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BACKGROUND Orbital exenteration (OE) is an ablative procedure used in the management of malignancies of the orbit of either primary or secondary origin. Publications evaluating this procedure have suffered from small patient numbers, heterogeneity of pathologies, and poor patient follow-up. The purpose of this study was to assess patient outcomes in a large cohort of patients undergoing OE at a tertiary cancer center. METHODS A retrospective review was conducted of 180 consecutive patients who underwent OE at the authors' institution. Overall survival (OS) was the primary end point measured in the study. Time to locoregional recurrence (progression-free survival [PFS]) and disease-free survival were secondary end points. RESULTS Between the years 1993 and 2011, 180 consecutive patients received OE for craniofacial malignancy at the authors' institution. The median follow-up for the cohort was 9.7 years (116 months). The median OS was 73 months, and the median PFS was 96 months. The presence of perineural invasion was associated with shorter OS (P = .01) and PFS (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter PFS than negative margins (P < .01) but with no change in OS (P = .15). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5), and there was 1 death observed (0.6%). CONCLUSIONS Used judiciously in the setting of a multidisciplinary management plan, OE for tumor control is a safe therapy. LAY SUMMARY Between the years 1993 and 2011, 180 consecutive patients received orbital exenteration for craniofacial malignancy at the MD Anderson Cancer Center. The median follow-up for the cohort was 9.7 years. The presence of perineural invasion was associated with shorter overall survival (P = .01) and progression-free survival (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter progression-free survival than negative margins (P < .01). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5).

Background Squamous cell carcinoma is the most common type of sinonasal malignancy. Despite improvements in surgical resection and adjuvant therapy, which are considered the standard of care, the outcome for patients with locoregionally advanced disease remains poor. The objective of this study was to investigate the role of induction chemotherapy in patients with locoregionally advanced sinonasal squamous cell carcinoma and to determine the oncologic outcomes in those patients. Methods The study included 123 consecutive patients with previously untreated, locoregionally advanced (stage III and IV) sinonasal squamous cell carcinoma who were treated with curative intent at The University of Texas MD Anderson Cancer Center between 1988 and 2017 with induction chemotherapy followed by definitive local therapy. Patient demographics, tumor staging, treatment details, and oncologic outcomes were reviewed. The outcomes of this study included response to induction chemotherapy, recurrence, organ preservation, and survival. Results The median follow-up was 32.6 months (range, 12.4-240 months). Of the 123 patients, 110 (89%) had T4 disease, and 13 (11%) had T3 disease. Lymph node metastasis at the time of presentation was observed in 36 patients (29.3%). The overall stage was stage IV in 111 patients (90.2%) and stage III in 12 patients (9.8%). The chemotherapy regimen consisted of the combination of a platinum and taxanes in most cases (109 patients; 88.6%), either as a doublet (41 patients) or in combination with a third agent, such as 5-fluorouracil (34 patients), ifosfamide (26 patients), or cetuximab (8 patients). After induction chemotherapy, 71 patients (57.8%) achieved at least a partial response, and 6 patients had a complete response. Subsequent treatment after induction chemotherapy was either: 1) definitive chemoradiation or radiation followed by surgical salvage for any residual disease, or 2) surgery followed by adjuvant radiation or chemoradiation. Overall, 54 patients (49.5%) underwent surgical resection. The 2-year overall and disease-free survival rates for the whole cohort were 61.4% and 67.9%, respectively. The rate of orbital preservation was 81.5%. The recurrence rate was 26.8% (33 patients), and distant metastases occurred in 8 patients (6.5%). Patients who had at least a partial response or stable disease had significantly better overall and disease-free survival than those who had progressive disease (P = .028 and P = .021, respectively). Conclusions The current results indicate that a high proportion of patients with sinonasal squamous cell carcinoma achieved a favorable response to induction chemotherapy. The data suggest that response to induction chemotherapy is associated with an improved outcome and a good chance of organ preservation. The oncologic outcomes in this cohort with locally advanced (mostly T4) disease are better than those historically reported in the literature. Further study of induction chemotherapy in patients with advanced sinonasal squamous carcinoma is warranted.

