Effect of postoperative systemic prednisolone on short-term and long-term outcomes in chronic rhinosinusitis with nasal polyps: A multi-centered randomized clinical trial.

Introduction: The objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures. Methods: This was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels. Results: 106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups. Conclusion: In conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.

Impact of COVID-19 lockdown on hospital admissions for epistaxis in Germany.

BACKGROUND: Reports of a decrease in hospital admissions during the coronavirus disease 2019 (COVID-19) lockdown period have raised concerns about delayed or missed diagnoses and treatments for non-COVID-19-related illnesses. AIM: To investigate the impact of the COVID-19 pandemic-induced lockdown and its end on hospital admissions of patients with epistaxis in Germany. METHODS: A retrospective analysis based on the national database of the Hospital Remuneration System was used to compare hospital admissions during defined time periods between 2019 and 2022 with the lockdown period as the reference period. This was done on a weekly basis before, during, and after the lockdown. An Interrupted Time Series was used as the analysis method. RESULTS: In our analysis, we included 26183 patients. The implementation of the lockdown led to a substantial reduction in the overall occurrence of epistaxis among patients (P < 0.05). This effect was most pronounced in the age group of 0-39 years, where the decrease was highly significant (P < 0.001). However, there was no change observed in patients aged 80 years and older (not significant). With the end of the lockdown period, the overall number of patients, especially in the youngest age group, increased abruptly and significantly (P < 0.01). CONCLUSION: During the lockdown period, there was a decrease in hospital admissions for younger patients with epistaxis, possibly due to the fear of COVID-19 exposure. We also conclude that the severity of epistaxis was not underestimated in the elderly during the pandemic.

Functional requirements for polymeric implant materials in head and neck surgery.

BACKGROUND: The pharyngeal reconstruction is a challenging aspect after pharyngeal tumor resection. The pharyngeal passage has to be restored to enable oral alimentation and speech rehabilitation. Several techniques like local transposition of skin, mucosa and/or muscle, regional flaps and free vascularized flaps have been developed to reconstruct pharyngeal defects following surgery, in order to restore function and aesthetics. The reconstruction of the pharynx by degradable, multifunctional polymeric materials would be a novel therapeutical option in head and neck surgery. MATERIALS AND METHODS: Samples of an ethylene-oxide sterilized polymer (diameter 10 mm, 200µm thick) were implanted for the reconstruction of a standardized defect of the gastric wall in rats in a prospective study. The stomach is a model for a "worst case" application site to test the stability of the implant material under extreme chemical, enzymatical, bacterial, and mechanical load. RESULTS: Fundamental parameters investigated in this animal model were a local tight closure between the polymer and surrounding tissues, histological findings of tissue regeneration and systemic responses to inflammation. A tight anastomosis between the polymer and the adjacent stomach wall was found in all animals after polymer implantation (n = 42). Histologically, a regeneration with glandular epithelium was found in the polymer group. No differences in the systemic responses to inflammation were found between the polymer group (n = 42) and the control group (n = 21) with primary wound closure of the defect of the gastric wall. CONCLUSIONS: A sufficient stability of the polymeric material is a requirement for the pharyngeal reconstruction with implant materials.

Tumor-associated antigenic pattern in squamous cell carcinomas of the head and neck--analysed by SEREX.

Most immuno-therapeutic approaches are based on tumor-associated antigens and many newly identified proteins have led to trials exploiting their possible therapeutic applicability. So far only limited information on the antigenic profile of head and neck squamous cell carcinomas (HNSCC) exists. Serological analysis of tumor antigens by recombinant cDNA expression cloning (SEREX) was used to identify the immunogenic patterns in our HNSCC patient collective. A cDNA expression library derived from a pharynx HNSCC case was screened with autologous and heterologous sera. Thirty-seven positive clones coding for 17 immunoreactive gene products, which elicited an in vivo tumor response, were found. Results were confirmed and extended by expression analysis using RT-PCR and in situ-hybridisation. The protein-sequence of five clones exists so far only hypothetically. Of all identified proteins only KIAA0530 has previously been associated with a HNSCC related immune response. All other proteins have not yet been described in a context with HNSCC antigenic patterns. Antibodies against a heat shock transcription factor 2 (HSF2) were found in 2 out of 10 sera from HNSCC patients. In summary, using the SEREX technique, we isolated 17 immunogenic antigens in HNSCC's and confirmed the clinical relevance of KIAA0530. Further analysis concerning their feasibility as target structures for an immunotherapy approach is currently conducted.

