The FSCN1 gene rs2966447 variant is associated with increased serum fascin-1 levels and breast cancer susceptibility.

Fascin-1 (FSCN1) is recognized as an actin-binding protein, commonly exhibits up-regulation in breast cancer (BC) and is crucial for tumor invasion and metastasis. The existence of FSCN1 gene polymorphisms may raise the potential for developing BC, and there are still no studies focusing on the relationship between the FSCN1 rs2966447 variant and BC risk in Egyptian females. Thus, we investigated the serum fascin-1 levels in BC patients and the association between the FSCN1 rs2966447 variant with its serum levels and BC susceptibility. Genotyping was conducted in 153 treatment-naïve BC females with different stages and 144 apparent healthy females by TaqMan® allelic discrimination assay, whereas serum fascin-1 level quantification was employed by ELISA. The FSCN1 rs2966447 variant demonstrated a significant association with BC susceptibility under all utilized genetic models, cancer stages and estrogen receptor negativity. Also, BC females with AT and TT genotypes had higher serum fascin-1 levels and tumor size than those with the AA genotype. Moreover, serum fascin-1 levels were significantly elevated in the BC females, notably in those with advanced-stages. Furthermore, serum fascin-1 levels were markedly positively correlated with number of positive lymph nodes as well as tumor size. Collectively, these findings revealed that the FSCN1 rs2966447 variant may be regarded as a strong candidate for BC susceptibility. Also, this intronic variant is associated with increased serum fascin-1 levels and tumor size.

The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients.

PURPOSE: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. METHODS: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. RESULTS: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. CONCLUSIONS: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

The crucial role of fascin-1 in the pathogenesis, metastasis, and chemotherapeutic resistance of breast cancer.

Breast cancer (BC) is the most common type of cancer in women to be diagnosed, and it is also the second leading cause of cancer death in women globally. It is the disease that causes the most life years adjusted for disability lost among women, making it a serious worldwide health issue. Understanding and interpreting carcinogenesis and metastatic pathways is critical for curing malignancy. Fascin-1 was recognized as an actin-bundling protein with parallel, rigid bundles as a result of the cross-linking of F-actin microfilaments. Increasing levels of fascin-1 have been associated with bad prognostic profiles, aggressiveness of clinical courses, and poor survival outcomes in a variety of human malignancies. Cancer cells that overexpress fascin-1 have higher capabilities for proliferation, invasion, migration, and metastasis. Fascin-1 is being considered as a potential target for therapy as well as a potential biomarker for diagnostics in a variety of cancer types. This review aims to provide an overview of the FSCN1 gene and its protein structure, elucidate its physiological and pathological roles, and throw light on its involvement in the initiation, development, and chemotherapeutic resistance of BC.

Compartmental Syndecan-1 (CD138) expression as a novel prognostic marker in triple-negative metaplastic breast cancer.

BACKGROUND: Metaplastic breast cancer (MpBC) is rare, aggressive, and mostly triple-negative (TN) subtype of BC. We aimed to investigate the potential prognostic significance of Syndecan-1 (SDC1/CD138) expression in this unique tumor. METHODS: Archived charts of 50 TNBC patients [21 MpBC and 29 invasive ductal carcinoma (IDC)] were retrospectively evaluated. Corresponding paraffin blocks were used for immunohistochemical (IHC) staining of SDC1. Compartmental (epithelial membranous, stromal, and cytoplasmic) staining scores were expressed in quartiles (Q) and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: The median follow-up period was 54.6 months (range: 2.2-112.7). MpBC patients showed significantly worse DFS and OS than IDC (p = 0.007 and 0.004, respectively). MpBC demonstrated significantly higher Q4 stromal and membranous SDC1 compared to IDC (p = 0.016 and 0.021, respectively), whereas IDC exhibited significantly higher cytoplasmic Q4 SDC1 than MpBC (p = 0.015). Stromal Q4 SDC1 expression was found to be an independent factor associated with MpBC relative to IDC (OR: 6.7, 95% CI: 1.24-36.90; p = 0.028). Stromal Q4 SDC1 expression was also an independent prognostic parameter for worse DFS and OS compared to Q1-3 in the whole cohort (HR: 4.2, 95% CI: 1.6-10.5; p = 0.003 and HR: 5.8; 95% CI: 2.2-15.3; p < 0.001, respectively). In MpBC, cytoplasmic Q1-3 SDC1 expression was an independent prognostic indicator for worse OS compared with their IDC counterparts (HR: 2.837, 95% CI: 1.048-7.682; p = 0.04). CONCLUSION: This study suggests, for the first time, that differential expression and localization of SDC1 may contribute to the pathogenesis and prognosis of TN-MpBC. Therefore, targeting SDC1 (CD138) could emerge as a novel therapeutic approach for this devastating disease.

