Marwa Mahmoud Hussein

Circulating Serum miRNAs as Diagnostic Markers for Colorectal Cancer

Aim The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy. Methods The study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis. Results Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04). Conclusion Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.

Can teledermatology be a useful diagnostic tool in dermatology practice in remote areas? An Egyptian experience with 600 patients.

Introduction The paucity of studies evaluating teledermatology (TD) in developing countries was the impetus behind conducting this work. We aimed to evaluate the feasibility and reliability of TD in remote areas where medical facilities and consultant dermatologists are not available, through measurement of diagnostic concordance rates between face-to-face diagnosis and store-and-forward (SAF) TD diagnosis. Methods A total of 600 patients with dermatological ailments who attended Abshway Hospital were recruited into the study, examined by an on-site dermatology resident, and offered a diagnosis. The clinical images and patients’ history were collected and transferred (through the Dropbox application) to two remote consultant dermatologists. The reliability of the three physicians’ agreement rates was assessed. Results Diagnostic agreement rates between the face-to-face dermatologist and the two teledermatologists were 86.7% and 87% respectively. Of the cases, 97% had complete or partial agreement and 81.3% of cases showed complete agreement between the three physicians. The reliability of the three physicians’ agreement rates was assessed statistically using Cohen’s kappa coefficient (κ) and this showed a range of 0.46–0.52. Conclusion This study might aid in enhancing the utilization of this tool in our country, especially in remote areas with a lack of a proper dermatological service. The simplicity and low cost of the adopted technique might facilitate its use over large sectors. It opens the door for gaining the benefit of this technology in other aspects such as teaching and monitoring health care providers.

Efficacy and Toxicity of Metronomic Chemotherapy in Metastatic Breast Cancer: Egyptian Experience

Micro‐Abstract Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We assessed this approach using cyclophosphamide and methotrexate in 50 heavily pretreated patients with metastatic breast cancer and found it effective and safe. We noticed that patients who experienced toxicity, those with good performance status, and patients who had achieved response benefited from this type of treatment. Background: Metronomic chemotherapy (MC) has shown efficacy in patients with metastatic breast cancer (MBC). We therefore tested the efficacy and toxicity of MC in pretreated MBC. Patients and Methods: This prospective phase II study included 50 patients with heavily pretreated MBC who received MC in the form of continuous oral cyclophosphamide 50 mg/day and oral methotrexate 2.5 mg twice per day on days 1 and 2 every week. The primary end point was progression‐free survival (PFS), whereas the secondary end points were response rate, overall survival (OS), and safety. Results: Forty‐eight patients were assessed. One patient achieved complete response and 10 patients had partial response, whereas 19 patients had stable disease. The median PFS was 5 months, whereas the median OS was 7 months. Patients with negative progesterone receptors, Eastern Cooperative Oncology Group performance status (PS) 1, achieving response, and those who developed leucopenia, neutropenia, and anemia had significant prolonged PFS, whereas patients with early stage at presentation, receiving < 5 previous treatment lines, achieving response, and experiencing anemia with MC had significant superior OS. In multivariate analysis, achieving response, PS 1, a longer time interval from initial diagnosis until starting MC, and anemia were independent prognostic factors for longer PFS. Initial stage at presentation, number of previous treatment lines, and response were independent prognostic factors for OS. Conclusions: MC is an attractive treatment approach that is effective and less toxic. There are certain groups of patients who seem to benefit more, especially those who experienced toxicity with treatment. Larger trials are warranted to assess this approach early in the course of the disease and with other more active agents.

Aberrant expression of miRNAs predicts recurrence and survival in stage-II colorectal cancer patients from Egypt

BackgroundPatients with stage II CRC have a varying survival outcome. Therefore, it is critical to identify prognostic biomarkers that can define more aggressive forms of the disease. We assessed the expression levels of five miRNAs that have been previously addressed in relation to the development and progression of solid and hematological tumors.MethodsWe measured the expression levels of miR-21, miR-137, miR-145, miR-320 and miR-498in stage II CRC patients from Egypt (124 tissues and 41 blood samples) by quantitative real time PCR (qPCR). The results were correlated with relevant clinicopathological factors, response to treatment and survival rates of the patients.ResultsmiR-137, miR-145 and miR-320 were significantly reduced in 39.5%, 48.4% and 52.4%; respectively whereas miR-21 and miR-498 were significantly overexpressed in 48.4% and 40.3% of the CRC tissues compared to the control group. In patients’ blood, miR-137, miR-145 and miR-320 were significantly reduced in 46.3%, 46.3% and 51.2%; respectively whereas mir-21 and miR-498 were significantly overexpressed in 46.3% and 43.9% of the cases, respectively. The concordance between tissue and blood was weak for miR-320 and miR-145 (kappa 40-65%), intermediate for miR-498 and miR-137 (kappa 65-75%) and strong for miR-21 (kappa 75-85%). In univariate analysis performance status, over-expression of miR-21 and miR-498 and reduced miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS. However, in multivariate analysis, miR-498 and miR-320 were independent prognostic factors for DFS whereas miR-21 was independent prognostic factors for OS.ConclusionsmiRNAs play an important role in the development and progression of stage II CRC. A five markers panel (miR-21, miR-498, miR-137, miR-145 and miR-320) can predict recurrence and survival in stage II CRC patients from Egypt.