PURPOSE: To report cancer control outcomes and health-related quality of life (HRQoL) outcomes after highly conformal skull-based re-irradiation (re-RT). METHODS: Patients planned for curative intent re-RT to a recurrent or new skull base tumor were enrolled. HRQoL were assessed using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) and the anterior skull base surgery quality of life (ASBQ) questionnaires. RESULTS: Thirty-nine patients were treated with stereotactic body RT or intensity modulated RT. Median follow-up was 14 months. Progression free survival was 71% at 1-year. There was mild clinically significant worsening of fatigue, lack of appetite and drowsiness (MDASI-BT), and physical function (ASBQ) at the end of RT, followed by recovery to baseline on subsequent follow-ups. Subjective emotions were clinically improved at 12 months, with patients reporting feeling less tense/nervous. CONCLUSION: Conformal skull base re-RT is associated with mild immediate deterioration in physical function followed by rapid and sustained recovery.

Background Mucosal melanomas in the head and neck region are most often located in the nasal cavity and paranasal sinuses. To the authors' knowledge, the prognostic effects of lymph node metastasis in patients with sinonasal mucosal melanoma (SNMM) have not been established. Therefore, the objective of the current study was to determine the effects of lymph node metastasis on survival. Methods The current study included 198 patients with SNMM who had been treated between 1985 and 2016 at The University of Texas MD Anderson Cancer Center in Houston. Patients' clinical and pathologic lymph node statuses were evaluated and characterized. A multivariate analysis was used to assess the associations between regional spread and survival outcomes. Results Therapeutic neck dissection was performed in 23 patients with SNMM (11.6%). Regional disease recurrence occurred in 7 of the patients who had lymph node metastasis at the time of presentation (30.4%) and in 30 of those who had N0 disease at the time of presentation (17.1%) (P = .15). Metastasis to the contralateral lymph nodes was present in 7 patients (3.5%). The 5-year disease-specific survival rate was 66% in patients with lymph node spread compared with 45% in patients with N0 status (P = .04, log-rank test). A multivariate analysis demonstrated that distant metastasis was the only variable found to be independently associated with both overall survival (hazard ratio, 2.96; 95% confidence interval, 1.54-6.95 [P = .01]) and disease-specific survival (hazard ratio, 3.32; 95% confidence interval, 1.79-7.14 [P = 0.01]). Conclusions The results of the current study demonstrated that lymph node status in patients with SNMM was not a significant predictor of outcome. This finding, together with the low incidence of lymph node metastases in patients with SNMM, suggests that elective treatment of the neck should be highly selective in this patient population. Cancer 2018;124:514-20. © 2017 American Cancer Society.

Introduction Pediatric tubes are increasingly used for drawing blood for hemostasis testing. This study has investigated the potential impact of low volume citrate tubes on results of first-line hemostasis testing. Methods The study population comprised 34 patients on warfarin therapy and 17 ostensibly healthy volunteers. Blood was collected into five different evacuated blood tubes from each subject. On right arm, blood was drawn directly into two standard evacuated blood tubes (3-mL Vacuette and 2-mL Vacutest) and one evacuated low volume blood tube (1-mL Vacuette) by straight needle venipuncture. On left arm, blood was drawn using a 5-mL syringe and then transferred within two nonevacuated microtubes (0.5 mL MiniCollect and 0.5 mL Micro Test). Prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen were assayed on ACL TOP 700. Results Spearman's correlation of PT, APTT, and fibrinogen values obtained using different tubes was always satisfactory (ie, ≥0.93). A statistically significant bias was frequently found by comparing values obtained in different tubes. Nevertheless, the minimum quality specifications for bias were exceeded only by comparing data of Vacuette 1 mL with those of all other blood tubes for PT, by comparing data of Micro Test 0.5 mL with those of all other blood tubes for APTT, and by comparing data of Micro Test 0.5-mL blood tubes with those of Vacuette 3 mL and Vacuette 1. Conclusion First-line hemostasis testing using low volume citrate tubes may display differences sometimes exceeding the minimum quality specifications.

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2259-E2266, 2016.

