Transoral laser microsurgery in early glottic cancer involving the anterior commissure.

PURPOSE: Treatment modalities for glottic cancer comprise surgery, (chemo-)radiation, and combined treatment options. Glottic cancer involving the anterior commissure (AC) requires special preoperative assessment and surgical skills, as it is commonly considered a risk factor for local recurrence. The aim of this study is to analyze the oncological effectiveness of transoral laser microsurgery (TLM) in the early glottic cancer involving the AC. METHODS: We retrospectively analyzed the data of all patients with primary, early staged (T1-2) glottic squamous cell carcinoma who were treated between 2004 and 2014. Patients were preferably treated by TLM (rather than open surgical techniques) if appropriated transoral exposure of the endolarynx was ensured. Voice outcomes were not assessed. RESULTS: 186 patients with early glottic cancer were included, 143 were treated by TLM and 43 by other therapy modalities [OT open surgical techniques (n = 32) or primary (chemo-)radiation (n = 11)], respectively. In 84 patients (59%) of the TLM cohort, the AC was involved (OT cohort n = 29 (73%), p = 0.143). The 1-, 3-, and 5-year local control rates after TLM were 91%, 86%, and 81% in patients without AC infiltration and 84%, 74%, and 70% in patients with AC infiltration, respectively, showing no statistical difference (p = 0.180). The 5-year disease-free survival and laryngeal preservation rate (LPR) did not differ with regard to AC infiltration (p = 0.215 and p = 0.261). Comparing the treatment modalities, the 5-year LPR was 90% for TLM and 83% for OT regardless of infiltration of the AC (p = 0,653 and p = 0.267, respectively). CONCLUSION: TLM is an effective surgical treatment for early glottic cancer with AC involvement in patients with adequate transoral laryngeal exposure.

Reconstruction of laryngopharyngectomy defects: Comparison between the supraclavicular artery island flap, the radial forearm flap, and the anterolateral thigh flap.

OBJECTIVES: The purpose of this study was to evaluate the application of the supraclavicular artery island flap (SCAIF) for the reconstruction of laryngopharyngectomy defects in comparison with reconstructions with the anterolateral thigh flap (ALT) and the radial forearm flap (RFF). PATIENTS AND METHODS: A retrospective study was performed. We compared indications for surgery, reconstructive techniques, operative time, time of hospitalization, and complication rates between patients treated with SCAIF, RFF and ALT following laryngopharyngectomy. Seventy-seven patients were included, 18 underwent reconstruction with SCAIF (23%), 36 with RFF (47%), and 22 with ALT (29%). Seventy-five laryngopharyngectomies (97%) were performed due to oncologic indications, 27 patients (35%) had been treated with prior radiotherapy. Fifty-seven defects (74%) were partial defects, whereas 20 (26%) were circumferential. RESULTS: No statistical differences in operative time between the groups (298 min ± 53 [SCAIF] vs 301 min ± 54 [ALT] vs 302 min ± 47 [RFF]; P = .806) were observed. Preoperative radiation was found to be an independent risk factor for flap loss (P < .001), the development of fistula (P = .032), and pharyngeal stenosis (P = .034) in our cohort. Nevertheless, no differences between the different groups were detected (fistula rate: 11% [SCAIF] vs 14% [ALT] vs 11% [RFF]; P = .944, stenosis rate: 11% [SCAIF] vs 14% [ALT] vs16% [RFF]; P = .874, gastric tube dependency: 28% [SCAIF] vs 23% [ALT] vs16% [RFF]; P = .590). CONCLUSION: The SCAIF is an equivalent alternative compared to well-established techniques, such as the RFF and the ALT regarding reconstruction of defects after laryngopharyngectomy.

Preoperative anemia and perioperative blood transfusion in head and neck squamous cell carcinoma.

