Human papillomavirus prevalence and clinicopathological associations in oropharyngeal squamous cell carcinoma in the Lebanese population.

OBJECTIVES: To evaluate for the first time the prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in a Middle-Eastern population, and to determine associations between human papillomavirus profiles and clinicopathological characteristics. METHODS: A retrospective chart review was conducted of all patients treated for oropharyngeal squamous cell carcinoma at the Hotel Dieu de France University Hospital (Beirut, Lebanon) between January 2010 and 2016. Existing formalin-fixed paraffin-embedded tumour samples were analysed. Human papillomavirus DNA viral load and p16 expression were evaluated using polymerase chain reaction and immunohistochemistry respectively. RESULTS: Thirty patients (mean age of 60 years) were included. Twenty-seven per cent of patients were p16-positive/human papillomavirus DNA positive, 53 per cent were p16-negative/human papillomavirus DNA negative and 20 per cent were p16-positive/human papillomavirus DNA negative. Human papillomavirus 16 was the most frequent subtype (75 per cent). Smoking and alcohol consumption were significantly lower in the human papillomavirus positive group compared to the human papillomavirus negative group (p = 0.049 and 0.004, respectively). CONCLUSION: Human papillomavirus rate was lower than reported rates in Western populations. Possible explanations include differences in social and cultural behaviours.

Construction of bacterial ghosts for transfer and expression of a chimeric hepatitis C virus gene in macrophages.

The bacterial ghost (BG) production is a field of biotechnology for applications in vaccine and drug delivery. We assessed the capacity of BG for delivery of a recombinant gene encoded for both cell mediated and antibody dependent epitopes of hepatitis C virus (HCV) into murine macrophages. Escherichia coli (E. coli) cells were transformed with the lysis plasmid (pHH43). To produce chimeric gene, NS3 (non-structural protein 3) and core regions of HCV genome were fused together by splicing by overlap extension (SOEing) PCR and were cloned into plasmid pEGFP-C1. Bacterial ghosts were loaded with recombinant pEGFP-C1 and then were transferred to murine macrophages (RAW 264.7). To investigate plasmid transfection and chimeric mRNA transcription, fluorescent microscopy and RT-PCR were used. In vitro studies indicated that bacterial ghosts loaded with pEGFP-C1 plasmid were efficiently taken up by murine macrophages and indicated a high transfection rate (62%), as shown by fluorescent microscopy. RT-PCR from extracted intracellular mRNAs for chimeric Core-NS3 gene showed a specific 607 bp fragment of the gene. The sequence analysis of purified PCR products demonstrated the expected unique mRNA sequence. We constructed a chimeric HCV gene containing both cell mediated and antibody dependent epitopes with a significant expression in murine macrophages delivered by bacterial ghost.

Epidemiological Study of Thyroid Pathology in a University Hospital.

OBJECTIVES: The incidence of papillary thyroid carcinoma increased in several countries. The purpose of this study was to quantify the changes in thyroid carcinomas in our University Hospital. STUDY DESIGN: Retrospective study. METHODS: All 1.927 thyroidectomy cases studied in the Pathology Department of Hotel-Dieu de France Hospital (Beirut, Lebanon), between 2003 and 2013, were included. RESULTS: The Female/Male Sex Ratio of the studied population was 3.7/1. The mean age of female patients was significantly lower than that of male patients. The most frequent diagnoses were multinodular goiter (78%) and papillary-carcinoma (26%). 337 cases had a single lesion on gross examination. 21 of them were diagnosed with follicular carcinoma and 59 with follicular adenoma. A statistically significant correlation was found between the unicity of the lesion on gross examination and the final diagnosis of a follicular neoplasm. Thyroid carcinoma was multifocal in 33% of the cases and bilateral in 24%. A statistically significant increase in thyroid carcinoma proportion (from 15% in 2003 to 44% in 2013) was found. Among all thyroid carcinomas, the proportion of papillary type increased from 65% in 2003 to 94% in 2013 ; this increase remained statistically significant after the exclusion of papillary micro-carcinomas, whose proportion was stable throughout the 11 years. CONCLUSIONS: In this study, we noted a statistically significant increase in the frequency of thyroid carcinoma, especially of the papillary type. The unicity of the lesion on gross examination is significantly associated with a follicular neoplasm.