Objectives/Hypothesis To examine our experience with surgically treated radiation-associated malignancy (RAM) of the temporal bone. Study Design Retrospective chart review. Methods Thirteen patients treated surgically for temporal-bone RAM during 1999 to 2012 were identified. Demographics, symptoms at presentation with RAM, interval between initial radiotherapy and diagnosis of RAM, pathologic features of RAM, treatment, and recurrence and survival were obtained from medical records. Results Ten patients had squamous cell carcinoma; three had sarcoma. The mean period between completion of radiotherapy and diagnosis of RAM was 13.38 years (range, 4.5–33.3 years). Three-year overall and disease-free survival rates were 59.8% and 42.3%, respectively. Seven patients (54%) had RAM limited to the external auditory canal (LEAC); six had RAM extending beyond it (EEAC). The mean age was 66.5 years for LEAC patients versus 41.1 years for EEAC patients (P = .0161). Compared to patients with EEAC disease, patients with LEAC disease were more likely to have negative margins (100% vs. 33%; P = .021) and less likely to have postoperative adjuvant therapy (0% vs. 67%; P = .0209). The 3-year disease-specific survival was significantly better for patients with LEAC disease versus EEAC (log rank P = .023). Conclusions To our knowledge, this is the largest reported series of surgically treated RAM of the ear canal or temporal bone. This study highlights the need for vigilance for RAM in patients treated with head and neck radiation. Level of Evidence 4. Laryngoscope, 125:1198–1204, 2015

While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within-grade heterogeneity with respect to recurrence-free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on hematoxylin and eosin sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment, we evaluated 363 meningiomas with phospho-histone H3 (Ser10) and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grade I (n = 268), grade II (n = 84) and grade III (n = 11) tumors were 1, 4 and 12. Classification and regression tree analysis to categorize cut-offs identified three subgroups defined by mitotic indices of 0-2, 3-4 and ≥5, which on univariate analysis were associated with RFS (P < 0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (P < 0.01) after adjustment for Simpson grade, WHO grade and MIB-1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and grade II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.

Streptococcus mutans is the leading cause of dental caries worldwide. The bacterium accumulates a glycogen-like internal polysaccharide, which mainly contributes to its carionegic capacity. S.mutans has two genes (glgC and glgD) respectively encoding putative ADP-glucose pyrophosphorylases (ADP-Glc PPase), a key enzyme for glycogen synthesis in most bacteria. Herein, we report the molecular cloning and recombinant expression of both genes (separately or together) followed by the characterization of the respective enzymes. When expressed individually GlgC had ADP-Glc PPase activity, whereas GlgD was inactive. Interestingly, the coexpressed GlgC/GlgD protein was one order of magnitude more active than GlgC alone. Kinetic characterization of GlgC and GlgC/GlgD pointed out remarkable differences between them. Fructose-1,6-bis-phosphate activated GlgC by twofold, but had no effect on GlgC/GlgD. Conversely, phospho-enol-pyruvate and inorganic salts inhibited GlgC/GlgD without affecting GlgC. However, in the presence of fructose-1,6-bis-phosphate GlgC acquired a GlgC/GlgD-like behaviour, becoming sensitive to the stated inhibitors. Results indicate that S. mutans ADP-Glc PPase is an allosteric regulatory enzyme exhibiting sensitivity to modulation by key intermediates of carbohydrates metabolism in the cell. The particular regulatory properties of the S.mutans enzyme agree with phylogenetic analysis, where GlgC and GlgD proteins found in other Firmicutes arrange in distinctive clusters.

Background Esthesioneuroblastoma is a rare cancer of the anterior cranial base that arises in the region of the olfactory rootlets. The purpose of this study was to review the long-term outcomes of patients diagnosed with esthesioneuroblastoma (ENB) treated at a single institution to determine factors associated with improved disease control and survival. Methods A retrospective review of 70 patients with ENB treated at the University of Texas MD Anderson Cancer Center between 1992 and 2007 was undertaken. Survival and recurrence was analyzed and compared using the Kaplan–Meier method and log-rank statistics. Results Seventy patients were reviewed. The majority (77%) had T3 or T4 disease at presentation, 38% identified as modified Kadish stage C or D. Ninety percent of patients received surgical resection as part of their treatment, and 66% received postoperative radiation or chemoradiation. The median follow-up was 91.4 months (7.6 years). Forty-eight percent of patients developed recurrent disease and the median time to recurrence was 6.9 years. Overall and disease-specific median survival was 10.5 and 11.6 years, respectively. Patients who were treated with surgery alone had a median disease-specific survival of 87.9 months, whereas those who were treated with surgery and postoperative radiation had a median disease-specific survival of 218.5 months (p = .047). Conclusion Patients with ENB can achieve favorable long-term survival, even if disease is locally advanced. Survival is improved considerably when surgical resection is followed by postoperative radiation. However, recurrence rates and mortality remain high, and therefore long-term observation in these patients is warranted. © 2013 Wiley Periodicals, Inc. Head Neck 36: 524–530, 2014

