Stavros Vassiliou

Methylenetetrahydrofolate reductase polymorphism and minor increase of risk for oral cancer

Purpose: We investigated whether the mutant methylenetetrahydrofolate reductase (MTHFR) increases risk for oral cancer. The common germ-line mutation C677T in the MTHFR gene significantly diminishes specific activity of the enzyme, which is responsible for the circulating form of folate. Folate deficiency is associated with increased risk for thrombosis, as well as for several types of cancer, through disruption of DNA methylation, DNA synthesis and deficient DNA repair. Methods: We searched for the C677T mutation by restriction fragment analysis of PCR products in DNA samples of 110 patients with oral squamous cell carcinoma and 120 healthy controls of comparable ethnicity, age and sex. Results: The number of heterozygotes was significantly different in the two groups (P<0.005), as well as in subgroups of patients with or without a positive family history for cancer, compared to normal controls (P<0.01 and P<0.005, respectively). Furthermore, the subgroup of patients with a positive family history for thrombophilia had a significant increase both in the frequencies of mutant alleles (P<0.01) and heterozygotes (P<0.001) in comparison to normal controls. Conclusions: The obtained results suggest that the MTHFR mutation is a minor contributing factor in oncogenesis in the oral region, in conjunction with low dietary uptake of folate.

Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer

Genetic association studies have implicated functional DNA polymorphisms in genes encoding factors related to angiogenesis, inflammation and thrombosis with increased risk for oral squamous cell carcinoma (OSCC). This study examines possible interactions between nine such genotype polymorphisms and their combinatory effect in assessing the OSCC risk in a European population. OSCC cases (N=162) and healthy controls (N=168) of comparable age, gender, and ethnicity (Greeks and Germans) were studied. Multivariate logistic regression models were constructed in order to assess the contribution of homozygous or heterozygous variant genotypes of polymorphisms MMP-1 (-1607 1G/2G), MMP-3 (-1171 5A/6A), MMP-9 (-1562C/T), TIMP-2 (-418C/G), VEGF (+936C/T), GPI-alpha (+807C/T), PAI-1 (4G/5G), ACE (intron 16D/I) and TAFI (+325C/T) upon overall, early and advanced stages of OSCC. Four out of nine polymorphisms affecting PAI-1, MMP-9, TIMP-2 and ACE expression contributed significantly in OSCC prediction in the various logistic regression models. Based on these findings and previous reports, possible interactions of the implicated factors leading to OSCC development, as well as an algorithm of risk estimation are discussed.

Orbital cellulitis, orbital subperiosteal and intraorbital abscess. Report of three cases and review of the literature

INTRODUCTION Orbital cellulitis is usually a complication of paranasal sinus infection. Either the infection may dissect under the periosteum and lead to subperiosteal abscess (SPA) or intraorbital abscess may be formed secondary to a progressive and localized cellulitis. Without appropriate treatment orbital infection may lead to serious complications, even death. REPORT OF CASES Three cases are described, one of orbital cellulitis, one of SPA and one of intraorbital abscess and the literature is being reviewed. CONCLUSION Prompt treatment is mandatory to avoid visual loss or intracranial complications. Initially, IV antibiotics may be administered, but if no improvement appears within 48h, surgical drainage of the orbit and the affected sinuses must be performed. In medial or medial-inferior SPA a transnasal approach is used, but in superior orbital abscess an external incision is required.

Strong association of interleukin-6 -174 G>C promoter polymorphism with increased risk of oral cancer.

In view of the recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of interleukin-6 (IL-6) with an increased risk of oral cancer. In DNA samples of 162 patients with oral squamous cell carcinoma and 156 healthy controls of comparable ethnicity, age and sex, we studied the -174 G>C polymorphism in the IL-6 gene, which affects its transcription. C allele frequencies were significantly increased in patients compared to controls, 42.6% versus 23.1% (p<0.001). The CC homozygotes had a 7-fold greater risk of developing oral cancer (odds ratio 7.39, 95% CI 2.61-20.92), while the GC heterozygotes had a 4-fold greater risk (odds ratio 3.74, 95% CI 2.29-6.11). A significant increase in C alleles was observed in patients regardless of their smoking or alcohol consumption habits, early or advanced stage of cancer, and presence or absence of a family history for cancer or thrombophilia (p<0.001; Fishers exact test). These findings suggest that the -174 G>C polymorphism, by affecting IL-6 gene expression, is strongly associated with oral oncogenesis.

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with increased risk for oral cancer

Introduction. In light to recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of angiotensin I- converting enzyme (ACE) with increased risk for oral cancer. Materials and methods. In DNA samples of 160 patients with oral squamous cell carcinoma and 153 healthy controls of comparable ethnicity, age and sex, we studied the insertion/deletion (I/D) polymorphism in the ACE gene, which affects its transcription. Results. The I allele frequencies were significantly increased in patients compared to controls, 40.6% versus 27.5% (p < 0.001), respectively. The II homozygotes had a three-fold greater risk for developing oral cancer (odds ratio 3.17, 95% C.I. 1.32-7.61). A significant increase of I alleles was observed in patients regardless their smoking or alcohol consumption habits, early or advanced stage of cancer, presence or absence of a family history for cancer or thrombophilia (Fischer values p < 0.05). Discussion. These findings suggest that the I/D polymorphism, by affecting the ACE gene expression, is associated with the progress of oral oncogenesis.

Bisphosphonate-Induced Avascular Osteonecrosis of the Mandible Associated With a Common Thrombophilic Mutation in the Prothrombin Gene

6. Schechter MS, Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome: Technical report: Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 109:e69, 2002 7. Wildhaber J, Moeller A: Sleep and respiration in children: Time to wake up! Swiss Med Wkly 137:689, 2007 8. Mathijssen I, Arnaud E, Marchac D, et al: Respiratory outcome of midface advancement with distraction: A comparison be-

Delayed appearance of diplopia due to orbital emphysema after repair of orbital fractures

A 38-year-old caucasian male, after continuous nose blowing caused by common flu, developed left diplopia, especially in downward gaze, and complained of orbital dull pain during the preceding 48 hours. Clinical signs included left lower eyelid crepitant edema, mild exophthalmos and restriction of the eye movement. The patient had been operated on for orbital fractures 12 days previously. Open reduction had been performed, stabilization had been achieved with osteosynthesis miniplates, and the orbital floor defect was reconstructed with a piece of Liodura. Orbital computerized tomographic scan demonstrated a large air collection, diagnostic of emphysema, without displacement of the fractures. Under local anesthesia, aspiration-decompression was performed using a 25-gauge needle. On the next day, the patient was free of pain, and 2 days after surgery the diplopia and exophthalmos resolved with no sequelae.