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.

Management of ST-segment elevation myocardial infarction in comparison to European society of cardiology guidelines in Alexandria University Hospitals, Egypt.

BACKGROUND: For patients with ST-elevation myocardial infarction (STEMI), early reperfusion with primary percutaneous coronary intervention (PPCI) or thrombolytic treatment is essential to prevent major adverse cardiac events. The aim of the study is to compare the current status of managing STEMI patients at **** with European Society of Cardiology guidelines recommendations. Prospective cohort of all patients presenting with ST-elevation myocardial infarction (STEMI) between March 2020 and February 2021 in Alexandria University hospitals. Reporting patterns, causes of delay, and reperfusion status for all STEMI patients were noted. MACE: (Mortality, Re-infarction, Stroke, or Heart failure) was reported and compared among different management strategies. RESULTS: The study was conducted over one year on 436 patients, 280 (64.2%) of them underwent PPCI, 32 (7.3%) received thrombolysis, and 124 (28.5%) had a conservative strategy. Patients' mean age was 55.2 years, 72.2% were smokers and 80.9% were men. Family history was positive in 14.2% of patients, 33.5% had diabetes, 7.3% had renal impairment, and 41.5% had hypertension. The median pre-hospital waiting time was 360 min; the mean pre-hospital waiting time was 629.0 ± 796.7 min. The median Emergency Room waiting time was 48.24 ± 89.30 min. The median time from CCU admission to wire crossing was 40.0 min with a mean value 53.86 ± 49.0 min. The mean ischemia duration was 408 min, while the total ischemic time was 372 min. All patients who presented within 12 h received reperfusion therapy either a PPCI or thrombolysis at a rate of 71.5%, with 35.0% of those patients achieving prompt reperfusion in accordance with ESC guidelines. The PPCI group mortality rate was 2.9%, in comparison to 12.9% in the conservative group, which was statistically significant (P < 0.001). Overall in-hospital mortality was 5.5%, and total MACE was 27.3%. A statistically significant difference was observed between the three management groups as regards MACE rate, being 15%, 28.1%, and 54.8% in PPCI, thrombolysis, and conservative groups, respectively. CONCLUSIONS: Despite financial and technical constraints, appropriate, timely reperfusion was near to achieving the ESC guidelines for the management of STEMI. The most common reperfusion strategy was PPCI, with an in-hospital death rate of less than 5% in the PPCI group. There was a concern about the increase in the total ischemia time due to some financial and technical constraints.

Long-term effects of percutaneous coronary intervention versus coronary artery surgery in elderly with multi-vessel coronary artery disease.

BACKGROUND: The most prevalent illness among the elderly is coronary artery disease (CAD), and most of this population present with multi-vessel CAD which constitutes a common management difficulty among elderly people. This study aimed to compare long-term consequences of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) revascularization in elderly patients with multi-vessel coronary artery disease. RESULTS: This retrospective study evaluated 100 elderly patients with multi-vessel CAD divided into two groups, group 1 the PCI group and group 2 the CABG group. The main findings of the study showed that CABG group had a longer hospital stay than the PCI group (8.16 vs. 2.02 days; P < 0.001). A considerably higher mean residual SYNTAX score was observed in the PCI group than CABG group which was 1.15 and 0.2, respectively (p-value < 0.001). The in-hospital major adverse cardiac events rate (MACE) in both groups was not statistically significant. Regarding the in-hospital mortality rate, although it was higher in the CABG group (6%) versus 2% in the PCI group, yet it was not statistically significant. The long-term MACE in this study revealed that 12.2% of PCI patients had heart failure compared to 6.4% in the CABG group, which was statistically insignificant. In the long-term follow-up, the revascularization rate of CABG group was higher than the PCI group; however, it was statistically insignificant. CABG group had a higher rate of stroke than PCI group being 4.3% and 2%, respectively; yet this difference was not statistically considerable. The long-term mortality rate among the PCI and CABG group was 10.2% and 4.3%, respectively. CONCLUSIONS: Elderly patients with multi-vessel CAD, PCI with stenting, and CABG were statistically equivalent in long-term death and MI rates, stroke, repeat revascularization. A non-statistically notable distinction between the two groups as regards MACE, composite of death or MI, and all-cause mortality was found. This may have implication on choice of management strategy among elderly patients with multi-vessel CAD.

