Clinical Case Summary

Melanosis coli is a well-known condition associated with the use of anthranoid laxatives; however, pseudomelanosis of the small intestine is extremely rare. Duodenum and jejuni pseudomelanosis is a rare benign condition characterized by black-brown speckled pigmentation of the duodenal and jejunal mucosa. Some medications such as AT2 antagonists have been related to this condition. We report the case of 3 patients with diabetes mellitus and hypertension who were sent for capsule endoscopy due to suspicion of small bowel bleeding. The Three patients had Telmisartan Intake.The capsule endoscopy showed multiple diminutive black spots throughout the duodenum and jejunum, ulcers were found in two patients. Histology showed multiple foci of a brown-black granular pigment inside macrophages within the tips of the villi. In conclusion, duodenal and jejunal pseudomelanosis occurs predominantly in middle-aged to old adults and more commonly in females. There is a strong association with chronic renal failure, arterial hypertension, diabetes mellitus and the use of some medications such as ferrous sulfate, hydralazine, AT2, hydrochlorothiazide and furosemide. Some cases have been associated with gastrointestinal bleeding.

References

• D'Ercole M, Lopez G, Elli L et al. A Rare Case of Duodenal Pseudomelanosis. Diagnostics (Basel). 2021 Nov 20;11(11):2152
• Zakaria A, Abdu B, Al Share B, et al. Pseudomelanosis intestini "from pylorus to jejunum:" A rare endoscopic finding in a patient with GI bleeding. J Family Med Prim Care. 2018 Sep-Oct;7(5):1120-1122
• Lopez G, D'Ercole M, Ferrero S, et al. Duodenal Pseudomelanosis: A Literature Review. Diagnostics (Basel). 2021 Oct 24;11(11):1974

Disclosure

Nothing to declare

Introduction

Liquid biopsy in patients with pancreatic ductal adenocarcinoma (PDAC) has been challenged by the limited information obtained from systemic circulation (SC). Circulating Tumour Cells (CTCs) in portal circulation (PC) are deemed to be biologically relevant and potentially carrying prognostic significance, despite mostly been evaluated during surgery.

Aims & Methods

This prospective, single-centre, interventional study enrolled PDAC patients to assess the feasibility and safety of EUS-guided transgastric and transhepatic Portal Vein sampling (EUS-PVS) for isolating, enumerating, and characterizing CTCs. PC and paired SC samples underwent microfluidic enrichment and dielectrophoretic (DEP) single-cell sorting based on immunostaining for epithelial and mesenchymal biomarkers. Targeted next-generation KRAS sequencing was performed on CTC subpopulations in a subset of patients.

Results

Between May 2022 and October 2023, 20 PDAC patients (25% metastatic) underwent EUS-PVS with 100% feasibility and safety. CTCs were isolated in all patients from both districts, but the total CTC concentration was significantly higher in PC compared to SC (8.1 [5.8-21.3] vs. 4.1 [2.3-6] / 7.5 ml of blood, p= 0.01), particularly for mesenchymal CTCs. No associations with baseline clinical variables or disease stage were observed. A subset of CTCs exhibited KRAS codon 12 mutations, undetected in paired white blood cells.

Conclusion

EUS-PVS is a feasible, safe, and effective method for portal blood sampling, supporting subsequent molecular investigations. Despite more sensitive enrichment modalities enhance the yield of peripheral CTCs evaluation, portal circulation remains more informative, especially for detecting epithelial-to-mesenchymal transition events. DEP single-cell sorting was feasible in all patients, providing libraries of viable cells with specific 100%-pure phenotypes, potentially suitable for downstream molecular applications.

