Asmaa Salama

Outcome of Muscle-Invasive Urothelial Bladder Cancer After Radical Cystectomy

UNLABELLED We aimed at clarification of reasons for recurrence of urothelial carcinoma after radical cystectomy in a retrospective study that included 189 patients. Presence of lymphovascular invasion even in node-negative cases, high tumor grade, and high nodal stage appeared to be independent predictors for recurrence. This raises the necessity for postoperative multimodality treatment to improve disease-free survival. BACKGROUND Radical cystectomy remains the gold standard for local control of muscle-invasive bladder cancer. Despite that, a significant proportion of patients develop disease recurrence. Several predictors for recurrence have been described and the implication of such factors on development of recurrence will help in modification of treatment strategies to improve the prognosis of bladder cancer patients. PATIENTS AND METHODS This is a retrospective study carried on patients with muscle-invasive urothelial carcinoma who underwent radical cystectomy at the National Cancer Institute in 3 years; January 2007 to December 2009, and analyzed for the development of recurrence and potential risk factors. RESULTS The 3-year disease-free survival (DFS) rate was 56%. Seventy patients (37%) developed disease recurrence during the follow-up period. Of these recurrences, 17 patients (24.3%) developed local and/or regional recurrences, 45 patients (64.3%) developed distant metastasis, and 8 patients (11.4%) developed local and/or regional and distant recurrences. In univariate analysis, lymph node metastasis (P < .001), lymphovascular invasion (LVI) (P < .001), high grade (P = .005), and advanced tumor stage (P = .002) were significantly associated with development of recurrence. In multivariate analysis, lymph node metastasis, LVI, and high grade were significantly associated with tumor recurrence and poor DFS. CONCLUSION Lymph node metastasis, LVI, and high tumor grade were independent prognostic factors that affected tumor recurrence and DFS. LVI status should be reported in radical cystectomy specimens to help in risk assessment of patients especially in node-negative cases.

A case of synchronous double primary breast carcinoma and osteosarcoma: Mismatch repair genes mutations as a possible cause for multiple early onset malignant tumors

Summary Background: Simultaneous or consequent development of multiple solid tumors might be faced in some patients, especially the young. These tumors might be related to certain hereditary cancer syndromes or certain genetic predispositions. Case Report: We present the case of a 19-year-old woman with metastatic breast cancer to the contralateral axillary lymph node, associated with simultaneous osteosarcoma of the left lower femur. As she did not fit into any of the familial cancer syndromes, genetic predisposition was suspected. We detected MLH1 and MSH2 promotor methylation (PM), microsatellite instability (MSI), and different mutational events in both tumors. BRCA1 gene mutations were detected in the breast tumor, with reduced mRNA expression of BRCA1&2. ERCC1, MLH1 and MSH2, especially in OS, and RRM1 was overexpressed in both tumors. Conclusions: Aberrations in MMR genes could explain simultaneous or consequent development of multiple solid tumors, especially in a young patient. We recommend detecting these defects, close follow-up for those patients, and genetic counseling for their family members. Further studies in a larger population are essential to support our results.

TAp73 and ΔNp73 relative expression in Egyptian patients with lymphoid neoplasms.

Background and aims The p73 gene has different isoforms with opposing anti- and pro-apoptotic functions. The pro-apoptotic activities are inhibited by overexpression of the dominant ΔNp73 isoform. The aim of this study was to detect the expression of the TAp73 and ΔNp73 isoforms in Egyptian patients with malignant lymphoid neoplasms. Their expression was analyzed by quantitative RT-PCR. Patients and Methods The study included 30 B-NHL patients, 24 T-NHL patients, 16 ALL patients, 18 CLL patients, 22 patients with reactive lymphoid hyperplasia, and 6 healthy control subjects. Results ALL and CLL patients expressed both isoforms at higher levels compared to lymphoma patients. Higher expression of TAp73 was found in both B-NHL and T-NHL (around 4-fold and 16-fold, respectively) in comparison to ΔNp73 (2-fold and 14-fold, respectively). In CLL patients both isoforms showed higher expression levels in comparison to normal peripheral blood lymphocytes controls: nearly 27-fold for TAp73 and 233-fold for ΔNp73. All ALL patients showed higher expression of both studied isoforms than controls (9-fold for TAp73 and 386-fold for ΔNp73). The highest ΔNp73 expression along with a higher ΔNp73/TAp73 ratio (67-fold) was found in ALL patients compared with CLL patients (21-fold). Conclusions A considerable number of lymphoma patients lacked the expression of either or both isoforms, while all lymphoid leukemia patients expressed both isoforms. The expression pattern differences of p73 isoforms may reflect differences in the biology of these malignancies.