A 47-year old male with a cerebellopontine angle tumor.

A 47-year old man presented with a five-year history of fluctuating hearing impairment in the left ear. There was no tinnitus or vertigo. Imaging studies demonstrated a contrast-enhancing cerebellopontine angle mass in the left internal auditory canal. Surgically the lesion was attached to the cochlear nerve. Pathological evaluation revealed what is best described as an angiolipomatous hamartoma of the cochlear nerve. Similar lesions have only rarely been described.

Metastatic and inflammatory cervical lymph nodes as analyzed by contrast-enhanced color-coded Doppler ultrasonography: quantitative dynamic perfusion patterns and histopathologic correlation.

Use of contrast-enhanced color-coded Doppler (ultra)sonography (CCDS) in evaluating enlarged lymph nodes has been subject to numerous attempts to define criteria for differentiation between benign and malignant lesions. Evaluation of dynamic perfusion patterns with contrast-enhanced CCDS in cervical lymph nodes offers new possibilities of differential diagnosis. A total of 28 patients with clinically enlarged lymph nodes were included in this study. Contrast-enhanced CCDS was performed on each patient. The color signals from nodes <15 mm in diameter were analyzed with a specialized computer program. Each node was later examined through immunohistochemical staining. Vascularization as shown by unenhanced CCDS was significantly greater in metastatic lymph nodes than in reactively enlarged lymph nodes (8.66% versus 2.81%; p = .01). The maximum vascularization area after contrast injection did not show any significant change (26.61% versus 28.63%; p = .75). Comparison of values obtained before and after contrast enhancement showed the largest relative increase in vascularization in inflammatory lymph nodes, from a factor of 19.55 to a factor of 10.03 (p = .025). Dynamic values such as contrast enhancement, behavior of dynamic values referred to time, and the evaluated vascularized area did not show any significant difference. The metastatic lymph nodes (5.46 versus 3.33; p = .007) predominantly consisted of large blood vessels. The increased vascularization in the unenhanced CCDS examination of metastatic lymph nodes seems to be associated with the increased number of large blood vessels. An increased vessel density, due to a greater number of total vessels, is related to an inflammatory process. Color Doppler mapping has been proven to depict useful aspects distinguishing benign from malignant lymph nodes of the neck; however, a definitive differentiation between lymph nodes involved with malignancy and inflammatory changes remains difficult.

Olfactory neuroblastoma: the University of Erlangen-Nuremberg experience 1975-2000.

OBJECTIVE: Olfactory neuroblastoma constitutes a rare and, in clinical terms, biologically variable tumor of the nasal cavity, paranasal sinuses, and the base of the skull and presents a challenge to a modern multidisciplinary therapy. Generally acknowledged prognostic factors and a standard therapy fail to exist. METHODS: Between 1975 and 2000 we diagnosed and treated 26 patients with an olfactory neuroblastoma. According to Kadish's classification, 1 patient (4%) showed stage A, 16 patients (53%) stage B, and 11 cases (43%) stage C. Hyams grading was established in 81% of all cases. Fifty-two percent were thus classified as low-grade and 48% as high-grade tumors. Surgical therapy was performed on 23 patients (88.5%), surgery being the exclusive form of therapy (monotherapy) in 5 of these patients. Combined therapy was carried out in 18 cases (surgery, radiotherapy, chemotherapy). RESULTS: Currently, 16 of 26 treated patients (61.5%) are alive. The disease-specific 10- and 15-year survival determined according to Kaplan-Meier is 76.2%. Fifteen-year survival amounts to 86.7% for smaller tumors (Kadish A/B) and 63.6% for advanced tumors (Kadish C). Seven (26.9%) of the overall group of treated patients developed a recurrence. Salvage therapy was successful in 60% (3 of 5 patients). Fifteen-year survival following salvage therapy amounts to 60%. Patients with high-grade tumors exhibit a significantly reduced 10-year survival (40%) compared to patients with low-grade tumors (100%). CONCLUSIONS: The therapy of olfactory neuroblastoma calls for an interdisciplinary multimodal therapeutic strategy, particularly in the case of advanced tumors. Tumor staging and histopathologic grading according to Hyams are important factors for survival and prognosis. Aggressive salvage therapy can lead to a distinct improvement of long-term survival.

