Raman spectroscopy in oral cavity and oropharyngeal cancer: a systematic review.

Due to the high incidence of head and neck cancer and under-diagnosis in the early stages, non-invasive and highly accurate diagnostic tests are required for cancer detection. Recent advances in Raman spectroscopy techniques have yielded promising sensitivity and specificity results in the evaluation of cancer. The aim of this study was to investigate the potential value of Raman spectroscopy in oral cavity and oropharyngeal cancer diagnosis based on currently available scientific papers. A search of the PubMed database was performed using a specific strategy and according to the PRISMA guidelines. Raman spectroscopy achieved a maximum accuracy of 98% in cancer detection, while accuracy was 97.24% for tumour grading evaluation, 95% for cancer treatment assessment, and 77% for the detection of cancer recurrence. Moreover, early-stage cancer can be identified by Raman spectroscopy investigation of liquid biopsy samples. An in vivo technique with direct mucosa examination by fibre-optic Raman spectroscopy obtained a maximum accuracy of 94% in cancer diagnosis. The most prominent markers of the presence of malignancy were an increase in Raman signal intensity for proteins, nucleic acids, and water and a decrease for lipids. These cancer discriminants were detected in both fingerprint and high wavenumber regions. In conclusion, Raman spectroscopy is a promising tool for oral cavity and oropharyngeal cancer screening.

Rapid and noninvasive diagnosis of oral and oropharyngeal cancer based on micro-Raman and FT-IR spectra of saliva.

Fast, sensitive, and noninvasive techniques are needed for better health care management, particularly when traditional biopsies could be replaced with appropriate analyses of body fluids, such as saliva. Here is presented a proof-of-concept study, which aims to test a recently developed saliva samples preparation method, for oral and oropharyngeal cancer diagnosis, using micro-Raman and Fourier transform infrared (FT-IR) spectroscopic techniques. The detected biomarker bands and the cancer classification rates are compared and discussed. Saliva samples were collected from healthy donors and pathologically confirmed oral and oropharyngeal cancer patients. Principal components analysis (PCA) and principal components analysis-linear discriminant analysis (PCA-LDA) chemometric methods were applied to build discrimination models for the test and control groups. Based on the differences between salivary spectra of healthy and cancer patients, several biomarker bands were identified. Noteworthy, a significant vibrational biomarker band at 2064 cm-1, assigned to thiocyanate, was observed in both the FT-IR and Raman data-set. Other cancer characteristic Raman bands were 754 cm-1 (tryptophan), 530 and 927 cm-1 (lysozyme), 1001 cm-1 (phenylalanine), while the FT-IR biomarker band was located at 1075 cm-1 (phosphodiester bonds stretching in DNA, RNA). The oral and oropharyngeal cancer was classified with an accuracy of 90% based on the micro-Raman data and 82% based on the FT-IR data set, respectively. The study showed that oral and oropharyngeal cancer can be differentiated from control saliva samples based on their respective micro-Raman and FT-IR spectral signatures, due to the biomolecular modifications induced by the disease.

Age of onset of recurrent respiratory papillomatosis: a distribution analysis.

OBJECTIVE: Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample. DESIGN: Cross-sectional distribution analysis. PARTICIPANTS: Laryngologists from 12 European hospitals provided information on date of birth and date of onset of all their RRP patients treated between 1998 and 2012. Centers that exclusively treated either patients with juvenile onset RRP or patients with adult onset RRP, or were less accessible for one of these groups, were excluded to prevent skewness. MAIN OUTCOME MEASURES: A mixture model was implemented to describe distribution of age of onset. The best fitting model was selected using the Bayesian information criterion. RESULTS: Six hundred and thirty-nine patients were included in the analysis. Age of onset was described by a three component mixture distribution with lognormally distributed components. Recurrent respiratory papillomatosis starts at three median ages 7, 35 and 64 years. CONCLUSIONS: Distribution of age of onset of RRP shows three peaks. In addition to the already adopted idea of age peaks at paediatric and adult age, there is an additional peak around the age of 64.

Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients.

Intralesional use of cidofovir (Vistide(®)) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2-6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.

[Lymphatic and vascular invasion in laryngeal and pyriform sinus carcinomas]. / Die lymphatische und vaskuläre Ausbreitung von Larynx- und Sinus piriformis Plattenepithelkarzinomen.

BACKGROUND: To investigate prognostic significance of the lymphatic and vascular invasion in patients with squamous cell carcinoma of the larynx and pyriform sinus. MATERIAL AND METHODS: Patients with squamous cell carcinoma of the larynx and pyriform sinus who underwent laryngectomies between 2002 and 2006 in the ENT Clinic of Cluj-Napoca were investigated for lymphatic and vascular invasion and their effect on disease-free survival and recurrence rates. RESULTS: The present study included 396 patients. The mean disease-free survival of patients with or without lymphatic invasion was statistically significant (p=0.000000). The mean disease-free survival of patients with or without vascular invasion was statistically significant (p=0.000021). In multivariant analysis, the lymphatic invasion was significantly correlated only with surgical resection borders (p=0.0004), while vascular invasion was significantly correlated with surgical resection borders (p=0.0000), nodes diameter (p=0.0075) and postoperative radiotherapy and/or chemotherapy (p=0.0002). CONCLUSION: Lymphatic and vascular invasion have a significant prognostic value and influence the disease-free survival, regional and distant metastasis rates significantly.

Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos?

The production of carbon nanofibers and nanotubes (CNF/CNT) and their composite products is increasing globally. CNF are generating great interest in industrial sectors such as energy production and electronics, where alternative materials may have limited performance or are produced at a much higher cost. However, despite the increasing industrial use of carbon nanofibers, information on their potential adverse health effects is limited. In the current study, we examine the cytotoxic and genotoxic potential of carbon-based nanofibers (Pyrograf®-III) and compare this material with the effects of asbestos fibers (crocidolite) or single-walled carbon nanotubes (SWCNT). The genotoxic effects in the lung fibroblast (V79) cell line were examined using two complementary assays: the comet assay and micronucleus (MN) test. In addition, we utilized fluorescence in situ hybridization to detect the chromatin pan-centromeric signals within the MN indicating their origin by aneugenic (chromosomal malsegregation) or clastogenic (chromosome breakage) mechanisms. Cytotoxicity tests revealed a concentration- and time-dependent loss of V79 cell viability after exposure to all tested materials in the following sequence: asbestos>CNF>SWCNT. Additionally, cellular uptake and generation of oxygen radicals was seen in the murine RAW264.7 macrophages following exposure to CNF or asbestos but not after administration of SWCNT. DNA damage and MN induction were found after exposure to all tested materials with the strongest effect seen for CNF. Finally, we demonstrated that CNF induced predominantly centromere-positive MN in primary human small airway epithelial cells (SAEC) indicating aneugenic events. Further investigations are warranted to elucidate the possible mechanisms involved in CNF-induced genotoxicity.

Surgical management of Gerhardt syndrome.

Adduction bilateral vocal fold immobility syndrome may be due by both recurrent laryngeal nerves paralysis--Gerhardt syndrome--and all intrinsic laryngeal muscles paralysis--Riegel syndrome. Etiology of Gerhardt syndrome is thyroid surgery, intubation's maneuver, trauma, neurological disorders, extrala-ryngeal malignancies. The manifestations of Gerhardt syndrome are inspiratory dyspnea and slightly influenced voicing by paramedian vocal folds paralysis with an important narrowing of the airway at the glottic level. The surgical procedures for enlargement of the glottic space can be classified in many ways and their major characteristics are: changes at the glottic level; surgical approach: open neck or endoscopic, with or without opening of the mucosal lining; the need for tracheostomy; the equipment used. The aim of this review is to expound the variety of interventions through the last century marked by the development of the diagnostic methods, the anesthesia and the surgical armament with sophisticated instruments and technologies.

Vagal paraganglioma: imaging versus intraoperative findings.