The conundrum of metaplastic breast cancer: a single Egyptian institution retrospective 10-year experience (2011-2020).

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.

Evaluation of short-term outcomes of neoadjuvant chemotherapy followed by radical cystectomy in muscle-invasive bladder cancer: a single Egyptian institution experience.

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.

Prevalence of pain and its association with quality of life of patients with heart failure in a developing country: findings from a multicenter cross-sectional study.

BACKGROUND: Heart failure (HF) is considered one of the main causes of morbidity and death among chronic diseases worldwide. Patients have increasingly reported chronic pain in long-standing heart failure as a disturbing symptom. Its unknown etiology and mechanism, in addition to its insidious progressive nature, made both the doctor and the patient not notice it until it affects the quality of life (QoL) and general health status. The primary objective of this study is to find the prevalence of pain in chronic heart failure patients and its impact on their QoL. The secondary objective is to determine the predictors of QoL in HF patients. METHODS: A multicenter cross-sectional design was used. The European Quality of Life scale five dimensions scale and the Brief Pain Inventory were adopted to evaluate QoL and pain, respectively. The Statistical Package for the Social Sciences version 25 was applied to present the data. The Mann-Whitney U, Kruskal-Wallis, and Cronbach alpha tests were used. RESULTS: The final study had a total of 142 individuals. The prevalence of pain among HF patients was 84.5%. Knee pain was the main complaint among patients. Our patients' median pain severity score was 18 [5.00-25.00], while the median pain interference score was 39 [24.75-53.00]. They had a median EQ-5D score of 0.34 [0.0-0.6] and an EQ-VAS score of 50 [30-70]. Pain severity (p = 0.004 and p < 0.001, respectively) and pain interference (p < 0.001 and p = 0.001, respectively) were found to significantly associated with both QoL scores; the visual analogue scale (EQ-VAS) and EQ-5D-5L. In multivariate analysis, monthly income was the only variable significantly correlated with EQ-VAS and EQ-5D-5L, along with pain variables. CONCLUSIONS: Pain is a common symptom among patients with HF and is significantly associated with their QoL. Low income is also highly associated with poor QoL. Definitive guidelines should be achieved to increase awareness and understanding of the importance of pain management, reaching a higher QoL level, less pain, and good adherence to HF medications.

Distal Radial Artery Access in comparison to Forearm Radial Artery Access for Cardiac Catheterization: A Randomized Controlled Trial (DARFORA Trial).

Background: In our clinical practice, conventional radial access has been employed routinely for coronary procedures. The distal radial artery (DRA) access site has recently emerged as a novel technique in cardiac procedures. Objectives: This study compares distal radial access to standard forearm radial access (FRA) in terms of feasibility, outcomes, and complications. Method: This prospective, randomized trial was conducted at a single center. The patients were chosen from An-Najah National University Hospital's catheterization laboratory between December 2019 and November 2020. A total of 209 patients were randomized into two groups: DRA group (n = 104) and FRA group (n = 105). Results: Access was successful in 98% of patients in both the groups. The DRA group had a longer puncture duration and a higher number of attempts (duration: 56.6 ± 61.1 s DRA vs. 20.0 ± 18.4 s FRA, p < 0.001, attempts: 1.9 ± 1.3 DRA vs. 1.2 ± 0.60 FRA, p < 0.001). Puncture-associated pain was greater in the DRA group (4 ± 2.2 DRA vs. 3 ± 2.1 FRA, p=0.001). There were two radial artery occlusions in the FRA group and none in the DRA group (p=0.139). Percutaneous coronary intervention (PCI) was performed in 26% of the DRA group and 37.1% of the FRA group. The DRA group had significantly shorter procedure times (p=0.006), fluoroscopy times (p=0.002), and hemostasis times (p=0.002). Over time, the learning curve demonstrated improved puncture duration and a decrease in the number of puncture attempts. Conclusions: DRA is a safe and practical alternative to FRA for coronary angiography and intervention. The overtime learning curve is expected to improve puncture-related outcomes.

