The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Role of endoscopic ultrasound in the characterization of solid pseudopapillary neoplasm of the pancreas.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) is an uncommon pathology of the pancreas with unpredictable malignant potential. Endoscopic ultrasound (EUS) assessment plays a vital role in lesion characterization and confirmation of the tissue diagnosis. However, there is a paucity of data regarding the imaging assessment of these lesions. AIM: To determine the characteristic EUS features of SPN and define its role in preoperative assessment. METHODS: This was an international, multicenter, retrospective, observational study of prospective cohorts from 7 large hepatopancreaticobiliary centers. All cases with postoperative histology of SPN were included in the study. Data collected included clinical, biochemical, histological and EUS characteristics. RESULTS: One hundred and six patients with the diagnosis of SPN were included. The mean age was 26 years (range 9 to 70 years), with female predominance (89.6%). The most frequent clinical presentation was abdominal pain (80/106; 75.5%). The mean diameter of the lesion was 53.7 mm (range 15 to 130 mm), with the slight predominant location in the head of the pancreas (44/106; 41.5%). The majority of lesions presented with solid imaging features (59/106; 55.7%) although 33.0% (35/106) had mixed solid/cystic characteristics and 11.3% (12/106) had cystic morphology. Calcification was observed in only 4 (3.8%) cases. Main pancreatic duct dilation was uncommon, evident in only 2 cases (1.9%), whilst common bile duct dilation was observed in 5 (11.3%) cases. One patient demonstrated a double duct sign at presentation. Elastography and Doppler evaluation demonstrated inconsistent appearances with no emergence of a predictable pattern. EUS guided biopsy was performed using three different types of needles: Fine needle aspiration (67/106; 63.2%), fine needle biopsy (37/106; 34.9%), and Sonar Trucut (2/106; 1.9%). The diagnosis was conclusive in 103 (97.2%) cases. Ninety-seven patients were treated surgically (91.5%) and the post-surgical SPN diagnosis was confirmed in all cases. During the 2-year follow-up period, no recurrence was observed. CONCLUSION: SPN presented primarily as a solid lesion on endosonographic assessment. The lesion tended to be located in the head or body of the pancreas. There was no consistent characteristic pattern apparent on either elastography or Doppler assessment. Similarly SPN did not frequently cause stricture of the pancreatic duct or common bile duct. Importantly, we confirmed that EUS-guided biopsy was an efficient and safe diagnostic tool. The needle type used does not appear to have a significant impact on the diagnostic yield. Overall SPN remains a challenging diagnosis based on EUS imaging with no pathognomonic features. EUS guided biopsy remains the gold standard in establishing the diagnosis.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUND: Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIM: To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-ß), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODS: This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTS: The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1ß, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSION: EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Oropharyngeal Candidiasis among Egyptian COVID-19 Patients: Clinical Characteristics, Species Identification, and Antifungal Susceptibility, with Disease Severity and Fungal Coinfection Prediction Models.

The study aimed to investigate the causative species, antifungal susceptibility, and factors associated with oropharyngeal candidiasis (OPC) among Egyptian COVID-19 patients. This is an observational, case-controlled, single-center study that included three groups: COVID-19 patients (30), COVID-19 patients with OPC (39), and healthy individuals (31). Patients' demographic data (age, sex), laboratory tests, comorbidities, treatment, and outcomes were included. Candida species were isolated from COVID-OPC patient's oropharyngeal swabs by convenient microbiological methods. Isolated strains were tested for antimicrobial susceptibility, biofilm production, aspartyl protease, and phospholipase activities. The most common respiratory symptoms reported were dyspnea (36/39; 92.4%) and cough (33/39; 84.7%). Candida albicans was the most common isolated species, accounting for 74.36% (29/39), followed by Candida tropicalis and Candida glabrata (15.38% and 10.26%, respectively). Amphotericin was effective against all isolates, while fluconazole was effective against 61.5%. A total of 53.8% of the isolates were biofilm producers. The phospholipase activity of C. albicans was detected among 58.6% (17/29) of the isolates. Significant variables from this study were used to create two equations from a regression model that can predict the severity of disease course and liability to fungal infection, with a stativity of 87% and 91%, respectively. According to our findings, COVID-19 patients with moderate to severe infection under prolonged use of broad-spectrum antibiotics and corticosteroids should be considered a high-risk group for developing OPC, and prophylactic measures are recommended to be included in the treatment protocols. In addition, due to the increased rate of fluconazole resistance, other new antifungals should be considered.

NON-INVASIVE PREDICTORS FOR THE PRESENCE, GRADE AND RISK OF BLEEDING FROM ESOPHAGEAL VARICES IN PATIENTS WITH POST-HEPATITIC CIRRHOSIS.

