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Biomedical subjects

Jochen A Werner

Publications and source records attributed to Jochen A Werner.

At least 19 recordsLinked to original sources

Evolution of the management of laryngeal cancer.

The treatment of laryngeal cancer has evolved through several phases, starting with wide extirpative surgical resection, and evolving through an era of conservation surgery and, finally, planned treatment using modalities of irradiation, chemotherapy and surgery in various combinations. Attempts to extirpate laryngeal cancer date to the nineteenth century, but only by the mid-twentieth century did advances in anesthesia, blood transfusion and antibiotics, make this surgery safe and reliable. Techniques of partial laryngectomy by external approach developed in the second half of the twentieth century, and endoscopic use of the laser refined the concept and provided a new paradigm for surgical treatment, particularly for early lesions. During most of this era, radiation was employed as an alternative method of treatment, with surgery reserved for salvage of radiation failure. By the last decade of the twentieth century, and to the present time, the value of combined modality therapy, using planned combinations of irradiation, chemotherapy and surgery became the standard of care for advanced laryngeal cancer, permitting maximal laryngeal preservation with the highest attainable cure rates.

Antineoplastic Agents↗

Options for salvage after failed initial treatment of anterior vocal commissure squamous carcinoma.

Persistence or recurrent cancer in the anterior commissure (AC) after primary radiotherapy may remain localized to its pretreatment anatomical site. If so, endoscopic CO(2) laser excision, in experienced hands, may achieve complete tumor excision and result in cure for many patients. Occasionally, second and third recurrences may be similarly salvaged by further endoscopic surgery. The use of the vertical hemilaryngectomy is an alternative treatment for similar localized lesions, with a higher first time surgical tumor eradication rate, but with a more protracted hospitalization and a less satisfactory voice and swallowing outcome. In both types of such surgical salvage, CT scanning must demonstrate no evidence of cartilage invasion or destruction. When there is evidence of minimal thyroid cartilage invasion, then the supracricoid partial laryngectomy is an alternative conservation option, and is likely to result in a cure, with the retention of a voicing larynx without a stoma. When the tumor has increased in size from the original pretreatment dimension and/or site, then imaging must be used to identify possible cartilage invasion, in which case the likelihood of tumor eradication by endoscopic or external vertical partial laryngectomy is highly unlikely. The indications for the routine use of total laryngectomy for the treatment of recurrent or persistent cancer involving the AC must be reviewed; there is current evidence that cure can be achieved by a less radical procedure. However, total laryngectomy may remain the only treatment option for advanced or aggressive first time recurrence, or in patients who develop subsequent recurrence following previous less aggressive surgery (endoscopic or external).

Carcinoma, Squamous Cell↗

Neck dissection: then and now.

The significance of metastatic disease in the lymph nodes of the neck as a critical independent prognostic factor in head and neck cancer has long been appreciated. Although 19th century surgeons attempted to remove involved cervical lymph nodes at the time of resection of the primary cancer, a systematic approach to en bloc removal of cervical lymph node disease, described in detail by Jawdyński in 1888 and popularized and illustrated by Crile in the early 20th century, provided consistent and more effective treatment, and forms the basis of our current techniques. During the first half of the 20th century, developments included preservation of the accessory nerve in selected cases, elective neck dissection performed in association with resection of various primary tumors, bilateral neck dissection and limited neck dissection. The greatest impetus to the status of radical neck dissection came from Martin, whose technique consisted of resection of all lymph nodes from level I-V together with the accessory nerve, internal jugular vein, sternocleidomastoid muscle and various other structures in a single block of resected tissue. Martin's technical precepts were followed until the latter part of the 20th century when modifications in technique began to find general acceptance. The first description of an effective technique of modified radical neck dissection was published in Spanish by Suárez, in 1963. This technique, which preserves important structures, such as the internal jugular vein, sternocleidomastoid muscle and accessory nerve, was refined and popularized by various authors who published their results in the English language literature during the period from 1964 through 1990 and beyond. Modified or "functional" neck dissection avoids much of the morbidity of radical neck dissection while achieving equivalent degrees of control of regional disease in properly selected cases. By the late 20th century, the concept of selective neck dissection, consisting of resection of only the nodal groups at greatest risk for metastasis from a given primary site, was studied and developed. These limited dissections are now widely employed for elective, and in properly selected cases, therapeutic treatment and staging of the neck, and have been proposed for limited cervical recurrences after various chemoradiation protocols. Prospective studies have demonstrated similar rates of neck recurrence and survival after elective selective neck dissection compared to elective modified radical neck dissection. Other modifications and factors applied to treatment of cervical lymph node disease include the use of adjuvant and neo-adjuvant radiation and chemotherapy, a revised system for classification of neck dissections, the identification of various adverse prognostic factors such as extracapsular spread and extranodal soft tissue deposits, application of sentinel lymph node biopsy to staging of the neck, the use of immunohistochemical and molecular techniques for identification of lymph node metastases not detectable by light microscopy, and the possibility of endoscopic neck dissection. The authors conclude that neck dissection, as evolved over the past century, is a fundamental tool in management of patients with head and neck cancer, but is still a work in progress.

