Effects of nicotine on rat adrenal gland: crosstalk between oxidative and inflammatory markers, and amelioration by melatonin.

Although the risks of smoking are well known, the effects of exposure to nicotine on endocrine functions remain unclear. We investigated the deleterious effects of nicotine on the adrenal gland and the mechanisms of these changes in rats. The role of melatonin in ameliorating pathological changes also was investigated. We used 24 rats divided into four groups of six: group 1, control; group 2, nicotine treated; group 3, nicotine and melatonin treated; group 4, melatonin treated. We used histology; immunohistochemistry of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and tyrosine hydroxylase (TH); measured oxidative and antioxidative markers, malondialdehyde (MDA) and glutathione (GSH); and performed real-time PCR for NF-κB 65, IL1-B and IL6. We also performed histomorphometric analysis. Indentation and lamellar separation of the adrenal capsule, vacuolated degenerated cells and lymphocytic infiltration were observed in group 2. Vacuolated cells and cells with pyknotic nuclei also were detected in the zona reticularis and medulla of the same group. We observed improved shape and cellular lining of the gland in groups 3 and 4. Widespread expression of iNOS, VEGF and TH, increased area percent collagen, decreased GSH (56%) and increased MDA, NF-κB, IL1-B and IL-6 were observed in group 2. All parameters were ameliorated in groups 3 and 4. The effects of nicotine on the adrenal gland can be attributed to oxidative and inflammatory stress; melatonin ameliorates these effects.

Anaplastic Thyroid Cancer: a Retrospective analysis of 120 cases.

INTRODUCTION: Anaplastic Thyroid Cancer (ATC) is one of the most lethal malignancies with very short survival and extremely poor treatment outcome. ATC accounts for 2-5% of all thyroid cancers worldwide with an annual incidence of about 2 million. OBJECTIVE: To review the natural history and treatment outcome of ATC patients treated at King Faisal Specialist Hospital and Research Centre (KFSH and RC) located at Riyadh, Saudi Arabia. MATERIAL AND METHODS: Retrospective review of 120 Saudi cancer patients collected from registry data at KFSH & RC from 1976-2008. Search key words included: thyroid cancer, anaplastic, undifferentiated and not otherwise specified. Search was not restricted to particular age, gender, treatment or tumor size. Demographic information, baseline patient characteristics including date of diagnosis, type of treatment and date of death were obtained from KFSH & RC registry data and Saudi death registry. RESULTS: A total of 120 cases were identified at our cancer centre from 1976 to 2008. Of these total, 73 were females (60.8%) and 47 were males (39.2%). The average age at diagnosis was 63.34 +/- 12.8 years. Thirty-four patients underwent surgery (28.3%), 52 had a palliative radiation treatment (43.3%) and only 5 had chemotherapy (4.2%). The median survival was 53 days (0-457). CONCLUSION: Our review proves that ATC is rapidly fatal cancer and is unresponsive to currently available therapeutic options. More research is needed to understand the tumor biology and novel treatment options. KEYWORDS: thyroid cancer, anaplastic, undifferentiated, radiation treatment, chemotherapy, median survival, Riyadh and Saudi Arabia.

Association between normal tissue complications after radiotherapy and polymorphic variations in TGFB1 and XRCC1 genes.

Genetic predictive biomarkers of radiosensitivity are being sought to individualize radiation treatment of cancer patients. In this pilot case-control study, we tested the association between TGFB1 T869C codon 10 Leu/Pro (rs1982073), XRCC1 G28152A codon 399 Arg/Gln (rs25487), and XRCC3 C18067T codon 241 Thr/Met (rs861539) single-nucleotide polymorphisms (SNPs) and late reaction to radiotherapy in 60 nasopharyngeal cancer patients. Subcutaneous and deep tissue fibrosis was scored using the RTOG/EORTC grading system. Patients with moderate to severe fibrosis (radiosensitive cases, G2-3, n = 30) were matched and compared to those with little or no reaction (controls, G0-1, n = 30). The three nonsynonymous SNPs were genotyped by direct DNA sequencing. Significant association was observed for TGFB1 T869C and XRCC1 G28152A genotypes (P < or = 0.05). Both variant alleles, TGFB1 869C and XRCC1 28152A, were associated with a lower grade of fibrosis (odds ratios were 0.41, 95% CI: 0.20-0.86, P = 0.02 and 0.30, 95% CI: 0.10-0.89, P = 0.02, respectively), and therefore the wild-types were the risk alleles. Interestingly, there was a significant difference in the median number of risk alleles between the radiosensitive and the control groups (P = 0.006). We conclude that radiotherapy complications are associated with genetic variations in our nasopharynx cancer patients. Our findings support the assumption of the combined effects of multiple SNPs. Large-scale studies are required to confirm these findings before polymorphisms can be used as predictive markers to individualize radiation therapy on genetic bases.

