Impact of azole antifungal treatment on outcome in acute invasive fungal rhinosinusitis with orbitocranial involvement: a surgical perspective.

PURPOSE: To provide real-life data on azole treatment outcomes and the role of surgery in the current management of invasive fungal rhinosinusitis complicated by orbitocranial fungal infection (OCFI). METHODS: Data was collected retrospectively from a chart review from four participating centers and a systematic literature review. The study group included patients with OCFI treated with azole antifungals. The control cases were treated with other antifungal agents. The cranial and orbital involvement degree was staged based on the imaging. The extent of the surgical resection was also classified to allow for inter-group comparison. RESULTS: There were 125 patients in the azole-treated group and 153 in the control group. Among the patients with OCFI cranial extension, 23% were operated on in the azole-treated group and 18% in the control group. However, meninges and brain resection were performed only in the controls (11% of patients) and never in the azole antifungals group. Orbital involvement required surgery in 26% of azole-treated cases and 39% of controls. Despite a more aggressive cranial involvement, azole-treated patients' mortality was significantly lower than in controls, with an OCFI-specific mortality rate of 21% vs. 52%. A similar, though not statistically significant, trend was found for the extent of the orbital disease and surgery. CONCLUSION: Despite less aggressive surgical intervention for cranial involvement, OCFI patients treated with azoles had a higher survival rate. This finding suggests we may improve morbidity with a more conservative surgical approach in conjunction with azole treatment. The same trend is emerging for orbital involvement.

Analysis of the prognostic significance of lymph node related characteristics in papillary thyroid carcinoma patients presenting with pre- or intra-operative evidence of cervical lymph node metastases.

OBJECTIVE: To identify the prognostic significance of specific lymph node related characteristics for disease persistence and recurrence in patients with pre- or intra-operative evidence of neck metastases and no other risk factors. METHOD AND RESULTS: Sixty-eight patients were identified; 50 per cent had persistent or recurrent disease. All underwent the same treatment strategy. There were no statistically significant differences in any of the patient- or tumour-related parameters when patients with and without persistence or recurrence were compared. Patients with recurrent or persistent disease had significantly larger (>3 cm) metastatic lymph nodes, but there were no differences regarding other lymph node related parameters (i.e. number, extracapsular extension, number of lymph nodes with extracapsular extension, and central vs lateral neck location). On multivariate analysis, however, none of the parameters were predictive of persistent or recurrent disease. CONCLUSION: In papillary thyroid carcinoma patients with no other risk factors, pre- or intra-operative evidence of cervical metastases was associated with a very high rate of disease persistence or recurrence. Specific lymph node characteristics were not shown to have prognostic significance.

NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva.

Differentially methylated oral squamous cell carcinoma (OSCC) biomarkers, identified in vitro and validated in well-characterized surgical specimens, have shown poor clinical correlation in cohorts with different risk profiles. To overcome this lack of relevance, we used the HumanMethylation27 BeadChip, publicly available methylation and expression array data, and quantitative methylation specific PCR to uncover differential methylation in OSCC clinical samples with heterogeneous risk profiles. A two stage design consisting of discovery and prevalence screens was used to identify differential promoter methylation and deregulated pathways in patients diagnosed with OSCC and head and neck squamous cell carcinoma. Promoter methylation of KIF1A (κ = 0.64), HOXA9 (κ = 0.60), NID2 (κ = 0.60), and EDNRB (κ = 0.60) had a moderate to substantial agreement with clinical diagnosis in the discovery screen. HOXA9 had 68% sensitivity, 100% specificity, and a 0.81 Area Under the Curve (AUC). NID2 had 71% sensitivity, 100% specificity, and a 0.79 AUC. In the prevalence screen, HOXA9 (κ = 0.82) and NID2 (κ = 0.80) had an almost perfect agreement with histologic diagnosis. HOXA9 had 85% sensitivity, 97% specificity, and a 0.95 AUC. NID2 had 87% sensitivity, 95% specificity, and a 0.91 AUC. A HOXA9 and NID2 gene panel had 94% sensitivity, 97% specificity, and a 0.97 AUC. In saliva, from OSCC cases and controls, HOXA9 had 75% sensitivity, 53% specificity, and a 0.75 AUC. NID2 had 87% sensitivity, 21% specificity, and a 0.73 AUC. This phase I Biomarker Development Trial identified a panel of differentially methylated genes in normal and OSCC clinical samples from patients with heterogeneous risk profiles. This panel may be useful for early detection and cancer prevention studies.

