Journal of the Egyptian National Cancer Institute最新文献

Background: In the Ugandan setting, investigation for PHNM with CT uses a protocol with both unenhanced and contrast enhanced procedures hence doubling the ionizing radiation exposure. The purpose of this study was to determine the feasibility of single CT procedures in diagnosing PHNM.

Methods: This was a cross-sectional study using CT images from patients, aged fifteen years and below, investigated for head and neck malignancies at the Uganda Cancer Institute. Three radiologists, observers A, B and C, with 12, 5 and 2 years of experience, respectively, participated in the study. They independently reported contrast enhanced images (protocol A), unenhanced images (protocol B), then both unenhanced and contrast enhanced images (protocol C) in 2 months intervals. Inter- and intra- observer agreement was determined using Gwen's Agreement coefficient.

Results: Seventy-three CT scans of 36 boys and 37 girls, with a median age of 9 (3-13) years, were used. Intra-and inter-observer agreement on primary tumour location ranged from substantial to almost perfect with the highest intra-observer agreement observed when protocols A and C were compared. Inter-observer agreement for tumour calcifications was substantial for protocol A. Observers A and C demonstrated an almost perfect intra-observer agreement when protocols A and C were compared. There was a substantial inter-observer agreement on diagnosis for all protocols.

Conclusions: In our setting and examining a limited number of CT images, we demonstrated that contrast-enhanced CT scans provide sufficient information with no evidence of additional value of unenhanced images. Using contrast-enhanced images alone reduced the radiation exposure significantly.

Background: Gene selection from gene expression profiles is the appropriate tool for diagnosing and predicting cancers. The aim of this study is to perform a Precision Lasso regression model on gene expression of diffuse large B cell lymphoma patients and to find marker genes related to DLBCL.

Methods: In the present case-control study, the dataset included 180 gene expressions from 14 healthy individuals and 17 DLBCL patients. The marker genes were selected by fitting Ridge, Lasso, Elastic Net, and Precision Lasso regression models.

Results: Based on our findings, the Precision Lasso, the Ridge, the Elastic Net, and the Lasso models choose the most marker genes, respectively. In addition, the top 20 genes are based on models compared with the results of clinical studies. The Precision Lasso and the Ridge models selected the most common genes with the clinical results, respectively.

Conclusions: The performance of the Precision Lasso model in selecting related genes could be considered more acceptable rather than other models.

Background: Acute lymphoblastic leukemia (ALL) is a malignancy that leads to altered blast cell proliferation, survival, and maturation and eventually to the lethal accumulation of leukemic cells. Recently, dysregulated expression of various micro-RNAs (miRNAs) has been reported in hematologic malignancies, especially ALL. Cytomegalovirus infection can induce ALL in otherwise healthy individuals, so a more detailed evaluation of its role in ALL-endemic areas like Iran is required.

Methods: In this cross-sectional study, 70 newly diagnosed adults with ALL were recruited. The expression level of microRNA-155(miR-155) and microRNA-92(miR-92) was evaluated by real-time SYBR Green PCR. The correlations between the miRNAs mentioned above and the severity of disease, CMV infection, and acute graft vs. host disease after hematopoietic stem cell transplantation (HSCT) were assessed. B cell and T cell ALL distinction in the level of miRNAs was provided.

Results: After the statistical analysis, our results indicated a marked increase in the expression of miR-155 and miR-92 in ALL patients vs. healthy controls (*P = 0.002-*P = 0.03, respectively). Also, it was shown that the expression of miR-155 and miR-92 was higher in T cell ALL compared to B cell ALL (P = 0.01-P = 0.004, respectively), CMV seropositivity, and aGVHD.

Conclusion: Our study suggests that the plasma signature of microRNA expression may act as a powerful marker for diagnosis and prognosis, providing knowledge outside cytogenetics. Elevation of miR-155 in plasma can be a beneficial therapeutic target for ALL patients, with consideration of higher plasma levels of miR-92 and miR-155 in CMV + and post-HSCT aGVHD patients.

Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few accepted prognostic factors that limit the efficiency of therapy. The aim of the current study was to assess the clinical and laboratory features of T-cell receptor (TCR) aberrations and early T-cell precursor (ETP) subtype as well as their outcome to therapy.