We recently reported the engineering of monomeric streptavidin, mSA, corresponding to one subunit of wild type (wt) streptavidin tetramer. The monomer was designed by homology modeling, in which the streptavidin and rhizavidin sequences were combined to engineer a high affinity binding pocket containing residues from a single subunit only. Although mSA is stable and binds biotin with nanomolar affinity, its fast off rate (koff ) creates practical challenges during applications. We obtained a 1.9 A crystal structure of mSA bound to biotin to understand their interaction in detail, and used the structure to introduce targeted mutations to improve its binding kinetics. To this end, we compared mSA to shwanavidin, which contains a hydrophobic lid containing F43 in the binding pocket and binds biotin tightly. However, the T48F mutation in mSA, which introduces a comparable hydrophobic lid, only resulted in a modest 20-40% improvement in the measured koff . On the other hand, introducing the S25H mutation near the bicyclic ring of bound biotin increased the dissociation half life (t½ ) from 11 to 83 min at 20°C. Molecular dynamics (MD) simulations suggest that H25 stabilizes the binding loop L3,4 by interacting with A47, and protects key intermolecular hydrogen bonds by limiting solvent entry into the binding pocket. Concurrent T48F or T48W mutation clashes with H25 and partially abrogates the beneficial effects of H25. Taken together, this study suggests that stabilization of the binding loop and solvation of the binding pocket are important determinants of the dissociation kinetics in mSA.

Item does not contain fulltext Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E2259-E2266, 2016.

Background In scalp reconstruction, soft tissue and osseous defects frequently coexist. The purpose of this study was to compare outcomes of simultaneous scalp and calvarial reconstruction to scalp only reconstruction. Methods A review of microsurgical scalp reconstruction with or without cranioplasty over a 10-year period was performed. Results One hundred thirty-eight scalp reconstructions were performed, of which 48 involved concurrent cranioplasty. The overall rate of perioperative complications was 21.0%, whereas the rate of late recipient site complications was 11.6%. No significant differences in perioperative (p = .56) or late (p = .42) recipient site complications were observed between patients undergoing scalp and calvarial versus scalp only reconstruction. In terms of complications, muscle free flaps with skin grafts were as reliable as free flaps with skin paddles (p = .36). Conclusion Simultaneous scalp and calvarial reconstruction is associated with success rates equivalent to scalp only reconstruction. Muscle flaps covered with skin grafts and flaps with a skin paddle seem to be equally reliable. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Background. Neuroendocrine carcinoma (NEC) of the paranasal sinuses is rare, accounting for 5% of sinonasal malignancies. The purpose of this study was to assess prognostic factors and survival rates for sinonasal NEC. Methods. A retrospective review of patients with NEC treated from 1990 to 2004 was performed. Patient demographics, TNM classification, treatment modality, recurrences, and survival were evaluated. Results. NEC was identified in 28 patients; the most common primary site was the ethmoid sinuses. Most patients presented with advanced tumors; few had regional or distant metastasis. Local recurrence rate was 21%. Five-year overall survival (OS) and disease-specific survival (DSS) rates were 65% and 78%, respectively. Response to chemotherapy predicted for improved survival, although no differences in outcomes were noted between definitive management strategies. Conclusion. NEC of the paranasal sinuses is an exceedingly rare malignancy of the paranasal sinuses. Our data suggests definitive management with surgery or radiotherapy offers durable control. The response to chemotherapy may predict for overall outcomes. V C 2011 Wiley Periodicals, Inc. Head Neck 34: 1372-1376, 2012

