Closure of Nasal Septal Perforations Using a Diced Cartilage in Fascia Graft.

The spectrum of surgical techniques in the repair of nasal septal defects is wide. The objective of this study was to assess the feasibility of using a diced cartilage in fascia (DC-F) graft for successful closure of nasal septal perforations and to evaluate symptom reduction. This was a retrospective study of 18 patients undergoing surgical repair of symptomatic nasoseptal perforations of different etiologies using a DC-F graft from 2020 until 2021. The procedure was feasible in all of the 18 patients. Reconstruction of septal defects with a DC-F graft led to reduction of crust formation, reduction of epistaxis, and improvement of nasal breathing in 13 out of the 18 patients when seen for their 2-month follow-up. Reperforation occurred in three cases, leaving defects of 1, 7, and 5 mm in diameter. In one case, the reperforation was symptomatic. A DC-F graft proved to be a reliable and reproducible method for the closure of nasoseptal perforations of variable sizes, of different locations, and of different etiologies.

Vitamin D deficiency in head and neck cancer patients - prevalence, prognostic value and impact on immune function.

Vitamin D deficiency is frequently observed in human cancer patients and a prognostic relevance could be shown for some entities. Additionally, it is known that vitamin D can stimulate the patients' antitumor immunity. However, valid epidemiological data for head and neck squamous cell carcinoma (HNSCC) patients are sparse and functional studies on a possible connection between vitamin D and the patients' immune system are missing. 25-OH vitamin D serum levels were analyzed in 231 HNSCC patients and 232 healthy controls and correlated with clinical data and patient survival. Intra- and peritumoral infiltration with T-cell, NK-cell and macrophage populations was analyzed in 102 HNSCC patients by immunohistochemistry. In 11 HNSCC patients, NK-cells were isolated before and after vitamin D substitution and analyzed for their cytotoxic activity directed against a HNSCC cell line. Vitamin D serum levels were significantly lower in HNSCC patients compared with healthy controls. Low vitamin D levels were associated with lymphatic metastasis and a negative HPV status and were a significant predictor of poor overall survival. HNSCC patients with severe vitamin D deficiency showed significantly altered intra- and peritumoral immune cell infiltrate levels. After vitamin D substitution, the patients' NK cells showed a significant rise in cytotoxic activity. Taken together, we could show that Vitamin D deficiency is highly prevalent in HNSCC patients and is a predictor of poor survival. Vitamin D substitution used as an adjuvant in immune therapies such as cetuximab and nivolumab treatment could support antitumorigenic immune responses, thus contributing to the improvement of the patients' prognosis in the context of a multimodal therapy.

Intraductal Papillary Mucinous Neoplasms of Minor Salivary Glands With AKT1 p.Glu17Lys Mutation.

The spectrum of low-grade intraductal papillary proliferations of the salivary glands is heterogenous, and reproducible morphologic diagnostic criteria have not yet been established. Recognized types are sialadenoma papilliferum, inverted ductal papilloma, and intraductal papilloma, but some lesions have been possibly included in the morphologic spectrum of cystadenoma or low-grade intraductal carcinomas. We herein present detailed morphologic, immunophenotypic, and genotypic features of 3 minor salivary gland neoplasms affecting 2 men (aged 65 and 71 y) and 1 woman (aged 78 y). They ranged in size from 1 to 2.5 cm. All tumors showed atypical papillary intraductal growth that presented either as uninodular/unicystic lesions (intraductal papilloma-like; n=2) or as a discontinuous growth along the ductal system in a manner similar to pancreatic intraductal papillary mucinous neoplasm (n=1). Variable cytologic and architectural atypia was observed, ranging from bland intraductal papilloma-like features, to areas mimicking atypical ductal hyperplasia and low-grade ductal carcinoma in situ of the breast. Amplicon-based massive parallel sequencing revealed an identical AKT1 p.Glu17Lys mutation in all 3 cases, but absence of concurring mutations in other genes of the RAS or PI3K pathway. This small series represents the first genetic study on salivary intraductal papillary neoplasms. Our cases showed significant variation in the degree of cytologic and architectural atypia, which overlaps with intraductal papillomas at the one end and with low-grade intraductal carcinoma at the other end of the spectrum, suggesting a disease continuum. As the full biological and morphologic characteristics of these ductal papillary lesions remain to be defined, the noncommitted term "intraductal papillary neoplasms" might be more appropriate. Our novel genetic findings mirror similar activating mutations of AKT1 and other PI3K pathway members in intraductal papillary lesions of the breast and anogenital glands.