Head and Neck Neoplasms↗

Treatment of HNSCC cell lines with the EGFR-specific inhibitor cetuximab (Erbitux) results in paradox phosphorylation of tyrosine 1173 in the receptor.

Overexpression of the epidermal growth factor receptor (EGFR, ErbB1, HER1) is frequent in head and neck squamous cell carcinomas (HNSCCs) and correlates with disease progression. Inhibition of EGFR with the kinase inhibitor AG1478 abolished receptor phosphorylation and reduced cell proliferation. However, treatment of HNSCC cells with cetuximab (Erbitux), a monoclonal antibody designed to block the EGFR ligand binding site, led to paradox EGFR activation due to hyperphosphorylation of tyrosine 1173, however, with a concomitant reduction in Erk1/2 phosphorylation levels. No pronounced influence on cell proliferation levels could be observed after treatment with this antibody. Since cetuximab appears able to activate EGFR in HNSCC cell lines, it is necessary to rethink the exact mechanisms by which cetuximab that recently was approved for the treatment of advanced head and neck cancer, inhibits tumor growth.

Antibodies, Monoclonal↗

Androgen receptors and gender-specific distribution of alkaline phosphatase in human thyroid cartilage.

The degree of mineralization in human thyroid cartilage is gender specific. Until now, laryngeal tissue was tested for sexual hormone receptors by the use of radiolabelled hormones only without exact localization of the receptors. In this study immediately frozen cartilage specimens from seven male and one female patient who underwent laryngectomy were used for immunolocalization of sexual hormone receptors. Additionally, serum sexual hormone levels were measured by means of radioimmunoassay. Alkaline phosphatase was localized enzymohistochemically in another cohort of six male and four female cartilage specimens from laryngectomies and autopsies. Chondrocytes in thyroid cartilage from both sexes reacted with antibodies to the androgen receptor. The low serum testosterone levels, which varied between 1.5 and 3.9 ng/ml, did not correlate with insufficient mineralization of thyroid cartilage in men (r=0.363, P=0.432). Chondrocytes did not react with antibodies to the estrogen receptor alpha and the progesterone receptor in both sexes. Expression of alkaline phosphatase started about the middle of the second decade. Some chondrocytes near the mineralization front were positive for androgen receptor and alkaline phosphatase, other chondrocytes were negative for both. Our results suggest the involvement of androgen receptor positive chondrocytes in thyroid cartilage mineralization, probably by a testosterone-linked stimulation of alkaline phosphatase.

Adolescent↗

Complications after CO(2) laser surgery of laryngeal cancer in the elderly.

CONCLUSION: Cancer of the larynx in elderly patients should be treated with curative intention, if the extension of the primary tumour allows safe resection. Transoral CO(2) laser microsurgery is associated with a low rate of major complications and can be regarded as suitable even for elderly patients. Age itself should never be the sole factor in deciding which therapy should be undertaken. OBJECTIVES: In the industrialized nations the age group beyond 75 years will grow steadily, requiring special attention by medical professionals in the future. Nowadays laryngeal cancer is often treated by transoral CO(2) laser microsurgery. Because of a variety of comorbidities, the incidence of perioperative complications in the group of elderly patients is of increasing interest. To date, no references in the literature have discussed complications after transoral CO(2) laser microsurgery in this age group. Patients and methods. Twenty-four patients over the age of 75 suffering from squamous cell carcinoma of the larynx and treated by transoral CO(2) laser microsurgery since 1998 were analysed for intraoperative and postoperative complications. RESULTS: There was no evidence of surgery-related complications at all. Postoperatively, 6 of 24 patients complained about dysphagia. Due to intraoperative placement of nasogastric feeding tubes in these six cases further complications such as pneumonia resulting from aspiration could have been avoided.

Age Factors↗

Digital volume tomography: radiologic examinations of the temporal bone.

