer is found in the EMR specimen.

Aims & Methods

This is a retrospective observational study aimed to evaluate the prevalence, characteristics, and outcomes of covert carcinoma in LNPCPs resected by EMR in a two academic centers.
Data was collected from a prospective cohort of LNPCPs at two academic centers in Israel. We collected patient, lesion and procedural characteristics prospectively.
EMR was performed by 3 experienced endoscopist with dedicated EMR training. Piecemeal EMR was performed after endoscopic assessment for polyps that were deemed not to have sub-mucosal invasion according to accepted classification systems. Lesions suspected to containing invasive cancer were referred to surgery without endoscopic resection were excluded from the analysis.
For lesions containing invasive carcinoma, data was collected on Kikuchi classification, presence of tumor budding and lymphovascular invasion, grade of tumor differentiation, and status of the deep margin. Surgical data included presence of residual carcinoma in the surgical specimen, grading, margin involvement, and lymph node involvement.

Results

We analyzed 546 LNPCPs referred for resection at the two centers. We identified 27 cases of covert carcinoma, accounting for 4.9% of all LNPCPS resected by piecemeal EMR. A multidisciplinary tumor board deemed resection curative in 7 cases, and 18 patients were refferd for surgical resection. One patient refused surgery, and One patient was lost to follow up.
None of the surgical specimens had lymph node metastasis. In one case residual carcinoma was found in the bowel wall of the surgical specimen. No recurrence of colorectal cancer, presence of metastasis on imaging or elevation of CEA was documented for any of the patients during follow up of two year.

Conclusion

In conclusion, our study shows that covert carcinoma is relatively rare when EMR is performed in a high-volume center by expert endoscopists. In addition, the data suggests that even in these cases, the risk of metastatic disease is probably very low.

References

1. Kudo S ei, Lambert R, Allen JI, Fujii H, Fujii T, Kashida H, et al. Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc. 2008 Oct;68(4 SUPPL.).
2. Ferlitsch M, Moss A, Hassan C, Bhandari P, Dumonceau JM, Paspatis G, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Vol. 49, Endoscopy. Georg Thieme Verlag; 2017. p. 270–97.
3. Lopez A, Bouvier AM, Jooste V, Cottet V, Romain G, Faivre J, et al. Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population. Gut. 2019 Jan 1;68(1):111–7.
4. Choi YS, Kim WS, Hwang SW, Park SH, Yang DH, Ye BD, et al. Clinical outcomes of submucosal colorectal cancer diagnosed after endoscopic resection: A focus on the need for surgery. Intest Res. 2020 Jan 1;18(1):96–106.
5. Gibson DJ, Sidhu M, Zanati S, Tate DJ, Mangira D, Moss A, et al. Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer. Gut. 2022 Mar 7;

Disclosure

Conflicts of interest: None. Financial disclosures: None.

Introduction

Collagenous colitis (CC) is a debilitating, non-destructive inflammatory bowel disease (IBD) that causes intense watery, non-bloody diarrhoea. The abnormal immune response is thought to be initiated by deficient tolerance to commensal gut microbiota, and fecal sample analyses indicate similarities with classic IBD forms as ulcerative colitis and Crohn’s disease. Yet, the exact members of the microbiome that might trigger and maintain the disease remain unknown.

Aims & Methods

To identify primary microbial triggers of CC pathogenesis that could directly interact with intestinal epithelial and submucosal cells, we isolated subepithelial mucosa from CC and healthy control (Hc) formalin-fixed paraffin-embedded samples (n=7-10) by using a laser microdissection microscope (PALM MicroBeam LCM, Zeiss, Germany). Isolated nucleic acids were sequenced using shotgun metagenomics in a NovaSeq 6000 platform (Illumina, USA). Microbial communities were identified using MetaPhlan3/4, and microbial metabolic and molecular function pathways using Humann3.2 algorithms.

