Ahmad Zubaidi

Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages.

AIM To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. METHODS Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. RESULTS The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. CONCLUSION High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.

Rupture of multiple splenic artery aneurysms: A common presentation of a rare disease with a review of literature

The splenic artery is the most frequent site of visceral arterial aneurysms. Usually a splenic artery aneurysm occurs as a single event; rupture is frequent, sometimes occurring as the first symptom and is sometimes fatal. This article presents a case of ruptured multiple splenic artery aneurysms—the symptoms and signs, operative and perioperative management, as well as a literature review of this clinically important entity.

Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

BackgroundColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown.Methods3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29.ResultsMany anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3.ConclusionsOur findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.

Public awareness of colorectal cancer in Saudi Arabia: A survey of 1070 participants in Riyadh.

Background/Aims: The aim of this study was to investigate colorectal cancer (CRC) awareness in healthy individuals in Saudi Arabia in order to identify segments of the population that would most benefit from targeted education programs. Setting and Design: Survey/questionnaire. Patients and Methods: Random, healthy individuals from Riyadh, Saudi Arabia, were approached to participate in a 10-question multiple choice survey about CRC. Data were analyzed by demographic criteria, including age, gender, marital status, and level of education, to determine if members of these groups displayed differential knowledge. Statistical Analysis: Differences in responses by demographic data were analyzed using Pearsons Chi-square test. A P < 0.05 was considered statistically significant. Results: In total, 1070 participants completed the survey. Most respondents believe that screening for colon cancer should begin at symptom onset (42.9%). Less than 20% of all respondents believe that polyps are a risk factor for CRC, which varied significantly according to level of education; however, even the most educated answered correctly less than 50% of the time. Similarly, only 34.8% of all respondents knew that a family history of CRC imparted a personal risk for CRC. Conclusions: Although older individuals and those with higher education tended to answer questions correctly more often, there were some misconceptions regarding universally accepted screening protocols, symptoms, and general understanding of CRC in Saudi Arabia. A national education/screening program in Saudi Arabia is recommended to improve CRC knowledge.

Surgical Site Infection in a Teaching Hospital: A Prospective Study

Abstract Objectives To investigate the risk factors for surgical site infection together with the identification of the etiological pathogens and their antimicrobial susceptibility at King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. Methods A prospective case series study conducted at King Khalid University Hospital to all patients admitted to the surgical wards during the period between January 1 st and September 30 th 2007. The demographic data, diagnostic criteria, associated risk factors and laboratory data including gram stain, culture results and antimicrobial susceptibility of swabs from the surgical sites were collected. Results Out of the one hundred and thirty one patients recruited in the study, nine patients showed evidence of sepsis yielding an infection rate of 6.8%. Emergency operations and associated diabetes showed significantly higher rates of infection compared to their counterparts. The most commonly isolated bacteria were: E. coli, Pseudomonas aurigenosa and Staphylococcus aureus. Conclusion The rate of surgical site infection was 6.8% which was comparable to that reported literature. E. coli was the most commonly isolated bacteria. Neither MRSA nor Acinetobacter species were common isolates. The rate of infection in diabetics and those who underwent emergency operations was significantly higher than others. Other comorbidities did not directly affect the rate of surgical site infection in our series.

Cathepsin B expression in colorectal cancer in a Middle East population: Potential value as a tumor biomarker for late disease stages

Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA) family. The diagnostic and prognostic significance of increased CTSB in the serum of cancer patients have been evaluated for some tumor types. CTSB serum and protein levels have also been reported previously in colorectal cancer (CRC) with contradictory results. The aim of the present study was to investigate CTSB expression in CRC patients and the association of CTSB expression with various tumor stages in a Middle East population. Serum CTSB levels were evaluated in 70 patients and 20 healthy control subjects using enzyme-linked immunosorbant assay (ELISA) technique. CTSB expression was determined in 100 pairs of CRC tumor and adjacent normal colonic tissue using quantitative PCR for mRNA levels. Detection of CTSB protein expression in tissues was carried out using both immunohistochemistry and western blotting techniques. ELISA analysis showed that in sera obtained from CRC patients, the CTSB concentration was significantly higher in late stage patients with lymph node metastases when compared to early stage patients with values of 2.9 and 0.33 ng/ml, respectively (P=0.001). The majority of tumors studied had detectable CTSB protein expression with significant increased positive staining in tumors cells when compared with matched normal colon subjects (P=0.006). The mRNA expression in early stage CRC compared to late stage CRC was 0.04±0.01 and 0.07±0.02, respectively. Increased mRNA expression was more frequently observed in the advanced cancer stages with lymph node metastases when compared with the control (P=0.002). Mann-Whitney test and paired t-test were used to compare serum CTSB and mRNA levels in early and late tumor stage. A subset of four paired tissue extracts were analyzed by western blotting. The result confirmed a consistent increase in the CTSB protein expression level in tumor tissues compared with that noted in the adjacent normal mucosal cells. These findings indicate that CTSB may be an important prognostic biomarker for late stage CRC and cases with lymph node metastases in the Middle Eastern population. Monitoring serum CTSB in CRC patients may predict and/or diagnose cases with lymph node metastases.