Surgical application of a new robotic system for paranasal sinus surgery.

The applicability of a robotic system for fully automated surgical procedures approaching the sphenoid sinus is evaluated. An integrated robotic system, A73, for computer navigation-guided, fully automated, and telemanipulation robotic performance is described. Details of the system comprising newly designed surgical instruments for robotic operations and preoperative planning protocols are provided. Experiments with an operational accuracy of less than 1 mm were followed by surgical tests, in which the results of fully automated and telemanipulation performances on 5 cadaveric heads are seen. The A73 system has been successfully used for a reproducible and accurate resection of the anterior wall of the sphenoid sinus. Therefore, we conclude that this system is suited for further testing toward approaching fully automated and more complex procedures of paranasal surgery.

Effects of immediate and delayed facial-facial nerve suture on rat facial muscle.

OBJECTIVE: To investigate regeneration of the mimic musculature after delayed facial nerve repair. MATERIALS AND METHOD: In 30 rats the facial nerve on the right side was resected and immediately repaired with an end-to-end anastomosis. The entire levator labii muscle was removed on the right side and histochemically and morphometrically analyzed at 7, 14, 21, 28, 90 and 180 days after immediate nerve repair. In a further 20 rats, reinnervation was performed after 4 weeks in a further operation and the muscle was assessed at 14, 28, 90 and 180 days. Seven muscles of four normal rats were used as controls. RESULTS: Three muscle fiber types could be identified by comparative histochemical analysis of two enzymes of succinate dehydrogenase (SDH) and m-ATPase: oxidative glycolytic (FOG) fibers, fast glycolytic (FG) fibers and intermediate muscle fibers that were designated SDH-INT. The number of fibers and the frequency distribution of single-fiber cross-sectional areas were determined for each type of fiber. No significant difference in the cross-sectional area of all fiber types was noted after 180 days when comparing immediate and delayed end-to-end sutures. In contrast, comparison of the fiber-type composition showed a significant increase in the number of FG fibers in the delayed suture, at the expense of FOG fibers. After immediate reinnervation the muscle approximately attained its natural fiber-type composition, whereas after delayed reinnervation the muscle showed an overall loss of oxidative capacity and differentiation towards phasic activity. CONCLUSION: Changes in fiber-type composition following delayed nerve suture are irreversible and have specific effects on the precise function of the muscle. Immediate nerve repair improves axonal reinnervation.

Contrast-enhanced color Doppler sonography of parotid gland tumors.

The objective of the present study is to assess the potential of color Doppler sonography in imaging tumors of the parotid gland enhanced by application of ultrasound contrast agents. To this end 26 patients with tumors of the parotid gland were investigated. The color Doppler signal areas before and after administration of Doppler signal-enhancing agent (Levovist, Schering, Germany) were determined by means of computer-assisted analysis, and the relevant parameters were evaluated. The tumors can be classified as follows: 11 pleomorphic adenomas, 8 adenolymphomas and two squamous cell carcinomas of the parotid gland, two lymph nodes, one adenoma, one neurinoma of the facial nerve and one non-Hodgkin's lymphoma. Before the administration of Doppler signal-enhancing agent, the adenolymphomas showed a significantly stronger Doppler signal area as compared to the pleomorphic adenomas. The maximum color Doppler signal area after administration of Doppler signal-enhancing agent showed no difference within both groups. If one considers the relative change in the Doppler signal area before and after applying enhancing agent, however, a significantly stronger enhancement of perfusion (increase in Doppler signal area) is noted within pleomorphic adenomas. The changes in the Doppler signal area after administration of signal-enhancing agent show a different course depending on the histology of the investigated tumors.