Results

Bray-Curtis and Jaccard similarity coefficients showed that CC subepithelial microbiome was similar to that from Hc samples. Still, further analyses indicated that microbial metabolic pathways and molecular functions could differ. Microbiota that was associated with CC included Anoxybacillus and Barnesiella, whereas microbiota associated with Hc comprised Bacteroides, Leuconostoc and Lactobacillus.

Conclusion

Mucosa-associated microbiota in CC did not significantly differ from healthy microbiota. However, our results point to a relation of CC with bacteria that form biofilms (Anoxybacillus) and affect the variability of colitis development (Barnesiella). Thus, validation and further follow-up of these results could help us identify CC triggers in the future.

References

Carstens A. The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis. Clin Transl Gastroenterol. 2019 Jul;10(7):e00065

Disclosure

AM has received salary for consultancies from Tillotts Pharma AG, Ferring, Vifor and Dr Falk Pharma; speaker’s honoraria from Tillotts Pharma AG and Vifor. The remaining authors declare no conflicts of interest.

Introduction

The 6-minute withdrawal time for colonoscopy is widely considered the standard of care. However, there may not be appropriate if the 6-minute is equally divided into various colon segments. Since the adenoma detection in each colon segment is not the same, there may be differences with the withdrawal time in different colon segments.

Aims & Methods

Our objective was to evaluate the relationships between adenoma detection rate (ADR) and respective withdrawal time in different colon segments. Outpatients, age range 18-75 years, undertaking complete colonoscopy were enrolled in this study from November 2019 to November 2020 in the digestive endoscopy center. The entire colon was divided into four different segments: ascending colon, transverse colon, descending colon and rectosigmoid colon. The respective withdrawal time and ADR in each colon segment were recorded respectively.

Results

A total of 586 outpatients (279 males, 307 females) enrolled in this study and the general ADR was 38.2%. The positive withdrawal time (adenomas detected) was longer than negative withdrawal time (non-adenomas detected) (334.04±24.21 secs vs 303.65±5.20 secs, t=1.26, P<0.001). ADR in ascending colon, transverse colon, descending colon and rectosigmoid colon were respectively 30.5%, 2.9%, 3.1% and 7.5%. While all of their positive withdrawal time were longer than negative withdrawal time (94.34±33.76 secs vs 70.40±41.84 secs, t=3.31, P=0.001; 85.40±49.76 secs vs 71.66±36.87 secs, t=1.95, P=0.025; 80.29±39.85 secs vs 69.73±35.96 secs, t=1.40, P=0.016;100.95±55.92 secs vs 80.96±42.87 secs, t=3.61; P<0.001, respectively). The withdrawal time threshold in the ascending colon, transverse colon, descending colon, rectosigmoid colon determined by receiver operating characteristic (ROC) curve were 77s, 61s, 56s and 109s, respectively. In the ascending colon, ADR was significantly higher (47.0% vs 33.1%, P < 0 .001) when the colonoscopy withdrawal time was ≥77s. When the withdrawal time was ≥61s in the transverse colon (42.7% vs 32.7%, P = 0.013), ≥59s in the descending colon (42.3% vs 29.9%, P=0.004) and ≥109s in rectosigmoid colon (52.2% vs 33.9%, P < 0 .001), ADR was also significantly higher. After adjusting for age, sex and BMI, Logistic regression analysis showed that withdrawal time ≥ 77s in the ascending colon (OR, 1.796; 95% CI, 1.273-2.532; P < 0 .001), ≥ 61s in the transverse colon (OR, 1.535; 95% CI, 1.094-2.155; P = 0.013), ≥56s in the descending colon (OR, 1.722; 95%CI, 1.193-2.486; P =0.004) and ≥109s in the rectosigmoid colon (OR, 2.134; 95% CI, 1.446-2.350; P < 0.001) were independent risk factors for the increase of ADR.