Treatment of aggressive fibromatosis: the experience of a single institution.

AIMS: Aggressive fibromatosis is a locally aggressive infiltrative low-grade tumour, although pathologically benign, and it does not metastasise, yet it can cause serious local distressing symptoms by virtue of local destruction and impairment of local function. The aim of this study was to emphasise the role of radiotherapy and adequate surgery in the treatment of fibromatosis in patients presenting with newly diagnosed or recurrent disease and to analyse our treatment results over 15 years for this rare tumour type. MATERIALS AND METHODS: Fifty-four patients with confirmed diagnosis of aggressive fibromatosis treated at King Faisal Specialist Hospital between 1990 and 2006 were identified from our local cancer registry. Forty-seven patients had surgery: complete resection (R0) in 20 patients, incomplete surgery (R1/2) in 27 patients, and seven patients had biopsy only. Forty-five patients were treated with radiotherapy: 38 patients were treated with postoperative radiotherapy, three patients were treated with preoperative radiotherapy and four patients had radiotherapy as the only treatment. The radiotherapy dose ranged between 45 and 60Gy (median 50.4Gy). Three patients did not receive any form of treatment apart from biopsy, but were still included in the final analysis. RESULTS: Fifty-two per cent (28/54 patients) of our patient population had tumour recurrence when first presented to King Faisal Specialist Hospital. The median age was 29.5 years (range 2-63 years). The most common site of involvement was the extremities (28 patients). Among the 54 patients (with primary and recurrent presentation) there were 10 local recurrences, all of which were within the original primary site. The 5-year progression-free survival and overall survival rates for the whole group were 75 and 95%, respectively. Univariate and multivariate Cox regression analysis showed that the depth of invasion significantly affected progression-free survival. CONCLUSION: Aggressive fibromatosis is effectively treated with surgery and postoperative radiotherapy. Patients first presenting with tumour recurrence may still have local tumour control comparable with newly diagnosed patients.

Nasopharyngeal carcinoma in Saudi Arabia: clinical presentation and diagnostic delay.

Nasopharyngeal carcinoma is commonly advanced at diagnosis. In this study we evaluated the clinical presentation, diagnostic delay and factors affecting delay in nasopharyngeal carcinoma. Data were collected prospectively for 307 newly diagnosed patients, including detailed demographic data, disease history, health care consultations and referral process. Diagnostic delay was classified as patient, professional and overall. Neck lump and nasal obstruction were the commonest presenting symptoms. There was a significant association between delay time of > or = 3 months and advanced stage. Patient's age and otological symptoms were associated with increased overall delay time. Advanced clinical stage at diagnosis was associated with paitents' sociodemographic characteristics.

Nasopharyngeal carcinoma in Saudi Arabia: clinical presentation and diagnostic delay

Nasopharyngeal carcinoma is commonly advanced at diagnosis. In this study we evaluated the clinical presentation, diagnostic delay and factors affecting delay in nasopharyngeal carcinoma. Data were collected prospectively for 307 newly diagnosed patients, including detailed demographic data, disease history, health care consultations and referral process. Diagnostic delay was classified as patient, professional and overall. Neck lump and nasal obstruction were the commonest presenting symptoms. There was a significant association between delay time of >/= 3 months and advanced stage. Patient's age and otological symptoms were associated with increased overall delay time. Advanced clinical stage at diagnosis was associated with paitents' sociodemographic characteristics