Methods: Sixty-three newly diagnosed pediatric T-ALL patients were assessed for the ETP status using immunophenotyping. Screening of TCRA/D aberrations was done by fluorescent in situ hybridization (FISH). The data were correlated to the patients' clinical features, response to treatment, and survival rates.

Results: Seven patients (11%) had ETP-ALL. The ETP-ALL patients were older (P = 0.013), presented with lower white blood cell (WBC) count (P = 0.001) and lower percentage of peripheral blood (PB) blast cells (P = 0.037), more likely to have hyperdiploid karyotype (P = 0.009), and had been associated with TCRA/D gene amplification (P = 0.014) compared to other T-ALL patients. Of note, the same associations had been significantly observed in patients with TCRA/D gene amplification. Patients with TCRA/D amplification frequently coincided with TCRβ aberrations (P = 0.025). TCR-β aberrations were significantly associated with negative MRD at the end of induction compared to TCR-β-negative patients. There was a nonsignificant trend of ETP-positive cases to have lower overall survival (OS) (P = 0.06). Patients with TCR aberrations had no significant differences regarding disease-free survival (DFS) or OS rates compared to those with normal TCR.

Conclusion: ETP-ALL patients tend to have increased mortalities. There was no significant impact of TCR aberrations on the survival rates of the patients.

Background: Metaplastic breast cancer (MetBC) still represents a conundrum owing to its peculiar histogenesis and molecular drivers that render it extremely resistant to standard chemotherapy with ultimate dismal survival.

Aim: Describe the Egyptian National Cancer Institute's (NCI-E) experience with MetBC regarding its clinicopathologic features, treatment, and survival outcomes.

Patients and methods: Between 2011 and 2020, all MetBC patients presented to NCI-E were retrospectively evaluated. Original clinicopathologic data, therapeutic modalities, pathologic response to neoadjuvant chemotherapy (NACT), recurrence, and date of last follow-up/death were obtained from archived charts.

Results: A cohort of 135 females, the median age was 52 years, and median follow-up period was 40 months (range: 2.6-130.8). Two-thirds were triple negative (TN). Squamous carcinoma was prevalent in 74.8% followed by carcinoma with osseous/chondroid differentiation, spindle cell, and low-grade adenosquamous carcinoma encountered in 13.3, 7.4, and 4.5%, respectively. Modified radical mastectomy was done in 59.3%, and positive nodes (pN+) were depicted in 37.7%. Median Ki-67 was 45% (range: 10-88); grade III and lymphovascular invasion (LVI) were observed in 83.7 and 43.7%, respectively. Stage II was the most common (49%), whereas initial stage IV was encountered in 8.1%. Anthracyclines/taxane combinations were rampant in adjuvant/neoadjuvant settings. The latter was employed in 41 patients, with only 3 cases (7.3%) achieving pathologic complete response (pCR), while moderate/significant residual tumor burden was found in 83%. The 5-year DFS and OS were 56.4 and 57.6%, respectively. Spindle cell carcinoma showed the worst survival parameters in univariate analysis. On the multivariate level, higher tumor stage (pT3 & 4), Ki-67 ≥ 45%, and TN subtype were independent variables for worse DFS and OS; age ≥ 52 years and the presence of LVI were independent features for worse DFS, whereas pN+ was an independent parameter for worse OS.

Conclusions: This study further solidifies the dreadful response of MetBC to conventional chemotherapy regimens employed in common non-metaplastic pathologies. A radical shift in treatment standards tailored to combat the molecular landscape of this distinctive tumor is urgently needed. Immunotherapy and molecularly targeted agents demonstrated promising results in phase I and II trials with hopeful sooner implementation in phase III studies.

Background: A malignancy of the endocrine system, one of the most common types, is thyroid cancer. It is proven that children who receive radiation treatment for leukemia or lymphoma are at a heightened risk of thyroid cancer due to low-dose radiation exposure throughout childhood. Several factors can increase the risk of thyroid cancer (ThyCa), such as chromosomal and genetic mutations, iodine intake, TSH levels, autoimmune thyroid disorders, estrogen, obesity, lifestyle changes, and environmental contaminants.