Ultrasonographic evaluation of calcification patterns in costal cartilage: implications for rib graft harvesting.

IMPORTANCE: Complex augmentation rhinoplasty often requires the use of cartilaginous grafts, especially in revision surgery. When using costal cartilage, the possibility of inadequate cartilage material because of excessive calcification must always be kept in mind. Furthermore, cartilage may be harvested but found to be not ideal, causing unsatisfying results. OBJECTIVE: To report our experience with the use of preoperative ultrasonographic (US) examinations for quality analysis of costal cartilage. DESIGN, SETTING, AND PARTICIPANTS: In an academic research setting, US imaging of the anterior rib cage was performed before 83 revision rhinoplasties requiring costal cartilage grafting. MAIN OUTCOMES AND MEASURES: Cartilage volume, quality, sex-specific calcification patterns, and the location of hidden calcification islands within viable cartilage were recorded. RESULTS: Two different calcification patterns, 1 central and 1 peripheral, were identified. CONCLUSIONS AND RELEVANCE: We found this cost-effective technique to be a valuable tool for easy preoperative cartilage assessment. Furthermore, US screening guides the surgeon to areas of harvestable cartilage and to cartilage that is best suited for rhinoplasty in terms of distribution patterns of calcification areas. LEVEL OF EVIDENCE: NA.

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.

Immunological treatment options for locoregionally advanced head and neck squamous cell carcinoma.

Patients with squamous cell carcinoma of the head and neck (HNSCC) are usually treated by a multimodal approach with surgery and/or radiochemotherapy as the mainstay of local-regional treatment in cases with advanced disease. Both chemotherapy and radiation therapy have the disadvantage of causing severe side effects, while the clinical outcome of patients diagnosed with HNSCC has remained essentially unchanged over the last decade. The potential of immunotherapy is still largely unexplored. Here the authors review the current status of the art and discuss the future challenges in HNSCC treatment and prevention.

Perineurioma of the parotid gland: first case report.

SUMMARY: Neurogenic neoplasms account for approximately 1% of salivary gland tumors. A 45-year-old woman presented with a slowly growing unilateral parotid gland mass that was excised completely by lateral parotidectomy. No recurrence was detectable 6 months after surgery. The resection specimen contained a 1.7 × 1.2 × 1-cm whitish nodular lesion that was firm, well circumscribed, and completely surrounded by compressed normal glandular tissue. The tumor was composed of spindle cells with bipolar tapering, wavy nuclei, and palely stained cytoplasm. The tumor cells were arranged in storiform, lamellar, and whorled patterns. Nuclear atypia, necrosis, and significant mitotic activity were absent. Immunohistochemistry showed expression of epithelial membrane antigen, glucose transporter 1, claudin-1, and collagen IV. All other lineage-specific markers including protein S100 were negative in the tumor cells. To our knowledge, this case represents the first report of soft tissue perineurioma in the salivary gland. Lack of previous reports suggests underrecognition of this tumor entity at this unusual anatomical site.

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.

Localization and infliction pattern of iatrogenic skull base defects following endoscopic sinus surgery at a teaching hospital.

OBJECTIVE: Aim of this study is to evaluate the incidence, infliction patterns and management of dural injuries with cerebrospinal fluid (CSF) rhinorrhea following endoscopic sinus surgery at a teaching hospital. We present our results of over 14 years of experience from endoscopic repair of CSF rhinorrhea with long-term follow-up. METHODS: A retrospective study was performed by screening 14 years of sinus surgeries for iatrogenically inflicted CSF leaks of the anterior skull base. Obtained data were analyzed to determine the infliction pattern and location of CSF leaks, surgical closure techniques and outcomes. All incidences were further evaluated with regards to the surgeons training status. RESULTS: 144 patients out of 6908 sinus surgeries were diagnosed with CSF rhinorrhea and underwent subsequent surgical repair. 52 patients had iatrogenic CSF leaks with 32 of the defects inflicted by the department's physician personnel. Average follow-up was 62 months, with a range of 10-168 months. The side distribution was 56.3% to the patient's right side and in 40.6% to the patient's left side. 68.7% became apparent during the initial surgery whereas 31.3% only after surgery. The most common defect location was the anterior ethmoid at the attachment of the medial concha base with 43.7%, followed by the junction between the ethmoid and sphenoid sinus with 21.9%, the frontal sinus aditus with 18.7% and the medial ethmoid region with 9.4%. With increasing training status, surgeons were more prone to cause defects at the frontal sinus aditus whereas surgeons with lesser training status caused more defects at the anterior ethmoid at the medial concha base. The posterior ethmoid and sphenoid sinus was equally prone to defects over all stages of surgical training. Initial endoscopic repair was successful in 87.5% of patients and 95% after revision surgery. CONCLUSION: The obtained data confirm the safety of the endonasal sinus surgery according to Wigand's technique. The incidence of iatrogenic CSF leaks at a teaching hospital is not higher than at specialized rhinology departments. We observed a distinct pattern of inflicted skull base defects with different hot-spot areas, prone to damage in various stages of the surgeon's status of expertise.

