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Biomedical subjects

Stephan Schmid

Publications and source records attributed to Stephan Schmid.

16 recordsLinked to original sources

Kaposiform hemangioendothelioma arising in the ethmoid sinus of an 8-year-old girl with severe epistaxis.

BACKGROUND: Epistaxis is very common during childhood. It occurs primarily in boys and is usually self-limiting. Trauma and nose picking are among the most common causes. In general, epistaxis can be easily treated with anterior nasal packing or electrocoagulation. METHODS: We report a case of an 8-year-old girl with severe unilateral epistaxis. RESULTS: The bleeding originated from a kaposiform hemangioendothelioma arising in the left nasal cavity and ethmoid sinus. The feeding vessels originating from the maxillary artery were first embolized. The tumor was then surgically removed through a combined external ethmoidectomy and endonasal approach. The postoperative course was uneventful. MRI at 6 months after surgery showed no tumor recurrence. CONCLUSIONS: We report a previously undescribed cause of epistaxis in children, namely, a kaposiform hemangioendothelioma. To our knowledge, this is the first such case in the English-language literature. The differential diagnosis of severe unilateral nasal bleeding among the pediatric population should include the possibility of a kaposiform hemangioendothelioma.

Child↗

The effect of erythropoietin on gentamicin-induced auditory hair cell loss.

OBJECTIVE/HYPOTHESIS: Mammalian auditory hair cells that are unable to regenerate and various agents, including gentamicin, can irreversibly damage the hair cells. Erythropoietin, known as the primary regulator of erythropoiesis, exerts also neuroprotective effects by binding to its receptor. We tested whether erythropoietin can protect the hair cells from gentamicin-induced damage. STUDY DESIGN: This study localized the erythropoietin receptor in the cochlea and analyzed the effect of erythropoietin on gentamicin-damaged hair cells in vitro. METHODS: Expression of erythropoietin receptor in the rat cochlea was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Protection of auditory hair cells from gentamicin was tested in vitro by exposing cultured rat organs of Corti with increasing concentrations of erythropoietin (0.1 U/mL, 1 U/mL, and 10 U/mL). RESULTS: We detected erythropoietin and erythropoietin receptor mRNA expression in the organ of Corti, spiral ganglion, and stria vascularis by RT-PCR. Immunohistochemistry revealed that the erythropoietin receptor localizes to the outer and inner hair cells and supporting cells of the organ of Corti, as well as to the spiral ganglion cells and the stria vascularis. Significantly less hair cell loss occurred in the organs of Corti that were pretreated with 0.1 U/mL erythropoietin as compared with samples treated with gentamicin only. CONCLUSION: Decreased hair cell loss in erythropoietin-treated organs of Corti that had been exposed to gentamicin provides evidence for a protective effect of erythropoietin in aminoglycoside-induced hair cell death.

Animals↗

Partial cricotracheal resection for successful reversal of laryngotracheal separation in patients with chronic aspiration.

OBJECTIVE: To present our experience with successful reversal of laryngotracheal separation in patients with chronic aspiration, to discuss our surgical technique, and to review the literature. STUDY DESIGN: Retrospective case review. METHODS: The medical records of two patients who underwent a successful reversal of laryngotracheal reversal after separation were reviewed. The two patients were evaluated clinically with videostroboscopy and videofluoroscopy. RESULTS: Both patients presented with intractable aspiration despite protective tracheostomy because of impairment of lower cranial nerve function. After laryngotracheal separation, swallowing rehabilitation was safely possible, and neurologic improvement allowed reversal of the separation procedure. For reversal, we present the use of a partial cricotracheal resection with tracheocricothyropexia similar to the technique used for subglottic stenosis. Both patients were successfully reversed. Satisfactory voice and swallowing function 7 and 10 years after reversal, respectively, could be assessed through our evaluation. Review of the literature revealed a total of 13 cases of successful reversal after laryngotracheal separation. Technical details of surgery and functional results are rarely reported.

Adult↗

NF-kappaB is required for survival of immature auditory hair cells in vitro.