Effect of timing of pulmonary metastasis occurrence on the outcome of metastasectomy in osteosarcoma patients

BACKGROUND Complete metastasectomy is the best predictor of survival in patients with osteosarcoma pulmonary metastases. There has been some controversy in the literature regarding the prognostic significance of the timing of occurrence of lung metastasis. METHODS We reviewed the clinical course of all osteosarcoma patients with pulmonary metastases treated by metastasectomy in our hospital from January 2008 through December 2016. Each patient who underwent metastasectomy was placed into one of three groups based on whether lung metastases were present at initial presentation (Group 1), developed during chemotherapy (Group 2), or appeared after completion of chemotherapy (Group 3). Data were obtained retrospectively and follow-up was obtained until the end of June 2017. RESULTS We identified 170 patients with pulmonary nodules of whom 99 (58.2%) underwent at least one metastasectomy (149 thoracotomies). Eleven patients had benign pulmonary nodules and were excluded. The other 88 patients were classified as Group 1 (37), Group 2 (18) or Group 3 (33). The median follow-up was 35 months (range 8 to 99). Postmetastasis 5-year overall survival (OS) was 38.1 ± 6.4%; event-free survival (EFS) was 25 ± 5.3%. By group, postmetastasis 5-year OS and EFS were 34.3 ± 13% and 18 ± 9.3% in Group 1, 8 ± 6.5% and 6.5 ± 5% in Group 2, and 52 ± 11.4% and 25 ± 9% in Group 3 (P < 0.001). In univariate analysis, the only significant factors associated with survival were timing of occurrence of lung metastasis and the number of lung nodules found. CONCLUSION The timing of occurrence of lung metastasis is an important prognostic factor among osteosarcoma patients eligible for metastasectomy. Patients whose metastases occurred during chemotherapy had the worst survival. LEVEL OF EVIDENCE Level II.

Outcome of resectable pediatric Ewing sarcoma of the ribs

PURPOSE Was to evaluate the outcome of multimodality treatment in resectable primary Ewing sarcoma/primitive neuroectodermal tumor ES/PNET of the ribs and role of thoracoscopy in facilitating resection of these tumors. PATIENTS AND METHODS This was a retrospective study including 22 patients with primary ES/PNET of the ribs surgically treated at Childrens Cancer Hospital Egypt (CCHE) between January 2008 until the end of December 2014. RESULTS Median age was 8.5years (range 5months to 16years.). All patients received neoadjuvant chemotherapy. Thoracoscopic exploration was performed in 15 (68%) patients. Resection included 1,2,3 and 4 ribs in (7,4,8 and 3 patients) respectively, parts of the diaphragm (3 patients), wedge resection of the lung (10 patients) and pleural nodules (2 patients). Primary closure was feasible in 11 patients and rib transposition was done in one patient. Reconstruction by proline mesh covered by muscle flap was done in 10 patients. Margins were microscopically positive in 3 patients and close in 2 patients. Postoperative radiotherapy was given in 8 patients. With a median follow-up of 38.5months, the 3-year event -free survival (EFS) and overall survival(OS) rates were 31.6% and 55.6%, respectively. CONCLUSION Multimodality treatment is essential in the management of ES-PNET of the ribs. Neoadjuvant chemotherapy facilitates adequate resection. The role of thoracoscopy and the indications of postoperative radiotherapy need further evaluation.

