Bladder preservation by neoadjuvant chemotherapy followed by concurrent chemoradiation for muscle-invasive bladder cancer.

Introduction: In Egypt, bladder cancer (BC) represents about 8.7% of cancers in both sexes. In Egyptian men, it accounts for over 30% of all cancers, which makes it the second most frequent cancer. The standard curative treatment for patients with muscle-invasive bladder cancer (MIBC) has been radical cystectomy (RC) with urinary diversion and pelvic lymphadenectomy. Concomitant chemoradiation therapy (CCRT) in MIBC appears to produce results that are comparable to those of RC. Material and methods: Between January 2018 and March 2021, 34 BC- diagnosed patients, who refused RC, were enrolled. They received transurethral resection of the bladder tumour (TURBT) followed by 3 cycles of neoadjuvant chemotherapy (NACT) with gemcitabine, cisplatin, and CCRT. Concomitant chemoradiation therapy with cisplatin, as a chemosensitizer, was administered to patients who experienced a complete response (CR) and a partial response (PR) ≥ 50%. Results: Following NACT, CCRT was given to 27 patients (79.45%) who had either a PR > 50% or CR. Seven patients (20.5%) showed PR below 50%, stable disease, or progressive disease; 4 of them underwent RC followed by postoperative radiation. The average follow-up period was 46 months (range: 6-52 months). Twenty-three patients (67.6%) were still alive at the last check-up. Disease-free survival and 3-year overall survival were 70.8% and 65.1%, respectively. Conclusions: Bladder preservation provides survival rates comparable to those of MIBC patients, but with a higher quality of life. The findings show good survival rates without metastasis; nevertheless, more multicentre trials with larger sample sizes and longer follow-up periods are required to confirm these findings.

Outcome of docetaxel in treatment of metastatic hormone-sensitive prostate cancer and correlation with hemoglobin, albumin, lymphocyte and platelets score.

Introduction: We aimed to evaluate the outcome of treatment with docetaxel plus androgen deprivation therapy (ADT) in newly diagnosed patients with metastatic high tumor burden hormone-sensitive prostate cancer (mHSPC) and correlated the outcome with hemoglobin, albumin, lymphocyte and platelets (HALP) score. Material and methods: Six cycles of docetaxel plus ADT were given to 50 patients with high burden mHSPC. Baseline HALP score was calculated and disease outcome was tabulated; moreover, the prognostic impact of the HALP score in response to treatment and survival was calculated. Results: We found a significant association between high HALP score and response to treatment where a higher rate of complete response occurred in patients with a high HALP score than in patients with a low HALP score (53.8% vs. 5.4% respectively, p-value = 0.001). Patients with ≥ 12-month-duration castration-resistant prostate cancer (CRPC) had a significantly higher HALP score compared to patients with a lower HALP score (84.6% vs. 35.1% respectively, p-value = 0.002); 18-month-duration CRPC-free survival was significantly greater in patients with higher HALP score than patients with a lower HALP score (23.1% and 5.4% respectively, p-value < 0.001). Patients with a high HALP score had insignificantly higher mean overall survival than patients with a low HALP score (mean: 22.91 and 20.66 months respectively, p-value = 0.230). Conclusions: Our results confirmed the benefits of treatment with docetaxel plus ADT in high-burden mHSPC with accepted tolerance. HALP score was found to be an independent predictive factor for benefit from therapy; we can apply it as an easy way to stratify patients for appropriate selection of treatment for better tolerance and outcome.

Prognostic significance of lymphocyte-to-monocyte ratio in patients with classical Hodgkin lymphoma before and after receiving first-line chemotherapy.

Introduction: Despite the presence of a prognostic risk stratification sco-ring system for Hodgkin lymphoma (HL), the lymphocyte-to-monocyte ratio (LMR) is a simple and low-cost test that has been investigated as a prognostic marker to evaluate the clinical course and survival outcomes. Material and methods: We prospectively enrolled 92 patients with classical HL (CHL), who were diagnosed and treated in the period from April 2017 to April 2020. Lymphocyte monocyte ratio cut-off values were estimated using receiver operating characteristic curves. Results: We found that patients with LMR < 1.4 at the time of diagnosis had poorer progression-free survival (PFS) and overall survival (OS) than those with LMR > 1.4. Patients with increased LMR values after the first 2 cycles of chemotherapy had better PFS and OS; meanwhile, patients who had low LMR after the end of chemotherapy had poorer PFS and OS in comparison to patients who gained higher value after the completion of all cycles of chemotherapy. Conclusions: A rise of LMR value indicated better outcome and better survival rate, so it can be an independent prognostic factor for survival and to predict outcome in patients with CHL.

