Comparison of narrow band imaging and the Storz Professional Image Enhancement System for detection of laryngeal and hypopharyngeal pathologies.

OBJECTIVE: The aim of this study was to compare narrow band imaging (NBI) endoscopy and Storz Professional Image Enhancement System (SPIES) in observing epithelial and/or subepithelial microvascular irregularities and pathologies. METHODS: A total of 73 patients with laryngeal or hypopharyngeal lesions were investigated using high-definition NBI endoscopy preoperatively in local anesthesia and using SPIES system intraoperatively in general anesthesia from August 2016 to October 2017. Superficial vascular structures were classified preoperatively (NBI) and intraoperatively (SPIES) according to descriptive guidelines of vascular changes by Arens. All lesions were endoscopically evaluated and divided according to the histological examination into four groups (A-benign lesions, B-recurrent respiratory papillomatosis, C-low-grade dysplasia, D-high-grade dysplasia, carcinoma in situ or invasive squamous cell carcinoma), and results were compared with NBI and SPIES optical biopsy. RESULTS: Benign lesions (polyps, cysts, chronic inflammation, hyperkeratosis) were histologically confirmed in 26/73 (35.6%) cases and identified by NBI in 20/26 lesions (76.9%) and in 20/26 cases (76.9%) by SPIES, respectively. Recurrent respiratory papillomatosis was confirmed in 16/73 (21.9%) and detected in 15/16 cases (93.8%) by NBI and in 16/16 cases (100.0%) by SPIES. Low-grade dysplasia (mild and moderate dysplasia) was histologically detected in 7/73 patients (9.6%) and accurately identified by NBI in 6/7 (85.7%) and by SPIES in 6/7 (85.7%) cases, respectively. Histopathological features of severe dysplasia, carcinoma in situ or invasive squamous cell carcinoma were detected in 24/73 (32.9%) patients. According to the NBI endoscopy the suspected vascular neoangiogenesis was recognized in 19/24 cases (79.2%) and in 18/24 cases (75.0%) using SPIES endoscopy. Sensitivity and specificity of NBI endoscopy and SPIES system in correct prediction of histological diagnosis of already detected lesions were 83.0 and 98.0% and 86.0 and 96.0%, respectively. Results of NBI/SPIES endoscopy and histopathological features of laryngeal and hypopharyngeal lesions were compared and the level of agreement was 81.43%, kappa index κ = 0.7428 (95% CI 0.682-0.832) (p < 0.001) by NBI endoscopy and 81.16%, kappa index κ = 0.7379 (95% CI 0.638-0.880) (p < 0.001) by SPIES endoscopy, respectively. The agreement was confirmed as substantial and strong. Level of agreement of both endoscopic methods was 92.54%, kappa index κ = 0.8965 (95% CI 0.877-0.954) (p < 0.001), agreement was confirmed as almost perfect. Between NBI and SPIES endoscopic imaging methods is no significant differentiation. CONCLUSION: Both methods, NBI endoscopy and SPIES system, are comparable in detection and analysis of superficial neoangiogenesis, typical for benign lesion and for precancerous or cancerous changes in larynx and hypopharynx.

Laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis (prospective case-control study).

OBJECTIVE: The human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Although HPV prevalence is high, the incidence of papillomatosis is low. Thus, factors other than HPV infection probably contribute to RRP. This study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (ChT) and whether laryngopharyngeal reflux (LPR) occurs in this group of patients more often. DESIGN: Prospective case-control study. SETTING: Department of Otorhinolaryngology of University Hospital. PARTICIPANTS: The study included 20 patients with adult-onset RRP and 20 adult patients with vocal cord cyst and no pathology of laryngeal mucosa (control group). MAIN OUTCOME MEASURES: Immunohistochemical analysis of pepsin, HPV, herpes simplex virus type 2 and ChT was performed in biopsy specimens of laryngeal papillomas and of healthy laryngeal mucosa (control group) obtained from medial part of removed vocal cord cyst during microlaryngoscopy procedures. RESULTS: Pathologic LPR (pepsin in tissue) was diagnosed in 8/20 (40.0%) patients with papillomatosis and in 0/20 control patients (P = .003). Herpes simplex virus type 2 was present in 9/20 (45.0%) patients with papillomatosis and in 0/20 control patients (P = .001). Five specimens were positive for both pepsin and herpes simplex virus type 2. No samples were positive for ChT. There were no significant differences between groups for age, body mass index, diabetes mellitus and gastrooesophageal reflux disease. Tobacco exposure was not more frequent in RRP group either (P = .01). CONCLUSIONS: Results show that LPR and herpes simplex virus type 2 are significantly more often present in patients with RRP. LPR and herpes simplex virus type 2 might activate latent HPV infection and thereby be possible risk factors for RRP.

