Targeting average length of hospital stay as a control measure to decrease COVID-19 hospital-acquired infection in surgical cancer patients.

BACKGROUND: The global spread of coronaviruses had a great impact on the economic and social situation of most countries. As the backbone of any society, the health sector made a significant contribution through applying emergency risk management plans in order to control the pandemic. Monitoring the average length of hospital stay (ALOS) was an effective way to release the capacity of the health system during this time. The aim was to evaluate the effect of applying risk assessment/management strategies on ALOS and the impact of this ALOS on COVID-19 infection rates among cancer patients. METHODS: This is a prospective cohort study. All admitted cancer patients in 6 surgical departments from January to June 2021 were included. RESULTS: A total of 1287 patients were admitted to 6 surgical departments during the selected period. About 46% of them had surgery (n = 578), while 54% did not have surgery (n = 700). Among surgical patients, admission rates were highest in February and head and neck department (24% and 22.1%, respectively), and lowest in April and chest department (12.4% and 8%, respectively). ALOS was significantly different across the 6 months (p value < 0.001) with lower ALOS in (April, May, and June) than in (January-February, and March). No significant difference was found across the 6 surgical departments (p value = 0.423). Twenty-eight patients became COVID-19 positive after admission, 25 of them (89%) were infected from March to June-during the time of the third wave-and a significant decreasing linear trend (p value = 0.009) was found. CONCLUSION: ALOS had significantly reduced with commitment to infection control (IC) interventions and recommendations. The significant decreasing trend of COVID-19 infection from March to June (unlike the rising curve of the 3rd COVID-19 wave by that time) could be explained by improvement in ALOS.

Truth-telling in Oncology: Egyptian Patients' Attitudes and Preferences.

OBJECTIVE: Truth-telling in oncology is a major challenge, particularly in the absence of disclosure protocols in Egypt and the lack of Egyptian studies examining patients' preferences regarding cancer disclosure. This study aimed to reveal the preferences of patients seeking care at the National Cancer Institute - Cairo University regarding disclosing cancer diagnosis and the type and amount of information to be told. METHODS: This cross-sectional study was conducted on 200 patients selected consecutively from those attending the outpatient clinics of the National Cancer Institute - Cairo University. Face-to-face interviews were performed with the patients according to a structured questionnaire. The questionnaire consisted of five parts: socio-demographic characteristics, knowledge about cancer disease, attitudes towards cancer disease, experience during the disclosure of the diagnosis, and preferences regarding disclosure of cancer diagnosis. RESULTS: Most patients (89.5%) preferred to know the diagnosis. Of them, 94.4% wished to know from the physician. No agreement was found between most patients' preferences and physicians' practice. On multivariate logistic regression analysis, patients' education was the only significant predictor of the preference to know the diagnosis (OR = 5.298, 95% CI = 1.258 - 22.301, P = 0.023). CONCLUSION: Patients have a great desire to know the diagnosis and other information related to treatment and prognosis.

The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial.

AIM: The role of surgical castration and rosuvastatin treatment on lipid profile and lipid metabolism related markers was evaluated for their prognostic significance in metastatic prostate cancer (mPC) patients. METHODS: A total of 84 newly diagnosed castrated mPC patients treated with castration were recruited and divided into two groups: Group I served as control (statin non-users) while group II treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users. Prostate specific antigen (PSA), epidermal growth factor receptor (EGFR), Caveolin-1 (CAV1), lipid profile (LDL, HDL, triglycerides (TG) and total cholesterol (TC)) and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter A1 (ABCA1), and soluble low density lipoprotein receptor related protein 1 (SLDLRP1)) were measured at baseline, after 3 and 6 months. Overall survival (OS) was analyzed by Kaplan-Meier and COX regression for prognostic significance. RESULTS: Before castration, HMG-CoA reductase was elevated in patients <65 years (P = 0.009). Bone metastasis was associated with high PSA level (P = 0.013), but low HMGCR (P = 0.004). Patients with positive family history for prostate cancer showed high levels of EGFR, TG, TC, LDL, alkaline phosphatase (ALP), but low AKR1C4, SLDLRP1, CAV1 and ABCA-1 levels. Smokers had high CAV1 level (P = 0.017). After 6 months of castration and rosuvastatin administration, PSA, TG, LDL and TC were significantly reduced, while AKR1C4, HMGCR, SLDLRP1, CAV1 and ABCA-1 were significantly increased. Overall survival was reduced in patients with high baseline of SLDLRP1 (>3385 pg/ml, P = 0.001), PSA (>40 ng/ml, P = 0.003) and CAV1 (>4955 pg/ml, P = 0.021). CONCLUSION: Results of the current study suggest that the peripheral lipidogenic effects of rosuvastatin may have an impact on the treatment outcome and survival of castrated mPC patients. TRAIL REGISTRATION: This trial was registered at the Pan African Clinical Trial Registry with identification number PACTR202102664354163 and at ClinicalTrials.gov with identification number NCT04776889.