Damage to auditory hair cells in the inner ear as a consequence of aging, disease, acoustic trauma, or exposure to ototoxins underlies most cases of hearing impairment. Because the mammalian ear cannot replace damaged hair cells, loss of hearing is irreversible and progressive throughout life. One of the current goals of inner ear biology is to develop therapeutic strategies to prevent hair cell degeneration. Although important progress has been made in discovering factors that mediate hair cell death, very little is known about the molecular pathway(s) that signal survival. Here we considered the role of NF-kappaB, a ubiquitous transcription factor that plays a major role in the regulation of many apoptosis- and stress-related genes, in mediating hair cell survival. NF-kappaB was detected in a constitutively active form in the organ of Corti of 5-day-old rats. Selective inhibition of NF-kappaB through use of a cell-permeable inhibitory peptide in vitro caused massive degeneration of hair cells within 24 h of inhibitor application. Hair cell death occurred through an apoptotic pathway through activation of caspase-3 and may involve transcriptional down-regulation of the gadd45beta gene, an anti-apoptotic NF-kappaB target. In view of our results, it seems likely that NF-kappaB may participate in normal hair cell function.

Animals↗

Promyelocytic leukemia zinc finger protein localizes to the cochlear outer hair cells and interacts with prestin, the outer hair cell motor protein.

Hair cells in the auditory sensory organ are specialized mechanoreceptors common to mammalian and non-mammalian species. The mammalian cochlear outer hair cells (OHC) possess a distinct motile property, dubbed membrane-based electromotility, that enhances the receptor function. This electromotility is believed to be the basis of cochlear amplification that increases sensitivity of the mammalian ear to sound. Prestin, a unique voltage-sensitive motor molecule localized in the lateral membrane of OHC, is presumably responsible for OHC electromotility. It has been documented that prestin null-animals lack electromotility and suffer from approximately 50 dB loss of hearing sensitivity. To identify proteins that interact with prestin we carried out a yeast two-hybrid library screen using the C-terminal intracellular domain of prestin as bait. Seven bait-dependent prey clones were identified independently. Further analysis revealed that they encode partially over-lapping regions of a single protein: a transcriptional repressor, promyleocytic leukemia zinc finger protein (PLZF). PLZF encodes a POZ/domain Kruppel-type zinc finger transcription factor reported to have pro-apoptotic and anti-proliferative activity. The interaction between endogenous prestin and PLZF proteins in the cochlea was confirmed by co-immunoprecipitation using organ of Corti lysates. Furthermore, immunohistochemical studies strongly suggest that PLZF co-localizes with prestin near the lateral membrane of cochlear OHC. The physiological significance of this interaction remains to be explored.

Amino Acid Sequence↗

Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE: To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS: From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS: There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION: The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Adult↗

Positron emission tomography in the early follow-up of advanced head and neck cancer.

OBJECTIVE: To assess the clinical effect of an early follow-up positron emission tomography (PET) examination at the time of the first routine clinical control in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). DESIGN: Prospective, nonrandomized, case-control study. SETTING: Single referral center. PATIENTS AND INTERVENTION: A total of 26 patients (mean age, 56 years) with histologically confirmed stage III-IV HNSCC underwent PET before and approximately 6 weeks after the end of a combined treatment with radiation and chemotherapy with curative intent. The PET findings were confirmed by histologic analysis and a 6-month clinical follow-up. MAIN OUTCOME MEASURES: The presence of distant metastases, secondary synchronous cancers, and residual locoregional tissue was confirmed, and the effect on further clinical management was assessed. RESULTS: Using PET, we correctly identified residual tumor tissue, distant metastases, or a second primary tumor in 10 patients, 5 of whom had no clinical evidence of such findings. Results were true negative in 14 cases; false positive in 1; and false negative in 1. Sensitivity and specificity for follow-up PET scans were 90.9% and 93.3%, respectively. All patients with positive findings were evaluated for further treatment such as salvage surgery. CONCLUSIONS: Whole-body PET scanning approximately 6 weeks after completion of a combined treatment regimen with radiation and chemotherapy can reliably identify locoregional residual cancer and distant metastases or secondary tumors in patients with advanced-stage HNSCC and has a direct influence on management decisions.

Adult↗

Sentinel lymph node biopsy in thyroid tumors: a pilot study.