Isolated laryngeal plasmacytosis.

INTRODUCTION: Laryngeal plasmacytosis (LP) is a rare benign lesion of mature polyclonal plasma cells, which should be differentiated from extramedullary plasmacytoma. CASE REPORT: Isolated laryngeal plasmacytosis was discovered in a 59-year-old woman, free of symptoms other than chronic hoarseness. DISCUSSION: Histological presentation, treatment modalities and prognosis are discussed. CONCLUSION: Laryngeal plasmacytosis is a rare benign lesion that must be considered in case of submucosal polyclonal plasma cell infiltrate.

Intraparotid Kimura disease.

INTRODUCTION: Intraparotid locations are extremely rare in Kimura disease, especially in Europe. CASE REPORT: A 31-year-old man presented with intraparotid Kimura disease, managed by parotidectomy. DISCUSSION/CONCLUSION: The case was analyzed in the light of a review of the literature, focusing on the diagnostic and anatomopathologic problems encountered, and the physiopathology and treatment of this pathology. Any parotid mass found in a patient of Far-Eastern origin showing hypereosinophilia should suggest a diagnosis of intraparotid Kimura disease.

Pre-therapeutic histological and cytological assessment in head and neck squamous cell carcinomas. French Society of Otorhinolaryngology Guidelines--2012.

OBJECTIVES: The authors present the French Society of Otorhinolaryngology (SFORL) guidelines for histopathologic assessment of head and neck cancer. MATERIAL AND METHODS: [corrected] A multidisciplinary workgroup set up by the SFORL performed an exhaustive review of the literature according to levels of evidence, following the 2000 guidelines of the French national health approvals and assessment agency (ANAES). RESULTS: Comparison between histologic and clinical data is essential. In case of discrepancy between clinical, radiological and histological findings, reinterpretation or new biopsy may be required (professional consensus). Mere suspicion of carcinoma on fine-needle aspiration lymph-node biopsy only exceptionally warrants aggressive treatment (professional consensus). Exploration for HPV is not recommended as routine practice, being without therapeutic impact (professional consensus). Anti-p16 immunohistochemistry is optional, for epidemiological purposes (professional consensus). Tumor-bank tissue storage must conform strictly to prevailing legislation and good practice rules for sampling and preservation (professional consensus). CONCLUSION: Pathology assessment is mandatory in suspected H&N squamous cell carcinoma. The present guidelines are intended to optimize management.

Parathyroid carcinoma: a difficult histological diagnosis.

INTRODUCTION: Parathyroid carcinomas are rare and usually difficult to diagnose, both clinically and histologically. CASE REPORT: A 60-year-old man was hospitalised for hypotension. Investigations revealed renal failure associated with hypercalcaemia and elevated serum parathormone. (99m)Tc-sestamibi scintigraphy of the parathyroid glands (PT) revealed a mass in the right PT that was treated by parathyroidectomy and recurrent laryngeal lymph node dissection. Histological examination demonstrated a tumour with numerous cytonuclear atypias and immuno-histochemistry demonstrated PTH expression by tumour cells without loss of parafibromin expression. The diagnosis of PTC was based on criteria of invasion and local aggressiveness, despite the absence of lymph node metastasis. The patient developed four recurrences, treated surgically and by adjuvant radiotherapy. DISCUSSION: The diagnosis of PTC is usually difficult to establish on a simple histological examination in the absence of specific cytological, architectural or immuno-histochemical markers. This diagnosis must therefore be based on a combination of clinical, radiological and histological signs in a context of atypical presentation of parathyroid tumour.

Degradation of cyclin D3 independent of Thr-283 phosphorylation.