This paper deals with the fatigue behaviour of a short fibre reinforced thermoplastic under multi-axial cyclic stress. Based on experimental results on notched and plain specimens, limits of existing methods for the fatigue life estimation in the design process of components exposed to complex multi-axial loads were investigated. During the manufacturing process of short fibre reinforced thermoplastic components, a moderately anisotropic behaviour in stiffness and strength arises. Because of the material's anisotropy, classical failure hypotheses for the assessment of multiaxial load cases do not apply. In this study, a fatigue failure hypothesis was implemented that assesses the stress components in accordance with the correlating fatigue strengths in the material coordinate system, considering potential interaction between the stress components. Striving for a verified multi-usable fatigue life assessment method, multiaxial load cases were examined experimentally. The experimental results on unnotched and notched specimens and the fatigue life estimation on the basis of the Tsai-Wu-failure hypothesis will be presented. In diesem Beitrag wird das Ermudungsverhalten eines kurzglasfaserverstarkten Thermoplasts unter mehrachsiger zyklischer Belastung behandelt. Basierend auf Messwerten an gekerbten und ungekerbten Proben wurden die Grenzen vorhandener Methoden zur Lebensdauerabschatzung wahrend des Designprozesses von Bauteilen abgeschatzt, welche komplexen mehrachsigen Belastungen ausgesetzt sind. Durch den Herstellprozess stellt sich bei Bauteilen aus kurzglasfaserverstarkten Thermoplasten ein leicht anisotropes Steifigkeits- und Festigkeitsverhalten ein. Wegen des anisotropen Materialverhaltens konnen klassische Versagenskriterien nicht zur Berechnung mehrachsiger Lastfalle herangezogen werden. In der vorliegenden Untersuchung wurde ein Versagenskriterium angewandt, mit dem die Spannungskomponenten gemas den zugehorigen Ermudungsfestigkeiten im Materialkoordinatensystem bewertet werden. Dazu werden mogliche Wechselwirkungen zwischen den Spannungskomponenten berucksichtigt. Um die universell einsetzbare Methode zur Lebensdauerabschatzung zu uberprufen, wurden mehrachsige Lastfalle experimentell untersucht. In dieser Arbeit werden die experimentellen Ergebnisse an ungekerbten und gekerbten Proben und die Lebensdauerabschatzung auf der Grundlage des Tsai-Wu Versagenskriteriums vorgestellt.

BACKGROUND: Although a rare complication of ionizing radiation, radiation-induced osteosarcoma is now more frequently recognized as radiation therapy has become common and cancer survival has increased. To date, publications on radiation-induced osteosarcoma of the cranium are limited to a few small series and case reports. METHODS: Data from 175 patients with a history of sarcoma of the head at The University of Texas M. D. Anderson Cancer Center from 1975 to 2007 were reviewed to identify patients with radiation-induced osteosarcoma. The diagnostic criteria were: 1) osteosarcoma arose within the previously irradiated field; 2) new sarcoma was histologically distinct from the original neoplasm; 3) no evidence of new sarcoma at the time of radiation; and 4) distinct latency period could be recognized. Frequencies and descriptive statistics were obtained for the various characteristics under study. RESULTS: The authors identified 16 patients with radiation-induced osteosarcoma of the cranium at their institution. The average age at diagnosis was 35 years. The median latency period was 12.5 years. Nine patients had skull base tumors, and 7 had calvarial tumors. Of the 14 patients treated surgically, 86% developed local recurrence. The median survival time was 29 months, and the 5-year survival rate was 29.6%. CONCLUSIONS: The authors report the largest series of cranial radiation-induced osteosarcoma. Although radiation-induced osteosarcoma is an uncommon but dire complication of radiotherapy, its incidence will probably increase in the future as the frequency of radiation treatment and cancer survival increase. These tumors are locally aggressive, and despite aggressive surgical and medical management, they have a high rate of local recurrence and mortality. Cancer 2011. © 2010 American Cancer Society.

The properties related to non‐radiative energy transfer of a number of enkephalin analogues with tryptophan substituted for phenylalanine in position 4 and n.m.r. 3JNH‐CαH coupling constants of corresponding [Phe4]‐enkephalin analogues are being derived from semi‐empirical conformational energy. The molecules considered contain a glycyl, a D‐alanyl or an L‐alanyl as second residue; two of the compounds are N‐methylated at position 4 or 5. The [Trp4]‐ enkephalin analogues and the corresponding [Phe4]‐enkephalin analogues display nearly parallel affinities in the opiate receptor binding assay (Schiller et al.(1)). The comparison of computed and experimental properties shows that an ensemble of conformers is a satisfactory representation of the state of these molecules in water. © 1981 Munksgaard International Publishers Ltd.

A statistical molecular model for hydrated peptides is used to simulate the behaviour of various peptide chains in aqueous solution. The reliability of the model is ascertained by the evolution of the characteristic ratio, Cn, for hydrophobic and hydrophilic polypeptide chains, such as, respectively, poly‐Ala and poly‐Ser. The comparison of computed and experimental properties related to non radiative energy transfer of angiotensin II analogs, assuming that an ensemble of conformers is a satisfactory representation of the state of these molecules in water, provides further support for the model. © 1982 Munksgaard International Publishers Ltd.