Nonlinear Thomson scattering with ponderomotive control.

In nonlinear Thomson scattering, a relativistic electron reradiates the photons of a laser pulse, converting optical light to x rays or beyond. While this extreme frequency conversion offers a promising source for probing high-energy-density materials and driving uncharted regimes of nonlinear quantum electrodynamics, conventional nonlinear Thomson scattering has inherent trade-offs in its scaling with laser intensity. Here we discover that the ponderomotive control afforded by spatiotemporal pulse shaping enables regimes of nonlinear Thomson scattering that substantially enhance the scaling of the radiated power, emission angle, and frequency with laser intensity. By appropriately setting the velocity of the intensity peak, a spatiotemporally shaped pulse can increase the power radiated by orders of magnitude. The enhanced scaling with laser intensity allows for operation at significantly lower electron energies or intensities.

[Radiological normal anatomy of the larynx and pharynx and imaging techniques]. / Radiologische Normalanatomie des Larynx und Pharynx sowie bildgebende Techniken.

The larynx and the pharynx represent anatomically as well as functionally a very complex organ which serves as an airway and a nutrition channel. Knowledge of anatomy and anatomical topography is therefore a fundamental basis for the evaluation of any pathological process. Beside the clinical examination and endoscopy performed by ear, nose and throat specialists, imaging techniques play a crucial role in pre-therapeutic and post-therapeutic diagnostics. The radiologist employs a conventional x-ray swallow examination, as well as contrast-enhanced multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), positron emission tomography (PET) and positron emission tomography-computed tomography (PET-CT), depending on the medical problem in question. The following article demonstrates the functional and especially the structural anatomy of the larynx and the pharynx. Furthermore, the broad range of imaging techniques in clinical use is discussed.

[Pathological changes of the hypopharynx in the focus of imaging]. / Pathologische Veränderungen des Hypopharynx im Brennpunkt der Bildgebung.

The spectrum of pathological changes in anatomical sections of the hypopharynx ranges from benign pathologies to hypopharyngeal carcinoma. Beside the clinical status and the endoscopic evaluation performed by ear, nose and throat specialists, imaging techniques play an important role in pre-therapeutic and post-therapeutic diagnostics and in the follow-up of pharyngeal disease patterns, especially for malignant lesions. A conventional x-ray swallow examination, contrast-enhanced multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI), as well as positron emission tomography (PET) and positron emission tomography computed tomography (PET-CT) are applied depending on the medical question and disease. Especially in radiological oncology, it is extremely important in regions which are clinically difficult to assess to determine the exact localization and extent of hypopharyngeal pathologies to plan the optimal therapy for the patient. This article demonstrates the radiological appearance of pathological changes of the hypopharynx and discusses in particular the hypopharynx carcinoma in the focus of pre-therapeutic and post-therapeutic imaging.

MALT lymphoma in patients with autoimmune diseases: a comparative analysis of characteristics and clinical course.