Objectives: The study aimed to identify a specific gene as an essential candidate for thyroid cancer progression. We might be able to focus on developing a better understanding of how thyroid cancer is inherited.

Methods: The review article uses electronic databases such as PubMed, Google Scholar, Ovid MEDLINE, Embase, and Cochrane Central. The most frequently associated genes with thyroid cancer found on PubMed were BAX, XRCC1, XRCC3, XPO5, IL-10, BRAF, RET, and K-RAS. To perform an electronic literature search, genes derived from DisGeNET: a database of gene-disease associations, including PRKAR1A, BRAF, RET, NRAS, and KRAS, are used.

Conclusion: Examining the genetics of thyroid cancer explicitly emphasizes the primary genes associated with the pathophysiology of young and older people with thyroid cancer. Developing such gene investigations at the beginning of the thyroid cancer development process can identify better outcomes and the most aggressive thyroid cancers.

Background: Breast cancer is the most common female cancer worldwide. Its diagnosis and prognosis remain scanty, imprecise, and poorly documented. Previous studies have indicated that some genetic mutational signatures are suspected to lead to progression of various breast cancer scenarios. There is paucity of data on the role of AI tools in delineating breast cancer mutational signatures. This study sought to investigate the relationship between breast cancer genetic mutational profiles using artificial intelligence models with a view to developing an accurate prognostic prediction based on breast cancer genetic signatures. Prior research on breast cancer has been based on symptoms, origin, and tumor size. It has not been investigated whether diagnosis of breast cancer can be made utilizing AI platforms like Cytoscape, Phenolyzer, and Geneshot with potential for better prognostic power. This is the first ever attempt for a combinatorial approach to breast cancer diagnosis using different AI platforms.

Method: Artificial intelligence (AI) are mathematical algorithms that simulate human cognitive abilities and solve difficult healthcare issues such as complicated biological abnormalities like those experienced in breast cancer scenarios. The current models aimed to predict outcomes and prognosis by correlating imaging phenotypes with genetic mutations, tumor profiles, and hormone receptor status and development of imaging biomarkers that combine tumor and patient-specific features. Geneshotsav 2021, Cytoscape 3.9.1, and Phenolyzer Nature Methods, 12:841-843 (2015) tools, were used to mine breast cancer-associated mutational signatures and provided useful alternative computational tools for discerning pathways and enriched networks of genes of similarity with the overall goal of providing a systematic view of the variety of mutational processes that lead to breast cancer development. The development of novel-tailored pharmaceuticals, as well as the distribution of prospective treatment alternatives, would be aided by the collection of massive datasets and the use of such tools as diagnostic markers.

Results: Specific DNA-maintenance defects, endogenous or environmental exposures, and cancer genomic signatures are connected. The PubMed database (Geneshot) search for the keywords yielded a total of 21,921 genes associated with breast cancer. Then, based on their propensity to result in gene mutations, the genes were screened using the Phenolyzer software. These platforms lend credence to the fact that breast cancer diagnosis using Cytoscape 3.9.1, Phenolyzer, and Geneshot 2021 reveals high profile of the following mutational signatures: BRCA1, BRCA2, TP53, CHEK2, PTEN, CDH1, BRIP1, RAD51C, CASP3, CREBBP, and SMAD3.

Background: The prognostic value of the level of programmed death ligand 1 (PD-L1) expression in non-Hodgkin lymphoma (NHL) is still debatable. This study examined the effect of the level of PD-L1 expression on the clinicopathological characteristics and prognosis of diffuse large B cell lymphoma (DLBCL).

Methods: A retrospective study was conducted on formalin-fixed paraffin-embedded tissue blocks of one hundred de novo DLBCL patients diagnosed from 2013 to 2016. PD-L1 expression was defined by a modified Combined-Positive Score (CPS) and their medical records were reviewed to collect their clinical, laboratory and radiological data, treatment, and outcome.

