Impact of cyclooxygenase-2 over-expression on the prognosis of colorectal cancer patients. An experience from Western Saudi Arabia.

OBJECTIVES: To evaluate cyclooxygenase-2 (COX-2) over-expression in colorectal cancer (CRC) and its role in carcinogenesis and prognosis. METHODS: It was a retrospective study. Archival samples were obtained from Pathology Department at King Fahad Hospital, Madinah, Saudi Arabia, over 11 years' period (January 2006 to December 2017). Samples were analyzed using immunohistochemistry for COX-2 and Ki67 over-expression in 324 CRC patients, 40 cases of colorectal adenomas and 20 cases of normal colonic mucosa. RESULTS: Cyclooxygenase-2 over-expression was observed in 40% of normal colonic mucosa, 65% of colorectal adenoma and 84.6% of CRC cases. There were no significant correlations between COX-2 over-expression and age, gender, tumor site, or tumor size. However, COX-2 over-expression revealed highly significant correlations with tumor differentiation, lymph node metastasis, lympho-vascular invasion, distant metastasis, advanced stages, and high Ki67 expression. Univariate Kaplan-Meir survival analysis showed that patients with high COX-2 expression had significantly shorter periods of survival. Multivariate analysis by means of the COX-2 regression model revealed that high COX-2 over-expression, AJCC, and Ki67 expression were the only significant independent prognostic indicators. CONCLUSION: Cyclooxygenase-2 over-expression increases during normal-adenoma-carcinoma sequence, moreover COX-2 over-expression is associated with advanced tumor stage and Ki67 over-expression. These findings suggest a significant role of COX-2 in the carcinogenesis and prognosis of CRC in our study population.

Histopathological pattern of testicular diseases in western Saudi Arabia.

OBJECTIVES: To determine the histopathological pattern of testicular diseases among Saudi patients in Madinah, Saudi Arabia. METHODS: This retrospective histopathology-based study was conducted in a tertiary care hospital in Madinah, Saudi Arabia, from January 2006 to December 2017. The data collected were entered into MS-Excel and  analyzed using the Statistical Packages for Social Sciences Version 19. RESULTS: Of the 199 testicular specimens received, 108 (54.3%) of the biopsies were taken for diagnostic test, while 91 (45.7%) were for therapeutic test. The male infertility was the only indication in the diagnostic group, accounting for 108 (54.3%) with a mean age of 28±7.9 years. Benign conditions of the testes were the most common indication in the therapeutic group accounting for 76 cases (38.2%), followed by 15 cases (7.5%) of testicular tumors. Hemorrhagic infarction from testicular torsion was the most common histologic patterns in benign testicular conditions group, accounting for 46 (23.2%) of the cases with a mean age of patients 32.1±8.1 years. Mixed non-seminomatous germ cell tumor was the most common primary tumor in 7 (3.5%) cases, followed by seminoma occurring in 5 (2.5%) cases. Mean ages for these patients were 33.7±8.1 years for primary tumor and 35.6±9.1 years for seminoma. CONCLUSIONS: The pattern of testicular diseases on the basis of histopathology experience in the Madinah region appears to conform to world literature and KSA.

Clinicopathologic Patterns of Adult Renal Tumors.

BACKGROUND AND AIM: Adult renal tumors (ARTs) are rare as compared with tumors of other organs and systems; however, it is important to have demographic and pathology data of rare tumors, including ART. No such data are available from the Kingdom of Saudi Arabia (KSA). Therefore, we aimed to study the demographic and pathological data of ART from King Fahad Hospital, Al-Madinah, KSA. MATERIALS AND METHODS: This is a retrospective study of computerized data from the histopathology laboratory of King Fahad Hospital during a 10-year period (January 2006-September 2015). RESULTS: There were 42 cases of ART, comprising 28 males and 14 females (male:female ratio of 2:1). The study group ranged in age from 17 to 83 years, with a mean of 54.5 years. In the study cohort, 93% of the patients had malignant tumors and 7% had benign lesions. Renal cell carcinoma (RCC) accounted for 85.8% of cases, followed by squamous cell carcinoma and sarcoma. The benign tumors recorded in our series were oncocytoma (4.7%) and angiomyolipoma (2.4%). The tumor size of RCC ranged from 4 to 17 cm, with a mean of 7.4 cm. The majority of patients (68%) had Fuhrman Grade II tumor. Gross capsular invasion, renal vein invasion and lymph node metastases were present in one case each. CONCLUSION: We conclude that the pathological findings of ART from the Madinah region are in concordance with studies in national and international literature.

