Real-Life Study of Patient Preference for Dupilumab or Revision Surgery for Recurrent Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high rate of recurrence in patients, despite therapy with local corticosteroids and functional endoscopic sinus surgery. Dupilumab, a recombinant monoclonal human IgG4 antibody directed against the IL-4 receptor α that inhibits both IL-4 and IL-13 signal transduction, is available for symptomatic therapy. Patient preference between repeated surgery and injection therapy with Dupilumab is not known. (2) Methods: Patients who had experienced at least one surgical intervention for nasal polyps and were treated with Dupilumab for at least 3 months completed a retrospective patient questionnaire. (3) Results: In a cohort of 75 previously operated CRSwNP patients, 91.5% preferred therapy with Dupilumab to repeated surgery for nasal polyps. Preference for Dupilumab in the subgroups of patients with concomitant Non-steroidal Anti-inflammatory Drugs Exacerbated Respiratory Disease (N-ERD) (n = 32), patients with concomitant asthma (n = 25), and patients without concomitant disease (n = 18) was 100%, 96%, and 72%, respectively. (4) Conclusions: Patient preference for Dupilumab over repeat surgery is strongest in previously operated CRSwNP patients with concomitant asthma or N-ERD, but remains very high in patients without concomitant disease.

Long-term improvement of clinical symptoms after endoscopic sinus surgery in patients suffered from endocrine ophthalmopathy and orbital complications of rhinosinusitis.

Background: Rhinosinusitis may cause serious complications, such as secondary orbital infections, resulting in expansion and erosion of process through the orbital wall. Aims: The aim is to evaluate long-term outcome of ESS in patients suffered from endocrine ophthalmopathy and orbital complications of rhinosinusitis. Material and methods: Thirteen patients with loss of vision, endocrine ophthalmopathy and orbital complication of rhinosinusitis were treated by ESS. Preoperative and postoperative vision was rated by best-corrected visual acuity (BCVA) testing. Nine (69%) have been reinvestigated after 6 years by ophthalmology examination and 10-point scale for assessment of clinical symptoms. Results: The mean BCVA significantly increased after surgery comparing to results before surgery (0.84, 0.62; respectively) (p = .007). The mean values of 10-point scale for subjective assessment of symptoms 6 years after surgery were: headache 2.11, sinonasal pressure 1.72, subjective estimation of vision quality on the affected eye was 7.33 and olfaction 7.66. None of the patients developed impairment of vision loss in postoperative period. Conclusions: Long-term outcome of ESS showed decreased symptoms in patients who had endocrine ophthalmopathy and orbital complication of rhinosinusitis. Significance: ESS has numerous advantages for patients with orbital complication and vision loss comparing to conservative treatment and should be considered even in abscess absence.

1,25(OH)2Vitamin D3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck.

BACKGROUND: 1Alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2) Vitamin D(3)] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)(2)Vitamin D(3), which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). METHODS: Synchronized cells were treated with 1,25(OH)(2)Vitamin D(3) over 96 h. The cell cycle status and expression of cell cycle-regulating proteins was determined by fluorescence-activated cell sorting (FACS) and Western blotting. An overexpression of p18 in 1,25(OH)(2)Vitamin D(3) vs. ethanol-treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. CONCLUSION: One mechanism by which 1,25(OH)(2)Vitamin D(3) controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)(2)Vitamin D(3) in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)(2)Vitamin D(3) in SCC25.

Nimesulide and indomethacin induce apoptosis in head and neck cancer cells.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to inhibit the enzyme cyclooxygenase (COX). There are two isoforms of the enzyme. Recent investigations indicate that both isoforms, COX-1 and COX-2, are involved in carcinogenesis. METHODS: We investigated the effects of nimesulide, a COX-2 selective and indomethacin, a non-selective NSAID on the head and neck squamous cell carcinoma (HNSCC) cell lines SCC-9 and SCC-25. Effects on cell numbers and apoptosis were assayed by cell counting, immunofluorescence and fluorescence activated cell sorting (FACS). COX expression was examined by Western blotting. RESULTS: The investigated cell lines express COX-1 and COX-2. Nimesulide and indomethacin induce apoptosis and cause a reduction of cell number. Incubation with NSAIDs upregulated COX-2 expression. CONCLUSION: The results of our study on HNSCC cells together with data from different studies showing anti-cancer activity of NSAIDs suggest that COX inhibitors could play a role in HNSCC treatment and prevention.

