Management of parotid gland surgery in a university teaching hospital.

The aim of our study was the evaluation of two controversial procedures used in surgical management of parotid tumours in a university teaching hospital: fine needle aspiration cytology (FNAC) and continuous operative facial monitoring with nerve integrity monitor (NIM). We present a retrospective study of 96 consecutive cases of parotid gland surgical procedures, performed in our department of ENT Surgery (Bichat University Hospital) during a 2-year period. After the exclusion of nine patients (4 recurrent tumours, 3 insufficient data and 2 obviously malignant tumours with preoperative facial paralysis and necessary peroperative facial nerve sacrifice), the final group included 40 men and 47 women (mean age 46 years). FNAC, final histological diagnosis, NIM use, postoperative facial disorders and operative time were analysed. Other variables included age, sex, type of surgery and other postoperative complications. FNAC: 78 patients underwent FNAC. Positive predictive value for malignancy was 100%; negative predictive value 94.4%; sensitivity 63.6%; specificity 100%. NIM: surgery was performed without NIM for 41 patients, with for 46 patients. There was no significant difference in occurrence of facial disorders between the two groups. Operative time was significantly lower in group operated with NIM for extracapsular dissection, superficial parotidectomy and total parotidectomy. Because continuous efforts of modern health systems to improve operating room schedules may threaten resident surgeons training, using NIM and performing preoperative FNAC may help operative planning and improve medical education in a teaching hospital.

Epithelium expression and function of retinoid receptors in asthma.

Abnormal epithelial repair to damage participates in airway remodeling in asthma by the paracrine regulation of mesenchymal cell functions. Retinoids control epithelial functions through nuclear retinoic acid receptor (RAR) and retinoid X receptor (RXR) activation, yet their expression and contribution to epithelial repair and to airway remodeling in asthma are unknown. We determined the plasma levels of retinol and the immunohistochemical expression of retinoid receptors in damaged and repaired bronchial epithelium from 9 control subjects, 10 subjects with intermittent asthma, 8 subjects with mild-to-moderate asthma, and 8 subjects with severe asthma. In addition, the effect of the retinoid receptor ligands, all-trans-retinoic acid, and 9-cis retinoic acid, on the synthesis of 38 factors potentially involved in epithelial repair and in airway remodeling was determined in human cultured airway epithelial cells and correlated with cell migration and proliferation. Circulating retinol was similar in the three patient groups. In contrast, the epithelial expression of RARgamma, RXRalpha, and RXRgamma was greater in subjects with severe asthma, as compared with patients with milder disease and to control subjects. Retinoid receptor expression correlated positively with the proportion of morphologically intact epithelium. In vitro, retinoids up-regulated the expression of the transcripts encoding transforming growth factor (TGF)-beta1, metalloproteinase-9, beta1-integrin, and hepatocyte growth factor receptor, and promoted wound repair and chemokinesis of human airway epithelial cells without altering proliferation. Cell treatment with an anti-TGF-beta1 monoclonal antibody partially reduced retinoid-induced effects. Persistent interaction between retinoids and some of their receptors, which are overexpressed by the bronchial epithelium of individuals with severe asthma, may contribute to an abnormal repair and to airway remodeling, partly through TGF-beta1 production.

Nasal inverted papilloma expresses the muscle segment homeobox gene Msx2: possible prognostic implications.

Nasal inverted papilloma is a rare benign tumor of epithelial origin with aggressive evolution, bone destruction, recurrence, and malignant transformation. Msx2 is a homeobox gene implicated in organ development, bone metabolism, and tumorigenesis. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry, Msx2 expression was examined in nasal inverted papilloma and in nontumorigenic tissue counterparts. For the first time, Msx2 was detected in all inverted papillomas but not in the nasal polyps or in the normal mucosa. The protein expression level was directly and significantly associated with tumor recurrence. Furthermore, Msx2 was associated with bone resorption markers receptor activator of nuclear factor-kappa B ligand and tartrate-resistant acid phosphatase, suggesting a role in osteolysis. In conclusion, Msx2 expression may represent a useful prognostic marker in inverted papilloma.

Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group.

PURPOSE: To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis. PATIENTS AND METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety. RESULTS: At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms. CONCLUSION: Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation.

Immunohistochemical localization of plakophilins (PKP1, PKP2, PKP3, and p0071) in primary oropharyngeal tumors: correlation with clinical parameters.

Plakophilins (PKPs) are members of the armadillo multigene family. Armadillo-related proteins function in both cell adhesion and signal transduction, and also play a central role in tumorigenesis. Here we report the immunohistochemical localization of PKPs in 37 cases of human primary squamous cell carcinoma of the oropharynx lacking overt distant metastases that were followed clinically for 3 years. Immunoreactivity for the PKPs PKP1, PKP2, PKP3, and p0071 (also known as PKP4) was assessed on frozen unfixed sections using a semiquantitative scoring system. Results were correlated with tumor grade, clinicopathologic parameters, and patient survival. Only p0071 was associated with tumor growth, demonstrating an inverse correlation with tumor size. PKP1 and PKP3 immunoreactivity was inversely correlated with tumor histological grade and was observed only in tumors that did not metastasize. In contrast, strong PKP2 immunoreactivity was observed in 85.7% of metastatic tumors. Interestingly, patients with tumors in which PKP1 and PKP3 immunoreactivity was reduced or absent exhibited local recurrences or metastases, or both, as well as poor survival. Correlation of the subcellular localization of PKPs with routine histological and clinical parameters suggests that these proteins may serve as useful markers for predicting the clinical outcome of the disease. Although the 4 PKPs displayed different levels and patterns of subcellular distribution in tumors, there was a positive correlation between immunoreactivity for PKP2 and PKP3, as well as for PKP2 and p0071, suggesting possible functional similarities associated with differentiation, tumor growth, and disease prognosis. Nevertheless, the mechanisms involved in altering the subcellular localization in tumors compared with normal epithelium are unknown, and further investigation is needed to determine whether PKPs are causative factors for oral carcinogenesis or are merely characteristic of the phenotype.

Total glossectomy without laryngectomy as first-line or salvage therapy.

OBJECTIVES/HYPOTHESIS: Advanced carcinoma of the tongue can require total glossectomy. Although radiation therapy is of limited efficacy in T3 and T4 tumors involving the base of the tongue, many surgeons are reluctant to suggest highly mutilating surgery. STUDY DESIGN: Retrospective cohort study. METHODS: We compared early postoperative complications, hospital stay duration, function, and oncological outcomes in patients who underwent total glossectomy without laryngectomy as first-line or salvage therapy. RESULTS: Postoperative course and functional outcomes were similar in the two groups. Overall survival was 32% at 3 years and 21% at 5 years. The risk factors for shorter survival were positive margins of resection (P =.002) and tumor spread into the mandible (P =.04). Salvage surgery was not associated with significantly lower survival (P =.09 [NS]). CONCLUSIONS: Postoperative morbidity and functional outcomes are similar after first-line and salvage total glossectomy without laryngectomy. Local tumor control is the main factor influencing survival.

Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial.