The purpose of this study was to assess the feasibility of sentinel lymph node (SLN) biopsy in thyroid neoplasms. Ten patients with uninodular thyroid disease and no evidence of lymph node metastases were examined. Lymph node mapping was performed by preoperative lymphoscintigraphy and intraoperative use of a hand-held gammaprobe. Following thyroidectomy, the SLN(s) were selectively excised and worked-up histologically for occult metastases. Overall detection of SLNs was possible in 50% of the cases with lymphoscintigraphy and in 100% with the gammaprobe. All SLNs in the lateral compartment and upper mediastinum were accurately detected with lymphoscintigraphy. One patient with a papillary carcinoma showed a metastasis in the SLN. One patient experienced temporary lesion of the recurrent laryngeal nerve. In conclusion, sentinel lymph node biopsy is technically feasible. The combination of lymphoscintigraphy and gammaprobe accurately reveals SLNs in the central and lateral compartment and in the mediastinum. Search for SLNs in the lower central compartment enhances the risk of injuring the recurrent laryngeal nerve. The clinical relevance of SLN biopsy in papillary thyroid cancer is unclear, and the subgroup of patients benefiting from it has still to be defined.

Adult↗

Early glottic carcinoma: treatment according patient's preference?

BACKGROUND: To analyze the results in early (stage I and II) glottic carcinoma of a single institution with a patient-oriented concept. METHODS: After diagnostic workup and multidisciplinary counseling, either radiotherapy or CO(2) laser surgery was chosen with respect to the patient's preference. RESULTS: Sixty-five patients underwent laser surgery and 75 had radiotherapy. For T1 tumors, the 5-year overall survival, disease-specific survival, and initial local control rate after laser surgery and radiotherapy were comparable (OS, 85% vs 88%; DSS, 96% vs 93%; LCR, 86% vs 85%). In contrast, initial local control for T2 tumors was significantly more favorable after surgery (OS, 83% vs 78%; DSS, 83% vs 88%; LCR, 89% vs 67%). Larynx preservation was significantly higher after surgery in T1 tumors (96% vs 82%) and in T2 tumors (89% vs 77%). CONCLUSIONS: Selection of the treatment modality according to patient's preference results in a comparable control of disease for T1 tumors. The initial local control for T2 tumors is significantly better after surgery. In both stages laser surgery warrants a better larynx preservation rate.

Adult↗

Impact of positron emission tomography on the initial staging and therapy in locoregional advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To evaluate the impact of 18F-fluoro-deoxy-glucose positron emission tomography after standard diagnostic workup in patients with advanced head and neck squamous cell carcinoma on staging and radiation treatment planning. STUDY DESIGN: Prospective controlled study. METHODS: Forty-eight patients (42 men and 6 women; mean age, 61 y; age range, 35-85 y) with histologically confirmed, advanced-stage (any T, N> or =N2 or T> or =T3, any N) mucosal head and neck squamous cell carcinoma underwent positron emission tomography. The routine workup consisting of physical examination, panendoscopy, chest x-ray film, and contrast-enhanced high-resolution helical computed tomography scan (HRCT) was used for comparison. End points were the extent of lymph node disease, distant metastases, and second primary tumors. RESULTS: In 41 of 48 patients (85%) the lymph node findings between HRCT and positron emission tomography were concordant. In three patients positron emission tomography led to an upstaging of the tumor in its N category, and in four patients positron emission tomography underestimated lymph node involvement. Positron emission tomography revealed more difficulties in delineating lymph node metastases adjacent to the primary tumor than did HRCT, but was superior for the detection of distant and contralateral lymph node metastases. Positron emission tomography suggested distant metastatic lesions in 6 of 48 patients (13%). Cytological workup confirmed distant metastases in two (4%) and second primary tumors in another two patients (4%). Positron emission tomography results were false-positive in two (4%) patients because of inflammatory changes. CONCLUSIONS: Whole-body PET is able to assess lymph node involvement, distant metastases, and second primaries in a single study. Even after a routine clinical staging, positron emission tomography leads to a change of treatment in approximately 8% of patients.

Adult↗

Quality of life after different treatment modalities for carcinoma of the oropharynx.