Impact of Prone Position on 12-Lead Electrocardiogram in Healthy Adults: A Comparison Study with Standard Electrocardiogram.

BACKGROUND: The standard electrocardiogram (ECG) is commonly performed in the supine posture. It may be difficult to report ECG in a supine posture for those who are unable to adopt the supine posture because of certain circumstances such as acute respiratory distress syndrome-patients who are placed in a prone position for long periods to improve oxygenation. Few data are available on the impact of the prone position on the ECG recording with electrodes on the posterior chest. Examining and analyzing the type and extent of changes observed in the prone ECG in healthy adults have become vitally valuable. METHODS: A cross-sectional observational study enrolled forty healthy adults (24 males and 16 females) aged between 18 and 40 years. The ECG was performed in two different body positions, supine and prone. Influence of prone position on the heart rate, mean QRS axis, amplitude, morphology, duration, mean T wave axis and polarity, mean P wave axis, PR, and mean QTc duration was evaluated. RESULTS: The mean heart rate was higher in the prone position (73.2 ± 12.4 bpm) compared with the supine position (69.5 ± 11.5 bpm, p = 0.03). The QRS duration decreased considerably from supine (92.8 ± 12.6 ms) to prone (84.9 ± 11.9 ms, p < 0.001). The mean QRS axis moved to the left in the prone posture (40.5° ± 32°) relative to the supine (49° ± 28°, p=0.015). The QRS amplitude in the precordial leads was significantly decreased from supine (7.42 ± 3.1 mV) to prone (3.68 ± 1.7 mV, p < 0.001). In addition, changes in the QRS morphology in leads V1-V3 with the appearance of new Q waves were noted. A notable variation in the mean corrected QT (QTc) period with decrease in duration in prone posture ECG (385 ± 64.8) relative to supine (406 ± 18.8, p=0.05). CONCLUSIONS: Prone position ECG resulted in significant changes in healthy adults that should be aware of this as this can affect diagnosis and management strategies. Further studies are needed to investigate the impact of prone position on ECG recording in patients with cardiovascular diseases.

Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer.

The therapeutic potential of Musashi (MSI) RNA-binding proteins, important stemness-associated gene expression regulators, remains insufficiently understood in breast cancer. This study identifies the interplay between MSI protein expression, stem cell characteristics, radioresistance, cell invasiveness and migration. MSI-1, MSI-2 and Notch pathway elements were investigated via quantitative polymerase chain reaction (qPCR) in 19 triple-negative breast cancer samples. Measurements were repeated in MDA-MB-231 cells after MSI-1 and -2 siRNA-mediated double knockdown, with further experiments performed after MSI silencing. Flow cytometry helped quantify expression of CD44 and leukemia inhibitory factor receptor (LIFR), changes in apoptosis and cell cycle progression. Proliferation and irradiation-induced effects were assessed using colony formation assays. Radiation-related proteins were investigated via Western blots. Finally, cell invasion assays and digital holographic microscopy for cell migration were performed. MSI proteins showed strong correlations with Notch pathway elements. MSI knockdown resulted in reduction of stem cell marker expression, cell cycle progression and proliferation, while increasing apoptosis. Cells were radiosensitized as radioresistance-conferring proteins were downregulated. However, MSI-silencing-mediated LIFR downregulation resulted in enhanced cell invasion and migration. We conclude that, while MSI knockdown results in several therapeutically desirable consequences, enhanced invasion and migration need to be counteracted before knockdown advantages can be fully exploited.

The Possible Role of Adipokines in HCV Associated Hepatocellular Carcinoma.