Pitfalls in scientific research: critical appraisal of articles published in one of the international journals in Egypt.

BACKGROUND: To identify and report flaws of Internet-published articles in the Journal of the Egyptian National Cancer Institute (JENCI), Cairo University, through a retrospective documentary study on articles published during the period from 2011 to 2016. All sections were reviewed against a collective checklist. Articles were grouped by publication year into 2 intervals: early (from 2011 to 2013) and recent (from 2014 to 2016) to identify changes in study characteristics over time. RESULTS: The study included 139 original articles. Half of the titles represented aim and 9.4% represented study design. Abstracts were concise, clear, with structured writing format in 98.6%, 93.5%, and 35.3%, respectively. Most introductions included the study aim, while 41% had a rationale. Study timing was reported in 59.0%, while the study design was reported in 25.9%. Inclusion and exclusion criteria were clearly reported in 43.1% and 40.1%, respectively. Statistical methods were mentioned in 80.6%, complete in 30.4%, and appropriate in 85.7%. Four studies reported sample size estimation. Only 52.5% and 58.3% of results were exhaustive and answer the research question, respectively. Incorrect statistical calculations occurred in 41.0%, inappropriate statistical tests or descriptive parameter selection in 26.6%, while inappropriate test application occurred in 49.1%. About 60% of discussions did not completely cover results, 31.7% fully justified the findings, 56.1% followed a logical flow, and 36.7% had contradiction within the text. Conclusions were mostly linked to aim, imprecise, and extrapolating beyond results. On comparing both periods, only a significant less misuse of statistical terms, more reporting conflict of interest, more missing references for cited texts in the recent period, and more participation of NCI over other institutes in the early period were found. CONCLUSION: Articles published in JENCI (from 2011 to 2016) had many methodological and reporting defects and some points of strength. Using the collective checklist developed by this study, continuous training of researchers, involving epidemiologists throughout the whole research process, and applying strict journal reporting and publication rules should be encouraged.

New insight into HCV E1/E2 region of genotype 4a.

INTRODUCTION: Hepatitis C virus (HCV) genome contains two envelope proteins (E1 and E2) responsible for the virus entry into the cell. There is a substantial lack of sequences covering the full length of E1/E2 region for genotype 4. Our study aims at providing new sequences as well as characterizing the genetic divergence of the E1/E2 region of HCV 4a using our new sequences along with all publicly available datasets. METHODS: The genomic segments covering the whole E1/E2 region were isolated from Egyptian HCV patients and sequenced. The resulting 36 sequences 36 were analyzed using sequence analysis techniques to study variability within and among hosts in the same time point. Furthermore, previously published HCV E1/E2 sequence datasets for genotype 4a were retrieved and categorized according to the geographical location and date of isolation and were used for further analysis of variability among Egyptian over a period of 15 years, also compared with non-Egyptian sequences to figure out region-specific variability. RESULTS: Phylogenetic analysis of the new sequences has shown variability within the host and among different individuals in the same time point. Analysis of the 36 sequences along with the Egyptian sequences (254 sequences in E1 in the period from 1997 to 2010 and 8 E2 sequences in the period from 2006 to 2010) has shown temporal change over time. Analysis of the new HCV sequences with the non-Egyptian sequences (182 sequences in E1 and 155 sequences in the E2) has shown region specific variability. The molecular clock rate of E1 was estimated to be 5E-3 per site per year for Egyptian and 5.38E-3 for non-Egyptian. The clock rate of E2 was estimated to be 8.48E per site per year for Egyptian and 6.3E-3 for non-Egyptian. CONCLUSION: The results of this study support the high rate of evolution of the Egyptian HCV genotype 4a. It has also revealed significant level of genetic variability among sequences from different regions in the world.

Role of thyroid transcription factor-1 and P63 immunocytochemistry in cytologic typing of non-small cell lung carcinomas.