Conclusion

ADR and withdrawal time are all various in individual colon segments. During the operation of colonoscopy, withdrawal time in the ascending colon may be shortened appropriately. The adenomas in the rectosigmoid colon are more likely to be detected and do not take longer withdrawal times. We need to choose the appropriate time according to different colon segments.

References

[1] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians 2021;71(3): 209-249.
[2] Shaukat A, Kahi C J, Burke C A, et al. ACG clinical guidelines: colorectal cancer screening 2021. Official journal of the American College of Gastroenterology ACG 2021;116(3): 458-479.
[3] Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021;14(10):101174.
[4] Araghi M, Soerjomataram I, Bardot A, et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. The lancet Gastroenterology & hepatology 2019;4(7): 511-518.
[5] Siegel RL, Torre LA, Soerjomataram I, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 2019;68(12):2179-2185.
[6] Kaminski MF, Robertson DJ, Senore C, et al. Optimizing the Quality of Colorectal Cancer Screening Worldwide. Gastroenterology 2020;158(2):404-417.
[7] Lee JK, Jensen CD, Levin TR, et al. Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings. JAMA Intern Med 2019;179(2):153-160.
[8] Ladabaum U, Dominitz JA, Kahi C, et al. Strategies for colorectal cancer screening. Gastroenterology 2020;158(2):418-432.

Introduction

Inflammatory bowel disease (IBD) is a growing cause for concern and often missed or not thought of among pediatric population in developing economies. It is reported that about 25% of IBDs present before the age of 20.
Growing plethora of investigations have not been able to replace the role of direct visualisation of intestinal mucosa in various colorectal issues. Macroscopic findings may or may not help in clinching the diagnosis of IBD, hence “Biopsy” remains the Elixir of diagnosis. In this article, we review and attempt to correlate colonoscopic(macroscopy) and histological (microscopy) findings of colonoscopies in pediatric population, done over a period of 1 year.

Aims & Methods

Aim and objectives: To compare macroscopic findings versus histopathology findings of colonoscopies in pediatric population in suspected IBD.
To study the correlation of macroscopic findings with histopathologic findings of colonoscopies in pediatric population and to assess the frequency and pattern of microscopic impressions of colonoscopies in our cohort.
Material and methods: A prospective observational study carried out in a tertiary referral centre in children who underwent colonoscopies, aged 1 month to 17 years over a period of 12 months.
All children whose parents consented were included in the study. Inclusion and Exclusion criteria were formulated. Informed consent was obtained from the parents. Clinical details, colonoscopy findings and histopathology reports were. A total of 135 cases were enrolled during our study period. Results were collated using Microsoft Excel ™.
© Ethical clearance was obtained from the institutional ethical committee.

Results

We found that the diagnosis of IBD was much more specific than expected with good sensitivity when data was matched between Macroscopy and Microscopy

Conclusion

• It is our standard practice to do colonoscopic biopsies from 7 areas (terminal ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) of the colon to exclude microscopic colitis which may be missed by the endoscopist or marked as ‘normal’.
• Microscopic findings are considered as ‘Gold standard’ in the diagnosis of IBD and we envisage that it will remain the gold standard in the many next decades to come
• Our data of sensitivity and sensitivity of the microscopic findings inclined the relevance of colonic mucosal biopsies in children with a normal-appearing mucosa and also the need to analyse every segment of the colon to diagnose IBD that may masquerade as “normal” in children which will add burden to the family, society and health care system and more importantly to the child’s quality of life.

References

1. Manfredi, Michael A et al. “Good agreement between endoscopic findings and biopsy reports supports limited tissue sampling during pediatric colonoscopy.” Journal of pediatric gastroenterology and nutrition vol. 58,6 (2014): 773-8.
2. Altamimi, Eyad & Odeh, Yousef & Al-Quraan, Tuka & Mohamed, Elmi & Rawabdeh, Naif. (2022). Diagnostic and therapeutic outcomes of pediatric colonoscopies in Jordanian children. Journal of Pediatric and Neonatal Individualized Medicine. 11.