Cyclin D3 has been shown to play a major role in the regulation of cell cycle progression in lymphocytes. It is therefore important to understand the mechanisms involved in the regulation of this protein. We have previously shown that both basal and cAMP-induced degradation of cyclin D3 in Reh cells is dependent on Thr-283 phosphorylation by glycogen synthase kinase-3beta (GSK-3beta). We now provide evidence of an alternative mechanism being involved in the regulation of cyclin D3 degradation. Treatment of lymphoid cells with okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A (PP1 and PP2A), induces rapid phosphorylation and proteasomal degradation of cyclin D3. This degradation is not inhibited by the GSK-3beta inhibitors lithium or Kenpaullone, or by substitution of Thr-283 with Ala on cyclin D3, indicating that cyclin D3 can be degraded independently of Thr-283 phosphorylation and GSK-3beta activity. Interestingly, in vitro experiments revealed that PP1, but not PP2A, was able to dephosphorylate cyclin D3 efficiently, and PP1 was found to associate with His-tagged cyclin D3. These results support the hypothesis that PP1 constitutively keeps cyclin D3 in a stable, dephosphorylated state, and that treatment of cells with OA leads to phosphorylation and degradation of cyclin D3 through inhibition of PP1.

A retrospective review of cervical corpectomy: indications, complications and outcome.

BACKGROUND: Cervical corpectomy is a common spinal surgery procedure used to decompress the spinal cord in numerous degenerative, traumatic and neoplastic conditions. The aim of this study was to investigate the indications, complications and outcomes in past cervical corpectomy cases at one centre. METHOD: 72 patients who underwent cervical corpectomy between February 1992 and June 2001 were retrospectively investigated. FINDINGS: The indications for this operation were degenerative spondylitic disease (26 cases; 36.1%), trauma (18 cases; 25%), tumour (11 cases; 15.3%), infection (10 cases; 13.9%), and ossification of the posterior longitudinal ligament (7 cases; 9.7%). Thirty-seven patients (51.4%) underwent one-level corpectomy, and 35 (48.6%) underwent two-level corpectomy. Autografts were used in 13 cases (18.1%) and allografts were used in 59 cases (81.9%). Anterior plate-screw fixation was performed in all cases. There were 31 postoperative complications in 15 (20.8%) patients. Twelve of the complications were surgical, 5 were graft-related, 7 were plating-related, and 7 were medical. Solid bony fusion was achieved in 65 (92.9%) of the 70 surviving patients. The mean follow-up time was 23.4 months. An overall favourable outcome was achieved in 88% of cases. CONCLUSION: The outcomes in this series indicate that cervical corpectomy is an effective method for treating traumatic lesions, degenerative disease, tumours and infectious processes involving the anterior and middle portions of the cervical spine.

Ossified thoracic spinal meningioma in childhood: a case report and review of the literature.

Spinal ossified meningiomas are extremely rare. This is a report of a study on a 15-year-old boy with thoracic spinal ossified meningioma. The meningioma was resected totally. Histopathological examination revealed a transitional meningioma (psammomatous+meningothelial). Immunohistochemically, Ki 67 antibody was applied but no positive staining was present. The surgical and pathological aspects of spinal ossified meningiomas were reviewed.

Further cranial settling of the upper cervical spine following odontoidectomy. Report of two cases.

A variety of diseases may affect the craniovertebral junction and require a decompressive and fusion procedure. Craniovertebral junction instability is expected after a fusion procedure. The authors describe two patients with basilar invagination who underwent transoral odontoidectomy and occipitocervical fixation. Despite an uneventful immediate postoperative course, further cranial settling of the C-2 vertebral body (VB) was demonstrated. One patient experienced neurological deterioration and required a second decompressive procedure, whereas the second patient was asymptomatic and required no additional surgery. It was concluded that the odontoidectomy may have led to horizontal separation of the C-1 lateral masses, resulting in further cranial settling of the C-2 VB. Preservation of one aspect of the C-1 anterior arch minimizes C-1 lateral mass offset and, in turn, further cranial settling of the C-2 VB. In addition, a more rigid fixation of C-2 may minimize the possibility of horizontal separation of the C-1 lateral masses after transoral odontoidectomy.

Trigeminal root recording in normal trigeminal function.