OBJECTIVES: To assess the long-term posttreatment quality of life of patients with carcinoma of the oropharynx treated with different treatment modalities. STUDY DESIGN: Retrospective chart review and patient response to EORTC quality of life core questionnaire QLQ-C30 and EORTC quality of life core head and neck cancer module QLQ-H&N35 questionnaires. METHODS: Two hundred and seventeen patients with carcinoma of the oropharynx were treated with curative intent between 1990 and 1998. In January 2001, a total of 111 disease-free survivors were identified and included in this study. The questionnaires were completed by 99 patients (89% completion rate). RESULTS: Of 99 patients, 31 patients were treated with surgery alone, 19 with radiation therapy alone and 49 with surgery followed by postoperative irradiation. Median follow-up for the entire study group was 71 months. Physical, role, emotional, cognitive and social functioning reflected in the functional scale scores of the global EORTC QLQ-C30 were generally good and showed no significant differences for the different treatment modalities. Comparison of the head and neck specific EORTC QLQ-H&N35 scores revealed significantly less troubles with swallowing (P = 0.006), social eating (P = 0.007) and social contact (P = 0.008), dry mouth (P < 0.0001), sticky saliva (P = 0.0001) and mouth opening (P = 0.001) in non-irradiated patients versus those treated with any either primary or postoperative radiation therapy. Patients undergoing surgery (with and without postoperative irradiation) had less pain (P = 0.04), less problems with social eating (P = 0.009) and less restricted mouth opening (P = 0.03) than the nonsurgically treated patients. CONCLUSIONS: Quality of life after curative treatment of oropharyngeal carcinoma is generally good. Differences regarding quality of life between the different treatment modalities manifest themselves in the head and neck specific EORTC QLQ-H&N35 module, not in the global core questionnaire EORTC QLQ-C30.

Affect↗

Is there a role for positron emission tomography with 18F-fluorodeoxyglucose in the initial staging of nodal negative oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The aim of our study was to assess the value of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) for the staging of clinically nodal negative necks in oral and oropharyngeal squamous cell carcinoma (SCC) using sentinel lymph node (SLN) biopsy and elective neck dissection (END) as "gold standard" for comparison. METHODS: Twelve patients (10 men, 2 women) with oral or oropharyngeal squamous cell carcinoma and no evidence of lymph node metastasis in the physical and radiologic examinations were eligible. At least 24 hours before surgery PET with FDG were performed. The SLN was localized by preoperative lymphoscintigraphy with 99m-Tc-Nanocoll and intraoperative use of a hand-held gamma-probe and selectively excised. All patients then underwent END. RESULTS: SLN and END revealed occult metastasis in 5 of 12 cases. SLN biopsy was accurately feasible in all 12 patients and diagnosed all 5 cases of occult metastasis (sensitivity and specificity of 100%). PET suggested two patients having occult metastasis, of which one turned out to be false positive (sensitivity 25%, specificity 88%). The mean size of the micrometastasis was 1.4 mm (range, 1.2-1.5 mm). CONCLUSIONS: PET with FDG turned out to have a poor sensitivity and specificity in revealing occult metastasis and has no role for the evaluation of otherwise clinically N0 necks. The failure to detect micrometastasis by PET is due to the technical limitations of resolution (4-5 mm). SLN biopsy, with END in cases of positive SLN, provides a highly accurate staging of N0 necks in oral and oropharyngeal carcinoma. Patients with negative SLN could be spared the risks and the morbidity of END.

Adult↗

Loss of heterozygosity at chromosome 6q23-25 correlates with clinical and histologic parameters in salivary gland adenoid cystic carcinoma.