PURPOSE: Evaluation of the value of thyroid transcription factor (TTF-1) and P63 in subtyping of non-small cell lung cancer in cytologic material. PATIENTS AND METHODS: This is a retrospective study including 40 cases of primary lung lesions who underwent image guided FNAC from pulmonary nodules. The final histopathologic diagnosis was the gold standard. Cell blocks were stained with anti-TTF-1, and P63. Nuclear immunoreactivity for both markers was considered specific. Sensitivity, specificity, positive and negative predictive values, of the cytologic diagnosis and of the two markers, as well as the accuracy of the combined markers were calculated. RESULTS: Cytomorphology achieved a sensitivity of 83.3%, specificity of 91%, PPV of 91%, and NPV of 83.3%, for the diagnosis of AC, and 91% sensitivity, 83.3% specificity, 83.3% PPV, and 91% NPV, for the diagnosis of SCC. The concordance between cytologic and histopathologic diagnoses of AC and SCC was 87%. TTF-1 achieved 87.5% sensitivity, 94.7% specificity, 95.5% PPV, and 85.7% NPV for AC, while P63 achieved 94.7% sensitivity, 95.8% specificity, 94.7% PPV, and 95.8% NPV for SCC. TTF-1 enhanced the sensitivity of cytomorphology for AC from 83.3% to 87.5%, and specificity from 91% to 94.7%. Similarly P63 enhanced the sensitivity for SCC from 91% to 94.7%, and specificity from 83.3% to 95.8%. CONCLUSION: TTF-1 achieved moderate sensitivity, and high specificity in the diagnosis of AC, while P63 was highly sensitive and specific for the diagnosis of SCC. Immunocytochemistry raised the sensitivity and specificity of FNAC in diagnosing AC and SCC using TTF-1 and P63, respectively.

Aberrant expression of cell cycle regulatory genes predicts overall and disease free survival in malignant pleural mesothelioma patients.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM. PATIENTS AND METHODS: Aberrant expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP), p53, mdm2 and Rb was assessed in 55 MPM cases from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological prognostic factors, overall and disease free survival (OS&DFS). RESULTS: Altered expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP1), Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%, and 50.8% of cases, respectively. SV40 infection significantly correlated with p14(ARF), 16(INK4A), p27(kip1) and Rb aberrations (p=0.014, p=0.02, p=0.01, p=-0.01). Asbestos exposure significantly correlated with p53, p21(waf) and mdm2 aberrations (p=0.001, p=0.03, p=0.02). On multivariate analysis PS ≥ 2, p27(KIP1) and Rb aberrations were independent prognostic factors for OS (p=0.016, p=0.011, p=0.003) whereas on tumor recurrence, p27(KIP1) and Rb aberrations were independent prognostic factors for DFS (p=0.002, p=0.03, p=0.01). CONCLUSIONS: MPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell cycle regulatory genes. p14(ARF), p16(INK4A), Rb and p27(KIP1) seem to be involved in SV40-associated MPM whereas mdm2, p53 and p21(WAF) are related to asbestos exposure. In addition to recurrence and PS, only p27(KIP1)and Rb could be used as molecular prognostic markers in MPM.

Molecular prognostic profile of Egyptian HCC cases infected with hepatitis C virus.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common and aggressive malignancy. Despite of the improvements in its treatment, HCC prognosis remains poor due to its recurrence after resection. This study provides complete genetic profile for Egyptian HCC. Genome-wide analyses were performed to identify the predictive signatures. PATIENTS AND METHODS: Liver tissue was collected from 31 patients with diagnosis of HCC and gene expression levels in the tumours and their adjacent non-neoplastic tissues samples were studied by analyzing changes by microarray then correlate these with the clinico-pathological parameters. Genes were validated in an independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progression to mitosis; unregulated DNA damage check-points, and apoptosis. RESULT: Nine hundred fifty eight transcripts out of the 25,000 studied cDNAs were differentially expressed; 503 were up-regulated and 455 were down-regulated. A total of 19 pathways were up-regulated through 27 genes and 13 pathways were down-regulated through 19 genes. Thirty-seven genes showed significant differences in their expression between HCC cases with high and low Alpha Feto Protein (AFP≥600 IU/ml). The validation for the microarray was done by real time PCR assay in which PPP3CA, ATG-5, BACE genes showed down-regulation and ABCG2, RXRA, ELOVL2, CXR3 genes showed up-regulation. cDNA microarrays showed that among the major upregulated genes in HCC are sets. CONCLUSION: The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.