Clinical significance of cytokeratin 19 and OCT4 as survival markers in non-metastatic and metastatic breast cancer patients.

Introduction: Cytokeratin 19 (CK19) is highly expressed in epithelial tumours such as breast cancer (BC). Octamer-binding transcription factor 4 (OCT4), a transcription factor of the POU (Pit-Oct-UNC) family, plays a criti-cal role in the self-renewal and maintenance of pluripotency of embryonic stem cells; therefore, it has been used as a promising CSC marker. Material and methods: CK19 was assessed in peripheral blood using flow-cytometric analysis while OCT4 was evaluated in breast tissue samples by immunohistochemistry from 70 patients (non-metastatic BC, meta-static BC, and non-malignant breast tumours). Results: CK19 and OCT4 were significantly associated with BC patients compared to control (p < 0.001). CK19 was detected in 38 patients with BC (62.2%); meanwhile, OCT4 was positive in 37 BC patients (60.6%). CK19 was positively associated with grade (p = 0.002), HER2 (p = 0.009), metastasis (p = 0.026), molecular subtypes and LN (p < 0.001), and stage (p = 0.001) while OCT4 expression was positively associated with BMI (p < 0.023), aggressive molecular subtype (p < 0.019), ER expression (p = 0.025), presence of LN metastases (p < 0.017), and distant metastasis (p < 0.018). A non-significant relation was found between the expression of CK19 and OCT (p = 0.291). The positive expression of CK19 and OCT4 was significantly and inversely associated with both 3-year OS and 3-year PFS. Conclusions: CK19 and OCT4 are associated with BC, so they can be considered as prognostic and predictive markers for poor OS and PFS in non-metastatic as well as metastatic BC patients.

Choosing the Appropriate Individualized Adjuvant Chemotherapy in Stage III Colon Cancer Patients Under and Over 70 Years.

BACKGROUND: Colon cancer is one of the leading causes of cancer-related deaths worldwide. The increased incidence of comorbid diseases in elderly patients above 70 leads to the need of less aggressive strategies to be used in the adjuvant setting of stage III colon cancer. METHOD: Our prospective cohort study was performed in the period from April 2017 to March 2020. Seventy-five patients with newly diagnosed stage III colon cancer received adjuvant chemotherapy after surgery. Patients who either received adjuvant chemotherapy less than 3 months due to intolerability or toxicity from medications or who have more than one type of cancers or metastatic disease from the start were excluded from the study. Patients' clinicopathological characteristics in relation to oxaliplatin- and non-oxaliplatin-based chemotherapeutic regimens were analyzed with survival assessment. RESULTS: In our study, patients above 70 had better overall survival (OS) in the non-oxaliplatin chemotherapy group (p-value = 0.032) in contrast to OS in patients under 70 which was better in the oxaliplatin group (p-value < 0.001). By comparing the OS between the two age groups, the OS was better in patients < 70 years (p-value = 0.001). Additionally, we found that the DFS in patients above 70 was better in oxaliplatin-based regimens than in the non-oxaliplatin group (p-value = 0.011) with better survival rates (81.8% vs 15.7%), and markedly high DFS in patients under 70 for oxaliplatin based regimens (p-value < 0.001), with survival rates (31.1% vs 0%). By comparing the DFS between the two age groups, the DFS was better in patients < 70 years (p-value < 0.001). The disease recurrence was in favor of the non-oxaliplatin group with significant p-value = 0.003, while mortality occurred more in the oxaliplatin group (p-value < 0.001). CONCLUSIONS: The appropriate selection of a personalized strategy for treatment of stage III colon cancer plays an important role in the outcome of the disease. Our findings supported the use of oxaliplatin-based chemotherapy as a standard treatment option in the adjuvant management of stage III colon cancer patients in all age groups. The benefit of non-oxaliplatin-based chemotherapy was limited to patients above 70 which might be an effective option for elderly patients.

