Journal of the Egyptian National Cancer Institute

Inside front cover

2012-03-01

Evaluation of c-kit expression in classic Kaposi’s sarcoma in a cohort of Egyptian patients

Tarek M. Hussein, Bassma M. El-Sabaa, Nesrine F. Hanafy — 2012-02-27

Abstract: Background: Kaposi’s sarcoma (KS) is an angioproliferative disorder associated with human herpesvirus 8 infection. Classic KS is the most prevalent type of KS in countries of the Mediterranean basin including Egypt. Several in vitro studies have detected c-kit expression in AIDS related-KS however, only a few studies addressed this issue in the classic type with no data on the ethnicity of studied cases. The prospect of installing targeted anti- c-kit treatment to KS patients presents a promising avenue in KS therapeutics.Aim: To elucidate the expression of c-kit in classic KS cases and study possible relations with expression of HHV8 latency-associated nuclear antigen-1 (LANA-1) and other clinicopathological parameters.Methods: Twenty four cases of classic KS of the plaque and nodular stages in the lower limb were studied. Immunohistochemical detection of HHV8-LANA-1 and c-kit was carried out on archival paraffin embedded tissue, possession of the Pathology and Dermatology Departments, Alexandria School Of Medicine, Egypt. Statistical analysis of possible relations between both antigens and clinicopathological parameters (patient’s age and gender and histological stage) was performed.Results: HHV8 expression was detected in 100% of cases while c-kit immunoreactivity was found in 54.2% of cases. There was no correlation between c-kit and HHV8 immunoreactivity or any of the studied clinicopathological parameters.Conclusions: This is the first report of c-kit expression in classic KS in an ethnically homogeneous cohort of Arabs of the Mediterranean region. We detected c-kit expression in about half the cases with no relationship to HHV8 LANA expression or clinicopathological parameters.

Prognostic significance of ploidy and S-phase fraction in primary intraoral squamous cell carcinoma and their corresponding metastatic lymph nodes

M.F. El-Deftar, S.M. El Gerzawi, A.A. Abdel-Azim, S.M. Tohamy — 2012-01-11

Abstract: Background: Despite improvements in diagnosis and therapy of oral and oro-pharyngeal carcinomas during the past 30years the 5-year disease-free survival is still poor. Patient’s prognosis is affected by cervical lymph node metastasis rather than primary tumors. The DNA ploidy and S-phase fraction (SPF) are associated with tumor aggressiveness and patient outcome in many solid tumors.Purpose: Analysis of DNA ploidy and SPF in primary oral squamous cell carcinoma (OSCC) and corresponding node metastasis as prognostic markers in relation to conventional prognostic factors and disease-free survival (DFS).Methods: Ploidy status and SPF (mean value) of 37 formalin-fixed paraffin embedded (FFPE) primary OSCC tumors and their corresponding lymph node metastasis were assessed by flow cytometry (FCM) and correlated with clinicopathologic prognostic parameters and DFS.Results: Most of OSCC tumors (86.5%) were Grade II. Among primary OSCC the incidence of aneuploidy was 19%, 51.4% showed high SPF (>10.62%) and 48.6% had low SPF (<10.62%). Border line significance (P=0.10) was detected between ploidy status and SPF in primary tumors. In lymph node metastases all tumors were diploid, 78.4% of metastatic tumors revealed low SPF and only 21.6% showed high SPF. There was a statistically significant correlation (p=0.02) between site of tumors and DFS and a highly statistically significant correlation (p=0.01) between SPF of primary tumors and DFS.Conclusions: High SPF of primary OSCC tumors assessed by FCM was significantly associated with decreased disease free survival rates. DNA ploidy showed no relationship to bad prognostic indicators in either primary OSCC or their metastatic tumors.

