This article gives an overview on different current strategies of assay-based response evaluation in head and neck squamous cell carcinomas (HNSCC) and critically summarizes their role and needs for future clinical evaluation. Due to a growing amount of data of phase III clinical trials of multimodality treatment options for HNSCC, treatment planning in regard to optimal outcome is becoming an interdisciplinary challenge. New concepts such as induction chemotherapy with bi- or ternary combinations of chemotherapeutics, integration of targeted therapies, concurrent and sequential chemoradiation concepts, and multimodality-based organ preservation strategies strongly compete with traditional definitive surgical procedures. Moreover, the outcome is difficult to predict due to heterogeneity of a tumor's response, impaired late functional outcome, and increased late toxicity if simultaneously applied to radiation. Retrospectively looking at non-responders with tumors classified as resectable, primary surgery is very likely to have achieved better results, since chemoradiation causes a high degree of early and late toxicities leading to extremely complicated terms and conditions in surgery following current multimodal therapeutic strategies. Unfortunately, predictive information on response characteristics of a given tumor before starting the therapy is not available in daily routine, although heterogeneity in response of a given tumor entity to treatments has been known for decades. Therefore, current therapy strategies for HNSCC still have to ignore this fact, creating an urgent need for the development of proper predictive assays. There are interesting clinical observations showing that response on induction chemotherapy may predict the outcome after radiotherapy. Some trials use this empiric phenomenon to pre-select non-responders for primary surgical treatment avoiding severe salvage complications after failure of complete chemoradiation treatment. Moving one step further, recent literature and our own investigations implicate that response evaluation of the individual patient's HNSCC in a suitable ex vivo assay just before starting the treatment is mature for clinical research. To this end, essential needs and hints are addressed and discussed.
The direct closure procedure is quick, simple and can be performed without secondary donor site morbidity. For wound healing, cosmetic and function of the forearm and hand, no inferior results can be measured for the direct procedure compared to the indirect coverage technique.
Background: In multimodal therapy concepts for advanced head and neck squamous cell carcinoma (HNSCC), a valid predictive assay for the quick detection of efficient chemotherapeutic agents is desirable. Questionable so far was whether tissue samples of about 100 mg correctly reflect the chemoresponse of a whole HNSCC. This was proven using an ex-vivo colony-forming assay. Materials and Methods: Of 14 HNSCC, 3 biopsies each were taken from separate sites, minced, and collagenase digested. HNSCC digests were added to microtiter plates containing serial dilutions of chemotherapeutic agents or medium as control. After 72-h incubation, wells were washed and cultures methanol-fixed before Giemsa-staining. Epithelial colonies were counted. Results: 11/14 HNSCC (78.6%) showed sufficient colony formation allowing reliable cut-off detection. Cut-off concentrations (complete chemotherapeutically suppressed colony formation) between 3.3 μM and >50 μM cisplatin, and 0.55 μM and 17.6 μM docetaxel were detected. Inhibition of colony formation to 50% of colonies detected in controls (IC50) was found between 0.2 μM and 17.9 μM cisplatin or 1.5 μM and 13.7 μM docetaxel. Cut-off concentrations and IC50 of the HNSCC fragments showed a strong correlation (docetaxel: r > 0.80, p < 0.005; cisplatin: r > 0.67, p < 0.044), while being only insignificantly different in the t-test for paired samples (docetaxel: p > 0.163; cisplatin: p > 0.167). Conclusion: In most cases, tissue samples of about 100 mg allow a representative assessment of chemoresponse of HNSCC.
Dacryocystorhinostomy (DCR) is performed in patients with saccal or postsaccal lacrimal duct obstruction. Focusing on the endonasal approach, we compared success rates, clinical outcome, complications and patient satisfaction of endoscopic vs. non-endoscopic techniques in endonasal DCR. We analyzed the results of 173 patients who underwent an endonasal DCR either utilizing a non-endoscopic (Group I) or an endoscopic technique (Group II) between 2006 and 2011. Irrigation tests followed the first day and at least 3 months after surgery. Postoperative patients' satisfaction and the occurrence of symptoms were documented and evaluated in a follow-up questionnaire. The minor complication rates of both endonasal DCR techniques were similarly low (10%) without severe adverse events. The use of the endoscope prolonged the operating time significantly (28 ± 9 min Group I vs. 34 ± 14 min Group II, p = 0.003). The success rate was 90.2% in Group II compared to only 57.9% in Group I (p < 0.000). Further, we determined the absence of reflux during the irrigation test 1 day after surgery as a significant predictor for the later outcome (R = 1.598, p = 0.005). The follow-up questionnaire revealed a significant improvement in subjectively perceived symptoms by the surgical intervention for both endonasal techniques (p < 0.000). The endoscopically assisted DCR is a safe and successful endonasal technique for patients with saccal or postsaccal lacrimal duct obstructions. The use of the endoscope led to significant higher success rates compared to non-endoscopic techniques in our collective.
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