Variceal bleeding is the last step of a chain of events initiatedby an increase in portal pressure, followed by the development and progressive dilation ofvarices until these finally rupture and bleed. The ideal method to diagnose portal hypertension should be accurate, noninvasive, objective, and reproducible. The study evaluated the predictive value of two non-invasive parameters for the diagnosis of esophageal varices (EV): 1-Right liver lobe diameter/serum albumin ratios (RLLD/S. albumin), and 2-Platelet count/splenic bipolar diameter ratios (Platelets count/SBPD). This study included eighty Egyptian patients with post-hepatitic cirrhosis (45 males and 35 females). They underwent laboratory ultrasono-graphic and endoscopic examinations within one week. RLLD/S. albumin and Platelets count/SBPD ratios were calculated. The results showed that EV were not detected by upper digestive endoscopy in 25%, while grade I of EV was found in 17.5%, grade II in 17.5%, grade III in 20%, & grade IV in 20%. RLLD/S. albumin concentration ratio diagnosed the varices at cut off value of 3.43 with 95% sensitivity and 80% specificity. Also, it was positively correlated with grading of E.V, when this ratio increased the grading of E.V increases and vice versa. Besides, it predicted bleeding from E.V. at cut off value of 5.096 with 63% sensitivity and 73% specificity. Platelet count/SBPD ratio predicted the presence of varices at cut off value 1847 with 95% sensitivity and 93% specificity, and negatively correlated with grading of EV, when this ratio decreased grading of E.V increase and vice versa. It also predicted bleeding from E.V. at cut off value of 4809 with 50% sensitivity and 93% specificity.

Clinical significance of aflatoxin, mutant P53 gene and sIL-2 receptor in liver cirrhosis and hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) varies widely worldwide. Chronic infection with hepatitis B virus (HBV) and exposure to aflatoxins in foodstuffs are the main risk factors. AAG to AGT transversion at codon 249 of the P53 gene arg-ser (249ser) has been identified as a hotspot, reflecting DNA damage caused by aflatoxin B1 metabolites in HCC. Because HBV infection is often endemic in high aflatoxin exposure areas, it is still not clear whether HBV acts as a con-founder or as a synergistic partner in the development of the 249ser P53 mutation. Serum levels of soluble interleukin 2 receptor (sIL-2R) correlated with the progression of liver cirrhosis independently of its etiology. This fact may reflect the stimulation of T-lymphocytes, monocytes and macrophages in liver cirrhosis. The inter-relationship among aflatoxin exposure, HBV & HCV infections, P53 & sIL-2R in patients with liver cirrhosis and hepatocellular carcinoma was studied. The results revealed significant increase in serum levels of mutant P53, sIL-2R and aflatoxin B1 in patients with cirrhosis and those with HCC compared to the controls. HCC patients showed levels of all the three parameters significantly higher than both cirrhotics and controls (P<0.001). Correlations were found between serum aflatoxin B1, mutant P53 and sIL-2R in HCC group. The results were discussed.

A cross sectional study of hepatitis B, C, some trace elements, heavy metals, aflatoxin B1 and schistosomiasis in a rural population, Egypt.

Chronic liver diseases are disastrous to health. Many factors are associated with their prevalence, hence endemicity. These are mainly infectious, parasitic and toxic. A survey was conducted in a village south to Cairo. Large industries concerned with iron and steel industry, metals smelting, cement manufacturing and electric station were located north to the village. A systematic random sample of houses was selected. All individuals inside the houses were invited to share in the study. Sample size was 84 individuals. Hepatitis markers were done (HBsAg and anti-HCV antibodies). The levels of some heavy metals were assessed; which were lead, mercury, arsenic, aluminum, manganese, nickel, chromium and cadmium. Levels of some trace elements were assessed. These were copper, iron, selenium and zinc. Aflatoxin B1 was assessed in serum. Assessment of schistosomal circulating antigen and antibodies was carried out. Abdominal ultrasonograghy was done to assess liver condition. Univariate logistic regression analysis was done to assess the association between studied variables and HBsAg or anti-HCV sero-positive subjects. The association between studied variables and bilharzial or fatty liver, diagnosed by ultrasonography, were also assessed. The univariate logistic regression analysis revealed odds ratios at the following results. For HBsAg seropositive subjects, aflatoxin B1, lead, chromium and schistosomal antigen and antibodies were higher than negative ones where odds ratios were; 6.2, 1.6, 1.6, 1.6 and 1.7, respectively. None of the variables showed statistically significant difference. For anti-HCV antibodies sero-positive subjects, aflatoxin B1 and chromium had the highest odds ratios among the studied variables, (odds ratios were 2.5 and 2.4, respectively). Bilharzial liver showed higher significant positivity of anti-HCV antibodies and insignificant decreased level of zinc than negative ones (odds ratios were 7.2 and 4.5, respectively). Fatty liver cases showed higher statistically significant positivity of anti-HCV antibodies and chromium than negative ones. Odds ratios were 8.0 and 7.1, respectively. Statistically significant lower level of aflatoxin B1 was shown in fatty liver than normal liver subjects. Multivariate logistic regression analysis for fatty liver showed that only anti-HCV antibodies sero-positivity had statistically significant odds ratio in comparison to chromium level and aflatoxin B1. It is concluded that some heavy metals, and Aflatoxin B1 had a definite association with liver diseases in the area under study. Having anti-HCV antibodies had a relation with fatty liver and with bilharzial liver more than having HBsAg. It is recommended that environmental management to factories nearby the village is urgently needed to decrease exposure to heavy metals. Prevention of hepatitis infection and aflatoxin exposure through different means is also recommended, other wise health care authorities would be confronted with unusual cases of HCC in the nearby future.