Prognostic Significances of NEDD-9 and FOXL-1 Expression in Intestinal Type Gastric Carcinoma: an Immunohistochemical Study.

BACKGROUND: Gastric cancer (GC) is mostly diagnosed at advanced stage, so prognosis is poor. Therefore, it is necessary to understand the molecular mechanism of GC development to design new targeted treatment to improve the prognosis of gastric cancer patients. AIM OF THE WORK: To assess the prognostic value of NEDD-9 and FOXL-1 expression in intestinal type gastric cancer patients, as well as their relationship to clinicopathologic features of the disease and patients outcome. PATIENTS AND METHODS: This is a retrospective study; we included 50 sections from formalin-fixed, paraffin-embedded tissue samples which included intestinal type GC and adjacent non-neoplastic gastric mucosa in the same block that were subjected to immunohistochemistry with anti-NEDD-9 and anti-FOXL-1 antibody. Patients were retrospectively followed up for about 5 years for assessment of tumor progression and survival in relation to marker expression. RESULTS: High NEDD-9 and low FOXL-1 expression were found in intestinal type GC more than adjacent non-neoplastic mucosa (p < 0.001). NEDD-9 high expression and FOXL-1 low expression were associated with presence of helicobacter pylori gastritis (p = 0.010, 0.049), high grade (p = 0.007, 0.004), high stage (p < 0.001), presence of distant metastases (p = 0.029, 0.021), poor DFS (p = 0.003), and OS rates (< 0.001). CONCLUSION: NEDD-9 overexpression and FOXL-1 deficiency in intestinal type GC can help in prediction of tumor prognosis and it can guide the selection of patients for future therapies in gastric carcinoma.

Tolerability and outcome of sunitinib by giving 4/2 schedule versus 2/1 schedule in metastatic renal cell carcinoma patients: a prospective randomized multi-centric Egyptian study.

INTRODUCTION: Sunitinib is a standard of care first line treatment for patients with metastatic renal cell carcinoma (RCC). Sunitinib standard dose is 50 mg once daily for 4 consecutive weeks followed by 2 weeks' off (4/2 schedule). Long-term and high exposure to this medication lead to severe adverse events (AEs); therefore, this trial was done to find the best schedule which gives the best outcome with minimal toxicity. MATERIALS AND METHODS: Seventy patients were randomly assigned into 2 groups, then received 50 mg/day of sunitinib. Group 1 (40 patients) received sunitinib for 4 consecutive weeks followed by 2 weeks off (4/2 schedule) while 30 patients were admitted to group 2 with 2 weeks on and 1 week off (2/1 schedule). RESULTS: All patients (100%) had significantly higher AEs on schedule 4/2 vs. 73.3% on schedule 2/1 (p = 0.001). Furthermore, the grade 3 AEs on schedule 2/1 were significantly lower than those on schedule 4/2 (26.7% vs. 82.5%) respectively (p = 0.001), such as fatigue, diarrhea, hypertension, hand foot syndrome (HFS) and mucositis. Progression-free survival (PFS) rate was significantly higher in 2/1 schedule (60.9% vs. 38.6%) than in 4/2 schedule (p < 0.008). Multivariate analysis suggested that: age > 60 years, poor International Metastatic RCC Database Consortium (IMDC) risk category, tumor size > 10 cm and treatment schedule (group 1) were poor prognostic factors of PFS. CONCLUSIONS: Our study supported the use of 2/1 schedule of sunitinib in patients with metastatic RCC because of lower toxicity profile and better efficacy with improved PFS in comparison to 4/2 schedule.

The utility of diffusion-weighted imaging in improving the sensitivity of LI-RADS classification of small hepatic observations suspected of malignancy.