Background. We report a rare case of endodermal sinus tumor (EST) of the paranasal sinus in a 59-year-old man with a 6-week history of nasal obstruction. Methods and Results. High-resolution MRI showed a right nasoethmoid mass with obstructive changes in the sphenoid, frontal, and right maxillary sinuses and orbital and intracranial extension. Histologic analysis showed 2 distinct histologic features: poorly differentiated carcinoma and EST. Immunohistochemical studies showed strong keratin staining in both components and restricted positivity of α-fetoprotein in the endodermal sinus-like component. The patient underwent 3 cycles of neoadjuvant chemotherapy consisting of ifosfamide, paclitaxel, and cisplatin, which resulted in significant regression of the tumor, but after the fourth cycle, the mass showed a slight increase in size. The tumor was excised with clear margins through an anterior craniofacial approach to the skull base. Histologic examination of the resected specimen showed extensive fibrosis with residual areas of viable tumor composed mainly of the poorly differentiated component with only residual microscopic foci of EST. Adjuvant postoperative intensity-modulated radiation therapy was administered. At 1-year follow-up, the patient was tumor free, with normal α-fetoprotein levels. Conclusion. Because of the rarity of this entity, no standardized treatment protocol has been defined. The involvement of the anterior skull base in our case necessitated a radical craniofacial resection, despite a partial response to chemotherapy. © 2007 Wiley Periodicals, Inc. Head Neck, 2008

OBJECTIVES: To describe the quality of dementia care within one U.S. metropolitan area and to investigate associations between variations in quality and patient, caregiver, and health system characteristics. DESIGN: Observational, cross-sectional. SETTING AND PARTICIPANTS: Three hundred eighty-seven patient-caregiver pairs from three healthcare organizations MEASUREMENTS: Using caregiver surveys and medical record abstraction to assess 18 dementia care processes drawn from existing guidelines, the proportion adherent to each care process was calculated, as well as mean percentages of adherence aggregated within four care dimensions: assessment (6 processes), treatment (6 processes), education and support (3 processes), and safety (3 processes). For each dimension, associations between adherence and patient, caregiver, and health system characteristics were investigated using multivariable models. RESULTS: Adherence ranged from 9% to 79% for the 18 individual care processes; 11 processes had less than 40% adherence. Mean percentage adherence across the four care dimensions was 37% for assessment, 33% for treatment, 52% for education and support, and 21% for safety. Higher comorbidity was associated with greater adherence across all four dimensions, whereas greater caregiver knowledge (in particular, one item) was associated with higher care quality in three of four care dimensions. For selected dimensions, greater adherence was also associated with greater dementia severity and with more geriatrics or neurologist visits. CONCLUSION: In general, dementia care quality has considerable room for improvement. Although greater comorbidity and dementia severity were associated with better quality, caregiver knowledge was the most consistent caregiver characteristic associated with better adherence. These findings offer opportunities for targeting low quality and suggest potential focused interventions.

Objectives To evaluate the effect of a multicomponent dementia care management program on primary care provider knowledge, attitudes, and perceptions of quality of dementia care. Design A clinic-level randomized, controlled trial of a comprehensive care management program for patients with dementia and their nonprofessional caregivers. The program included provider education and protocols for care managers to communicate with patients' medical providers. Setting Eighteen clinics (nine intervention, nine [corrected] usual care) in three healthcare systems in San Diego, California. Participants Two hundred thirty-two medical providers; 129 from nine [corrected] intervention clinics; 103 from nine [corrected] usual-care clinics. Measurements Providers were surveyed 9 months after intervention onset on knowledge (five items on four topics), attitudes about dementia (three items), and perception of quality of dementia care in their practice setting (three items). Multivariable linear and logistic regression models were used to evaluate the differences between intervention and usual-care providers, adjusting for covariate effects across groups and clustering by clinic. Results One hundred sixty-six of 232 (72%) providers responded. Intervention providers had better knowledge about assessing decision-making capacity than usual-care providers (adjusted difference in percentage correct = 12%; adjusted odds ratio = 2.4, 95% confidence interval = 1.2-4.8). Intervention providers viewed dementia patients as more difficult to manage in primary care than usual-care providers (P = .03). There were no other differences in knowledge, attitudes, or care quality perceptions across intervention and usual-care providers. Conclusion A comprehensive dementia care management model resulted in few differences in provider knowledge or attitudes favorable to dementia care, suggesting that this care model's effects on quality were primarily mediated through other components of the care management program.