The impact of positive resection margins in partial laryngectomy for advanced laryngeal carcinomas and radiation failures.

OBJECTIVES: To investigate the prognostic significance of positive margin and disease course in partial laryngectomy for advanced laryngeal carcinoma and radiation failure. DESIGN: Retrospective case control study. SETTING: A major tertiary referral centre. PARTICIPANTS: Patients who underwent partial laryngectomy for advanced laryngeal carcinoma or for radiation failure with at least 2 years of follow-up. MAIN OUTCOME MEASURES: Margin status versus primary treatment and salvage treatment versus disease-free survival and overall survival. RESULTS: Twenty nine patients with sufficient follow-up data were found. Twelve patients had histological positive margin. Five of the 12 patients with a histological positive margin failed surgery as did four patients with clear margins. A positive margin had no effect on disease-free survival (P = 0.287) but was associated with poorer overall survival (P = 0.051). Of 11 patients treated primarily with surgery, recurrence was documented in one of eight with a positive margin and none of three with clear margins. Of 18 patients who underwent surgery secondary to radiation failure, recurrence was documented in all four with a positive margin and 4 of 14 with negative margins. Extended frontolateral resection, performed only in radiation failures, was associated with worse disease-free survival. CONCLUSIONS: Non-irradiated patients with involvement of a single margin after partial laryngectomy may be spared total laryngectomy if adjuvant radiation is administered. Patients who fail radiation should undergo radical partial laryngectomy, with conversion to total laryngectomy in those with a positive margin.

Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome.

OBJECTIVE: To assess the possible effect of young age on clinical behaviour and survival outcome of squamous cell carcinoma of the oral tongue. DESIGN: Retrospective, case control study. SETTING: A major tertiary referral centre. PARTICIPANTS: Eighty-five patients with oral tongue squamous cell carcinoma with at least 2 years of follow-up. MAIN OUTCOME MEASUREMENTS: Clinical and histopathological staging, disease-free survival, disease-specific survival and overall survival. RESULTS: Eleven patients (13%) were younger than 30 years. Compared to the older patients, they had a significantly worse N stage (P = 0.041), more perineural invasion (P = 0.012), and higher rates, though not significant, of treatment failure (46%, including 60% with distant metastases, versus 35%, nearly all locoregional) and mortality (100% of treatment failures versus 73%). There were no significant between-group differences in 5-year disease-free, disease-specific, and overall survival. CONCLUSION: In this study, patients younger than 30 years of age presented with advanced tumour stages and with a different failure pattern compared to the older age group. This may be attributable to age-related biologic behaviour or delayed cancer diagnosis. Differences in disease free survival and overall survival could not be established.

Predicting facial nerve invasion by parotid gland carcinoma and outcome of facial reanimation.

We sought to define risk factors for facial nerve involvement in parotid gland carcinoma and assess the outcome of facial nerve reanimation. Medical records were reviewed of 66 patients who underwent surgery for parotid carcinoma in 2000­2007 at a tertiary hospital. Patient and tumor characteristics were compared between patients with and without facial nerve involvement and were analyzed on their influence on functional outcome following reanimation. Facial nerve involvement was verified intraoperatively in 24 patients, of whom 16 underwent reanimation during ablative surgery. Deep lobe invasion was significantly associated with intraoperative finding of facial nerve involvement. Tumors larger than 4 cm and salivary duct carcinoma had an obvious trend for facial nerve involvement. House-Brackmann score at 12 months was 3-4 in most patients. Deep lobe involvement and large tumor size may identify patients at risk of facial nerve involvement. Reanimation is associated with good functional outcome regardless of patient's age.

Supracricoid partial laryngectomy: an alternative to total laryngectomy for locally advanced laryngeal cancers.

OBJECTIVES: The management of advanced laryngeal cancer has evolved in the last century, from total laryngectomy to chemoradiation. The aim of this study was to examine our experience with supracricoid partial laryngectomy as a possible solution for patients with advanced laryngeal tumours, with a focus on the oncological safety of the procedure and the functionality of the preserved larynges. STUDY DESIGN: We reviewed the medical records of patients with laryngeal cancer who had undergone primary or salvage supracricoid partial laryngectomy at our department between 1998 and 2004. RESULTS: Twenty-three patients treated with supracricoid partial laryngectomy for endolaryngeal squamous cell carcinoma were identified. Median follow-up time was 35 months. Twelve patients had advanced laryngeal tumours. Eight patients were radiation failures. These factors were not associated with increased local recurrence or with decreased survival. CONCLUSION: Supracricoid partial laryngectomy appears to be a feasible option for the treatment of laryngeal tumours, even in the advanced stage or after failure of radiation therapy.