BACKGROUND: Adipokines play an important role in the regulation of inflammation and tumor progression. AIM: Assessment of the possible role of adiponectin, leptin and visfatin in HCV associated hepatocellular carcinoma (HCC). METHODS: patients were classified into 85 patients with HCV associated HCC, 100 patients with chronic hepatitis C viral (HCV) infection compared to 50 normal control (NC) subjects. All subjects included in the study were assessed for HCV infection by seropositive HCV antibodies, as well as HCV RNA by RT-PCR. Serum levels of adiponectin, leptin and visfatin were assessed using enzyme linked immunosorbent assay (ELISA). The data were correlated to the relevant clinic-pathological features of the patients, and the overall survival (OS) rate. RESULTS: There was a significant difference in the serum levels of adiponectin and visfatin among HCC, HCV and NC groups (P<0.001). The serum levels of leptin and alpha fetoprotein (AFP) were significantly higher in HCC group (P<0.001). There was a significant association between the serum level of adiponectin and advanced Child class liver cirrhosis (P=0.03), as well as with poor performance status (ECOG, P=0.02). Serum leptin associated significantly with the number of lesions in the liver (P=0.006), visfatin associated with increased mortality rate (P<0.001). Adiponectin, leptin and visfatin associated significantly with liver cirrhosis in HCV patients (P<0.01). Leptin achieved the highest sensitivity (98.8%). visfatin achieved the highest specificity (100%) and PPV (100%) for detection of HCC. The combination of serum leptin and visfatin for the diagnosis of HCV associated HCC showed sensitivity, specificity, PPV, NPV and accuracy (100%, 96.6%, 93.4%, 100% and 97.4%; respectively). CONCLUSION: Adiponectin, leptin and visfatin have an important role(s) in the pathogenesis of HCV associated HCC. 
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Induction of heparanase via IL-10 correlates with a high infiltration of CD163+ M2-type tumor-associated macrophages in inflammatory breast carcinomas.

Inflammatory breast cancer (IBC) is the most aggressive and lethal form of breast cancer, characterized by a high infiltration of tumor-associated macrophages and poor prognosis. To identify new biomarkers and to elucidate the molecular mechanisms underlying IBC pathogenesis, we investigated the expression pattern of heparanase (HPSE) and its activator cathepsin L (CTSL). First, we quantitated the HPSE and CTSL mRNA levels in a cohort of breast cancer patients after curative surgery (20 IBC and 20-non-IBC). We discovered that both HPSE and CTSL mRNA levels were significantly induced in IBC tissue vis-à-vis non-IBC patients (p <0 .05 and p <0 .001, respectively). According to the molecular subtypes, HPSE mRNA levels were significantly higher in carcinoma tissues of triple negative (TN)-IBC as compared to TN-non-IBC (p <0 .05). Mechanistically, we discovered that pharmacological inhibition of HPSE activity resulted in a significant reduction of invasiveness in the IBC SUM149 cell line. Moreover, siRNA-mediated HPSE knockdown significantly downregulated the expression of the metastasis-related gene MMP2 and the cancer stem cell marker CD44. We also found that IBC tumors revealed robust heparanase immune-reactivity and CD163+ M2-type tumor-associated macrophages, with a positive correlation of both markers. Moreover, the secretome of axillary tributaries blood IBC CD14+ monocytes and the cytokine IL-10 significantly upregulated HPSE mRNA and protein expression in SUM149 cells. Intriguingly, massively elevated IL-10 mRNA expression with a trend of positive correlation with HPSE mRNA expression was detected in carcinoma tissue of IBC. Our findings highlight a possible role played by CD14+ monocytes and CD163+ M2-type tumor-associated macrophages in regulating HPSE expression possibly via IL-10. Overall, we suggest that heparanase, cathepsin L and CD14+ monocytes-derived IL-10 may play an important role in the pathogenesis of IBC and their targeting could have therapeutic implications.

A combined treatment of curcumin, piperine, and taurine alters the circulating levels of IL-10 and miR-21 in hepatocellular carcinoma patients: a pilot study.

