Introduction

Hepatocellular Carcinoma (HCC) is a major type of primary liver cancer and one of the most frequent human malignant neoplasm. Owing to the lack of reliable clinical HCC markers, fewer than 20% of patients are diagnosed at a stage where curative treatment can be performed. It is now clear that microRNAs (miRNAs) can potentially regulate every aspect of cellular activity, including differentiation and development and proliferation; they play a role in regulating apoptotic cell death and tumorigenesis. MiRNA‑192 is hepatocyte‑specific miRNA and it is released from damaged hepatocytes early in liver injury in animal models have made miRNA‑192 an attractive biomarker for liver damage. Many studies have demonstrated that miRNA expression profiles in HCC and nontumor tissue are significantly different.

Aims & Methods

The aim is to evaluate the role of serum miRNA‑192 as potential serum marker of HCC among HCV related liver cirrhosis.
The study was carried out on 80 Egyptian patients with HCV related liver cirrhosis (Liver cirrhosis (LC) group: 40 patients with HCV related liver cirrhosis without HCC and HCC group: 40 patients with HCV related liver cirrhosis and HCC) and 20 healthy volunteers as controls from Menoufia University Hospitals (Egypt). They underwent history taking, physical examination and laboratory investigations (CBC, liver profile {ALT, AST, albumin, bilirubin, INR}, urea, creatinine, AFP, HBsAg, HCV Ab and serum miRNA‑192). Abdominal ultrasonography was done for all patients and controls. HCC is further confirmed by triphasic CT. Patients with malignancy other than HCC, received previous treatment for HCC or chronic liver disease other than HCV were excluded from the study.

Results

In HCC group, according to BCLC classification, one patient (2.5%) at very early stage, 3 (7.5%) at early stage, 13 (32.5%) at intermediate stage, 8 (20%) at advanced stage and 15 (37.5%) at terminal stage. In HCC group, 10 patients (25%) had HCC size˂3 cm and 30 patients (75%) had HCC size˃3 cm. 65% of the patients (n=26) had single lesion, 5% (n=2) had 2 lesions and 30% (n=12) had multifocal lesions. Eleven patients (27.5%) have portal vein thrombosis (PVT). Serum miRNA‑192 ratio was significantly higher in HCC group (195.8±256.3) than LC (42.6±35.6) and control group (25.7±18.2) (P=0.001 for all) but there was no significant difference between LC and controls (P=0.06). In HCC group, miRNA‑192 ratio was higher in patients with tumor size ˃3 cm (317.9±402) than tumor size ˂3cm (170.7±254.5) (P=0.02) but there was no significant difference according to number of focal lesion or presence of PVT (P˃0.05). AFP level (ng/ml) was significantly higher in HCC group (6572±12563) than LC (28.1±35.1) and control group (14.7±13.3) (P=0.006 for both) but there was no significant difference between LC and controls (P=0.1). Serum miRNA‑192 ratio cutoff level >62.6 have 77.5% sensitivity and 82.5% specificity for detection of HCC. AFP at cutoff level >35.7 ng/ml have 70% sensitivity and 65% specificity for detection of HCC. MELD score, APRI score and FIB-4 were significantly higher in HCC group (20.5±3.5, 3.2±2.7 and 7.2±4.5 respectively) than LC group (7.9±2.2, 0.76±0.92 and 2.3±2.9 respectively) (P˂0.001 for all). In HCC and LC groups, there was a significant positive correlation between miRNA‑192 ratio and AFP (P˂0.001)

Conclusion

MiRNA‑192 could be used as a diagnostic biomarker for detection of HCC in HCV‑related cirrhosis, as it showed significant upregulation in patients with HCC in comparison with non‑HCC patients with higher sensitivity and specificity than AFP for detection of HCC.

References

1-Giordano S and Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology 2013; 57:840–847.
2-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012; 56:1946–1957.
3-Blanco‑Calvo M, Calvo L, Figueroa A, Haz‑Conde M, Anton‑Aparicio L, Valladares‑Ayerbes M. Circulating microRNAs: molecular microsensors in gastrointestinal cancer. Sensors 2012; 12:9349–9362.
4-Bala S, Petrasek J, Mundkur S, Catalano D, Levin I, Ward J, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases.
Hepatology 2012; 56:1946–1957.