Optimum duration of ureteral prestenting dwelling time in children undergoing retrograde intrarenal surgery.

INTRODUCTION AND OBJECTIVES: Ureteral prestenting before retrograde intrarenal surgery (RIRS) causes passive dilatation of the ureter, improves stone-free rate and is associated with shorter operative time. However, the presence of a ureteric stent may increase the risk for septic complications, which accelerates with increased dwelling time duration. The aim of the present study is to explore the impact of ureteral prestenting timing in a group of children undergoing retrograde intrarenal surgery (RIRS) on perioperative outcomes and complication rates and to define the optimum duration of prestenting dwelling time. PATIENTS AND METHODS: A retrospective study on 60 children aged less than 14 years, presented with upper tract urinary stones, who were subdivided into two groups: Group 1 and 2, each included 30 children who had undergone RIRS after ureteric stenting for two weeks and four weeks respectively. Success of ureteroscope introduction, operative time, stone free rate (SFR), intraoperative and postoperative complications and number of retreatment procedures after definitive RIRS were recorded and compared between the two treatment groups. RESULTS: Ureteric access was successfully obtained in all children in both groups. Patients in group 1 and 2 had a SFR of 86.6% and 90%, respectively (p = 0.199). The mean operative time of group 1 and 2 were 56.5 and 52.9 min (p = 0.612). Postoperative UTI rates increased with prolonged dwelling time from 6.7% in group 1 to 30% in group 2. No patient in both groups developed high grade complications. CONCLUSIONS: Increasing prestenting dwelling time from two to four weeks had no statistically significant effect on the successful ureteroscopic access nor the stone free rate in children undergoing RIRS. Reducing the ureteric stent dwelling time minimizes the rate of postoperative UTI without compromising the success of operative outcomes.

Klotho (rs1207568 and rs564481) gene variants and colorectal cancer risk.

BACKGROUND/AIMS: Whereas colorectal cancer (CRC) is the third most common cancer worldwide, klotho gene has been reported as a tumor suppressor gene. Therefore, the aim of this study was to investigate the association between klotho (rs1207568 and rs564481) variants and CRC in Egyptian patients. MATERIALS AND METHODS: A case-control study comprising 100 patients with CRC and 100 age- and sex-matched healthy controls was conducted. Genotyping of klotho was performed by polymerase chain reaction with confronting two-pair primers. RESULTS: The frequencies of the A allele of rs1207568 and the AC haplotype were significantly higher in patients with CRC than in the controls (p=0.019 and p=0.005, respectively). CONCLUSION: We propose that klotho (rs1207568 and rs564481) variants play a significant role in colorectal carcinogenesis and that the klotho protein could be a target for oncotherapy.

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.

Methods of Treatment and Outcome for Ovarian Germ Cell Tumors.

Ovarian germ cell tumors account for about 15-20% of all ovarian tumors. They occur mainly in girls, adolescents, and young adults. This study aims to assess the different clinico-pathological factors of ovarian germ cell tumors, treatment methods, and outcome. This is a retrospective observational cohort study including 54 cases with OGCTs which were studied from the period between January 2013 and December 2016. The study was performed at National Cancer Institute (NCI)-Cairo University, Egypt. All cases had cytoreductive surgery in the form of unilateral salpingo-oophorectomy in 42 cases and total abdominal hysterectomy in 12 cases. Complete cytoreduction was achieved in 46 cases while 8 cases had residual disease after surgery. Adjuvant chemotherapy was given in 26 cases (stage II, III, and IV malignant OGCTs). The main treatment of ovarian germ cell tumors is complete cytoreductive surgery which can be achieved in many cases with unilateral salpingo-oophorectomy. Adjuvant chemotherapy is highly recommended in case of malignant ovarian germ cell tumors.