Molecular analysis of p21 promoter activity isolated from squamous carcinoma cell lines of the head and neck under the influence of 1,25(OH)2 vitamin D3 and its analogs.

OBJECTIVE: The biologically active 1,25(OH)2 vitamin D3 and its analogs have been shown to have antiproliferative and differentiating effects in a variety of malignant and non-malignant cells. For squamous carcinoma cell lines of the head and neck (SCCHN) we could show that this antiproliferative activity of 1,25(OH)2 vitamin D3 is due to induced expression of the cell-cycle inhibitory proteins p21 and p27, causing an arrest in the G0/G1 cell-cycle phase. MATERIAL AND METHODS: In this work we investigated the effects of three vitamin D3 analogs, EB1089, MC1288 and CB1093, on proliferation behavior and cell-cycle status in a laryngeal carcinoma cell line (JPPA) as well as in control human immortalized keratinocytes (HaCaT). To study the molecular mechanism the functional activity of the promoter region of p21, a potential target gene of vitamin D3 transcriptional regulation, was investigated. For this reason a 2.7-kb fragment of the p21 promoter was isolated by polymerase chain reaction from HaCaT, JPPA and SCC9 (tongue carcinoma) cells and directionally cloned into an enhanced green fluorescence protein (EGFP) reporter gene vector system. A construct was used to stably transfect HaCaT cells and to monitor the expression of the EGFP gene by confocal microscopy. RESULTS: Analysis of proliferation and cell-cycle status revealed decreased growth rates and G0/G1I cell-cycle arrest in cells treated with 1,25(OH)2 vitamin D3 and its analogs The EGFP reporter gene-transfected cells showed distinct fluorescence under the influence of 1,25(OH)2 vitamin D3 and its analogs compared to control cells. CONCLUSION: These results demonstrate that the cell-cycle inhibitor protein p21 is a direct target gene of biologically active 1,25(OH)2 vitamin D3, inducing G0/G1 cell-cycle arrest. The ability of vitamin D analogs to act via the same molecular mechanism as the natural hormone but with less hypercalcemic activity may have therapeutic implications for patients with SCCHN malignancy.

Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells.

BACKGROUND: A new compound, betulinic acid, has been found to be cytotoxic against a variety of tumor cells originating from the neural crest. Its efficacy against head and neck squamous cellular carcinoma cell lines has so far not been tested. METHODS: Cell numbers were assayed by automated counting; caspase activation and programmed cell death were determined using an antibody specific for an apoptosis-associated epitope in epithelial cells. The expression pattern of Bcl-2 family members was assessed by Western blotting. RESULTS: In two HNSCC cell lines betulinic acid induced apoptosis, which was characterized by a dose-dependent reduction in cell numbers, emergence of apoptotic cells, and an increase in caspase activity. Western blot analysis of the expression of various Bcl-2 family members in betulinic acid-treated cells showed, surprisingly, a suppression of the expression of the proapoptotic protein Bax but no changes in Mcl-1 or Bcl-2 expression. CONCLUSION: These data clearly demonstrate for the first time that betulinic acid has apoptotic activity against HNSCC cells.

Dysphagia due to a large schwannoma of the oropharynx: case report and review of the literature.