Objectives/Hypothesis: We reviewed our experience with craniofacial resection for advanced, nonmelanoma skin cancer of the head and neck to determine prognostic factors, local control rate, disease free survival, morbidity, and mortality. Study Design: Retrospective review of consecutive patients treated at a tertiary referral center from 1982 to 1993. Methods: Charts of patients having craniofacial resection for aggressive nonmelanoma cutaneous malignancies were reviewed and living patients followed for 10 additional years. Demographics, histology, previous interventions, treatment, surgical pathology, reconstructions, and complications were examined. The product-limit method was used to calculate survival functions, and the log-rank test was used to compare survival distributions. Results: Thirty-five patients, mean age 66.7 years, received treatment at our facility. Follow-up ranged from 2 to 191 (mean 47.4) months. Histology included 20 squamous cell carcinomas (SCC) and 15 basal cell carcinomas (BCC). Sixty percent had craniofacial resection alone, and 28.6% also had postoperative radiotherapy. There were two perioperative deaths, and 37.1% suffered early and 14.3% late surgical complications. Two- and five- year survival was significantly better (P = .02) with BCC (92% and 76%) than with SCC (54% and 24%). Long-term disease-specific survival was 20%, and 11.4% of our subjects were living with disease. Intracranial extension (P = .02), perineural invasion (P = .049), and prior radiotherapy significantly decreased 5-year survival. Conclusions: Acceptable mortality and morbidity is possible using craniofacial resection to treat advanced nonmelanoma skin cancer. Although disease-specific survival remains poor, positive trends were noted in local control beginning at 2 years of follow-up. Because patients often have few remaining options for cure, craniofacial resection is justified when technically feasible.

BACKGROUND Sinonasal neuroendocrine tumors are rare malignancies that are represented by a spectrum of histologies, including esthesioneuroblastoma (ENB), sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and small cell carcinoma (SmCC). The authors reviewed their institutional experience to determine whether sinonasal neuroendocrine tumors of different histologies have distinct clinical characteristics that warrant individualized treatment approaches. METHODS The authors treated 72 adults with pathologically proven, nonmetastatic, primary sinonasal neuroendocrine tumors from 1982 to 2002. There were 31 patients with ENB, 16 patients with SNUC, 18 patients with NEC, and 7 patients with SmCC. Patients with ENB usually were treated with local therapy alone (surgery and/or radiotherapy); only 3 of 31 patients (9.7%) received treatment (radiation) to regional lymphatics, and only 5 of 31 patients (16.1%) received chemotherapy. In contrast, patients with non-ENB histologies usually received chemotherapy (10 of 16 patients with SNUC, 12 of 18 patients with NEC, and 5 of 7 patients with SmCC), and nonsurgical locoregional therapy was used more frequently (6 of 16 patients with SNUC, 4 of 18 patients with NEC, and 5 of 7 patients with SmCC). RESULTS The median follow-up for surviving patients was 81.5 months (range, 6–266 months). The Kaplan–Meier estimate of overall survival at 5 years was 93.1% for patients with ENB, 62.5% for patients with SNUC, 64.2% for patients with NEC, and 28.6% for patients with SmCC (P = 0.0029; log-rank test). The local control rate at 5 years also was superior for patients who had ENB (96.2%) compared with patients who had SNUC (78.6%), NEC (72.6%), or SmCC (66.7%) (P = 0.04). The regional failure (RF) rate at 5 years was 8.7% for patients with ENB, 15.6% for patients with SNUC, 12.9% for patients with NEC, and 44.4% for patients with SmCC. Additional late events increased the RF rate for patients with ENB to 31.9% at 10 years. The distant metastasis rate at 5 years was 0.0% for patients with ENB, 25.4% for patients with SNUC, 14.1% for patients with NEC, and 75.0% for patients with SmCC. CONCLUSIONS This spectrum of malignancies with neuroendocrine features shares a common site of origin within the head and neck, but their natural histories appear to diverge into two main groups: ENB and non-ENB. Patients with ENB had excellent local and distant control rates with local therapy alone. Given the higher rates of systemic failure for patients with SNUC, NEC, and SmCC, the authors favor the use of combined-modality therapy for these patients. Cancer 2004. © 2004 American Cancer Society.