OBJECTIVE: We evaluated the clinical applicability and the value of digital volume tomography for visualization of the lateral skull base using temporal bone specimens. MATERIALS AND METHODS: Twelve temporal bone specimens were used to evaluate digital volume tomography on the lateral skull base. Aside from the initial examination of the temporal bones, radiologic control examinations were performed after insertion of titanium, gold, and platinum middle-ear implants and a cochlear implant. RESULTS: With high-resolution and almost artifact-free visualization of alloplastic middle-ear implants of titanium, gold, or platinum, it was possible to define the smallest bone structures or position of the prosthesis with high precision. Furthermore, the examination proved that digital volume tomography is useful in assessing the normal position of a cochlear implant. CONCLUSION: Digital volume tomography expands the application of diagnostic possibilities in the lateral skull base. Therefore, we believe improved preoperative diagnosis can be achieved along with more accurate planning of the surgical procedure. Digital volume tomography delivers a small radiation dose and a high resolution coupled with a low purchase price for the equipment.

Cochlear Implantation↗

In-vitro investigations evaluating the detection spectrum of cervical lymph nodes via handheld gamma probe.

BACKGROUND: Currently the significance of the sentinel node (SN) biopsy also for head and neck cancer is discussed intensively. Based on the complex anatomic structures of this region with a low distance between primary and sentinel node as well as approximately 300 lymph nodes an intensive discussion of the methodical basis of sentinel node detection seems to be essential. Thus it was the aim of the present study to examine the detection spectrum of a gamma probe for identification of cervical lymph nodes using an in vitro model to describe and objectify the particularities of measurement existing in the head and neck region. MATERIAL/METHODS: In an in vitro model the detection spectrum of a gamma probe is examined in 29 different series of measurements (variation of the specimen filled with 99m pertechnetat regarding activity, position, collimator distance, tissue sheath). RESULTS: The presented in vitro model reflects the clinical problem of narrow intranodal activity of neighbouring lymph nodes and reveals a direct relation between the number of radiation sources and their isolated evidence. Using muscle tissue with a thickness of 0.4 cm, two two-rowed radiation sources, the more powerful is placed 1.5 cm behind the other specimen, with a lateral difference of 3 cm, can be resolved only with a maximal detector distance of 1 cm. Not the difference of the tissue but the thickness of the tissue is decisive for detection. CONCLUSION: Especially for pharyngeal and laryngeal lymph nodes a transcutaneous measurement reflecting the exact localisation of hot nodes in the area of the deep jugular lymph nodes is not possible with increasing tissue thickness. The described results require a critical discussion of the different detection techniques varying among the different working groups of this field.

Gamma Rays↗

Acute haemorrhage in patients with advanced head and neck cancer: value of endovascular therapy as palliative treatment option.

AIMS: Acute or subacute haemorrhage is one of the most frightening complications in patients suffering from advanced head and neck cancer. Few articles report experience with superselective endovascular therapy for this purpose. Is endovascular therapy underestimated in the field of palliative head and neck cancer therapy? This study set out to investigate this question. PATIENTS AND METHODS: A review was undertaken of the clinical courses of seven patients (six men, one woman) suffering from incurable, advanced head and neck cancer (four pharyngeal, two laryngeal, one neck) and treated with superselective endovascular strategies as an emergency procedure for acute bleeding. RESULTS: All patients were successfully treated without evidence of neurological complication. Patients reached a median survival of 20 weeks (range eight-168 weeks). Following endovascular treatment all patients were discharged from the hospital within several days. Three patients survived almost free of symptoms for several weeks and were able to stay at home with their families until their death. CONCLUSION: We conclude that in the field of palliative care, superselective endovascular therapy deserves to be considered alongside standard treatment options for the management of acute haemorrhage from advanced head and neck cancer.

Acute Disease↗

Reduced cisplatin sensitivity of head and neck squamous cell carcinoma cell lines correlates with mutations affecting the COOH-terminal nuclear localization signal of p53.

