Mahmoud Al-Ahwal

Cisplatinum and docetaxel for ovarian cancer in pregnancy

BackgroundThere is limited data on chemotherapy for advanced ovarian cancer during pregnancy. Most women received cisplatin-based chemotherapy. There are no published reports on the use of docetaxel for ovarian cancer in pregnancy.CaseA 32-year-old pregnant lady underwent laparatomy at 18-week gestation for ruptured ovarian cyst. The pregnancy was the result of in vitro fertilization with intracytoplasmic sperm injection. Left salpingo-oophorectomy and omental biopsy were done. A diagnosis of stage IIIC, poorly differentiated papillary serous adenocarcinoma of the ovary was made. She was given four cycles of cisplatinum and docetaxel followed by cesarean hysterectomy, right salpingo-oophorectomy, and cytoreductive surgery. The mother is well and has completed six cycle of chemotherapy.ConclusionThis is the first report on the use of docetaxel during pregnancy for ovarian cancer.

First national survival data for colorectal cancer among Saudis between 1994 and 2004: what’s next?

BackgroundColorectal cancer (CRC) is the second most common malignancy in the Saudi population. This study aimed to review CRC data from the Saudi Cancer Registry (SCR) in order to evaluate the prognostic factors for CRC survival in Saudi patients.MethodsThis study was a retrospective censored overall survival (OS) analysis of CRC data for the period 1994–2004 obtained from the SCR. Data were collected from all 13 administrative regions of the Kingdom of Saudi Arabia (KSA) by the SCR in collaboration with the National Information Center of the Ministry of Interior. The Kaplan-Meier method was used to calculate the cumulative survival rate, which was then stratified by gender and by period (1994–1999 versus 2000–2004). The clinico-pathological variables that might affect CRC survival were analyzed by Cox regression analysis.ResultsBetween 1994 and 2004, 549 CRC cases were diagnosed (363 [66.1%] in males and 186 [33.9%] in females). The OS for CRC during this period was 44.6% (44.7% for 1994–1999 and 44.3% for 2000–2004 [p=0.7]). There was a significant (p=0.003) discrepancy of 9.6% between the male five-year OS (41.0%) and the female five-year OS (50.6%). The five-year OS was 63.3% for patients with localized disease, 50.2% for those with regional disease, and 14.7% for patients with metastases. By Cox regression analysis, age and extent were significant prognostic factors of survival in patients with colon cancer; the risk was higher in patients with distant metastasis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.17-5.45; p=0.01). In patients with rectal cancer, the risk was lower in males (HR, 0.66; CI, 0.45-0.98; p=0.04), but higher in patients with unknown tumor extent (HR, 3.70; 95% CI, 1.66-8.24; p=0.01).ConclusionsThe five-year OS for 1994–2004 was 44.6% for patients with CRC. More so, five-year OS based on CRC stage was generally lower than the typically reported survival rates. The establishment of a national screening program and increased access to specialized medical faculties may be necessary to improve CRC survival in the KSA.

Methylation of the Polycomb Group Target Genes Is a Possible Biomarker for Favorable Prognosis in Colorectal Cancer

Background: Colorectal cancer (CRC) is the second most common cancer in the Kingdom of Saudi Arabia with ever increasing incidence rates. DNA methylation is a common event in CRC where it is now considered an important phenomenon in CRC carcinogenesis and useful for the classification and prognosis of CRC. Methods: To gain insight into the molecular mechanisms underpinning CRC in Saudi Arabian patients, we profiled the DNA methylation frequency of key genes (MLH1, MSH2, RASSF1A, SLIT2, HIC1, MGMT, SFRP1, MYOD1, APC, CDKN2A, as well as five CIMP markers) in 120 sporadic CRC cases. CRC tumors originating from the rectum, left, and right colons are represented in this cohort of formalin-fixed paraffin-embedded tissues. Results: The most common methylation frequency was detected in the polycomb group target genes (PCGT) including SFRP1 (70%), MYOD1 (60.8%), HIC1 (61.7%), and SLIT2 (56.7%). In addition, MGMT methylation was detected at a high frequency (68.3%). RASSF1A, APC, and CDKN2A methylation frequencies were 42.5%, 25%, and 32.8%, respectively. K-means clustering analysis of the methylation events results in the clustering of the CRC samples into three groups depending on the level of methylation detected. Conclusion: Group II (PCGT methylation and CIMP-negative) methylation signature carried a favorable prognosis for male patients, whereas older patients with group I rare methylation signature have a potentially poorer clinical outcome. Impact: Methylation of the PCGT genes along with RASSF1A, APC, and MGMT can be potentially used as a new biomarker for the classification and prognosis of CRC tumors and independently of where the tumor has originated. Cancer Epidemiol Biomarkers Prev; 21(11); 2069–75. ©2012 AACR.

Cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma.

AIM To correlate cyclooxygenase-2 (COX-2) expression profile with clinical and pathological variables to assess their prognostic/predictive value in colorectal carcinoma (CRC). METHODS Archival tumor samples were analyzed using immunohistochemistry for COX-2 expression in 94 patients with CRC. Patients were diagnosed and treated at the Departments of Surgery and Oncology, King Abdulaziz University Hospital, Saudi Arabia. RESULTS Fifty-six percent of the tumors showed positive cytoplasmic COX-2 expression, whereas 44% of cases were completely COX-2-negative. There were no significant correlations between COX-2 expression and sex, age, grade or tumor location. However, COX-2 expression revealed a significant correlation with tumor stage (P = 0.01) and distant metastasis (P = 0.02), and a borderline association with lymph node involvement (P = 0.07). Tumors with high COX-2 expression showed a higher recurrence rate than tumors with no expression (P < 0.009). In univariate Kaplan-Meier survival analysis, there was a significant (P = 0.026) difference in disease-free survival between COX-2-positive and negative tumors in favor of the latter. COX-2 expression did not significantly predict disease-specific survival, which was much shorter for COX-2-positive tumors. In multivariate (COX) models, COX-2 did not appear among the independent predictors of disease-free survival or disease-specific survival. CONCLUSION COX-2 expression seems to provide useful prognostic information in CRC, while predicting the patients at high risk for recurrent disease.

Chemotherapy and Fingerprint Loss: Beyond Cosmetic

Hand-foot syndrome (HFS) is a common adverse reaction to several chemotherapy drugs. Focus has been on the clinically relevant sequelae associated with this condition, with fingerprint loss receiving little attention. We report the case of a 53-year old male patient with terminal metastatic adenocarcinoma of the rectum involving the liver and lungs who developed grade 3 HFS while on capecitabine therapy. This resulted in his inability to process required government papers as a result of the loss of his fingerprints, imposing significant inconvenience and frustration on a person severely challenged by his deteriorating health. We believe clinicians should pay more attention to this possible outcome that can add additional stress in the lives of patients whose quality of life is already severely compromised.

High expression of matrix metalloproteinases: MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma

AIM To evaluate the expression pattern of matrix metalloproteinases (MMPs); MMP-2, MMP-7 and MMP-9 in colorectal cancer (CRC) and determine its prognostic potential. PATIENTS & METHODS CRC samples of 127 patients were studied. Protein expressions of MMP-2, -7 and -9 were analyzed by immunohistochemistry and association with clinicopathological variables was statistically analyzed. RESULTS Overexpressions of MMP-2 and MMP-9 correlated with poor outcome as evaluated by univariate Kaplan-Meier for disease-free survival (p = 0.04, p = 0.0001) and disease-specific survival (p = 0.01, p = 0.01), respectively. Cox analysis of MMP-2 and -9 were significant independent predictors of disease-free survival (p = 0.006, p = 0.018) and disease-specific survival (p = 0.004, p = 0.049), respectively. CONCLUSION MMPs expression patterns provide useful prognostic information in CRC, while predicting the patients at high risk for recurrent disease.

Pattern of colorectal cancer at two hospitals in the western region of Saudi Arabia

PATIENTS AND METHODS Data of all patients with CRC treated at two hospitals in the Western region of the Kingdom of Saudi Arabia (KSA), between 1993 and 2002, were collected and analyzed. RESULTS Out of the 121 patients evaluated, ten were excluded because of incomplete data. Out of 111 patients, 59 (53.2%) were males, with a male to female ratio of 1.13: 1 and 49 (44.1 %) were Saudis. Thirty-three patients (29.7%) were 40 years or less and 78 (70.3%) were more than 40 years. Colon cancer was found in 69 patients (62.2%) and rectal cancer in 42 (37.8%). Stages at presentation were; stage 0 (2.7%), stage I (11.7%), stage II (23.4%), stage III (20.7%), stage IV (22.5%) and the staging was unknown in 18.9% of the patients. The most common tumor grade was moderately differentiated (38.7%), followed by poorly differentiated (20.7%) and well differentiated 19.8% of the patients. Forty-four patients (39.6%) were alive at the time of data collection, 43 (38.7%) expired and 24 (21.6%) were lost to follow up. Correlation between age groups revealed that young patients had more advanced stage and poorly differentiated tumors than > 40 years old (p= 0.005 and 0.024 respectively). CONCLUSION Compared to data from Western countries, colorectal cancer in this population is more common in younger patients. It presents more commonly in a more advanced stage and poorly differentiated type than in older patients.