Schwannoma is a benign, encapsulated tumor that is derived from Schwann cells. Approximately 25% to 45% of schwannomas occur in the head and neck. The most common site is the parapharyngeal space of the neck; intrapharyngeal occurrence is extremely rare. To our knowledge, this is the first report of a pedunculated schwannoma in the supraglottic oropharynx. Because of the location and mass of the tumor, the main symptom was dysphagia. The tumor was excised via direct microlaryngoscopy, and no recurrence was seen after 2 years of follow-up. When schwannomas are located in the pharynx, they may cause dyspnea and dysphagia or impair phonation. Therefore, when dysphagia is present, a thorough diagnostic procedure should be performed to evaluate the morphology and function of the upper aerodigestive tract.

Mitoxantrone and cisplatin in recurrent and/or metastatic salivary gland malignancies.

A phase II study was performed to assess the safety and efficacy of mitoxantrone and cisplatin in locally recurrent and/or metastatic carcinomas of the salivary glands. Between May 1997 and March 2001, a total of 14 patients were entered on this trial. All of them had previously undergone radical resection and 10 were subsequently treated with adjuvant radiation therapy with (n=3) or without (n=7) concomitant chemotherapy. Therapy according to the study protocol consisted of mitoxantrone given as i.v. bolus on day 1 at a dose of 12 mg/m2 and cisplatin given as 90-min infusion at a dose of 30 mg/m2 on days 1-3. We observed two partial responses (14.3%) and stabilization of disease in nine patients (64.3%); progression during therapy was noted in only three cases (21.4%). The median time to progression was 15 months (range 2-36) and the median survival time was 27 months (range 4-54). Myelosuppression was commonly observed. Leukocytopenia occurred in all patients, and was grade 3 or 4 in three (21%) and four (29%) patients. WHO grade 3 thrombocytopenia and anemia was seen in three (21%) and four (29%) patients, respectively. Non-hematologic toxicity was in general mild to moderate except for two cases (14%) of grade 3 nausea and vomiting; overall incidence rates were nausea and vomiting (n=14), stomatitis (n=6), diarrhea (n=3), alopecia (n=11), infection (n=7), increase of serum creatinine (n=3), and peripheral neuropathy (n=3). The combination of mitoxantrone and cisplatin seems to be an active and fairly well-tolerated regimen for the treatment of advanced salivary gland cancers. According to the observed high rate of abrogating progressive disease for a long duration, and the resulting promising progression-free and overall survival time, further investigation seems warranted.

Increased expression of lymphocyte-derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation.

BACKGROUND: Benign prostatic hyperplasia (BPH) frequently exhibit infiltration of CD4 (+)/CD45RO (+) memory-T-lymphocytes. Expression and impact of lymphocyte-derived growth factors on prostatic stromal cell (PSC) growth were investigated. METHODS; Lymphokine synthesis in normal prostate tissues (n = 3), BPH-tissues (n = 13), BPH-derived T-cells (n = 6), BPH-derived epithelial cells (BPH-EC) (n = 5), normal prostate-derived (n = 3) and BPH-derived stromal cell lines (BPH-SC) (n = 6), and prostate cancer (CaP) lines (n = 3) was analyzed by RT-PCR and Southern-blotting. The effect of interleukin (IL)-2, -4, -7, and interferon-gamma (IFN-gamma) on normal and BPH-SC growth was investigated by (3)H-thymidine incorporation assays. RESULTS: All BPH-tissues and, to a lesser degree, normal prostates, expressed significant amounts of IFN-gamma mRNA. However, only BPH-tissues contained IL-2 and IL-4 mRNA (ratio: 10:13). BPH-T-cell lines were heterogeneous in composition and expressed significant amounts of IFN-gamma, IL-2, and IL-4 mRNA. Low level expression of these lymphokines was also observed in BPH-EC, CaP lines, and PSC lines. IL-2, -7 and IFN-gamma stimulated the proliferation of BPH-PSC lines but not that of normal PSC, while IL-4 inhibited BPH-PSC growth. CONCLUSIONS: Chronic inflammation may induce an increased growth pattern of fibromuscular tissue in BPH similar to that of wound healing.