The prognosis of salivary gland adenoid cystic carcinoma (ACC) depends on the clinical stage, the location of the primary tumor, and the histologic growth pattern. ACCs with a cribriform growth pattern have a better prognosis than those with a solid growth pattern; however, clear-cut grading criteria have not yet been established, and therefore prognostic indicators on a molecular level are of special interest. In order to analyze tumor tissue with different growth patterns, cribriform and solid tumor areas of 25 patients were microdissected and separately analyzed for loss of heterozygosity (LOH) at nine polymorphic microsatellite markers located between 6q14 and 6q27. LOH was detected in 19/25 (76%) patients and LOH rates were highest at markers D6S441, D6S310, D6S311 and UTRN, which are located at 6q23-25. Combined analysis of LOH at these four markers shows that in primary tumor subtype foci with cribriform growth pattern LOH is associated with high TNM stages (P<0.01), high T stages (P=0.01), positive lymph node status (P=0.03), an unfavorable disease course (P=0.02), and the presence of >10% solid growth pattern (P=0.05). In contrast, in primary tumor subtype foci with solid growth pattern, no significant differences in LOH rates were found in patients from prognostically and histologically favorable versus unfavorable patient groups. The frequent occurrence of LOH at 6q23-25 and the correlation of LOH rates with prognostic parameters indicate that a prognostically important tumor suppressor gene is located in this chromosomal area.

Adult↗

Endoscopic stapler-assisted diverticuloesophagostomy for Zenker's diverticulum: patient satisfaction and subjective relief of symptoms.

BACKGROUND: We assessed the results of endoscopic stapler-assisted diverticuloesophagostomy for Zenker's diverticulum, with emphasis on patient satisfaction and subjective relief of symptoms. METHODS: A retrospective cohort analysis was performed on all patients operated on from 1997 to 2000. Patients' charts were reviewed with respect to intraoperative and postoperative complications. The severity of preoperative and postoperative symptoms by patient self-assessment was compared by means of a 4-point scale (0-3) on a standardized questionnaire, as well as assessment of patient satisfaction (poor, fair, moderate, high). RESULTS: Thirty patients (22 men, 8 women) with a mean age of 72 years (range, 42-97 years) were part of the study. The mean follow-up was 13.2 months (range, 2-39 months). No major intraoperative or postoperative complications were observed. The most frequent preoperative symptoms were regurgitation of undigested food and dysphagia for solid consistencies (87%). Both of these preoperative symptoms were improved from a mean preoperative score of 2.2 and 2.7 to 0.1 and 0.4, respectively (P <.0001). Postprandial coughing (32%), halitosis (21%), and globus sensation (32%) were less common but also significantly improved. All but 1 patient (96%) were highly satisfied with the procedure. CONCLUSIONS: Endoscopic stapler-assisted treatment of Zenker's diverticulum offers a very low complication rate, a very high degree of symptom relief, and patient satisfaction.

Adult↗

Histopathological features of occult metastasis detected by sentinel lymph node biopsy in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVES: Sentinel lymph node biopsy has been introduced for head and neck cancer with promising results. Research in breast cancer has revealed different histopathological features of occult lymph node metastasis with possibly different clinical and prognostic implications. The aim of the study was to evaluate the histopathological features of occult metastasis detected by sentinel lymph node in oral and oropharyngeal squamous cell carcinoma. STUDY DESIGN: Prospective. METHODS: According to Hermanek (5), occult metastasis was differentiated into isolated tumor cells and infiltration of lymph node parenchyma smaller than 2 mm in diameter (micrometastasis) and larger than 2 mm in diameter (metastasis). RESULTS: Occult metastases were found in 6 of 19 (32%) sentinel lymph nodes. Three patients showed micrometastasis with a mean size of 1.4 mm (range, 1.2-1.5 mm), the first with three separate micrometastases within the same sentinel lymph node, the second with an additional cluster of isolated tumor cells within the same sentinel lymph node, and the third with an additional micrometastasis in one lymph node of the elective neck dissection. Two patients had macrometastasis (3.4 and 8 mm), both with multiple metastases in the elective neck dissection. One patient had two clusters of isolated tumor cells in the sentinel lymph node and an additional cluster of isolated tumor cells in one lymph node of the elective neck dissection. CONCLUSIONS: Occult metastasis can be subdivided histopathologically in isolated tumor cells, micrometastasis, and macrometastasis. We present the first study describing a great variety of these subtypes in sentinel lymph nodes from head and neck squamous cell carcinoma. Because the independent prognostic factor and clinical relevance of these subtypes is still unclear, we emphasize the importance of reporting these findings uniformly and according to well-established criteria.

Adult↗