Combined surgical lipectomy and liposuction in the treatment of benign symmetrical lipomatosis of the head and neck.

Benign symmetrical lipomatosis (Madelung syndrome) is a rare disease of unknown aetiology, which is characterised by diffuse growth of non-encapsulated lipomas. Between 1995 and 2000 we treated 11 patients with benign symmetrical lipomatosis in the head and neck. The group comprised 10 men and one woman aged 34 to 62 years (mean 47). The most common complaints were reduced range of movement of the head and obstruction when eating or speaking. Combined lipectomy and liposuction were done for all patients, with liposuction being done at a second session. The mean follow-up period was 2.7 years. The functional results were satisfactory in all patients. Nine of the 11 patients were also satisfied with the aesthetic outcome. Two patients developed recurrence 1.5 and 2 years after the operation, respectively. There were no serious complications. We think that combined lipectomy and liposuction is a successful procedure for treating benign symmetrical lipomatosis in the head and neck region. Nevertheless, the advantages and drawbacks of the two techniques should be considered preoperatively.

Altered DNA repair capacity in young patients suffering from multiple cancers.

Young patients less than 45 years old suffering from multiple cancers but lacking typical risk factors were evaluated for genetic instability. Peripheral blood lymphocytes were isolated and DNA repair capacity was investigated using alkaline microgel electrophoresis and compared to matched normal controls. While normal lymphocytes had an average DNA repair capacity of 95.3%, those isolated from cancer patients had 81.3% (p<0.01). While 10 patients with multiple cancer showed compatible repair capacity to healthy donors, 9 patients had a distinct reduced DNA repair capacity much lower than triple standard deviation. It must be assumed, that this subgroup of the cancer patients has a genetic background of reduced DNA repair capacity or processing and that development of multiple cancer may be due to genetic instability. These results will impact not only the developing of new diagnostic and screening strategies, but will also guide further research targeting the underlying mechanisms of DNA repair relating to cancer.

Neck dissection following radiochemotherapy of advanced head and neck cancer--for selected cases only?

PURPOSE: To address the value of neck dissection (ND) in patients with advanced head and neck cancer following primary radiochemotherapy and to specifically analyse its impact on locoregional tumour control, survival and toxicity. PATIENTS AND METHODS: Between 1987 and 1997 (9,335), a total of 142 patients (pts) were treated by primary radiochemotherapy (RCT) according to prospective protocols. There were 64 pts with involvement of the hypopharynx, 57 pts with oropharyngeal and 21 with oral cavity carcinoma. UICC (1997) stages included: 16 pts in stage III, 113 pts in stage IV A, 13 pts in stage IV B. All pts received platin-based RCT up to a median total dose of 70 Gy (range, 60-72 Gy). Six weeks after RCT, pts with complete response of the primary tumour (N=97) were offered a uni- or bilateral ND depending on the initially diagnosed nodal disease as part of a strict institutional policy. Fifty-six pts consented to ND and 41 refused. These two groups were analysed in terms of characteristics, local and regional tumour control, survival and long-term side effects. Median follow-up was 37 months (range, 22-124 months). RESULTS: Among the 56 pts receiving ND, a total of 13 (23%) was found to have residual tumour in the neck specimen. The rates of positive histology according to clinical N category after RCT were: yN0 (2/22[9%]), yN1 (2/10[20%]), yN2a-b (2/10[20%), yN2c-3 (7/14[54%]). Five-year overall survival and disease-specific survival rates for pts with ND were 44 and 55%, for pts without ND 42 and 47%, respectively (P=0.9). No difference was seen for long-term local and regional control between the two patient groups. Comparing the group of patients with and without ND, a trend towards higher subjective morbidity of grade 3 and 4 (LENT-SOMA), i.e. pain recording (24% vs. 17%), dysphagia (48% vs. 35%) and hoarseness (20% vs. 9%) was evident in patients with ND. CONCLUSION: No clear evidence for routine clinical use of ND after RCT in advanced head and neck tumours can be derived from these data. ND may be contemplated in selected cases with multiple residual nodes only.