The early light-induced protein is also produced during leaf senescence of Nicotiana tabacum.

To better understand the genetic controls of leaf senescence, a tobacco (Nicotiana tabacum L. cv. SR1) mRNA that is up-regulated during senescence was isolated by the cDNA-amplified restriction fragment polymorphism method and the cDNA was cloned. The mRNA coded for the early light-induced protein (ELIP), a member of the chlorophyll a/b-binding protein family that has been implicated in assembly or repair of the photosynthetic machinery during early chloroplast development and abiotic stress. A protein antigenically recognized by antibodies to ELIP appeared during senescence with kinetics similar to those of its mRNA. The mRNA, designated ELIP-TOB, was detected earlier when senescence was enhanced by leaf detachment and treatment with 1-amino-cyclopropane-1-carboxylic acid, and was detected later when senescence was retarded by benzyladenine. However, no ELIP-TOB mRNA was seen in the dark even though senescence was accelerated under these conditions. Furthermore, water stress and anaerobiosis stimulated the appearance of ELIP-TOB mRNA before losses of chlorophyll could be detected. We discuss the conditions that may lead to the up-regulation of ELIP-TOB during senescence and speculate as to the role of the gene product in this terminal phase of leaf development.

Cytokinin, acting through ethylene, restores gravitropism to Arabidopsis seedlings grown under red light.

Cytokinin replaces light in several aspects of the photomorphogenesis of dicot seedlings. Arabidopsis thaliana seedlings grown under red light have been shown to become disoriented, losing the negative hypocotyl gravitropism that has been observed in seedlings grown in darkness or white light. We report here that cytokinin at micromolar concentrations restores gravitropism to seedlings grown under red light. Cytokinin cancels the effect of red light on the gravity-sensing system and at the same time replaces light in the inhibition of hypocotyl elongation. Furthermore, application of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid acts similarly to cytokinin. Cytokinin cannot restore gravitropism under red light to an ethylene-insensitive mutant that is defective at the EIN2 locus. Stimulation of ethylene production, therefore, can explain the action of cytokinin in restoring negative gravitropism to the hypocotyls of Arabidopsis seedlings grown under continuous red light.

Adipocyte conversion of CHEF cells in serum-free medium.

When grown in the presence of serum with added insulin, Chinese hamster embryonic fibroblasts (CHEF/18) cells can be induced to become preadipocytes that are committed to the adipocyte pathway of terminal differentiation (Sager, R., and P. Kovac, 1982, Proc. Natl. Acad. Sci. USA, 79:480-484). We found that commitment to the adipocyte pathway, as well as terminal differentiation to form mature adipocytes, can occur in a defined serum-free medium containing insulin. When CHEF/18 cells are plated in serum-containing medium, only 5-10% of cells in each colony undergo terminal differentiation, whereas in serum-free medium, greater than 90% of the cells became adipocytes. These and other results show that CHEF/18 cells require no adipogenic factors in addition to insulin and the other components of the serum-free medium (transferrin, epithelial growth factor, thrombin) to form adipocytes, and furthermore, that serum inhibits the rate of terminal adipocyte differentiation of these cells. As little as 10 ng/ml insulin added to serum-containing medium can induce adipogenesis, suggesting that insulin rather than an insulinlike growth factor is the active agent. The results further demonstrate that virtually every CHEF/18 cell can be induced into the adipocyte pathway.

Ribonucleic acid bacteriophage release: requirement for host-controlled protein synthesis.

The release of the ribonucleic acid (RNA)-containing phage MS2 from Escherichia coli is accompanied by cellular lysis at 37 C, whereas at 30 C phage are released from intact cells. Chloramphenicol or rifampin prevents the release of progeny phage particles at both temperatures. Neither drug causes an immediate cessation of phage release and after inhibition of protein synthesis by chloramphenicol phage release proceeds for about 17 min at 37 C and about 35 min at 30 C. Rifampin does not inhibit phage release from mutant cells possessing a rifampin-resistant deoxyribonucleic acid-dependent RNA polymerase. The results indicate that a short-lived host-controlled protein(s) is essential for the release of RNA phage particles at both temperatures.

Inhibition of ribonucleic acid bacteriophage release from its host by rifampin.

Rifampin, in addition to interfering with intracellular growth of the ribonucleic acid-containing phage MS2, also inhibits the release of mature phage particles from Escherichia coli cells.