Hyperthermic Intraperitoneal Chemotherapy as a Treatment for Epithelial Ovarian Cancer.

Treatment by cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has been an option for selected patients with peritoneal carcinomatosis. This study aims to evaluate the impact of HIPEC in epithelial ovarian cancer (EOC). A retrospective observational cohort study including 48 EOC patients treated and followed up between 2012 and 2016. Thirty-seven cases were treated by CRS only, while 11 cases were treated by CRS and HIPEC. The study was performed at National Cancer Institute (NCI)-Cairo University. There was no statistically significant difference regarding overall survival or disease-free survival between the group of EOC patients treated by CRS only and the one treated by CRS and HIPEC. Presence of ascites and histological types (serous/non-serous) were the significant independent variables related to overall survival. Presence of ascites was the only independent variable associated with a significant relation to disease-free survival. No statistically significant impact of HIPEC in treatment of EOC was found in this study.

Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as a treatment for recurrent epithelial ovarian cancer-National Cancer Institute experience.

BACKGROUND: Complete cytoreduction has been associated with survival benefit in the treatment of recurrent epithelial ovarian cancer (EOC). In this study, the aim is to investigate the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of recurrent EOC. PATIENTS AND METHODS: This is a descriptive (case series) study including 9 patients with recurrent EOC treated by CRS and HIPEC. They were treated and followed up between December 2011 and December 2017. The study was performed at The National Cancer Institute (NCI) - Cairo University (CU). RESULTS: Postoperative death occurred in 2 cases, while recurrence occurred in one case. Six cases had smooth postoperative course and free follow-up. Median follow-up period was 39 months, ranging from 29 to 47 months. Median overall survival was 42 months while median disease-free survival was not reached. CONCLUSIONS: Treatment of recurrent EOC by CRS and HIPEC appears to be promising. However, this line of treatment requires further evaluations and larger studies for better assessment of the potential survival benefits and possible complications.

Incidence and outcome of cardiac injury in patients with severe head trauma.

BACKGROUND: Although cardiac injury has been reported in patients with various neurological conditions, few data report cardiac injury in patients with traumatic brain injury (TBI). The aim of this work is to report the incidence of cardiac injury in patients with TBI and its impact on patient outcome. METHODS: A prospective observational study was conducted on a cohort of 50 patients with severe TBI. Only patients with isolated severe TBI defined as Glascow coma scale (GCS) < 8 were included in the study. Acute physiology and chronic health evaluation (APACHE) II score, GCS, hemodynamic data, serum Troponin I, electrocardiogram (ECG), and echocardiographic examination, and patients' outcome were recorded. A neurogenic cardiac injury score (NCIS) was calculated for all patients (rising troponin = 1, abnormal echocardiography = 1, hypotension = 1). Univariate and multivariate analyses for risk factors for mortality were done for all risk factors. RESULTS AND DISCUSSION: Fifty patients were included; age was 31 ± 12, APACHE II was 21 ± 5, and male patients were 45 (90 %). Troponin I was elevated in 27 (54 %) patients, abnormal echocardiography and hypotension were documented in 14 (28 %) and 16 (32 %) patients, respectively. The in-hospital mortality was 36 %. Risk factors for mortality by univariate analysis were age, GCS, APACHE II score, serum troponin level, NCIS, and hypotension. However, in multivariate analysis, the only two independent risk factors for mortality were APACHE II score (OR = 1.25, 95 % confidence interval: 1.02-1.54, P = 0.03) and NCIS score (OR = 8.38, 95 % confidence interval: 1.44-48.74, P = 0.018). CONCLUSIONS: Cardiac injury is common in patients with TBI and is associated with increased mortality. The association of high NCIS and poor outcome in these patients warrants a further larger study.