Characterization of chronic HCV infection-induced apoptosis.

BACKGROUND: To understand the complex and largely not well-understood apoptotic pathway and immune system evasion mechanisms in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and HCV associated chronic hepatitis (CH), we studied the expression patterns of a number of pro-apoptotic and anti-apoptotic genes (Fas, FasL, Bcl-2, Bcl-xL and Bak) in HepG2 cell line harboring HCV- genotype-4 replication. For confirmation, we also assessed the expression levels of the same group of genes in clinical samples obtained from 35 HCC and 34 CH patients. METHODS: Viral replication was assessed in the tissue culture medium by RT-PCR, quantitative Real-Time PCR (qRT-PCR); detection of HCV core protein by western blot and inhibition of HCV replication with siRNA. The expression level of Fas, FasL, Bcl-2, Bcl-xL and Bak was assessed by immunohistochemistry and RT-PCR whereas caspases 3, 8 and 9 were assessed by colorimetric assay kits up to 135 days post infection. RESULTS: There was a consistent increase in apoptotic activity for the first 4 weeks post-CV infection followed by a consistent decrease up to the end of the experiment. The concordance between the changes in the expression levels of Fas, FasL, Bcl-2, Bcl-xL and Bak in vitro and in situ was statistically significant (p < 0.05). Fas was highly expressed at early stages of infection in cell lines and in normal control liver tissues followed by a dramatic reduction post-HCV infection and an increase in the expression level of FasL post HCV infection. The effect of HCV infection on other apoptotic proteins started very early post-infection, suggesting that hepatitis C modulating apoptosis by modulating intracellular pro-apoptotic signals. CONCLUSIONS: Chronic HCV infection differently modulates the apoptotic machinery during the course of infection, where the virus induces apoptosis early in the course of infection, and as the disease progresses apoptosis is modulated. This study could open a new opportunity for understanding the various signaling of apoptosis and in the developing a targeted therapy to inhibit viral persistence and HCC development.

Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease.

AIM: To assess the utility of an autologous CD34(+) and CD133(+) stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases. METHODS: One hundred and forty patients with end-stage liver diseases were randomized into two groups. Group 1, comprising 90 patients, received granulocyte colony stimulating factor for five days followed by autologous CD34(+) and CD133(+) stem cell infusion in the portal vein. Group 2, comprising 50 patients, received regular liver treatment only and served as a control group. RESULTS: Near normalization of liver enzymes and improvement in synthetic function were observed in 54.5% of the group 1 patients; 13.6% of the patients showed stable states in the infused group. None of the patients in the control group showed improvement. No adverse effects were noted. CONCLUSION: Our data showed that a CD34(+) and CD133(+) stem cells infusion can be used as supportive treatment for end-stage liver disease with satisfactory tolerability.

Hepatitis C virus-NS3P in relation to p53, p21waf, mdm2, p21-ras and c-erbB2 in hepatocarcinogenesis.

BACKGROUND: The non-structural protein 3 (NS3P) of hepatitis C virus (HCV) genome was linked to the neoplastic transformation of normal hepatocytes in chronically infected patients. However, the exact mechanisms involved in this process are unidentified yet, especially in the Egyptian population where the commonest type is genotype 4. METHODS: We investigated 32 HCV reverse transcriptase-polymerase chain reaction (RT-PCR) positive hepatocellular carcinoma (HCC) cases and 18 morphologically normal hepatic tissues distant to tumors (MNT) for the correlation between HCV-NS3P, p53, p21(waf), mdm2, p21ras and c-erbB2 and DNA content by immunohistochemistry and image analysis. RESULTS: The NS3P expression was lower in HCC (65.6%) than in MNT (94.4%) patients. The expression level of studied genes in HCC was: p53 (56.25%), p21(waf) (43.7%), mdm2 (59.4%), p21-ras (73.3%) and c-erbB2 (75%). Whereas in MNT, it was 22.2, 61.1, 44.4, 41.2 and 77.8%, respectively. The NS3P expression showed a significant correlation with the presence of cirrhosis, chronic active hepatitis (CAH) and tumor grade (P < 0.05). c-erbB2 overexpression and p21(waf) loss were higher in MNT than in HCC patients, however, this did not reach a statistically significant level. There was a statistically significant correlation between NS3P, c-erbB2 and p21(waf) (P < 0.01). There was also a significant correlation between p21(waf) loss and CAH (P = 0.01) as well as between mdm2, c-erbB2 and cirrhosis (P = 0.025 and 0.001) in HCC cases. There was a statistically significant difference in the ploidy status between HCC and MNT, but there was no significant relationship between the ploidy status and other clinicopathological features. CONCLUSION: The carcinogenic effect of NS3P is probably exerted at an early stage of HCC possibly through a pathway involving c-erbB2 and p21(waf) alterations. In contrast, p53, p21ras and mdm2 alterations are late events in hepatocarcinogenesis and are usually associated with an aggressive phenotype.