Background Adenocarcinoma is a rare tumor of the sinonasal tract. The purpose of this study was to characterize a single institution's experience with this malignancy. Methods Retrospective review was performed of patients with adenocarcinoma of the sinonasal tract from 1993 to 2009. Demographic data, disease presentation, treatment, and survival rates were collected and evaluated. Results We identified 66 patients with sinonasal adenocarcinoma; 48 were men and 18 women. Average age at time of diagnosis was 57.1 years (range, 20–88 years), and median follow-up was 55.3 months (range, 1–238 months). The ethmoid sinus (38%) and nasal cavity (36%) were the most common sites of origin. Nasal obstruction (36%), epistaxis (30%), and nasal discharge (21%) were the most common presenting symptoms. Fifty-one percent of patients presented with T1 or T2 tumors. Surgery was the primary form of treatment in 81% of patients. Twenty-six percent of surgical patients underwent an endoscopic tumor resection. Adjuvant radiation was utilized in 50% of patients and chemotherapy in 10%. Recurrence was seen in 24 patients (37%): 29% recurred locally and 7.6% recurred distantly. The overall 5-year survival was 65.9%. Survival was decreased significantly in patients with T4 tumors (p < .05), high-grade histology (p < .05), and sphenoid sinus involvement (p < .05). Survival was not affected by surgical approach between endoscopic and open approaches (p = .76). Conclusion Sinonasal adenocarcinomas are commonly identified in the sinonasal cavity and are associated with a relatively favorable prognosis, despite a substantial local failure rate of 30%. Advanced-stage tumors, sphenoid sinus and skull base invasion, and high-grade histology portend poor prognosis. In our experience, endoscopic resection was not associated with adverse outcomes and suggests that this minimally invasive approach can provide acceptable oncologic outcomes in selected patients. © 2014 Wiley Periodicals, Inc. Head Neck, 36: 1490–1496, 2014

The KlDIM1 gene encoding the m2(6)A rRNA dimethylase was cloned from a Kluyveromyces lactis genomic library using a PCR amplicon from the Saccharomyces cerevisiae ScDIM1 gene as probe. The KlDIM1 gene encodes a 320-amino acid protein which shows 81% identity to ScDim1p from S. cerevisiae and 25% identity to ksgAp from Escherichia coli. Complementation of the kasugamycin-resistant ksgA-mutant of E. coli lacking dimethylase activity demonstrates that KlDim1p is the functional homologue of the bacterial enzyme. Multiple alignment of dimethylases from prokaryotes and yeasts shows that the two yeast enzymes display distinctive structural motives including a putative nuclear localization signal.

Streptococcus mutans is the leading cause of dental caries worldwide. The bacterium accumulates a glycogen-like internal polysaccharide, which mainly contributes to its carionegic capacity. S. mutans has two genes (glgC and glgD) respectively encoding putative ADP-glucose pyrophosphorylases (ADP-Glc PPase), a key enzyme for glycogen synthesis in most bacteria. Herein, we report the molecular cloning and recombinant expression of both genes (separately or together) followed by the characterization of the respective enzymes. When expressed individually GlgC had ADP-Glc PPase activity, whereas GlgD was inactive. Interestingly, the coexpressed GlgC/GlgD protein was one order of magnitude more active than GlgC alone. Kinetic characterization of GlgC and GlgC/GlgD pointed out remarkable differences between them. Fructose-1,6-bis-phosphate activated GlgC by twofold, but had no effect on GlgC/GlgD. Conversely, phospho-enol-pyruvate and inorganic salts inhibited GlgC/GlgD without affecting GlgC. However, in the presence of fructose-1,6-bis-phosphate GlgC acquired a GlgC/GlgD-like behaviour, becoming sensitive to the stated inhibitors. Results indicate that S. mutans ADP-Glc PPase is an allosteric regulatory enzyme exhibiting sensitivity to modulation by key intermediates of carbohydrates metabolism in the cell. The particular regulatory properties of the S. mutans enzyme agree with phylogenetic analysis, where GlgC and GlgD proteins found in other Firmicutes arrange in distinctive clusters. Fil: Asención Diez, Matías Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina. Loyola University Chicago. Department of Chemistry and Biochemistry; Estados Unidos Fil: Demonte, Ana María Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina Fil: Guerrero, Sergio Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina Fil: Ballicora, Miguel A.. Loyola University Chicago. Department of Chemistry and Biochemistry; Estados Unidos Fil: Iglesias, Alberto Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; Argentina