Oculopharyngeal muscular dystrophy as a rare differential diagnosis for unexplained dysphagia: a case report.

INTRODUCTION: We wish to report on a rare cause of dysphagia; oculopharyngeal muscular dystrophy (OPMD). It is a late adult onset autosomal dominant form of muscular dystrophy that constitutes as a rare diagnosis for any place outside of Canada and first case in southern Germany. CASE PRESENTATION: We report the medical odyssey of a 57-year old male Caucasian patient. He was referred at our hospital for further clarification of a progressive dysphagia, which, at first view, was thought to be tumor related due to the patient's typical anamnesis. CONCLUSION: The present report outlines the importance of considering this rare disease for general medicine practitioners as well as head and neck specialists as a differential diagnosis for swallowing disorders with, even at second view, uncertain cause.

Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells.

BACKGROUND: Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates in vitro, significant and rapid cytotoxic T-lymphocyte (CTL) responses against viral antigens. METHODS: We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV) gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1), expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then investigated the efficiency of the CTLs in killing IE1 targeted cells. RESULTS: A significant MHC Class I-restricted, anti-IE1-specific CTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC) after one, in vitro, stimulation. CONCLUSION: In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.

Intra-operative image update: first experiences with new software in computer-assisted sinus surgery.

BACKGROUND: So far, conventional navigation systems do not provide the opportunity for any modification of acquired image datasets. In particular, the surgical progress in the operating field cannot be visualized unless new imaging scans are performed. METHODS: In a feasibility study, new software creating intra-operative image updates by virtual means was tested in conjunction with conventional navigation. With this new software, surgically removed tissue volumes can be traced and viewed directly within the diagnostic image data. RESULTS AND CONCLUSIONS: The new software represents an interesting and helpful amendment to conventional computer-assisted surgery in selected cases. During surgical procedures around bony structures, the surgeon gets an accurate virtual image update of the surgical progress in the operating field and the amount of tissue removed. However, in cases where mobile structures are present or soft tissue shifts are expected, this feature seems to be suitable only to a limited extent.

rAAV/Her-2/neu loading of dendritic cells for a potent cellular-mediated MHC class I restricted immune response against ovarian cancer.

Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates, in vitro, significant and rapid cytotoxic T-lymphocyte (CTL) responses against viral antigens. We used the rAAV system to induce specific CTLs against tumor antigens for the development of ovarian cancer (OC) gene therapy. As an extension of the versatility of the rAAV system, we incorporated a self-antigen, Her-2/neu, which is expressed in many cancers, including breast and ovarian. We analyzed two different vectors containing a short (157-612) and long domain (1-1197). Our rAAV vector induced strong stimulation of CTLs directed against the self tumor antigen, Her-2/neu. We then investigated the efficiency of the CTLs in killing Her-2/neu-targeted cells. A significant MHC class I-restricted, anti-Her-2/neu-specific CTL killing was demonstrated against Her-2/neu-positive OC cells after one in vitro stimulation. In summary, single peripheral blood mononuclear cell (PBMC) stimulation with rAAV/157-612- or rAAV/1-1197-pulsed DCs induces strong antigen-specific CTL generation. The CTLs were capable of lysing low doses of peptides pulsed into target cells or OC Her-2/neu(+) tumors. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against OC antigens.

Sialoscopy in cases of unclear swelling of the major salivary glands.