BACKGROUND: Investigating and evaluating possible alternative therapeutic strategies to control hepatocellular carcinoma (HCC) is a critical need because of its high prevalence and being one of the most lethal cancers. Curcumin and taurine showed potent anti-tumor activities in pre-clinical and clinical studies by targeting multiple pathways. Thus, this study was designed to assess the effect of a combined treatment consisted of curcumin, piperine, and taurine on circulating levels of interleukin-10 (IL-10), and microRNAs miR-141 and miR-21. METHODS: Twenty eligible HCC patients administrated an oral dose of 4 g curcumin, 40 mg piperine, and 500 mg taurine daily for three successive treatment cycles, each was a 30-day. The level of IL-10 along with the expression levels of miR-141, and miR-21 were monitored in serum before starting the treatment and after each cycle. Patients were followed-up for a period of 24 months. RESULTS: The combined treatment was able to produce a significant decrease in the levels of serum IL-10, and miR-21 while it resulted in a non-significant up-regulation of serum miR-141 expression level. At the end of the follow-up period, the median overall survival (OS) rate was found to be 17.00 months with a worse OS in patients with high baseline levels of circulating IL-10 and miR-21 compared to those with low levels. In contrast, a low baseline level of circulating miR-141 was associated with poor prognosis. CONCLUSIONS: The combined treatment may be able to increase the OS rate by altering the circulating level of IL-10 and miR-21.

Neuroendocrine tumors of the lung: A five-year retrospective experience of Egyptian NCI (2010-2014).

BACKGROUND: The spectrum of lung neuroendocrine tumors (NETs) encompasses low grade typical carcinoid (TC), intermediate grade atypical carcionid (AC) and high grade, both large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), with extreme differences in management and survival. OBJECTIVE: To study clinicopathologic and prognostic factors affecting survival of lung NETs. PATIENTS AND METHODS: This is a retrospective study evaluating 35 patients with primary lung NETs treated at National Cancer Institute of Egypt (NCI-E) between January 2010 and December 2014. Pathological diagnosis depended on definite morphology and positivity to at least one of the neuroendocrine markers by immunohistochemistry. RESULTS: The mean age of the patients was 53 ±â€¯11.2 years with male predominance. Performance status (PS) I was encountered in 48.6%. SCLC was the prevalent histology in 68.6%, followed by LCNEC & TC in 20 & 11.4%, respectively. Curative surgery was employed in 100 & 57% of TC & LCNEC patients, respectively. Stage IV was anticipated in 87.5 & 43% of SCLC & LCNEC, respectively. For the entire cohort, the median event-free survival (EFS) and overall survival (OS) were 8.0 and 13.7 months, respectively, whereas the 3-year EFS and OS were 17.8 & 20%, respectively. SCLC patients showed significantly the worst OS compared to other NETs (p = 0.001). Patients who presented with stage IV and PS > I demonstrated significantly shorter OS than those with locoregional and PS I (p = 0.00001 &p = 0.002, respectively). CONCLUSIONS: SCLC subtype, stage IV and initial PS > I are poor prognostic factors for lung NETs associated with shorter survival. This conclusion needs to be confirmed by larger studies.

Peritoneal carcinomatosis in colorectal cancer: Defining predictive factors for successful cytoreductive surgery and hyperthermic intraperitoneal chemotherapy - A pilot study.

BACKGROUND: Peritoneal carcinomatosis originating from colorectal cancer (PC-CRC) carries a dismal prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have been offered to those patients with substantial health and economic burden, nevertheless not all patients are fitting this treatment modality and outcome is generally still poor. OBJECTIVE: To elicit predictive factors associated with the success of CRS and HIPEC in PC-CRC patients. PATIENTS AND METHODS: This is a pilot study including 30 consecutive patients with PC-CRC; 20 of them (66.7%) presented with metachronous peritoneal disease. All patients were planned for CRS and HIPEC with Mitomycin-C after receiving preoperative systemic chemotherapy for 3 months. RESULTS: On exploration, CRS and HIPEC were successful in 17 patients (56.6%) who had completeness of cytoreduction score 0-1 (CC-0/1), whereas failure (CC-2) was encountered in 13 patients (43.3%). The presence of ascites, extensive peritoneal disease (PCI > 20) was significantly correlated with failure to achieve CRS and HIPEC (p < 0.001); also, the primary rectal site showed a trend towards significance (p = 0.08). The cumulative overall survival (OS) and progression-free survival (PFS) at 2 years were 66.6 and 62.6%, respectively. Patients who achieved CC-0/1 had significantly prolonged OS compared to CC-2 (p < 0.001). On multivariate analysis, the CC score and the original site were independent prognostic factors for OS (p = 0.04 and 0.02, respectively). CONCLUSION: In patients with PC-CRC, malignant ascites and PCI > 20 are poor prognostic factors associated with failure to accomplish CRS with consequent poor survival.