Clinical Case Summary

Introduction: Locally advanced pancreatic tumors can lead to both biliary and duodenal obstruction by invasion or compression. Quality of life is severely affected if obstruction occurs: jaundice, emesis and pain can become invalidating and patients become too frail for palliative chemotherapy and are sometimes declared unfit even for derivative surgery. Recently, endoscopic techniques under EUS or ERCP guidance are being used to create biliodigestive and enteral anastomoses.
Clinical case: A 75-year-old female was diagnosed with locally advanced pancreatic head adenocarcinoma in January 2024. The tumor was declared unresectable and chemotherapy was initiated. A plastic stent was inserted into the main biliary duct (MBD) to ensure biliary drainage. In May 2024, she presented with cholangitis and emesis. EGD revealed duodenal stenosis and ERCP failed due to tumor infiltration. A combined endoscopic approach was performed: EUS-guided hepatico-gastrostomy (EHG) for biliary drainage and EUS-guided gastro-enterostomy using a lumen-apposing metal stent (LAMS). In July 2024, the plastic stent was removed, and in August 2024, two fully covered 60 x 10 mm SEMS were inserted antegrade through the EHG into the MBD to improve patency. At 11 months post-intervention, the patient returned for routine reassessment, declaring good clinical performance: she remained asymptomatic, with routine blood tests, including bilirubin levels within normal range and with all stents patent and correctly positioned (confirmed radiologically and endoscopically). The patient was able to maintain oral intake and continue chemotherapy. No late adverse events were noted.
Conclusion: This case demonstrates the long-term clinical and technical success of a staged endoscopic triple bypass for the management of complex biliary and duodenal obstruction due to unresectable pancreatic cancer. The approach was minimally invasive, well tolerated and remarkably improved the patient's quality of life.

References

1. Adler, Douglas G MD; Baron, Todd H MD, FACP. Endoscopic Palliation of Malignant Gastric Outlet Obstruction Using Self-Expanding Metal Stents: Experience in 36 Patients. American Journal of Gastroenterology 97(1):p 72-78, January 2002. | DOI: 10.1111/j.1572-0241.2002.05423.x
2. Giovannini, Marc. (2019). EUS-guided hepaticogastrostomy. Endoscopic Ultrasound. 8. 35. 10.4103/eus.eus_47_19.
3. Dumonceau, Jean-Marc & Tringali, Andrea & Blero, Daniel & Devière, J & Laugiers, R & Heresbach, D & Costamagna, Guido. (2012). Biliary stenting: Indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy. 44. 277-98. 10.1055/s-0031-1291633.
4. Van Der Merwe, S. W., Van Wanrooij, R. L., Bronswijk, M., Everett, S., Lakhtakia, S., Rimbas, M., ... & Van Hooft, J. E. (2022). Therapeutic endoscopic ultrasound: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy, 54(02), 185-205. 10.1055/a-1717-1391

Clinical Case Summary

In advanced chronic liver disease (ACLD) patients, the endoscopic evidence of esophageal and/or gastric varices denotes the presence of clinically significant portal hypertension (CPSH), representing the main clinical consequence of portal hypertension (PH).
In this setting, although infrequently, besides typical sites (i.e., esophagus and stomach), PH-related varices can manifest even in other atypical portosystemic-shunt districts, including the vagina. CSPH-related vaginal varices bleeding can occur as a rare complication documented by limited case reports.
A 62-year-old female patient with viral (eradicated Hepatitis C Virus infection)-related- decompensated (grade 2 ascites)-ACLD, complicated by CSPH (grade F2 esophageal varices), was admitted to our Department in February 2025 for microcitic anemia. Anamnesis revealed a previous gastric cancer managed with total gastrectomy resection in 2021.
On admission, abdominal imaging showed radiological signs of ACLD/PH (coarse pattern, splenomegaly, dilated splenic-portal axis). Esophagogastroduodenoscopy ruled out active sources of bleeding, whereas colonoscopy revealed anal congestive not-bleeding varices. During the hospitalization, an episode of metrorrhagia imposed gynecologic evaluation with vaginal speculum examination. This assessment documented vaginal varices with the relative rupture as the current cause of the bleeding, suggesting this site is the further district for (CS)PH manifestation consequently to potentially occurred total gastrectomy-determined changes in abdominal vascular anatomy.
In ACLD patients receiving surgery altering abdominal vascularization, variceal bleeding represents a possible CSPH-related complication occurring even in atypical sites, such as the vagina. This scenario imposes an adequate tailored management, monitoring unusual bleeding signs, and adopting appropriate preventive strategies by including gynecologic evaluation in follow-up.

References

1. McHugh PP, Jeon H, Gedaly R, Johnston TD, Depriest PD, Ranjan D. Vaginal varices with massive hemorrhage in a patient with nonalcoholic steatohepatitis and portal hypertension: Successful treatment with liver transplantation. Liver Transpl. 2008 Oct;14(10):1538-40. doi: 10.1002/lt.21506. PMID: 18825698.
2. Kreek MJ, Raziano JV, Hardy RE, Jeffries GH. Portal hypertension with bleeding vaginal varices. Ann Intern Med. 1967 Apr;66(4):756-9. doi: 10.7326/0003-4819-66-4-756. PMID: 6067181.
3. Chan G, Taqi A, Drage M, Quan D. A case report of massive vaginal variceal hemorrhage in a patient with cirrhosis secondary to nonalcoholic steatohepatitis unresolved even after successful liver transplantation. Transplant Proc. 2013 Mar;45(2):835-7. doi: 10.1016/j.transproceed.2012.04.033. Epub 2012 Sep 19. PMID: 23267803.
4. Lebrec D, Benhamou JP. Ectopic varices in portal hypertension. Clin Gastroenterol. 1985 Jan;14(1):105-21. PMID: 3872747.
5. Nagata J, et al. Vaginal bleeding in a patient with type C liver cirrhosis without a past history of laparotomy: successful treatment with partial splenic artery embolization. Clin J Gastroenterol. 2012 Aug;5(4):275-81. doi: 10.1007/s12328-012-0316-3. Epub 2012 Jun 30. PMID: 26182393.