Multiple primary cancers of the colon, rectum, and the thyroid gland.

The major concern in the case of cancer, whether one or in worse case more than one, is the extent of treatment required and the prognosis. This article reports three cases with two cancers: colorectal cancer and thyroid cancer, in the same patient at the same time. It also discusses the related clinical presentation and management of the cancers, and a review of literature has been presented.

Differential expression of mucins in Middle Eastern patients with colorectal cancer

Mucin overexpression has been implicated in the tumorigenesis and progression of colorectal carcinoma (CRC). However, data obtained on the prognostic importance of mucin expression in CRC is inconsistent. Due to lack of data on mucin expression and the increase in CRC incidence in Saudi Arabia, the aim of the present study was to analyze the mucin expression profile in patients with CRC in this ethnic group. The present study consisted of 22 patients that underwent surgery for CRC. Histopathological and immunohistochemical staining was performed on CRC tumor and adjacent normal tissues. A tissue microarray was prepared from the tumor and normal adjacent samples to investigate the mucin expression profile using immunohistochemistry. Formalin-fixed paraffin-embedded human colorectal cancer tissues were immunostained with mucin 1 (MUC1), mucin 2 (MUC2) and mucin 5AC (MUC5AC) antibodies. Associations between mucin expression and histopathological variables were evaluated. The present study indicated that MUC1 was highly expressed in early (stage I and II; P=0.0016) and late (stage III and IV; P<0.0001) stage CRC tissues compared to normal adjacent tissues. However, MUC2 expression was observed to be downregulated in early and late stage CRC tissues compared to normal and adjacent tissues. Furthermore, serum MUC1 levels were observed to be increased in early and late stage CRC. The present findings indicate that MUC1 expression was significantly higher in early and late stage CRC tissues and MUC2 was downregulated in CRC tissues compared with normal adjacent tissues, and serum MUC1 protein was significantly higher in CRC patients compared to control serum. In conclusion, during colorectal tumorigenesis the pattern of MUC1 and MUC2 expression is altered in Saudi Arabian patients with CRC compared with normal. A higher expression of MUC1 may be used as an independent biomarker in various stages of CRC tumors, which would aid in the early detection of CRC.

Acquired hypernatremia in a general surgical Intensive Care Unit: Incidence and prognosis

Purpose: Intensive Care Unit (ICU)-acquired hypernatremia (IAH) is a serious electrolyte disturbance that recently was shown to present an independent risk factor for mortality in critically ill patients. IAH has not been widely investigated in Surgical ICU (SICU) patients. No study has specifically investigated IAH epidemiology in the Kingdome of Saudi Arabia (KSA) in general SICU. The objectives of this study are to assess the epidemiological characteristics and prognostic impact of IAH on SICU mortality and outcome in KSA and compare it with international figures. Materials and Methods: A retrospective observational study on a prospectively collected data of patients (14 years of age or older) admitted to SICU over 2 years, with normal serum sodium on admission and who developed IAH (serum sodium above 145 mmol/L) from day two of admission. Traumatic brain injury patients with therapeutic target sodium level above 145 mmol/L were excluded. Results: Over 2 years study period, 864 patients were admitted to SICU. A total of 50 (5.8%) developed IAH and were included in the study. Twenty-eight ( 56%) patients were male. The median age was 47 (14-84) years. The mean (± standard deviation) Acute Physiology and Chronic Health Evaluation II score was 17 ± 6.5. The incident density (the rate of occurrence of IAH per 100 days care for SICU admission for the first episode) was 0.71. Risk factors include mechanical ventilation, male sex, age ≥50 years, postgastrointestinal surgeries, weekend and night admission. SICU mortality was 40%. The SICU and hospital median (range) length of stay was 8.3 (2-53) and 28.8 (3-95), respectively. Conclusions: IAH is not uncommon in SICU patients and is associated with increased risk of SICU as well as hospital mortality.

Fatal air embolism during sigmoidoscopy performed under spinal anesthesia

Air embolism is an uncommon but potentially catastrophic event that occurs when air enters the vasculature. Because of a scared and friable colorectal mucosa, patients with anastomotic stricture are at an increased risk of complications associated with sigmoidoscopy such as bowel perforation and bleeding. This is a report of fatal air embolism confirmed on an immediate postmortem chest radiograph in a patient with a high colorectal anastomotic stricture undergoing sigmoidoscopy under spinal anesthesia is reported. The literature on air embolism in patients undergoing sigmoidoscopy/colonoscopy is reviewed.