MALT lymphoma, especially of extragastric origin, is thought to be associated with an underlying autoimmune disease (AD) in a significant proportion of patients. No systematic assessment of the clinical characteristics of MALT lymphoma arising in AD as opposed to patients without AD has been performed so far. Therefore, all patients diagnosed and treated for MALT lymphoma at our institution have prospectively undergone routine clinical and serological assessment for AD since 1997. In total, 158 patients were available for analysis, and 61 out of 158 patients (39%) were diagnosed with an underlying AD. Patients with AD were predominantly women and significantly younger at lymphoma diagnosis (56 versus 67 years, P=0.004), with a significantly higher rate of extragastric lymphomas (P=0.012). Furthermore, lymphomas in these patients showed a lower frequency of trisomy 3 (P=0.04) and a significantly lower response rate to Helicobacter pylori eradication therapy in the case of gastric lymphomas (P=0.03). All other parameters including estimated median time to relapse were comparable between both groups. Our data suggest that patients with AD develop MALT lymphoma significantly earlier in life. The clinical course, however, does not appear to be adversely influenced by the presence of AD, as neither rate of relapse nor times to relapse or survival are significantly different.

Saline injection to determine the volume required for personalised patulous Eustachian tube augmentation with long-standing material.

OBJECTIVE: There is currently no general consensus on patulous Eustachian tube management. Injection of autologous fat, cartilage or hydroxylapatite has been described for Eustachian tube occlusion, with promising results. However, complete resolution of symptoms is not achieved in all cases. This could be connected to the amount of material injected into the surroundings of the Eustachian tube, as this greatly differs among existing studies. Identifying the appropriate volume of injected material could be challenging because anatomical conditions vary among patients, and there is always a risk of chronic Eustachian tube obstruction and its related complications when too much long-standing material is injected.Case reportA case is presented wherein saline was injected under local anaesthesia to determine the volume required and to predict the success of patulous Eustachian tube augmentation with long-standing material. CONCLUSION: This approach could allow more personalised treatment and help identify patients likely to benefit from the procedure.

Modern imaging lymph node staging of the head and neck region.

The aim of this paper is to describe the modern imaging methods, their techniques, ability, and performance in staging head and neck lymph nodes. Also, the imaging morphologies of benign and malignant lymph nodes according to the different imaging techniques will be delineated. The imaging techniques of ultrasound including contrast-enhanced ultrasound, computed tomography and magnetic resonance imaging (MRI) including diffusing weighted imaging and contrast-enhanced iron oxide MRI are explained. Imaging examples of the different modalities of benign and malignant transformed lymph nodes will be demonstrated. Furthermore, the diagnostic sensitivity of each modality will be delineated and further aspects of modern lymph node staging of the head and neck region such as those with special contrast agents will be described. These modern imaging modalities have sensitivity rates of 70-80% depending on the technical equipment and ability and on the experience of the investigator. The technique of near-infrared-imaging will be mentioned in another article in this journal. Also the value of biopsy techniques including recently developed ultrasonography guided needle biopsy with molecular analysis of the cells of about 97-100% accuracy in diagnosing benign from malignant lymph nodes will be mentioned. Overall, the reader will get an overview of the present imaging modalities to potentially stage correctly lymph nodes in the head and neck region to facilitate the therapeutic procedure.

Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites.

Although several recurrent genetic aberrations are known to occur in MALT lymphoma, no comprehensive study on the most prevalent MALT lymphoma-associated genetic aberrations is available. We therefore screened 252 primary MALT lymphomas for translocations t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32), and trisomies 3 and 18. The above-listed translocations occurred mutually exclusively and were detected overall in 13.5, 10.8, and 1.6% of the cases; trisomy 3 and/or 18 occurred in 42.1%. The frequency at which the translocations occurred varied markedly with the primary site of disease. The t(11;18)(q21;q21) was mainly detected in pulmonary and gastric tumors, whereas the t(14;18)(q32;q21) was most commonly found in lesions of the ocular adnexa/orbit, skin, and salivary glands. Trisomies 3 and 18 each occurred most frequently in intestinal and salivary gland MALT lymphomas. Our results demonstrate that the three translocations and trisomies 3 and 18 occur at markedly variable frequencies in MALT lymphoma of different sites.

Beta-2-microglobulin levels in patients with extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type: a retrospective analysis.