The Role of Genetic Polymorphisms in Nrf2 and P73 in Egyptian Women with Breast Cancer

Background: Breast cancer is the commonest cancer in Egyptian females. Nrf2 is involved in oxidative stress while P73 functions in response to DNA damage. This study aimed to assess the role of Nrf2 promoter and P73 G4C14 to A4T14 SNPs in breast cancer in Egypt. Patients: Eighty-five female patients with breast tumours (41 malignant, 44 benign) were included. Nrf2 (rs6721961) and p73 (G4A) SNPs were determined by PCR- CTPP assay. Results: Genotype frequencies of the Nrf2 promoter SNP were 34.2% and 37.9% for AA in benign and malignant groups respectively, and 43.9% and 40.5% for CC and, 21.9 % and 21.6% for CA. Genotype frequencies for the P73 G4A SNP were 52.9% and 44.7% for GA in benign and malignant groups respectively, and 47.1% and 55.3% for GG. Discussion: Nrf2 genotypes in pre - and post-menopausal patients, showed significantly different distributions in the 2 patient groups, the AA genotype being significantly more common in pre-menopausal patients. The P73 G4A SNP showed no relation to age of disease onset. Conclusion: The Nrf2 (rs6721961) AA genotype might be related to early breast cancer onset. In contrast the P73 G4A polymorphism showed no relation to either disease risk or age at presentation.

The role of S100P and IMP3 in the cytologic diagnosis of pancreatic adenocarcinoma.

PURPOSE: The aim of this study was to assess the role of the two markers, S100P and IMP3, in differentiating between pancreatic ductal adenocarcinoma (PDA) and non-neoplastic pancreatic tissue in (fine needle aspiration cytology) FNAC. PATIENTS AND METHODS: This is a retrospective study that included 72 cases presented with pancreatic mass, where endoscopic guided FNAC was taken from pancreatic lesions. The final histopathologic diagnosis was considered the gold standard. Cell blocks were stained with anti S100P, and IMP3. Nuclear immunoreactivity with or without cytoplasmic staining for the first marker, and cytoplasmic staining for the second marker was considered specific. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and total accuracy of the two markers, as well as the combined accuracy of both markers were calculated. RESULTS: S100P achieved 96.4% sensitivity, 93.3% specificity, 98.2% PPV, 87.5% NPV and 95.8% total accuracy, while IMP3 achieved 91.2% sensitivity, 86.7% specificity, 96.2% PPV, 72.2% NPV and 90.3% total accuracy for PDA. Both markers showed a total combined accuracy of 89%. S100P showed strong and diffuse staining pattern in most of cases, while the staining pattern for IMP3 was moderate and focal in most of cases. CONCLUSION: Both markers were sensitive and specific for diagnosis of PDA. The staining pattern for S100P was easier to evaluate than IMP3.

Treatment Outcomes of Epithelial Ovarian Cancers Following Maximum Cytoreduction and Adjuvant Paclitaxel-Carboplatin Chemotherapy: Egyptian NCI Experience.

BACKGROUND: Epithelial ovarian cancer (EOC) is the commonest malignancy involving the ovaries. Maximum surgical cytoreduction (MCR) followed by adjuvant taxane-platinum chemotherapy are the standard of care treatments. AIMS: To study treatment outcomes of EOC patients that were maximally cyto-reduced and received adjuvant paclitaxel-carboplatin (PC) chemotherapy. MATERIALS AND METHODS: This retrospective cohort study included 174 patients with EOC treated at the Egyptian National Cancer Institute between 2006 and 2010. For inclusion, they should have had undergone MCR with no-gross residual followed by adjuvant PC chemotherapy. MCR was total abdominal hysterectomy/bilateral salpingo-oophorectomy [TAH/BSO] or unilateral salpingo- oophorectomy [USO] plus comprehensive staging. RESULTS: The median age was 50 years. Most patients were married (97.1%), had offspring (92.5%), were postmenopausal (53.4%), presented with abdominal/pelvic pain and swelling (93.7%), had tumors involving both ovaries (45.4%) without extra-ovarian extension i.e. stage I (55.2%) of serous histology (79.9%) and grade II (87.4%). TAH/BSO was performed in 97.7% of cases. A total of 1,014 PC chemotherapy cycles were administered and were generally tolerable with 93.7% completing 6 cycles. Alopecia and numbness were the commonest adverse events. The median follow up period was 42 months. The 2-year rates for disease free survival (DFS) and overall survival (OS) were 70.7% and 94.8%, respectively. The respective 5-year rates were 52.6% and 81.3%. Advanced stage and high-grade were significantly associated with poor DFS and OS (p<0.001). Age >65 years was associated with poor OS (p =0.008). Using Cox-regression, stage was independent predictor of poor DFS and OS. Age was an independent predictor of poor OS.