PURPOSE: Head and neck squamous cell carcinomas (HNSCC) are the most frequent malignancies of the upper aerodigestive tract. Cisplatin resistance is a major problem in the treatment of a large number of HNSCC cancer patients. In this study, nine randomly selected HNSCC cell lines were investigated regarding expression, presence of mutations, nucleocytoplasmic distribution of p53, and sensitivity to cisplatin. EXPERIMENTAL DESIGN: Protein expression was evaluated by Western blot analysis. The whole open reading frame of p53 was determined by reverse transcription-PCR sequencing. Nucleocytoplasmic distribution was evaluated by confocal laser scanning microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay was used to test for cisplatin sensitivity. RESULTS: p53 mutations were found in all nine investigated HNSCC cell lines. Nuclear p53 signal was detected in six cell lines, whereas three cell lines exhibited total loss of nuclear p53 signal. Nuclear signal depended on the presence or absence of the COOH-terminal nuclear localization signal in p53. Cisplatin sensitivity was highly reduced in the group with loss of nuclear p53 signal compared with those with detectable nuclear signal. Transfection of wild-type and mutant p53 into a rat embryonic cell system showed highly reduced activity of the nuclear localization signal mutant p53 protein. CONCLUSION: Taken together, these data suggest that "loss of nuclear p53 signal" correlates with cisplatin resistance in HNSCC. If these results can be validated on a larger number of tumor samples, including fresh tumor tissues, it potentially could help in sparing a subgroup of HNSCC patients the side effects associated with unnecessary chemotherapy by identifying cisplatin nonresponders before chemotherapy induction.

Adult↗

Expression of galectin-3 in adenoid cystic carcinoma of the head and neck and its relationship with distant metastasis.

PURPOSE: Adenoid cystic carcinoma (ACC) is one of the most common malignant tumours of the salivary glands characterized by multiple recurrences and distant metastasis resulting in significantly worsening prognosis. Galectin-3, a member of the beta-galactoside-binding lectin family, has been implicated in tumour progression, metastasis, and found to have prognostic value. The aim of the study was to determine galectin-3 expression in ACC and correlate it with clinicopathological features and patient survival. METHODS: Galectin-3 expression was investigated in paraffin sections of 35 ACC of the head and neck. Patients were divided into two groups based on a threshold of 5% positivity in the tumour cell population. The mean follow-up period for all patients was 90.1 months (range 3-300.1 months). RESULTS: Seventeen (48.6%) tumour specimens were considered galectin-3-positive. Galectin-3 reactivity was significantly associated with regional and distant metastasis (P=0.045 and P<0.001, respectively). There was no statistical significance in the correlation of galectin-3 expression and disease-free survival and overall survival rate (P=0.095 and 0.102, respectively). CONCLUSION: Galectin-3 may be used as an indicator in the prediction of metastatic spread in ACC.

Adult↗

Separation of beta2-transferrin by denaturing gel electrophoresis to detect cerebrospinal fluid in ear and nasal fluids.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a critical condition with a substantial risk of meningitis. We investigated the use of transferrin isoform analysis as a diagnostic marker for detection of CSF leakage in fluid samples. METHODS: We analyzed 241 samples from patients with CSF leakage, most commonly presenting as otorrhea or rhinorrhea, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with subsequent Western blotting and immunostaining for transferrin. Tears, saliva, nasal fluid, and ear secretions (20 samples each) were analyzed in parallel, and normal human serum served as a control in each experiment. We compared the minimum volume of added CSF that could be detected in secretions by our assay with the minimum volume detected by the prostaglandin-D synthase (beta-trace) test. CSF was admixed with blood in different proportions to determine the influence of blood contamination on the transferrin pattern. RESULTS: In all CSF samples, beta1- and beta2-transferrin were present in nearly equal amounts. In tears and ear secretions, beta2-transferrin migrated in the gel in the same manner as in CSF, but its concentration was noticeably lower than that of beta1-transferrin, a difference that allowed a clear distinction from the transferrin pattern of CSF. In saliva, both transferrin isoforms were also present but could be distinguished from those of other fluids by electrophoretic migration pattern rather than relative concentrations. With the beta-trace test, a minimum of 5 microL of CSF was needed for detection, whereas our beta2-transferrin assay yielded a signal of comparable intensity with a minimum of 2 microL of CSF. CONCLUSION: Analysis of the transferrin microheterogeneity pattern by SDS-PAGE for the identification of CSF leakage is a highly sensitive and specific method that merits consideration as a routine technique.

Biomarkers↗

Metaanalysis of the significance of matrix metalloproteinases for lymph node disease in patients with head and neck squamous cell carcinoma.