BACKGROUND: Serum levels of beta-2 microglobulin (B2M) have been reported as a predictor of clinical outcome, prognosis and tumor burden in patients with various types of lymphomas. In case of lymphoma of the mucosa-associated lymphoid tissue (MALT)-type, no clear data exist to define the role of B2M in terms of staging or prognosis. In a retrospective analysis we investigated the serum B2M-levels in patients suffering from histologically verified MALT-type lymphoma in correlation to stage and response to treatment. PATIENTS AND METHODS: All patients admitted to our institution since 1996 with a diagnosis of MALT-type lymphoma were retrospectively evaluated for staging procedures and measurements of serum B2M levels. Patients with a staging work-up including otorhinolaryngologic evaluation, gastroscopy with multiple biopsies, endosonography of the upper GI-tract, enteroclysis, colonoscopy, CT of thorax and abdomen and bone marrow biopsy were analysed, while staging was performed according to the Ann Arbor system as modified by Musshoff. In addition, only patients with histologic samples amenable to re-assessment by a reference pathologist were included. RESULTS: A total of 68 patients with a diagnosis of MALT-type lymphoma were identified from our records. However, only in 32 patients exact staging according to our inclusion criteria had been performed and serum B2M-levels prior to the initiation of therapy were available in all these patients. Twenty-five patients; suffered from gastric lymphoma, while the remaining 7 patients had extragastric manifestations. In total, 13 out of 32 patients presented with stage I disease, 17 patients were rated as stage II and 2 patients suffered from stage III disease. Nineteen patients had elevated B2M-levels prior to therapy: 6 patients were rated as stage 1, II had stage II and two had stage III disease. Five patients still had elevated B2M-levels following treatment despite radiologically and histologically verified complete remission. CONCLUSION: In this series, no correlation between serum B2M levels, tumor burden and clinical outcome was apparent in patients with MALT-type lymphomas. While the number of patients with disseminated disease was small we could not demonstrate a difference for B2M-levels between stage I and stage II. While we cannot rule out that B2M might be different in patients with stage I/II disease as compared to more advanced disease, further investigations are necessary to determine the role of this marker in patients with MALT-type lymphoma.

Local production of Aspergillus fumigatus specific immunoglobulin E in nasal polyps.

BACKGROUND: Aspergillus spp. play a significant role in the etiology of immunoglobulin (Ig)E mediated allergic fungal sinusitis (AFS). It is unclear whether Aspergillus spp. are also involved in nasal polyps without the characteristic clinical features of AFS. OBJECTIVES: The frequency of Aspergillus spp. and Aspergillus-specific IgE in nasal lavages and serum of patients with severe nasal polyps (n = 33) without clinical features of AFS should be investigated. STUDY DESIGN: Prospective study. METHODS: An aliquot of nasal lavage fluid was treated with dithiothreitol and examined for Aspergillus fumigatus by culture and an Aspergillus-specific polymerase chain reaction (PCR) assay. An additional aliquot of nasal fluid and serum of the same patient were tested for specific IgE (Unicap, Pharmacia, Freiburg, Germany) to recombinant Aspergillus fumigatus allergen (rAspf) 1 to 6. RESULTS: All patients had negative skin prick tests for Aspergillus fumigatus. Four of 33 (12%) lavage samples were positive for Aspergillus spp. by PCR. In one of these samples, rAspf-specific IgE was detected but none in the serum. Nasal lavage and serum samples of the remaining 29 patients were negative for rAspf-specific IgE. CONCLUSIONS: Aspergillus spp. detection is rare in patients with severe nasal polyps without characteristic clinical features of AFS. Specific IgE in nasal secretions may be elevated in patients with negative skin prick tests and serum IgE. In these cases, immunologic mechanisms similar to AFS may be involved. Fungal etiology has been proposed to underlie severe nasal polyps in general. However, Aspergillus spp. seem not to play a significant role.

Optimized growth medium for primary culture of human oral keratinocytes.