Untreated hepatocellular carcinoma in Egypt: outcome and prognostic factors

Background Hepatocellular carcinoma (HCC) is a common cancer worldwide as well as in Egypt with hepatitis C and B, alcohol and aflatoxins being the commonest risk factors. Aim The objective of this study was to assess the prognostic factors affecting overall survival (OS) of untreated HCC in Egypt. Methods This retrospective study was conducted at Tanta Cancer Center, Egypt where 288 HCC cases who received no specific therapy and were followed-up until death were identified. The impact of possible prognostic factors on OS was assessed using the log-rank test (univariate analyses) and Cox regression method (multivariate analysis). Results The median OS of untreated HCC was 2.3 months (95% confidence interval: 1.9–2.6). The 1, 3, 6, 12, 24 months OS rates were 84%, 42%, 21%, 9%, and 3%, respectively. All cases had died by 46 months. Male sex, advanced Child-Pugh class, the clinical presentation of ascites, cough, fatigue, and the presence of metastases were associated with poor survival (P<0.05 for all). In multivariate analysis; cough, presence of ascites, and Child-Pugh class were independent predictors of poor survival. Conclusion OS in untreated HCC in Egypt is very short. Many factors interact to produce this dismal survival.

Impact of Global DNA Methylation in Treatment Outcome of Colorectal Cancer Patients

Background: Global DNA methylation has an impact in cancer pathogenesis and progression. This study aimed at investigating the impact of global DNA methylation in treatment outcome of Colorectal Cancer (CRC). Patients and Methods: Global DNA methylation was measured by LC/MS/MS in peripheral blood leucocytes of 102, 48, and 32 Egyptian CRC patients at baseline and after 3 and 6 months of Fluoropyrimidine (FP) therapy respectively, in addition to 32 normal healthy matched in age and sex. The genetic expressions of DNA methyl transferases (DNMTs) were determined and correlated with patients‘ survival using univariate and multivariate methods of analyses. Results: Egyptian CRC patients had significant global hypomethylation of 5mC level and 5mC % with overexpression of DNMT3A and DNMT3B. Significant higher 5mC levels were shown in patients > 45 years, male gender, T2 tumors, stage II, negative lymph nodes, and absence of metastasis. FP therapy significantly reduced DNA methylation particularly in the subgroups of patients with high DNA methylation level at baseline and good prognostic features. After 3 years of follow up, patients with 5mC % > 8.02% had significant poor overall survival (OS) while, significant better event-free survival (EFS) was found in patients with 5mC level > 0.55. High initial CEA level and presence of metastasis were significantly associated with hazards of disease progression and death. Conclusion: Global DNA methylation has a significant impact on the treatment outcome and survival of Egyptian CRC patients treated with FP- based therapy.

Outcome and surgical strategy in critical sites in cases of psuedomyxoma peritonei

BACKGROUND For a long time peritoneal neoplasms were considered beyond surgical intervention and beyond cure, till the concept of cytoreductive surgery (CRS) and adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced. However this surgical intervention is technically demanding and associated with considerable postoperative morbidity. OBJECTIVE To describe the surgical strategy in resection of critical sites loaded by heavy tumor deposits and to evaluate short and long term results of CRS and HIPEC, in a cohort of Egyptian patients with pseudomyxoma peritonei (PMP) from appendiceal origin. PATIENTS AND METHODS 21 patients with PMP, age ranged from 40 to 63years, 12 males and 9 females. All were recruited from the department of surgery at the National Cancer Institute (NCI), Cairo University over the period from February 2011 to February 2016. They were subjected to CRS and HIPEC with mitomycin-C. RESULTS The median peritoneal carcinoma index (PCI) was 22 (range: 10-39). Optimal cytoreduction (CCR-0/1) was achieved in 19 patients (90.4%) of whom 17 patients (80.9%) had a complete cytoreduction (CCR-0). The median follow up period was 51.5months (range: 0.07-82.3months). The cumulative overall survival was 85.7% while the cumulative disease free survival was 76.9%. CONCLUSION To the best of our knowledge, this is the first study reporting five years postoperative outcome of CRS and HIPEC in Egyptian patients with PMP from appendiceal origin. Our results support that although technically demanding this treatment modality is safe and associated with favorable outcome.