BACKGROUND: The objective of the current metaanalysis was to evaluate the expression patterns of matrix metalloproteinases (MMPs) in patients with head and neck squamous cell carcinoma (HNSCC), to evaluate reported series, and to determine whether there is an expressed value to quantitate the risk of metastasis. METHODS: A review of the published literature was conducted according to defined selection criteria. Fixed and random effects models were applied for estimation of the summarized odds ratio and 95% confidence intervals, including a test for homogeneity of the odds ratios of the studies. Finally, forest plots were created to allow for visual comparison of the results and an estimation of heterogeneity. RESULTS: The heterogeneity of data collection and statistical methods did not allow final judgments on the significance of immunohistochemical MMP expression analysis in patients with HNSCC or the impact of MMPs in predicting metastatic behavior. Fourteen studies with 710 patients for 5 different MMPs (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-14) were included in the current metaanalysis. The results indicated that MMP-2, MMP-3, MMP-14 possibly played a role in the metastatic behavior of HNSCC tumors. CONCLUSIONS: The authors recommended the standardization of staining procedures and evaluation protocols as a necessary step to allow for valid comparisons of the multitude of results published by different study groups.

Carcinoma, Squamous Cell↗

Manifestations of hereditary hemorrhagic telangiectasia in children and adolescents.

The medical literature provides little information on manifestations of hereditary hemorrhagic telangiectasia (HHT) in children. The presented investigation was initiated to analyze early presenting symptoms in HHT, which should help to make the diagnosis at a young age and thus prevent potential complications from occult visceral arteriovenous malformations (AVM), which have commonly been described in HHT. A series of 15 children and adolescents with a suspicious diagnosis of HHT were examined clinically for typical signs and symptoms of the disorder. If the diagnosis of HHT seemed to be likely, recommendations for non-invasive screening procedures were given. Screening was directed at the detection of occult visceral AVMs. Main outcome measures were the definition of principal signs of HHT in children and adolescents. Family history was positive for HHT in 13 persons. The principal sign of recurrent epistaxis was present in 10/15 individuals and the earliest age of onset with regard to epistaxis was 4 years. Cutaneous vascular lesions were present in 5/15 patients. Screening for AVMs was performed in six individuals and revealed vascular lesions of the brain in two patients and vascular lesions of the lung in two patients. Gastrointestinal hemorrhages were present in one infant. Based on these findings, diagnosis of HHT seemed likely in ten individuals and unlikely in five individuals. Signs and symptoms of HHT in children and adolescents may be discrete, but are detectable at an earlier age than previously thought. Clinical examinations in children from HHT families may help identify candidates who will benefit from molecular genetic testing or screening imaging studies.

Adolescent↗

Elective and therapeutic selective neck dissection.

Selective neck dissection is a modification of the more comprehensive modified radical or radical neck dissection that is designed to remove only those nodal levels considered to be at risk for harboring nodal metastases. The role of selective neck dissection continues to evolve: while initially designed as a staging and diagnostic procedure for patients without clinical evidence of nodal disease, a growing body of literature suggests that selective neck dissection has a therapeutic role in patients with clinical and histologic evidence of nodal metastases. The rationale behind selective neck dissection, its application in the clinically negative but histologically node-positive neck and the extended application of selective neck dissection in patients with clinical evidence of nodal disease are discussed.

Carcinoma, Squamous Cell↗

Management of mandibular invasion: when is a marginal mandibulectomy appropriate?

There has been a great deal of controversy regarding the appropriate method of management of oral cavity and oropharyngeal tumors that invade the mandible. The inability to acquire intraoperative bone margins can make the decision process complex. Preoperative imaging offers several advantages, however, there is no single modality that has proven accurate. Intraoperative assessment has been suggested as a method of evaluation, however, this approach does not allow for preoperative planning. The following is a review of the current literature regarding mandibular invasion and the indications for a marginal mandibulectomy.

Carcinoma, Squamous Cell↗

Lymph node metastasis in an animal model: effect of piecemeal laser surgical resection.

BACKGROUND AND OBJECTIVES: Endoscopic laser surgical resection of advanced squamous cell carcinoma (SCC) often requires division of the tumor into several pieces. It is unknown if this approach influences the incidence of regional and distant metastases. STUDY DESIGN/MATERIALS AND METHODS: In 143 rabbits VX2 SCC was induced. Eight days later the tumor was resected by two different methods. In the first group en bloc cold steel resection was performed. In the second group piecemeal laser resection was performed. On the 51th day the animals were sacrificed and examined for lymph node and distant metastases. RESULTS: After piecemeal laser resection 47.7% of the animals had lymph node metastases compared to 24.6% after en bloc resection (P = 0.01). The incidence of distant metastases did not differ for the two groups. CONCLUSIONS: In our model narrow margin piecemeal laser resection was associated with a higher incidence of metastases compared to wide en bloc surgical resection. The exact mechanism responsible for this increase is unclear.

Animals↗