Expression of Cell Cycle Regulators P21 and P27 as Predictors of Disease Outcome in Colorectal Carcinoma

BackgroundRecent studies suggest that aberrations in cell cycle checkpoint controllers are a common feature in human malignancies and predict prognosis independent of stage.ObjectivesThis study correlated two cell cycle regulators (p27 and p21) with clinical and pathological variables in colorectal cancer (CRC) patients to assess their role as prognostic factors.Patients and MethodsA series of 65 CRC patients were analyzed for p27 and p21 expression in their tumors using immunohistochemistry.ResultsForty-six percent of tumors showed positive nuclear p27 expression, whereas 72% of cases were completely p21 negative. There were no significant correlations between p27 and p21 expression and gender, age, lymph node involvement, stage, and grade. However, p27 (but not p21) expression revealed highly significant correlation with tumor location (p < 0.01), depth of invasion (p < 0.03), and lympho-vascular invasion (p < 0.02). Tumors with high p27 expression showed a higher recurrence rate than tumors with no expression (p < 0.03). In Kaplan–Meier survival analysis, there was a significant (p = 0.046) difference in disease-free survival (DFS) between p27-positive and p27-negative tumors in favor of the latter. p21 did not show any predictive value of DFS (p < 0.7). Neither p27 nor p21 did predict disease-specific survival (DSS) in Kaplan–Meier analysis, but DSS time was much shorter for p27-positive tumors. In multivariate (Cox) model, p27 lost its value as independent predictor of DFS, and none of the covariates were independent predictors of DSS.Conclusionp27 expression seems to be more powerful than p21 expression in providing useful prognostic information in CRC, particularly in predicting the patients at high risk for recurrent disease. Larger cohort and longer follow-up are needed to fully elucidate the value of p27 (and p21) as independent predictors of disease outcome.

Functional Assessment of Quality of Life Using EORTC QLQ-CR29 inPatients with Colon Cancer at King Abdulaziz University Hospital

Objective: Colorectal cancer is the third most common cancer in the world. Quality of life is important to achieve successful treatment outcomes. The aim of this study was to assess the functional quality of life of patients with newly diagnosed colorectal cancer in order to improve our understanding as physicians of how cancer therapy influences the patients’ lives, and how we can help patients improve the quality of life on a daily basis. Method: This was a cross-sectional study conducted between January-September 2013, of a sample of 647 patients newly diagnosed with colon cancer at the King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Participants completed the EROTIC QLQ-CR29 questionnaire, translated into Arabic and modified for a KSA population by three oncologists. Results: In total, 40 patients were included (males, 25; females, 15). Similar findings were reported between both genders in terms of body image, postoperative complications and stomas, and these were significant issues in a substantial number of respondents. Conclusion: The quality of life of patients with colorectal cancer in KSA is poor in general, as a result of both physician- and patient-specific factors. Further studies to assess this issue are recommended. Am understanding of the difficulties that patients face should encourage physicians to consider this vital aspect of their care, positively influencing the treatment course with the aim of creating the conditions for a peaceful and optimal psychological, as well as disease, outcome.

Prognostic significance of VEGFR1/Flt-1 immunoexpression in colorectal carcinoma.

Colorectal carcinoma (CRC) is a major cause of morbidity and mortality. Vascular endothelial growth factor 1/Fms-like tyrosine kinase 1 (VEGFR1/Flt-1) regulates monocyte migration, recruits endothelial cell progenitors, increases the adhesive properties of natural killer cells and induces of growth factors. Flt-1 is expressed on tumour cells and has been implicated in tumour growth and progression. The objective of this study is to address the relation of Flt-1 expression to tumour prognostication. Paraffin blocks from 143 primary CRC and 48 regional nodal metastases were retrieved from the archives of the Department of Pathology at King Abdulaziz University. Tissue microarrays were designed and constructed. Immunohistochemistry for Flt-1 was performed. Staining intensity and extent of staining were assessed and combined. Results were dichotomised as low expression and high expression. Flt-1 was overexpressed in primary tumours and nodal metastasis (p < 0.001 and 0.001) with no difference between primary and nodal metastasis (p = 0.690). Flt-1 immunoexpression was not associated with the clinicopathological parameters. Flt-1 overexpression was an independent predictor of positive margin status, positive lymphovascular invasion and local disease recurrence (p < 0.001, p < 0.001 and p = 0.003, respectively). Flt-1 was not associated with survival (log-rank = 0.003, p = 0.959). Flt-1 was overexpressed in primary CRC and their nodal metastases. Flt-1 expression was an independent predictor of margin status, lymphovascular invasion and local disease recurrence. Therefore, expression profiling of Flt-1 seems to have a prognostic potential in CRC. However, to elucidate the association of overexpression of Flt-1 with tumour characteristics and prognostication, more in vivo and in vitro molecular investigations are recommended.