A 59-year-old woman presented with a mass on the jugulo-digastric level. Inspection of the oral cavity showed medial bulging of the left pharyngeal wall and tonsil. Transcutaneous ultrasonography showed a vascular tumor of the parapharyngeal space with complete encirclement of the internal carotid artery. Magnetic resonance angiography and common carotid angiography showed the bloody support from the external carotid artery of that tumor. During the surgical procedure, we identified the tumor, who arises from the vagus nerve and who had multiple fine arterial branches from the internal carotid artery until the skull base. We performed complete resection of the parapharyngeal tumor, by transcervical approach, with sacrificed the vagus nerve. The histopathological report showed a vagal paraganglioma. After one year is no sign of recurrence.

[Cortisone treatment in prevention of pharyngocutaneous fistula after total laryngectomy]. / Tratamentul cortizonic în prevenirea fistulei faringo-cutanate postlaringectomie totala.

PURPOSE: To identify a method of prophylaxis in pharyngocutaneous fistula (PCF) after radical surgery for cancer of larynx and pyriform fossa. MATERIALS AND METHODS: A prospective longitudinal study on patients who were operated for cancer of larynx and pyriform fossa, in year 2007 in ENT Department of Clinic Emergency County Hospital Cluj-Napoca, with total laryngectomy and partial hypo-pharyngectomy. These patients were distributed in two lots: case (who received postoperative treatment with hemisuccinate of hydrocortisone or dexamethasone) and witness (they didn't received cortisone or other treatment except the standard therapy). We followed the detection of PCF at these 2 lots of patients and the time of resumption for naturally feeding and hospitalization. We performed the bi-variant analysis (Spearman). RESULTS: 23 patient were accomplished the inclusion and exclusion criteria. 4 of those patients developed postoperative pharyngo-cutaneous fistula, only one in the case lot. Statistically, cortisone administrated postoperative brought benefits: PCF was developed in a significant reduced proportion (p=0.02) and the resumption of naturally feeding was made in a significant shorter time (p=0.003) and hospitalization time was significantly reduced (p=0.001). CONCLUSION: Cortisone administration after total laryngectomy and partial hypo-pharyngectomy seems to be a prophylactic method for pharyngocutaneous fistula.

Treatment with zincum metallicum CH5 in patients with liver cirrhosis. Preliminary study.

The zinc, an important enzymatic cofactor, is involved in many metabolic processes. Its deficiency might be due either to malabsorption or to excessive utilization. In the medical literature of the latest 10 years, zinc was considered to play a part in the immune processes. The authors of the present paper intend to study the zinc and immunoglobulin levels in various diseases, i.e., chronic progressive hepatitis, liver cirrhosis (LC), dermatitis, bronchial asthma. This preliminary investigation was carried out in 30 patients with LC in whom serum zinc values were assayed by atomic absorption spectrophotometry and the immunoglobulin levels were determined using the Mancini type simple radial immunodiffusion technique. All these patients presented considerable decrease of serum zinc concentration, the values ranging between 3.06 and 7.65 mumol/l as compared with 19.8 +/- 1.5 mumol/l in the controls, alongside with the increase of immunoglobulins G and M. In the patients treated with Zincum metallicum CH5 it was observed after about 30 days of treatment that the clinical state was considerably improved and IgG and IgM as well as serum zinc had resumed their normal values. This treatment should not be interrupted since in LC, without permanent additional supply, the serum zinc returns rapidly to the initial deficit or even lower.

The zinc-immunodeficiency relationship in old patients.

The influence of oral zinc sulphate therapy on the humoral immunity was investigated by dosages of serum immunoglobulins (Ig) and of plasma zinc levels in 12 patients with a mean age of 70 years, in comparison with other 11 patients treated with placebo and with a control group of 50 apparently healthy subjects. The results of this double-blind study demonstrated the zinc effect on the immunoregulation, as the Ig levels, and particularly those of the IgG class, initially high, were lowered in a statistically significant proportion. It is assumed that further clinical trials with various zinc concentrations could bring more information on this trace element participation in the humoral immunoregulation.