Ki67 expression in breast cancer. Correlation with prognostic markers and clinicopathological parameters in Saudi patients.

OBJECTIVES: To evaluate Ki67 immunoexpression pattern in Saudi breast cancer (BC) patients and investigate any possible predictive or prognostic value for Ki67. METHODS: This is a retrospective study designed to quantitatively assess the Ki67 proliferative index (PI) in retrieved paraffin blocks of 115 Saudi BC patients diagnosed between January 2005 and March 2015 at the Department of Pathology, King Fahd Hospital, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. The Ki67 PI was correlated with individual and combined immunoprofile data of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) with their clinicopathological parameters.   RESULTS: Ki67 immunoreactivity was highly expressed (greater than 25% of the tumor cells were positive) in 85 (73.9%) patients. The Ki67 PI was significantly associated with poor prognostic clinicopathological parameters including old age (p less than 0.02), high tumor grade (p less than 0.01), lymph node metastasis (p less than 0.001), and Her-2/neu positivity (p less than 0.009). However, the association with ER positivity, PR positivity, tumor size, and lymphovascular invasion were not statistically significant. The Ki67 PI was significantly associated with BC molecular subtypes that were Her2/neu positive (luminal B and HER-2) subtypes compared with the Her2/neu negative (luminal A) subtype (p less than 0.04). CONCLUSION: The Ki67 PI is significantly higher in Saudi BC patients comparing with the reported literature. Ki67 PI was highest in the HER-2 and luminal-B molecular subtypes. Along with other prognostic indicators, Ki67 PI may be useful in predicting prognosis and management of Saudi BC patients.

Molecular Profiling of Breast Carcinoma in Almadinah, KSA: Immunophenotyping and Clinicopathological Correlation.

PURPOSE: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. MATERIALS AND METHODS: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal- like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. RESULTS: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p< 0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p< 0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. CONCLUSIONS: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

Histopathological features of breast cancer in Al-Madinah region of Saudi Arabia.

OBJECTIVES: To observe the frequency of breast cancer among Saudi patients and to highlight the age variations and features of advanced cancer. METHODS: A retrospective study of breast cancer biopsies from all Saudi patients performed between January 2006 and December 2013 in King Fahad Hospital, Al-Madinah, Kingdom of Saudi Arabia. All the available demographic and tumor related data was analyzed. RESULTS: Of 1005 breast tissues reviewed, 982 specimens were from female, and 23 from male patients. In females, 398 specimens (40.5%) were diagnosed as malignant. Invasive ductal carcinoma (IDC) (85.2%) was most common, followed by ductal carcinoma in situ (8%), and invasive lobular carcinoma (2.7%). The mean age of Saudi females with IDC was 46.9 years. Approximately 48.7% IDC were Grade III tumors. A tumor size >2.5 cm  was found in 61.1% patients, whereas axillary nodal metastasis was present in 57.1% and lympho-vascular invasion in 64.1% who underwent axillary nodal dissection. In males, 4 specimens (17.4%) were malignant (all IDC). CONCLUSION: Our finding are consistent with previous reports of breast cancer being diagnosed in younger age group, in advanced stages, and with features of aggressive behavior; which signals the urgency for implementation of breast screening programs. 

Sclerosing Sertoli cell tumor of the testis.