PURPOSE: Osteoradionecrosis (ORN) is a nonhealing wound of the bone that is difficult to manage. Combined treatment with pentoxifylline and vitamin E reduces radiation-induced fibrosis and ORN with a good prognosis. We previously showed that the combination of pentoxifylline and vitamin E with clodronate (PENTOCLO) is useful in healing sternocostal and some mandibular ORN. Is PENTOCLO effective in ORN of poor prognosis? METHODS: 54 eligible patients previously irradiated for head and neck cancer (among 72 treated) a mean 5 years previously received exteriorized refractory mandibular ORN for 1.4 ± 1.8 years, mainly after local surgery and hyperbaric oxygen had been ineffective. The mean length of exposed bone (D) was 17 ± 8 mm as primary endpoint, and the mean Subjective, Objective, Management, and Analytic evaluation of injury (SOMA) score was 16 ± 4. Between August 2000 and August 2008, all patients were given daily oral PENTOCLO: 800 mg pentoxifylline, 1,000 IU vitamin E, and 1,600 mg clodronate 5 days per week alternating with 20 mg prednisone and 1,000 mg ciprofloxacin 2 days per week. The duration of treatment was related to consolidated healing. RESULTS: Prolonged treatment (16 ± 9 months) was safe and well tolerated. All patients improved, with an exponential progressive--(f[t] = a.exp(-b.t)--and significant (p < 0.0001) reduction of exposed bone (D), respectively (months): D(2) -42%, D(4) -62%, D(6) -77%, D(12) -92%, and D(18) -96%, combined with iterative spontaneous sequestrectomies in 36 patients. All patients experienced complete recovery in a median of 9 months. Clinical improvement was measured in terms of discontinuation of analgesics, new fracture, closed skin fistulae, and delayed radiologic improvement: SOMA(6) -64%, SOMA(12) -89%, and SOMA(30) -96%. CONCLUSION: Long-term PENTOCLO treatment is effective, safe, and curative for refractory ORN and induces mucosal and bone healing with significant symptom improvement. These findings will need to be confirmed in a randomized trial.

Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer.

Desmoplakin, a desmosomal component, is a key protein involved in cell-cell adhesion. Down-regulation of desmosomal proteins is associated with the invasive and metastatic ability of tumor cells. We examined 37 cases of human primary oropharyngeal squamous cell carcinomas lacking overt distant metastases to gain further insights on the potential role of desmoplakin in oral cancer. Desmoplakin expression was evaluated using reverse transcriptase-polymerase chain reaction and immunohistochemistry on frozen unfixed sections. Western blotting was performed to characterize the relative expression levels for each of the 2 desmoplakin protein isoforms, I and II. Desmoplakin expression was compared with histopathological grade, clinical stage, and patient outcome. Desmoplakin expression was prominent in highly differentiated tumors and reduced or absent in poorly differentiated tumors that developed distant metastases within the 3 years of follow-up period. Desmoplakin mRNA levels tracked with protein levels, suggesting that lack of desmoplakin protein expression is due to down-regulation of mRNA expression at the transcription level. Western blot analysis demonstrated that the 2 desmoplakin isoforms displayed different patterns of subcellular distribution in tumors, with the desmoplakin II detected only in patients in which desmoplakin immunoreactivity displayed an abnormal cytoplasmic localization. Our findings suggest that down-regulation of desmoplakin expression may represent a useful marker for evaluating the risk of distant metastasis formation in oropharyngeal squamous cell carcinomas. Interestingly, desmoplakin II was detected only in tumors associated with a poor clinical outcome, suggesting a potential specific function for this isoform in oral carcinogenesis. Characterizing DSP expression may improve evaluation risk of distant metastasis formation in oral cancer patients.

Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial.

BACKGROUND: Osteoradionecrosis (ORN) is a nonhealing wound of the bone that is difficult to manage. Is a treatment combining pentoxifylline (PTX) and tocopherol (vitamin E) boosted by clodronate effective in reversing this fibronecrotic process? METHODS: Eighteen consecutive patients previously irradiated for head and neck cancer had exteriorized mandible ORN. Length of exposed bone (L) was 13.4 +/- 8 mm, and the mean subjective objective medical management and analytic evaluation of injury (SOMA) score was 12.6 +/- 4.9. Between June 1995 and January 2002, all 18 were given a daily oral combination of 800 mg of PTX and 1000 IU of vitamin E for 6 to 24 months. In addition, the last eight patients who were the worst cases were given 1600 mg/day clodronate 5 days a week. RESULTS: The treatment was well tolerated. All patients improved at 6 months, with 84% mean L and 67% mean SOMA score reductions. Sixteen (89%) of 18 patients achieved complete recovery, 14 in 5 +/- 2.6 months. The remaining two patients exhibited a 75% response at 6 months. CONCLUSION: PTX-vitamin E boosted by clodronate is an effective treatment of mandibular ORN that induces mucosal and bone healing in a median period of 6 months.