OBJECTIVE: Sialoscopy has developed into an important diagnostic and therapeutic tool for diseases of the major salivary glands. STUDY DESIGN AND SETTING: We evaluated 103 patients with chronic swelling of the major salivary glands. Routine diagnostic measures revealed no clear diagnosis. The findings of 109 sialoscopies are described. A semi-rigid endoscope (with a diameter of 1.1 mm and 2 integrated working channels) was used for sialoscopy, 51.5% of the cases in Warthon's duct and 48.5% in Stensen's duct. RESULTS: Pathologic findings resulted in 83.0% of the submandibular and in 96% of the parotid ducts. Obstruction neither due to sialolithiasis nor stenosis was observed in 56.3%, whereas sialolithiasis was observed in 20.3% of the patients. In 36 (35%) patients, an interventional sialoscopy was performed. CONCLUSIONS: In cases of invisible salivary duct obstruction, especially in those with low mineralized calculi, strictures, stenoses, or postinflammatory changes, sialoscopy gives immediate and direct information about causal pathologies. Moreover, further therapy can be planned within the same procedure.

Sperm protein 17 expression defines 2 subsets of primary esthesioneuroblastoma.

Esthesioneuroblastomas (ENBs) are rare malignant tumors of the nasal vault, the origin, diagnosis, and management of which are still subjects of discussion. That there is no related prognostic factor or generally recognized therapeutic regimen highlights the need for further analyses of its underlying biologic features and investigations of new marker proteins that allow more reliable clinical testing. We here show that sperm protein 17 (Sp17) is expressed in the ciliated cells of the normal olfactory epithelium and in a proportion of primary ENB lesions. We found an association between Sp17 expression and metastases at relapse (P = .035), chromogranin expression (P = .014), and a female sex prevalence. A statistically nonsignificant relation was found between Sp17 and S-100, synaptophysin, and neurofilament expression. No correlation was also found between Sp17 expression and the proliferative capacity of the lesion that was evaluated by Ki-67 immunohistochemistry. The results of this study show the usefulness of Sp17 as a means of discriminating 2 subsets of primary ENB lesions and seem to suggest the existence of 2 distinct cell pathways in their origin and development.

New endoscopic instruments for paranasal sinus surgery.

BACKGROUND: Minimally invasive endoscopic and microscopic procedures represent state of the art paranasal sinus surgery techniques in both diagnostic and surgical fields. To combine favorable aspects of both techniques, we evaluated the clinical applicability and effectiveness of multifunctional microendoscopes, providing multiple features to ensure highest accuracy and surveillance when performing crucial steps in paranasal sinus surgery. METHODS: The study included both anatomic experiments on cadaveric heads and clinical tests on patients undergoing routine paranasal surgery. The systems applicability was evaluated in procedures approaching the frontal and sphenoid sinus. Three different endoscopes, 2 straight and the other 1 with a 90 degrees angle, were tested. They integrate canals for flushing and suction and a working canal for either drilling or obtaining biopsies with a miniaturized forceps. For stereotactic feedback, the applicability in combination with a computer-navigation system was evaluated. RESULTS: Anatomic tests were performed to optimize illumination and to test drilling features and forceps biopsies. In all cases, the frontal sinus ostium and the sphenoid sinus anterior wall was easily identified and enlarged by drilling under visual and stereotactic control. Continuous suction and irrigation ensured a constant visual surveillance by removing drilling debris and blood. Best suited for multifunctional endoscopic surgery were drill heads with a cylinder shape, for placing bore holes along the Z axis, and spherical drill heads, for furbishing and enlarging drill holes. CONCLUSION: These new instruments have proven their applicability in paranasal sinus surgery. Multifunctional endoscopic procedures were deemed best suited for maneuvers requiring highest precision, such as the surgery of the frontal and sphenoid sinus.

Rehabilitation of the trigeminal nerve.

When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts.In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available.

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.

Testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24.

Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates significant and rapid (one stimulation per week) cytotoxic T-lymphocyte (CTL) responses in vitro against viral antigens. As a more extensive analysis of the rAAV system, we have used a self-antigen, HM1.24, expressed in multiple myeloma (MM). Again, with one stimulation, significant major histocompatibility complex (MHC) class 1-restricted, anti-HM1.24-specific CTL killing was demonstrated against MM cells. Furthermore, higher expression of interferon-gamma (IFN-gamma) in T cells and higher expression levels of, in order of significance, CD80 (2.6- to 3.8-fold increase), CD86, and CD40 on DCs were also observed. The use of synthetic HM1.24-positive target cells further demonstrated the antigen specificity of these CTLs. There was also no evidence of natural killer cell involvement. These data extend our earlier studies and suggest that the rAAV-loading of DCs may be a particularly good protocol for generating CTLs against self-antigens, which may not otherwise be considered good targets because of their low immunogenicity. We also show that HM1.24 may be an effective antigen for targeting MM.