PURPOSE: We investigated the added value of diffusion-weighted imaging (DWI)/apparent diffusion coefficient (ADC) in the categorization of small hepatic observation (≤ 20 mm) detected in patients with chronic liver disease in reference to LI-RADS (liver imaging reporting and data system) classification system. METHODS: We prospectively evaluated 165 patients with chronic liver disease with small hepatic observations (≤ 20 mm) which were previously categorized as LI-RADS grade 3-5 on dynamic contrast-enhanced CT (DCE-CT). All patients were submitted to a functional MRI including DCE and DWI. Using LI-RADS v2017, two radiologists independently evaluated the observations and assigned a LI-RADS category to each observation using DCE-MRI alone and combined DCE-MRI and DWI/ADC. In the combined technique, the radiologists assigned a LI-RADS category based on a modified LI-RADS criteria in which restricted diffusion on DWI was considered a major feature of HCC. We evaluated the inter-reader agreement with Kappa statistics and compared the diagnostic performance of the LI-RADS with two imaging techniques by Fisher's exact test using histopathology as the reference standard. RESULTS: Combined technique in LI-RADS yielded better sensitivities (reader 1, 97% [65/67]; reader 2, 95.5% [64/67]) for HCC diagnosis than DCE-MRI alone (reader 1, 80.6% [54/67], p = 0.005; reader 2, 83.6% [56/67], p = 0.04). The specificities were insignificantly lower in combined technique (reader 1, 88.4% [107/121]; reader 2, 77.7% [94/121]) than in DCE-MRI alone (reader 1, 90.9% [110/121], p = 0.67; reader 2, 79.3% [96/121], p = 0.88). The inter-reader agreement of the LI-RADS scores between combined technique and DCE-MRI was good (κ = 0.765). CONCLUSION: The use of DWI/ADC as an additional major criterion, improved the sensitivity of LI-RADS in the diagnosis of HCC while keeping high specificity.

Prognostic and Clinic-Pathological Significances of SCF and COX-2 Expression in Inflammatory and Malignant Prostatic Lesions.

The initiation of prostatic malignancy has been linked to chronic inflammation. Stem cell factor (SCF) is an inflammatory cytokine that is specific to the c-KIT receptor which is type III receptor tyrosine kinase (RTK). Cyclooxygenases (COXs) are the main enzymes which are responsible for prostaglandins production from arachidonic acid. COX2 is an enzyme which is produced under different pathological conditions. The aim of our study; is to investigate the clinicopathological and the prognostic significance of SCF and COX-2 expression in prostatic adenocarcinoma (PC), chronic prostatitis and nodular prostatic hyperplasia (NPH) in a trial to clarify the role of inflammation as a risk factor for prostatic carcinogenesis and cancer progression. SCF and COX-2 tissue protein expression were evaluated in 50 cases of PC, 20 cases of chronic prostatitis and 10 cases of NPH using immunohistochemistry, patients were followed up for 5 years. The relationship between their levels of expressions, clinicopathological, and prognostic criteria were studied. SCF expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.010), higher Gleason score (p = 0.011). COX-2 expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.016), advanced D'Amico risk group (p = 0.038). High levels of expression of both SCF& COX-2 are associated with higher incidence of tumor relapse, worse disease overall survival and free survival (p < 0.001). SCF and COX-2 are associated with PC progression and associated with poor prognosis in PC patients.

SPOP, ZEB-1 and E-cadherin expression in clear cell renal cell carcinoma (cc-RCC): Clinicopathological and prognostic significance.

BACKGROUND: Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane. AIM: Was to assess the tissue protein markers SPOP, ZEB1 & E-cadherin expressions in benign areas of neoplastic kidney specimens and in cc-RCC patients, then correlating their expression levels with patients clinicopathological and prognostic data. METHODS: We evaluated SPOP, ZEB-1 & E-cadherin expression using immunohistochemistry in samples from 50 cc-RCC and 20 benign areas of neoplastic kidney specimens, then we followed our patients for 5 years and finally we have analyzed correlations between the levels of markers expressions with patients clinicopathological and prognostic criteria in cc-RCC. RESULTS: Positive expression of SPOP & ZEB1 in addition to negative E- cadherin expression was detected in cc-RCC more than benign areas of neoplastic kidney specimens (p = 0.004 and p < 0.001 respectively). In cc-RCC Positive expression of SPOP, ZEB1 and negative E- cadherin expression was associated with higher grade (p = 0.006, 0.007 & <0.001 respectively), advanced AJCC stage (p = 0.013, 0.023 & <0.001 respectively), presence of L.N metastases (p = 0.002 = 0.010 and <0.001 respectively), distant metastases (p = 0.001, 0.003 & 0.035 respectively), poor PFS and OS rates (p < 0.001 and p = 0.013 respectively). CONCLUSION: Positive expression of SPOP& ZEB1 in addition to negative E- cadherin are associated with poor prognosis in cc-RCC patients.