Metronomic chemotherapy in metastatic breast cancer: Impact on VEGF

Lobna R. Ezz El-Arab, Menha Swellam, Manal M. El Mahdy — 2012-01-19

Abstract: Background: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents; including cyclophosphamide (CTX) and capecitabine (Cap) when given at lower doses for prolonged period (metronomic chemotherapy) postulating an antiangiogenic activity as well.Aim of work: To evaluate the action and tolerability of metronomic chemotherapy (MC) and its impact on serum vascular endothelial growth factor (VEGF) levels in metastatic breast cancer (MBC) patients.Patients and methods: In this study we evaluated the clinical efficacy and tolerability of low dose, capecitabine (500mg twice daily) together with oral cyclophosphamide (CTX) (a dose of 50mg once daily) in patients with metastatic breast cancer. Vascular endothelial growth factor (VEGF), an angiogenic marker, was measured in the serum samples; at base line, and after 2 and 6months of therapy.Results: Sixty patients were evaluable. One achieved complete response (CR), 12 partial responses (PR), and 21 stable diseases (SD), while 26 were with progressive disease (PD). The overall response rate was 21.7% with overall disease control (CR, PR, and SD) 56.7%. The median time to progression was 7±2.59months and overall survival 16±8.02months. Toxicity was mild, Palmar–plantar erythrodythesia was the most common side effect and was observed in 22 patients (37%), leucopenia (G1+2) was the most common hematological toxicity, and it was reported in 27% of the cases. The median VEGF level was significantly declined after 2 and 6months of therapy compared to the base line among the patients with disease control (CR, PR, and SD). In multivariate logistic regression analysis, patients with post-menopausal, positive hormonal receptors, negative HER-2/Neu, and one metastatic site, were statistically significant and have a better disease control rate.Conclusions: MC induced drop in VEGF, and was effective, minimally toxic regimen for the treatment of metastatic breast cancer patients.

Predictors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node (Pilot study)

2012-01-25

Abstract: Background: Sentinel Lymph Node Biopsy (SLNB) procedure was found to be an accurate method of staging the axilla in patients with early stage breast cancer. The standard of care for breast cancer patients with positive SLN metastasis includes complete Axillary Lymph Node Dissection (ALND). However, in 40–70% of patients, the SLN is the only involved axillary node. Factors predicting non SLN metastasis should be identified in order to define subgroups of patients with positive SLN in whom the axilla may be staged by SLNB alone.Objectives: To identify the factors predicting metastatic involvement of the non-SLNs in breast cancer patients having SLN metastasis.Patients and Methods: Data were collected and analyzed from 80 patients with early stage invasive breast cancer (T1, T2, N0, M0) who underwent SLNB at the Surgical Oncology Department, Kuwait Cancer Control Center (KCCC) between November 2004 and February 2009. SLNB was performed using a combined technique (radioactive colloid, and blue dye) in the majority of cases. In some cases, only one technique was used. Complete ALND was performed in the case of failure of SLN identification and in patients with positive SLN. Multiple variables (patient, tumor, and SLN characteristics) were tested as possible predictors of nonsentinel lymph node metastasis.Results: The mean age of patients at diagnosis was 46.6years. The median tumor size was 2cm. The SLN identification rate was 96.2% (77 out of 80 patients). The SLN was positive in 24 patients (31%), and half of these showed evidence of capsular invasion. The median number of SLNs removed was two. The median number of positive SLNs was one. The incidence of non-SLN metastasis associated with positive SLN was 50% (12 out of 24 patients). Lymphovascular invasion was found to be the only factor associated with non-SLN metastases. In addition, two trends were observed, though they did not reach the statistical significance: the first is that the majority of patients having capsular invasion of the SLN (8 out of 12 patients, 67%) had positive non-SLN metastasis, and the second is that the patients having more than one SLN metastasis were more likely to have non-SLN metastasis (4 out of 5, 80%).Conclusion: In the current pilot study, only the lymphovascular invasion in the area of the primary tumor was found to be significantly related to the nonsentinel lymph node metastasis. There was a tendency toward higher incidence of nonsentinel lymph node metastasis associated with the number of positive SLN and capsular invasion of SLN, though this did not reach the statistical significance. This could be attributed to the small number of patients recruited. Further evaluation of the predictors of nonsentinel lymph node metastasis on a larger number of patients is required. The validation of these predictors in prospective studies may enable approximately half of early stage breast cancer patients with positive SLN to be staged with SLNB alone while avoiding the morbidity of unnecessary ALND.

Gastrointestinal stromal tumors (GISTs), 10-year experience: Patterns of failure and prognostic factors for survival of 127 patients