Despite many investigations on the detection of trigeminal evoked potentials (TEP), there is still no consensus on a technique or interpretation of its components. In order to obtain clear TEP waveforms and analyze the origin of early components, we recorded TEP by the conventional far-field technique at the ipsilateral auricula as well as by near-field technique with a bipolar electrode at the trigeminal root just distal to the entry zone of its root. Trigeminal recordings were performed in nine patients with intrameatal vestibular schwannomas and in three with trigeminal neuralgia without trigeminal nerve deficits. In near-field recording at the trigeminal root, a triphasic response was recorded, with the first component occurring at 3.16 ms, 2.98 ms, and 4.16 ms following supraorbital, infraorbital, and mandibular nerve stimulation, respectively. Using conventional farfield TEP, the first component recorded at the trigeminal root occurred later than the first component in all other recordings. This suggests that the N2.0 component of far-field TEP is of extra-axial origin and the N5 component is of brainstem origin. The N13.0 component may be of cortical origin. We conclude that the N5.0 component and N5.0-N13.0 interpeak latency may be used as electrophysiological parameters of brainstem function during posterior fossa surgery.

Spinal epidural gas after cardiac surgery.

The authors describe a patient with severe lower back and left leg pain in the early postoperative period after cardiac surgery. Radiologic examination revealed gas in the spinal epidural space at the level of L4-5. The pain could not be relieved with analgesics and the patient underwent lumber surgery after cardiac surgery. After decompression, the patient improved and was discharged with no symptoms.

Role of retinoblastoma tumor suppressor protein in DNA damage response.

Growth arrest induced by DNA damage in mammalian cells requires the function of the retinoblastoma tumor suppressor protein (RB). RB-deficient cells cannot undergo G1, mid-S or G2 arrest following DNA damage, although they can activate the G2 checkpoint, which is reversible. RB-deficient cells are also hypersensitive to DNA damage-induced apoptosis. Induction of apoptosis in RB wild-type cells is associated with the loss of RB protein through cleavage by caspase. Two substitution mutations in exon 25 of the Rb gene have been created in the mouse germline to generate the Rb-MI allele that codes for a caspase-resistant RB protein. The RB-MI protein desensitizes cells to apoptosis. Taken together, these results suggest that RB plays a critical role in determining the cell fate following DNA damage. Growth arrest is dependent on RB and apoptosis is activated following RB degradation.

RB-dependent S-phase response to DNA damage.

The retinoblastoma tumor suppressor protein (RB) is a potent inhibitor of cell proliferation. RB is expressed throughout the cell cycle, but its antiproliferative activity is neutralized by phosphorylation during the G(1)/S transition. RB plays an essential role in the G(1) arrest induced by a variety of growth inhibitory signals. In this report, RB is shown to also be required for an intra-S-phase response to DNA damage. Treatment with cisplatin, etoposide, or mitomycin C inhibited S-phase progression in Rb(+/+) but not in Rb(-/-) mouse embryo fibroblasts. Dephosphorylation of RB in S-phase cells temporally preceded the inhibition of DNA synthesis. This S-phase dephosphorylation of RB and subsequent inhibition of DNA replication was observed in p21(Cip1)-deficient cells. The induction of the RB-dependent intra-S-phase arrest persisted for days and correlated with a protection against DNA damage-induced cell death. These results demonstrate that RB plays a protective role in response to genotoxic stress by inhibiting cell cycle progression in G(1) and in S phase.

cAMP-mediated growth inhibition of lymphoid cells in G1: rapid down-regulation of cyclin D3 at the level of translation.