Clinical Case Summary

SARS-COV2 infection has accumulated more than 670 million cases since its onset in 2019. Its clinical spectrum varies from asymptomatic patients to bilateral pneumonia with a mortality rate of 1%. Digestive symptoms include nausea, abdominal pain and diarrhea. Multiple complications as hepatitis, pancreatitis, cholecystitis, mesenteric ischemia or venous thrombosis have also been described.
We present the case of a 60-year-old woman who came to ER for abdominal pain. A CT showed acute cholecystitis with a 30mm liver abscess and choledocholithiasis. It was treated with empirical Piperacillin-Tazobactam, thromboprophylaxis and drainage by ERCP. During admission the patient presented bilateral SARS-COV2 pneumonia requiring Dexamethasone and Remdesivir. Due to the reappearance of abdominal discomfort, an US was performed showing a new left portal thrombosis. Given these findings, a coagulation study was performed, with no genetic or cytological alterations. Finally it was decided to maintain antibiotic for 6 weeks and anticoagulation, performing outpatient US control, with deferred surgical treatment.
The portal thrombosis is a complication mostly related to chronic liver diseases and hepatic tumors, being much rarer the septic portal thrombophlebitis associated with abdominal infections or related to proliferative neoplasms. On the other hand, SARS-COV2 infection triggers an inflammatory reaction after binding to ACE-II receptor that leads to a generalized prothrombotic environment. In relation to this process, PTE, DVT and in multiple other locations has been described. One of the the most infrequent locations is abdominal, with very few cases described in the literature.
The scarce clinical repercussion of portal thrombosis and the serious complications derived from it, added to the high prevalence of SARS-COV2, means that we should early rule out this process in patients with abdominal infections with regular evolution and active or recent SARS-COV2 infection.

Clinical Case Summary

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in clinical practice. These patients have up to 50 times higher risk of developing cancer in comparison to the general population, with gastric adenocarcinoma being the leading cause of death in this population.
We describe a case of a 33-year-old woman with a history of CVID and Addison's disease, who was admitted for upper gastrointestinal hemorrhage with hemodynamic instability refractory to combined endoscopic hemostasis (noradrenaline, hemoclips, thermocoagulation and hemostatic spray) after partial resection of a 40 mm semipediculated gastric polyp (figures 1,2), finally requiring selective arterial embolization to control bleeding. Histological and immunohistochemical studies revealed gastric adenocarcinoma HER2+ with conserved expression of proteins encoded by DNA repair genes.
Multiple studies have demonstrated a dysfunctional immune system at the level of the non-neoplastic gastric mucosa of these patients, characterized by high rates of CD4+, CD8+, Foxp3+, GATA3+, PD-L1 and low numbers of CD20+ B-lymphocytes and CD138+ plasma cells compared to individuals without CVID. In addition, the expression of GATA3+ by cytotoxic T lymphocytes is identified in the literature as a mechanism for tumor escape from immunological surveillance and T-cell depletion. On the other hand, few studies have focused on analyzing the monogenic causes of CVID. This could be an interesting field of study since genes, such as NF-Kb1 deficiency, which is the most common monogenic cause of CVID, have in turn been directly related to the pathogenesis of gastric cancer in individuals without CVID. All this is very important when it comes to being able to stratify our patients according to the risk of developing malignant gastric pathology in order to establish standardized screening recommendations and to be able to carry out individualized follow-ups in order to detect premalignant lesions.

References

Bruns L, Panagiota V, von Hardenberg S, et al. Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors. Front Immunol. 2022;13:742530. Published 2022 Feb 17.
Pecoraro A, Crescenzi L, Varricchi G, Marone G, Spadaro G. Heterogeneity of Liver Disease in Common Variable Immunodeficiency Disorders. Front Immunol. 2020;11:338. Published 2020 Feb 28. doi:10.3389/fimmu.2020.00338
Pikkarainen S, Martelius T, Ristimäki A, Siitonen S, Seppänen MRJ, Färkkilä M. A High Prevalence of Gastrointestinal Manifestations in Common Variable Immunodeficiency. Am J Gastroenterol. 2019 Apr;114(4):648-655.
Pulvirenti F, Pecoraro A, Cinetto F, et al. Gastric Cancer Is the Leading Cause of Death in Italian Adult Patients With Common Variable Immunodeficiency. Front Immunol. 2018;9:2546. Published 2018 Nov 5.
Gullo I, Costa C, Silva SL, et al. The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer. Cells. 2020;9(6):1498. Published 2020 Jun 19.