M. Al-Kalaawy, Mohamed A. El-Zohairy, Ahmed Mostafa, A. Al-Kalaawy, H. El-Sebae — 2012-02-10

Abstract: Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT) and are believed to originate from the interstitial cell of Cajal. Management of GIST has evolved very rapidly in the last decade.Aim: To report our surgical experience in the treatment of GIST patients, to evaluate the prognostic factors and to discuss some controversial issues about the role of target therapy.Patients and methods: One hundred and twenty seven consecutive patients who underwent surgical resection for GISTs at Nasser Institute (98 patients) and NCI, Cairo University (29 patients) from January 2000 to December 2009 were reviewed retrospectively. The clinical and pathological features of patients were collected. Also data about treatment variables, patterns of failure and factors that predict survival were collected and analyzed.Results: Of the 127 patients, 81 (64%) had primary disease without metastasis, 11 (9%) had metastatic lesions at presentation, and 35 (27%) presented with recurrence (isolated, metastasis or both). Patients with primary disease underwent complete resection of gross disease. The 5-year overall survival was 53.4% and disease free survival (DFS) was 46.5%. The median DFS was 43.0months (95% CI: 21.2–64.9). On multivariate analysis, survival was affected by mode of presentation, gastric origin and tumor size. Failures after resection were predominantly intra-abdominal (original site, peritoneal, and liver), and rarely lungs.Conclusion: Surgical resection is the mainstay of treatment of GIST. Tumor size and gastric origin were the predicators for DFS in patients presenting with primary disease.

Importance of serum levels of angiopoietin-2 and survivin biomarkers in non-small cell lung cancer

2012-01-19

Abstract: Background: Angiogenesis is an essential process in cancer growth maintenance, and metastasis. Angiopoietin-2 promotes tumor angiogenesis by priming the vasculature and potentiating the effects of cytokines at the front of active neovascularization. Enhanced expression of angiopoietin-2 has been reported in lung cancer tissue. Survivin is one of the inhibitors of apoptosis protein that has been shown to play a key role in cancer progression, and in tumor angiogenesis. Also plays a key role in tumor cell resistance to anticancer agents and ionizing radiation.Aim: To measure the serum levels of angiopoietin-2 and survivin as possible angiogenic factors in lung cancer patients with the assessment of their interrelationships and clinical significance.Patients and methods: Patients with lung cancer as NSCLC (n=70) and healthy volunteers (n=10) were enrolled. Serum angiopoietin-2 and survivin concentrations were measured using enzyme-linked immunosorbent assay (ELIZA).Results: Median serum angiopoietin-2 levels with lung cancer (2730pg/mL) ranged from 1171 to 6541pg/mL was higher than the median of the control group (1795pg/mL) ranged from 1076 to 2730/mL, p<0.001. Median serum survivin levels were also higher in patients with lung cancer (53.0pg/mL) ranged from 39.3 to 96.3pg/mL than the median of the control group (48.8pg/mL) ranged from 38.0 to 74.6pg/mL, but did not reach statistical significance p=0.206.In all patients with lung cancer, serum angiopoietin-2 was not significantly correlated with survivin (r=0.073, p=0.657). Neither serum angiopoietin-2 nor survivin showed significant relation with the serum angiopoietin-2 or survivin levels depending on the cell types, stage progression, and metastasis among the patients with NSCLC.Conclusions: Our study suggests that serum angiopoietin-2 is a useful marker for the diagnosis of NSCLC by ELIZA technique.

Pancreaticoduodenectomy in a tertiary referral center in Saudi Arabia: A retrospective case series

2012-02-27

Abstract: Context: Perioperative outcome of pancreaticoduodenectomy is related to work load volume and to whether the procedure is carried out in a tertiary specialized hepato-pancreatico-biliary (HPB) unit.Objective: To evaluate the perioperative outcome associated with pancreaticoduodenectomy in a newly established HPB unit.Patients: Analysis of 32 patients who underwent pancreaticoduodenectomy (PD) for benign and malignant indications.Design: Retrospective collection of data on preoperative, intraoperative and postoperative care of all patients undergoing PD.Results: Thirty-two patients (16 male and 16 female) with a mean age of 59.5±12.7years were analyzed. The overall morbidity rate was high at 53%. The most common complication was wound infection (n=11; 34.4%). Pancreatic and biliary leaks were seen in 5 (15.6%) and 2 (6.2%) cases, respectively, while delayed gastric emptying was recorded in 7 (21.9%). The female sex was not associated with increased morbidity. Presence of co-morbid illness, pylorus-preserving PD, intra-operative blood loss ⩾1L, and perioperative blood transfusion were not associated with significantly increased morbidity. The overall hospital mortality was 3.1% and the cumulative overall (OS) and disease free survival (DFS) at 1year were 80% and 82.3%, respectively. The cumulative overall survival for pancreatic cancer vs ampullary tumor at 1year were 52% vs 80%, respectively.Conclusion: PD is associated with a low risk of operative death when performed by specialized HPB surgeons even in a tertiary referral hospital. However, the postoperative morbidity rate remains high, mostly due to wound infection. Further improvement by reducing postoperative infection may help curtail the high postoperative morbidity.