Clinical Case Summary

Intra-ampullary papillary tubular neoplasms (IAPNs) are rare neoplastic intraepithelial lesions that occur within the ampulla. Given their well-documented malignant potential, early recognition and intervention are paramount to prevent malignant transformation. We present a case of IAPN successfully managed via endoscopic papillectomy.
A 58-year-old male was incidentally found to have a bulky-appearing ampulla of vater during esophagogastroduodenoscopy as part of routine health screening. Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla, with histopathological evaluation demonstrating low-grade dysplasia (indeterminate for neoplasia). Laboratory investigations, including hematological parameters, biochemical profiles, and tumor markers, were within normal limits. Contrast-enhanced abdominal CT demonstrated a well-defined, homogeneously enhancing 20-mm lesion at the ampullary region without biliary/pancreatic duct dilation.
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application. Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%). The postoperative course was uncomplicated, with discharge achieved on the sixth postoperative day. At six-month follow-up evaluation, surveillance endoscopic ultrasonography showed no evidence of recurrence.
IAPN represents a distinct neoplastic ampullary entity within the spectrum of ampullary tumors. While endoscopic resection demonstrates therapeutic efficacy, its implementation requires advanced endoscopic expertise in specialized centers.

References

Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application.
Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%).

Clinical Case Summary

Introduction: Cirrhosis complicated by portal hypertension often leads to gastrointestinal bleeding, predominantly from esophageal varices. However, the occurrence of lower GI bleeding from rectal varices and angiodysplasias represents a rarer and more complex clinical scenario. We report the case of a 62-year-old man with cirrhosis and multiple vascular anomalies requiring multidisciplinary management.
Patient observation: The patient, with a history of Type 2 diabetes, coronary artery disease, and prior cholecystectomy, was diagnosed with cirrhosis of presumed autoimmune origin, despite non-confirmatory liver biopsy. He experienced recurrent upper GI bleeding from esophageal varices, managed with beta-blocker therapy. More recently, a massive lower GI bleed led to endoscopic assessment revealing gigantic rectal varices and diffuse colonic angiodysplasias. Stabilisation was achieved by treating the angioddysplasias endoscopically with APC.
Figure 1&2: endoscopic images
Discussion: This case illustrates the difficulty of managing complex portal hypertension complications. While beta-blockers reduce bleeding risk from esophageal varices, rectal varices and angiodysplasias pose additional therapeutic challenges. Endoscopic sclerotherapy, band ligation, or embolization may be required, but their efficacy in diffuse vascular anomalies remains limited. The presence of multiple bleeding sources demands vigilant surveillance and individualized management strategies. Moreover, coexisting comorbidities like diabetes and cardiovascular disease complicate procedural risks and therapeutic decisions.
Conclusion: Managing cirrhosis complicated by giant rectal varices and angiodysplasias requires a multidisciplinary and tailored approach. This case highlights the importance of ongoing surveillance, optimized medical therapy, and readiness for endoscopic or interventional radiology techniques to prevent further decompensations and preserve quality of life.

Clinical Case Summary

Sarcoidosis is a multisystem disease characterized by the presence of non-caseating granulomas in affected organs. Hepatic involvement is often silent and underdiagnosed. Otherwise, it can result in cholestasis and, more rarely, portal hypertension (PH) in long-standing hepatic disease. Here, we report the case of portal vein thrombosis (PVT) in a non-cirrhotic patient, revealing systemic sarcoidosis. A 58-year-old male presenting with dull abdominal pain and erythematous skin nodes on the lower limbs. The initial lab analysis revealed an elevation in GGT to 2.5 ULN and an elevated CRP level at 30 mg/L. Abdominal ultrasound showed dysmorphic liver and portal cavernoma. Thoraco-abdominopelvic CT revealed hilar and mediastinal enlarged lymph nodes, dysmorphic liver, thrombotic material within portal vein and the consequent development of a portal cavernoma and perisplenic collaterals. Ultrasound elastography showed a result of 4,4 KPa. Esophagogastroduodenoscopy was negative for varices. Thorough immunological workup, homocysteine, protein C and anti-thrombin III S assays were normal. The search for JAK2V617F and factor II mutations were negative as well as the flow cytometric measurement of PNH clone. Tuberculosis screening, including a tuberculin test, a chest x-ray and interferon gamma release assay (IGRA) was negative. Calcium and phosphorus levels were normals. Angiotensin converting enzyme (ACE) level was high at 101 UI/L. Spirometry, bronchial fibroscopy and bronchoalveolar lavage were normals. Skin biopsy showed granulomatous dermatitis without caseous necrosis. Liver biopsy revealed the presence of non-caseating granulomas in the lobules. Based on these results, the diagnosis of multisystemic sarcoidosis has been retained. The patient was put on direct oral anticoagulants, corticosteroids and hydroxychloroquine. His symptoms improved and a follow-up CT scan done four months later showed a repermeabilisation of the portal vein.

Disclosure

There is not any actual or potential conflict of interest