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival.

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.

Alterations of the fragile histidine triad gene in hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND AND AIM: The present study was conducted to address whether homozygous deletion (HZD) or transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCC). METHODS: Homozygous deletion of the FHIT gene at exons 3-9 was assessed as well as mRNA FHIT expression using reverse transcription polymerase chain reaction. The study included 23 samples of HCC, 11 on top of cirrhosis and 12 non-cirrhotic, in addition to five cases with chronic active hepatitis (CAH), as well as seven morphologically normal tissues distant to the tumor (NDT) and 10 normal liver samples from liver transplantation donors. RESULTS: Homozygous deletion was found in 18 of 23 HCC cases. The highest incidence of deletion was detected in exon 9 (52.0%) and the lowest in exon 7 (4.3%). Ten of the 18 cases (55.5%) showed deletion in more than one exon, eight in two exons, one in three exons and one in five exons. There was a significant association between HZD of exons 5 and 9 and HCC arising on top of cirrhosis (P = 0.041 and 0.006, respectively) as well as between exons 8 and 9 and the presence of CAH (P = 0.029 and 0.034, respectively). Aberrant FHIT transcripts were detected in 15 HCC cases (65.2%), 13 of them showed complete reduction of the mRNA transcripts and two showed abnormal bands. Sequence analysis of abnormal-sized transcripts revealed that they were generated by the fusion of exons 5 and 7 as well as exons 7 and 9. In contrast, six of the seven NDT samples tested (85.6%) showed HZD in one or more exons. None of the normal liver samples from liver transplantation donors showed any changes. The highest incidence of HZD was detected in exon 9 (five of six cases representing 83.3%) and the lowest was in exon 4 (one of six cases representing 16.7%). Four cases showed the same aberrant FHIT HZD in both NDT and matched HCC. CONCLUSIONS: The results of the present study indicate that the FHIT gene is a frequent target in hepatitis C virus-associated HCC and that alterations affecting this gene could be an early event in this type of neoplasm as they were detected in cirrhotic and CAH patients. However, this should be confirmed by a larger, extended study including more cases of cirrhotic and CAH patients as well as matched tumor and normal samples.

Risk factors for cytomegalovirus, hepatitis B and C virus reactivation after bone marrow transplantation.

To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-BMT risk factors that may be associated with an increased post-BMT death. Among those factors, the importance of pre-BMT viral hepatitis markers in BMT donors and recipients remains unsettled. In the present study, we have determined the effect of prior donor and recipient cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) exposure on the incidence of those viral infections after bone marrow transplantation (BMT). The study included 63 patients presented to the BMT unit; 28 of them underwent transplantation and 35 were not transplanted. All serum markers of CMV, HBV, and HCV infections were monitored using ELISA technique, as well as PCR-DNA for CMV, HBV and HCV RT-PCR techniques for HCV. The incidence of active CMV and HCV was 11/28 (39%) and 6/28 (21%) in post-BMT recipients compared to 2/35 (6%) and 2/35 (6%) in the 35 untransplanted patients (P=0.00003 and P=0.05). Whereas active HBV infection was non significantly (P=0.13) higher 3/28 (11%) in the BMT patients in comparison to 1/35 (3%) in untransplanted patients. Ten out of the 19 (53%) of the CMV-seropositive recipients developed CMV reactivation compared to 1/9 (11%) of the CMV-seronegative recipients who developed CMV seroconversion. In addition, 3/8 (38%) of the HBV-seropositive recipients developed HBV reactivation in comparison to 0/20 of the HBV-seronegative recipients. Moreover, 5/13 (39%) of the HCV-seropositive recipients developed HCV reactivation in comparison to 1/16 (6%) of the HCV-seronegative recipients who developed HCV seroconversion. In conclusion, previous exposure to CMV, HBV, and HCV infections in the recipients of BMT patients were found to influence the risk of developing those viral infections.