The effect of different media additives in defining optimal growth conditions for primary cultures of human oral keratinocytes was studied. A cocultivation technique with irradiated Swiss-3T3-fibroblasts in 96-well plates enables the comparison of additives for primary keratinocyte cultures derived from one patient. 3H-labeled thymidine uptake showed no growth or growth inhibition with adenine, choleratoxin or transferrin compared to basal medium (Dulbecco's modified Eagle's medium (DMEM) and 10% fetal calf serum). Among single additives, 5 micrograms/ml hydrocortisone, 5 micrograms/ml insulin, 10 ng/ml EGF, 2 micrograms/ml bovine pituitary extract, and 10(-9) M triiodothyronine showed the greatest capacity to promote keratinocyte growth. With all possible combinations of additives, maximum stimulation was found with a combination of EGF (10 ng/ml), insulin (5 micrograms/ml), and hydrocortisone (5 micrograms/ml); none of the other combinations were more effective. Our data indicate that in short-term cultures (up to 5 days) various media additives described in the literature are not necessarily required in this system of primary culture of human oral keratinocytes.

Non-radioactive semiquantitative testing for the expression levels of telomerase activity in head and neck squamous cell carcinomas may be indicative for biological tumour behaviour.

Head and neck cancer arises and progresses through specific genetic alterations which lead to an invasive immortal phenotype. The process of immortalization is associated with the activation of the enzyme telomerase, a ribonucleoprotein with reverse transcriptase activity which is capable of synthesizing telomeric repeats at the end of chromosomes. This enzyme is expressed in nearly all neoplasms and germline cells and is absent in most normal human somatic cells. Because of this expression pattern testing for telomerase activity may deliver useful diagnostic and/or prognostic information about clinical tumour behaviour. Telomerase activity was therefore analysed in 16 primary lesions of head and neck squamous cell carcinomas (HNSCC) using the polymerase chain reaction-based telomeric repeat amplification protocol (TRAP). For a sensitive semiquantitative analysis of telomerase activity TRAP products were mixed with Pico Green I and the fluorescence emission intensities were measured. All 16 samples tested positive. When the Pico Green I data were compared with clinical parameters, it was obvious that N0 necks revealed significantly (p < 0.05) lower emission intensities (i.e. telomerase activity) than N + necks. Our results indicate that a high telomerase activity in HNSCC may facilitate lymph node metastasis and that the estimation of telomerase activity is a useful diagnostic tool which could influence treatment modalities.

Different KGF expression in squamous cell carcinomas of the head and neck and in normal mucosa.

Fibroblast growth factors (FGFs) are major factors mediating epithelial-mesenchymal interactions in the epidermis and mucosa. In this study the expression of the FGFs keratinocyte growth factor (KGF), acidic FGF (aFGF) and basic FGF (bFGF) was examined in tumour tissue specimens from 14 patients with advanced-stage squamous cell carcinoma of the head and neck (SCCHN) and 3 SCC cell lines by reverse-transcribed polymerase chain reaction (RT-PCR) and immunohistochemistry. None of the SCC cell lines was positive for KGF mRNA, whereas all cell lines were highly positive for aFGF and bFGF. In SCCHN tissue samples the level of KGF mRNA expression was significantly lower than in normal mucosa. Tumour stroma and the submucosal areas of normal mucosa stained intensely with anti-KGF antibody in immunohistochemical slides, whereas tumour cell nests were negative. Exposure of SCC cells to KGF thus differs from normal mucosa both quantitatively and regarding spatial distribution. This fact and the overexpression of aFGF and bFGF by tumour cells potentially promote tumour growth, invasion and metastasis. Since these growth factors and their receptors are well characterized, these observations could lead to new therapeutic strategies in SCCHN, for instance by blocking their receptors or antisense targeting.

Non-steroidal anti-inflammatory drugs induce apoptosis in head and neck cancer cell lines.

Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit tumorigenesis in colorectal cancer due to the induction of apoptosis. Disturbances of cellular pathways ultimately leading to apoptosis may contribute to the process of neoplastic transformation and immortalization. In this study we wanted to determine the influence of different NSAIDs (indomethacin, ibuprofen and sodium salicylate) and hydrocortisone on Bcl-2 expression and the apoptotic behavior of head and neck tumor cell lines and normal oral keratinocytes. Bcl-2 expression was determined by monoclonal antibody staining and fluorescence-activated cell-sorting measurement. Apoptotic cells were visualized with a epifluorescence microscope after staining with CytoDeath M30 antibody. Indomethacin (1 mM) and ibuprofen (1 mM) significantly reduced Bcl-2 expression in the cancer cell lines tested and might be thought responsible for the observed increase in apoptosis. At all concentrations tested the influence of sodium salicylate and hydrocortisone on Bcl-2 expression was not significant. In contrast, the NSAIDs tested had only a minor influence on normal oral keratinocytes. Our results demonstrate a significant reduction in growth and an increase in apoptosis, possibly due to a reduction in Bcl-2 expression. after exposure to indomethacin and ibuprofen in the head and neck cancer cell lines tested.