Results: The included patients were aged from 23 to 85 years and treated by rituximab- cyclophosphamide, doxorubicin, oncovin, prednisone (R-CHOP); 49% were males; 85% of the cases were presented at Ann Arbor stages III, IV; 33% of patients were seropositive for HCV and 87% of cases were presented with intermediate and high IPI. All included cases expressed PD-L1 using modified CPS. 27% of patients showed low PD-L1 expression (≥ 5% to < 50% of total tumor cellularity) while 73% of patients showed high PD-L1expression (≥ 50% of total tumor cellularity). High PD-L1 expression is statistically correlated with advanced stage (p 0.01), high IPI score (p 0.017), high incidence of stationary and progressive disease (p 0.002) and high incidence of relapse (p value 0.01). Five-year disease-free survival (DFS) was 29% for patients with high PD-L1 expression compared with 84.8% for patients with low PD-L1 expression (p 0.001).

Conclusions: This study suggests that high PD-L1 expression in DLBCL is associated with aggressive clinicopathological features and a decreased response to R-CHOP. The level of PD-L1 expression could be an independent predictor of DFS of DLBCL. More research is mandatory to standardize the cutoff value and scoring methods.

Background and aim: Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) became the standard of care for muscle-invasive bladder cancer (MIBC) in the last few years. We aimed to evaluate the radiological, pathological responses to NAC, and the 30-day surgical outcomes after RC in MIBC.

Patients and methods: A retrospective cohort study involving adult patients with localized urothelial MIBC who received NAC followed by RC at the National Cancer Institute of Egypt (NCI-E) for 2 years (2017 and 2018). Out of 235 MIBC cases, we recognized 72 patients (30%) who fitted the eligibility criteria.

Results: A cohort of 72 patients with a median age of 60.5 years (range 34-87). Hydronephrosis, gross extravesical extension (cT3b), and radiologically negative nodes (cN0) were depicted initially in 45.8, 52.8, and 83.3% of patients, respectively. Gemcitabine and cisplatin (GC) was the rampant NAC employed in 95.8%. Radiological evaluation post NAC using RECIST v1.1 revealed a response rate (RR) of 65.3% in bladder tumor and progressive disease in the former and lymph nodes encountered in 19.4 and 13.9%, respectively. The median time from the end of NAC to surgery was 8.1 weeks (range 4-15). Open RC and ileal conduit were the most common types of surgery and urinary diversion, respectively. Pathological down-staging was encountered in 31.9%, and only 11 cases (15.3%) achieved pathological complete response (pCR). The latter was significantly correlated with the absence of hydronephrosis, low-risk tumors, and associated bilharziasis (p = 0.001, 0.029, and 0.039, respectively). By logistic regression, the high-risk category was the only independent factor associated with a poor likelihood of achieving pCR (OR 4.3; 95% CI 1.1-16.7; p = 0.038). Thirty-day mortality occurred in 5(7%) patients, and 16(22%) experienced morbidity, with intestinal leakage being the most frequent complication. cT4 was the only significant factor associated with post-RC morbidity and mortality compared to cT2 and cT3b (p = 0.01).

Conclusions: Our results are further supporting the radiological and pathological benefits of NAC in MIBC, evidenced by tumor downstaging and pCR. The complication rate after RC is still considerable; hence, more larger studies are necessary to postulate a comprehensive risk assessment tool for patients who would get the maximum benefit from NAC, hoping to accomplish higher complete response rates with ultimately increased adoption of the bladder preservation strategies.

Background: This study was performed to investigate the expression of different biomarkers in patients with hepatocellular carcinoma and its connection with detective biomarkers. To achieve this objective, seventy subjects were examined in this study, sub-grouped to forty HCC patients and thirty HCV-affected patients with matched thirty healthy individuals. The study involved several groups of participants who were matched based on their age and gender.

Methods: The expression pattern of biomarkers was monitored by quantitative polymerase chain reaction (qRT-PCR). Finally, we utilized a ROC curve to investigate the predictive accurateness of those distinct biomarkers as well as a traditional tumor marker, AFP, in detecting HCC cases.

Results: The baseline biomarker expression levels were markedly greater in HCC patients than in those affected by HCV or healthy subjects. We stated that the sensitivity and the specificity of the different biomarkers alone did not improve than that of AFP alone. When comparing AFP with different biomarkers, the diagnostic validity improves only when combining with CK-1.

Conclusions: Overall, our results indicate that CK-1 mRNA expression could help as a noninvasive tumor biomarker for HCC prognosis and diagnosis when combining with AFP.