Sclerosing Sertoli-cell tumor is a rare, sex-cord-stromal tumor of the testis with distinct clinical and pathological features with only 14 such cases reported in contemporary literature. We report such a tumor in a young diabetic and hypertensive male. Serum beta-HCG, alpha-protein and LDH levels were normal. Pathological examination of right radical orchidectomy specimen was consistent with sclerosing sub-type of Sertoli-cell testicular tumor with no invasion. He remains free of disease recurrence at 6 years following surgery.

Polymerase chain reaction in the detection of Helicobacter pylori infection.

OBJECTIVE: To determine the presence of Helicobacter pylori (H. pylori) infection, in patients suffering from gastritis and peptic ulcer disease by polymerase chain reaction (PCR) and correlate the results with the histological diagnosis. DESIGN: Analytical, comparative study. PLACE AND DURATION OF STUDY: Section of Gastroenterology, Department of Medicine and Pathology, Aga Khan University Hospital and School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore from November, 2001 to December, 2002. PATIENTS AND METHODS: Gastric antral biopsies were obtained from 64 patients attending the Gastroenterology Section of Aga Khan University Hospital. Patients on nonsteroidal-anti-inflammatory drugs (NSAIDS) were excluded. Gastric biopsies were sent for histopathology and used for DNA extraction and PCR amplification of H. pylori 16S ribosomal RNA (rRNA) gene. Results were compared and statistically analyzed. RESULTS: H. pylori were not visible by histology in 57.6 % (34/59) and could be seen in 42.4 % (25/59). PCR test was negative for H. pylori DNA in 44.1 % (26/59) and positive in 55.9 % (33/59) with p<0.001. CONCLUSION: PCR H. pylori DNA is a sensitive method for the diagnosis of H. pylori infection and its use as a diagnostic tool along with histology increases the detection rate of H. pylori infection. Two different staining methods for the organism should be used to avoid missing diagnosis of H. pylori infection.

Candida esophagitis: risk factors in non-HIV population in Pakistan.

AIM: Candida esophagitis is a frequent infection in immunocompromised patients. This study was designed to determine its characteristics in non- human immune deficiency virus (HIV) infected patients attending a teaching hospital. METHODS: Clinical records of all patients coded by international classification of diseases 9th revision with clinical modifications' (ICD-9-CM), with candida esophagitis diagnosed by esophagogastroduodenoscopy (EGD) and histopathology over a period of 5 years were studied. RESULTS: Fifty-one patients (27 males, 24 females, range 21-77 years old and mean age 52.9 years) fulfilled the criteria (0.34% of the EGD). The common predisposing factors were carcinoma (OR 3.87, CI 1.00-14.99) and diabetes mellitus (OR 4.39, CI 1.34-14.42). The frequent clinical symptoms were retrosternal discomfort, dysphagia and epigastric abdominal pain with endoscopic appearance of scattered mucosal plaques. Another endoscopic lesion was associated with candida esophagitis in 15% patients. CONCLUSION: Carcinomas, diabetes mellitus, corticosteroid and antibiotic therapy are major risk factors for candida esophagitis in Pakistan. It is an easily managed complication that responds to treatment with nystatin.

Candida oesophagitis with hepatitis C virus: an uncommon association.

Candida oesophagitis is an acquired immune deficiency syndrome (AIDS)-defining illness. We report a 28-year-old woman who presented with Candida oesophagitis with underlying chronic hepatitis C. The patient presented with anorexia and weakness and was noted to have raised serum transaminases. Upper-gastrointestinal endoscopy revealed Candida oesophagitis involving the whole oesophagus. Oesophageal biopsy demonstrated changes consistent with Candida oesophagitis. Serology was positive for hepatitis C antibodies, and polymerase chain reaction (PCR) genotyped hepatitis C virus (HCV) as genotype 3. Liver biopsy revealed chronic hepatitis with moderately active portal inflammation. A human immunodeficiency virus (HIV) test was non-reactive for types 1 and 2. The development of Candida oesophagitis in a patient with chronic HCV infection demands prompt consideration of general debility and immunosuppression as effects of HCV that led to an occurrence of opportunistic infection. Evaluation of this case provides insight into various mechanisms of immune suppression associated with HCV infection.