1,25(OH)2 vitamin D3 induces elevated expression of the cell cycle-regulating genes P21 and P27 in squamous carcinoma cell lines of the head and neck.

The biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], inhibits proliferation and induces differentiation for various malignant cells, including squamous cell carcinoma cell lines of the head and neck (SCCHN). These effects are due to an arrest of cells in the G0/G1 phase of the cell cycle and are predominantly mediated by the vitamin D receptor. To further explore the molecular mechanisms of the antiproliferative activity in SCCHN we studied the influence of 1,25(OH)2D3 on the expression of the G1 phase-regulating proteins cyclin D1, p21 and p27. Furthermore, as a direct target of G1 protein complexes, we investigated the phosphorylation status of the retinoblastoma protein (pRb). Synchronized cells of 2 SCCHN cell lines [JPPA (laryngeal carcinoma) and SCC 9 (tongue carcinoma)] and human immortalized keratinocytes (HaCaT) were cultured for 96 h in the presence or absence (ethanol as control) of 1,25(OH)2D3 (10(-7) M). At various time intervals the cell cycle status was detected by fluorescence-activated cell sorting (FACS) analysis and in parallel the expression of cell cycle-regulating proteins was determined at the protein and mRNA levels. In all cell lines tested 1,25(OH)2D3 caused an arrest of cells in the G0/G1 phase of the cell cycle and markedly induced the expression of the inhibitors p21 and p27. No influence was detectable on the expression of cyclin D1. Induction of p21 and p27 mRNA revealed transcriptional regulation by the vitamin D receptor. Simultaneously, hyperphosphorylated pRb was transformed to the hypophosphorylated form. Our results demonstrate that the biologically active form of vitamin D3 directly regulates the expression of p21 and p27, inducing a G0/G1 phase arrest: one mechanism by which 1,25(OH)2D3 controls cell proliferation inSCCHN.

IL-1 and TNF-alpha but no IL-2 expression is found in squamous cell carcinomas of the head and neck by RT-PCR.

We studied the expression of IL-1 (Interleukin 1), IL-2, IL-4, IL-10, GM-CSF (granulocyte/macrophage colony stimulating factor), TNF-alpha (tumor necrosis factor alpha) and IFN-gamma (Interferon gamma) in tumor specimens and adjacent mucosa from 12 patients with squamous cell carcinoma of the head and neck (SCCHN) by reverse-transcribed polymerase chain reaction (RT-PCR). No IL-2 and IL-4 expression was detected in any of the tumor specimens. High level expression of IL-1 and TNF-alpha was found in all 12 samples analyzed. Expression of GM-CSF was detected in 7 (58%) of 12 tumors, IL-10 was found in 3 (25%) and IFN-gamma in 6 (50%) of the samples. No qualitative differences in the cyotokine expression pattern were found between normal and tumor tissue. Our data indicate that there is a lack of cytokines typical for a specific, T-cell mediated immune response in SCCHN. A number of cytokines which are required for the initial steps of immune response however are produced. These results might have implications for future immuno-chemotherapeutical strategies.

Difficulties with the organ donation process in small hospitals in Germany.

The discrepancies between the need and the number of organs donated in Germany lead to a search for the causes of this deficit. In the present study, 78 small hospitals in Germany were interviewed about the difficulties with the organ donation process. Data were acquired by means of a structured telephone interview. No organ donor between 2004 and 2008, was reported by 44% of the participating hospitals while the remaining 56% had >or=1 donor. The main results show that one third of these small hospitals already had difficulties communicating with bereaved relatives about donation. In addition, 31% of the respondents reported problems during the organ removal process and 41% in identifying potential organ donors.