Zinc supplementation of chelation therapy in saturnism. Preliminary study.

The effect of zinc supplementation of chelation therapy in saturnism was studied in 20 patients hospitalized in the Clinic of Occupational Diseases of the Colentina Hospital. In 10 patients 400 mg/day zinc sulphate in two uptakes was administered concomitantly with the chelation therapy. The other 10 patients received only chelation therapy. The period necessary for the correction of the anemic syndrome was estimated comparatively by studying the evolution of the following parameters: hemoglobin, reticulocytes, red blood cells with basophilic granulations. Zinc supplementation of the chelation therapy had a favourable effect by reducing the necessary period for the correction of anemic syndrome.

The in vitro action of a succussed substance on the proliferative response of human lymphocytes stimulated with phytohemagglutinin.

Human peripheral blood lymphocytes from healthy controls, immunodepressed patients presenting chronic bacterial infections or neoplasias and from allergic patients were stimulated in vitro with phytohemagglutinin (PHA) in culture medium supplemented or not with 1 x 10(-7), 1 x 10(-15) or 1 x 10(-30) succussed dilutions or bee venom or phosphorus in tridistilled water. The most significant inhibition due to DNA incorporation was noted in lymphocytes from allergic patients cultivated in media supplemented with 1 x 10(-30) succussed substance dilution in the presence of PHA. The cells from immunodepressed patients did not show a significant inhibition at 1 x 10(-30) dilution. Hypothetically, we try to explain these findings as the expression of the changes induced by the succussed solution on the water molecule which in turn, influences the chemical structure of the cellular membrane and implicitly, its functions.

Houses and allergic respiratory syndromes.

A study was carried out in 49 flats in Bucharest inhabited by 265 persons. A quantitative analysis of fungi spores was performed as well as allergologic tests with Penicillium and Aspergillus fungi (A13), Aspergillus niger (M2), Alternaria tenuis (M1), Cladosporium herbarum (M3), Dermatophagoides pteronissinus (allergenic products supplied by the Bencard firm). The infested flats presented a high percentage of Aspergillus niger spores, particularly pathogenic. The main triggering factors for the appearance of the respiratory allergenic syndromes were found to be the conditions of humidity and the inadequate ventilation. Children are more affected by exposure to these conditions of the housing microclimate. Latent sensitization to fungi and to the Dermatophagoides pteronissinus mite in about 1/3 of the children and 1/5 of the adults represents a highly significant percentage of future candidates to bronchial asthma. A first requirement for the success of treatment in such subjects is the change of inhabiting conditions.

The IgD-zinc relationship in patients with allergic bronchial asthma.

In recent years, evidence was brought of the zinc ion (Zn++) interference in the mechanism of certain processes occurring at molecular level, i.e., the protein synthesis, the activity of some enzymatic complexes, the regulation of transmembranal transport or the processes of immune regulation. The present paper investigates the variations of the immunoglobulin classes in patients with bronchial asthma, particularly the relationship between IgD levels and those of the zinc ion in the blood serum.

Frequency of certain allergens in allergic bronchial asthma.

The frequency of some allergens involved in allergic bronchial asthma was studied in a group of 1177 patients who came for medical investigations to the Department of Allergy of the "N. Gh. Lupu" Institute of Internal Medicine--Bucharest between January 1980 and January 1982. The group presented a slight predominance of the female sex and the age group most affected was that of young adults. Of the allergens responsible for the onset bronchial asthma attacks the most frequent in the patients studied were: house dust (56%), moulds (53%), pollens (42%) and Dermatophagoides pteronissinus (28.3%). Of the pollens the most often involved was that of grasses. Almost a quarter of the patients started an attack of bronchospasm and presented positive reaction to certain drugs (24.39%) of which the most frequently involved was aspirin (17.4%), pyramidon (15.4%), biseptol, antibiotics (the latter being often used exagerately as self medication in the attacks of allergy mistaken for "colds"). The most frequent association of allergens were moulds--Dermatophagoides pt. (21%) and moulds--Dermatophagoides pt.--house dust (19%).