Mucoepidermoid carcinoma: a reappraisal of the influence of tumor grading on prognosis

Background Mucoepidermoid carcinoma is the most common malignant salivary gland tumor. The histopathologic grade of this tumor is the most important predictor of prognosis, which has a huge impact on the treatment protocols. Tumor behavior is worse with an aggressive outcome in high-grade than in low-grade mucoepidermoid carcinoma, leading to a need for more intensive treatment. Patients and methods A retrospective clinical study and review of histopathologic grading were carried out, using the two most well-known grading systems, of 60 patients with mucoepidermoid carcinoma diagnosed at the Pathology Department, National Cancer Institute, Cairo University, from 2005 to 2010. Results The recurrence rate was strongly correlated with high tumor grade according to Armed Forces Institute of Pathology and Brandwein grading systems (P=0.003 and 0.03, respectively). Male sex was significantly correlated with a high tumor grade (P=0.01). Lymph node status was significantly correlated with the overall survival (P=0.026). Using the Brandwein grading system, it was found that as the histologic grade increased from low and intermediate to high, disease-free survival (P=0.029) was significantly decreased. Conclusion The outcome of the cases with intermediate-grade mucoepidermoid carcinoma is less clear and may be categorized as low or high grade according to the grading system used. The Brandwein grading system may have a better predictive value than the Armed Forces Institute of Pathology systems as it identifies the low-grade cases very well.

The relevance of PDGFRα, p53, and Ki-67 in gastrointestinal stromal tumors

Background Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, which originates from the interstitial cells of Cajal. The detection of c-kit and platelet-derived growth factor receptor-&agr; (PDGFR&agr;) in GISTs has enabled the application of tyrosine kinase inhibitors such as imatinib as an effective and promising targeted therapy. Further prognostic markers, such as p53 and Ki-67, have been investigated to better identify variables that affect survival. This study was designed to evaluate the expression of PDGFR&agr;, p53, and Ki-67 in GIST to elucidate their possible value in diagnosis and prognosis as well as their association with risk assessment. Materials and methods The archival paraffin blocks of (74 cases) of GISTs diagnosed between 2005 and 2011 were retrieved from the Surgical Pathology Unit-Pathology Department, National Cancer Institute. Tumors were graded according to the National Institutes of Health consensus grading scheme. Slides were immunostained with PDGFR&agr;, p53, and Ki-67. Results The study group included 74 patients, 43 (58%) men and 31 (42%) women. In total, 61 patients (82.4%) presented with high-risk tumors, 10 patients (13.5%) had intermediate-risk tumors, and three patients (4.1%) had low-risk tumors. All c-kit-negative cases (17 cases) were positive for PDGFR&agr;; most of them (13 cases) showed a moderate and strong reaction. High-risk tumors were found in the majority of cases with high nuclear atypia (93.9%), with a highly significant statistical difference (P<0.001). About 85% of p53-positive cases had high-risk tumors compared with 14.9% of those with intermediate/low-risk tumors, but the difference was not statistically significant (P=0.5). p53 was associated significantly with tumor size (P=0.01). Ki-67 expression was strongly associated with the status of risk as all patients with intermediate/low-risk tumors were Ki-67 negative, whereas about half the patients with high-risk tumors were Ki-67 positive, with a high statistically significant difference (P=0.001). Both a high degree of atypia and cellularity were strongly associated with Ki-67 expression (P=0.005 and 0.008, respectively). Conclusion In our study, c-kit-negative GISTs always expressed PDGFR&agr;, another tyrosine kinase receptor that can be inhibited by imatinib, which might be helpful as an additional marker in the identification of c-kit-negative GISTs. Ki-67, like mitotic count, serves as a promising predictor of high-risk state especially when mitotic counting is not practical, such as in biopsies or in extensively necrotic tumors.