cAMP is an important physiological mediator of lymphoid growth inhibition. The purpose of the present study was to establish the link between cAMP and the cell cycle machinery leading to inhibition of G1/S transition in human peripheral blood lymphocytes (PBL). To unravel immediate effects of cAMP on this part of the cell cycle machinery, lymphocytes were synchronized in mid to late G1 after stimulation with phytohemaglutenin (PHA) for 32 h. We report that addition of forskolin or cAMP analogues to the cells resulted in dephosphorylation of retinoblastoma protein commencing as early as 30 min. A rapid effect of forskolin was noted on the activity of cyclin-dependent kinase (cdk) 4, which decreased significantly within 30 min of treatment. The decrease in cdk4 activity was concurrent with reduced levels of cyclin D3 protein and a decrease in the fraction of cdk4 associated with cyclin D3. The down-regulation of cyclin D3 was at the level of translation, and this event was preceded by a pronounced inhibition of Akt/protein kinase B phosphorylation at Ser 473. Taken together, our data imply that cyclin D3 is a major effector of cAMP-mediated inhibition of cell cycle progression in PBL, and that cAMP exerts its effect on cyclin D3 expression at the level of translation.

Co-induction of Mad1 and c-Myc in activated normal B lymphocytes.

The purpose of the present study was to examine the expression of the Myc network proteins c-Myc, Mad1 and Max in normal cells under different growth and differentiation conditions. A dominant view has been that Mad1 as a c-Myc antagonist plays a role in growth inhibition linked to differentiation. Of particular interest to us was therefore to study the regulation of Mad1 in cells undergoing differentiation in the absence of growth cessation. To do so we utilized normal B lymphocytes isolated from peripheral blood. The cells were induced to concomitant proliferation and differentiation by stimulation with a combination of anti-IgM antibodies (anti-mu) and the phorbol ester TPA. Thus, by 72 h of stimulation the percentage of plasmablasts increased from 3 to 17%, and the percentage of lymphocytes decreased from 89 to 27%. The most intriguing observation we made using this cell system was a pronounced coinduction of Mad1 and c-Myc. The levels of c-Myc and Mad1 mRNAs and proteins increased within 3 h of anti-mu stimulation, and the levels were further enhanced by TPA. Furthermore, the expressions of both c-Myc and Mad1 were reduced by forskolin, which also inhibited the anti-mu + TPA driven growth and differentiation of the B lymphocytes. The level of Max remained virtually unchanged. Taken together, our results indicate that a high level of Mad1 in normal human B cells is linked to differentiation and not to growth inhibition. Furthermore, the results demonstrate that Mad1 and c-Myc are not necessarily expressed in a reciprocal manner, which underlines an independent role of Mad1 unrelated to its function as a c-Myc antagonist.

Cervical facet dislocation: techniques for ventral reduction and stabilization.

OBJECT: To demonstrate the safety and utility of one surgical approach, the authors reviewed their experience with the ventral surgical approach for decompression, reduction, and stabilization in 10 patients with either unilateral or bilateral cervical facet dislocation. METHODS: Six patients presented with unilateral cervical facet dislocation and four patients with bilateral cervical facet dislocation. There were six male and four female patients who ranged in age from 17 to 72 years (average 37.1 years). The level of facet dislocation was C4-5 in one, C5-6 in four, and C6-7 in five patients. Three patients presented with a complete spinal cord injury (SCI), three patients with an incomplete SCI, three with radicular symptoms or myeloradiculopathy, and one patient was neurologically intact. All patients underwent plain radiography, magnetic resonance imaging, and computerized tomography evaluation of the cervical spine. All patients had sustained significant ligamentous injury with minimum or no bone disruption. All patients underwent ventral decompressive surgery, reduction of the dislocation, and stabilization of the cervical spine. Techniques for performing ventral reduction of unilateral or bilateral cervical facet dislocation are described. Decompression, reduction, and stabilization of the cervical spine via the ventral approach was accomplished in all but one patient. This patient underwent a ventral decompressive procedure and an attempt at ventral reduction and subsequent dorsal reduction and fusion in which a lateral mass screw plate fixation system was used; this was followed by ventral placement of instrumentation and fusion. There were no surgery-related complications. Postoperative neurological status was unchanged in four patients and improved in six patients. No patient experienced neurological deterioration after undergoing this surgical approach. CONCLUSIONS: The authors conclude that a ventral surgical decompression, reduction, and stabilization procedure provides a safe and effective alternative for the treatment of patients with unilateral or bilateral cervical facet dislocation without significant bone disruption.