Role of Ki67 in predicting resistance to adjuvant tamoxifen in postmenopausal breast cancer patients.

INTRODUCTION: Breast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology. AIM: To correlate the expression of Ki67 with the clinical outcomes of early hormone-receptor positive postmenopausal BC patients who are receiving tamoxifen. METHODS: This cohort study included 70 patients. They were followed up for a minimum of 2 years. Ki67 was assessed on paraffin-embedded blocks using immunohistochemistry methods. RESULTS: The median Ki67 value was 22.5% (IQR, 10%-50%). Ki67 was significantly higher in patients with HER2 positive tumors compared to HER2 negative tumors. After a median follow up period of 53 months, 22 patients (31%) developed disease recurrence either loco-regional or distant in 5.7% and 30%, respectively. Recurrent patients had significantly higher tumor stage, nodal stage and Ki67 values compared to non-recurrent cases. The 2-, 3- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 100% & 91%, 98% & 84% and 77% & 59%, respectively. DFS was significantly worse with higher TNM stage, lower ER expression and higher Ki67 values. OS was significantly worse in patients with Ki67 values ≥ 30%. Ki67 ≥ 30% was an independent predictor of recurrence, poor DFS and OS. CONCLUSION: High Ki67 expression is predictive of poor prognosis and of resistance to adjuvant tamoxifen therapy in postmenopausal BC. We recommend considering Ki67 as one of the risk factors that guide adjuvant treatment decisions.

An in vitro comparison of cast metal dowel retention using various luting agents and tensile loading.

STATEMENT OF PROBLEM: No clear consensus exists regarding the choice of luting agents for the retention of cast metal dowels used as a treatment alternative for endodontically treated teeth with excessive loss of coronal tooth structure. PURPOSE: The purpose of this in vitro study was to investigate the retention of the dowel/luting agent/tooth complex while applying different luting agents to cast metal dowels under vertical tensile loading. MATERIAL AND METHODS: Sixty extracted, noncarious mandibular premolars with roots of approximately 15-mm length were selected. For each tooth, a tapered root canal preparation was completed to a maximum diameter of 1.60 mm and a length of 11 mm, a common clinical configuration to accommodate cast metal dowels. Sixty cast metal dowels were fabricated for the tooth specimens and cemented with 1 of 3 luting agents (n = 20): zinc-phosphate cement (ZPC) as a control, phosphate-methacrylate resin luting agent (PMRL, Panavia F), and phosphate-methacrylate resin luting agent with metal dowel surfaces modified with a silane coating technique (PMRLS, Panavia F + Siloc). Tensile bond strength (TBS) of the specimens was measured with a universal testing machine at a crosshead speed of 0.5 mm/min. Data (kg) were statistically analyzed using a 1-way analysis of variance and a Scheffe multiple range test (alpha=.05). The homogeneity of variances was analyzed using the Levene test. RESULTS: The TBS values of ZPC (34.2 +/- 10.54 kg) were significantly higher than PMRL (22 +/- 9.57 kg) and PMRLS (21.7 +/- 7.64 kg). There was no significant difference between the PMRL and PMRLS groups. CONCLUSION: Within the limitations of this study, the use of zinc-phosphate cement provided greater TBS for cast metal dowels than the resin luting agent with and without the silane coating technique. The TBS values with and without the silane coating technique were not statistically different.