OBJECTIVES: To evaluate the impact of preoperative anemia and perioperative blood transfusion (PBT) on disease free (DFS) and overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective study of 354 patients primarily treated with surgery between 2006 and 2016. Cases were selected according to completeness and accuracy of available clinical data. Thus, a selection bias cannot be excluded. Patients who received PBT were identified by our controlling department and verified by our blood bank data base. RESULTS: Both, preoperative anemia and PBT significantly decreased OS in univariate analysis. Although PBT was needed more frequently by older patients in worse physical conditions with more advanced HNSCC, subgroup analysis also demonstrate a profoundly negative effect of PBT on OS in younger patients and early stage HNSCC. According to a restrictive transfusion policy at our hospital the transfusion rate was comparably low. We could not verify increasing effects of PBT on cancer recurrence rates as it was previously shown. DISCUSSION: Preoperative anemia is the most common paraneoplastic syndrome in HNSCC. Despite its devastating prognostic effect we suggest a restrictive transfusion policy whenever possible. Our data also show that anemia as an independent prognostic factor in head and neck surgical oncology is defined not only by low hemoglobin concentrations but low red blood cell counts as well.

Structured reporting in petrous bone MRI examinations: impact on report completeness and quality.

PURPOSE: To investigate whether structured reports (SRs) provide benefits regarding the completeness and the clarity of reports, as well as regarding the satisfaction of the referring physicians compared to narrative freetext reports (NRs) of MRI examinations of the petrous bone. METHODS: After sample size calculation, 32 patients with clinically indicated MRI examinations of the petrous bone were included in this retrospective study. The already existing NRs were taken from the radiologic information system. The corresponding SRs were retrospectively generated by two radiologists using an online-based application. All 64 reports (one NR and one SR per patient) were evaluated by two head and neck physicians using a questionnaire. RESULTS: While 41% of the SRs showed no missing report key feature, all NRs exhibited at least one missing key feature (p < 0.001). SRs achieved significantly higher satisfaction rates regarding the linguistic quality and overall report quality compared to NRs: Using a 6-point Likert scale (1 = insufficient to 6 = excellent), SRs were rated with a median value of 6 [interquartile range (IQR): 1] for linguistic as well as overall quality, and NRs were rated with a median of 5 (IQR: 0) for linguistic as well as overall quality (p < 0.001). CONCLUSIONS: Structured reporting of petrous bone MRI examinations may positively influence the completeness and quality of radiologic reports. Due to the easier readability and facilitation of information extraction, SRs improve the satisfaction level of the referring physicians.

Evaluation of margins in head and neck squamous cell carcinoma from the surgeon's perspective.

BACKGROUND: The surgeon's evaluation of resection status based on frozen section analysis during operation and pathological examination of resected specimens often differ. For this study, we recapitulated the surgeon's perspective during an operation, accordingly classified the evaluation of margins by the surgeon, and analyzed its impact on the outcome compared with the pathological results. METHODS: This was a retrospective analysis. As data sources, paper-based and digital patient files, as well as the Munich Cancer Registry database were used. RESULTS: Three hundred ninety-six cases were included in this analysis. Only the evaluation of margins by the surgeon influenced local control, and the pathological results influenced disease-free survival (DFS). Surprisingly, margins of >5 mm of normal tissue to cancer growth led to local control and overall survival (OS) significantly worse than 1 to 5-mm resections. CONCLUSION: The evaluation of margins by the surgeon is of significant importance for local control and OS. It is largely based on frozen section analysis, which, therefore, should be used whenever possible.

Is Perineural Invasion of Head and Neck Squamous Cell Carcinomas Linked to Tobacco Consumption?

Perineural invasion (PNI) is an underrecognized path of cancer spread, and its causes and mechanisms are poorly understood. Recent research indicates a mutual attraction of neuronal and cancer cells, largely dependent on neurotrophic factors and their receptors. Interestingly, the release of neurotrophic factors occurs upon cigarette smoke/nicotine exposure in a dose-dependent manner, and serum levels correlate with current smoking, number of smoking years, and smoking severity. Among cell types capable of neurotrophic factors secretion are lung and oral fibroblasts. In our study of 178 patients with head and neck squamous cell carcinoma, tumors of current and former smokers showed PNI significantly more often than tumors of never smokers. Moreover, PNI was a marker for aggressive tumor growth. Surprisingly, PNI was more significant for survival than p16 status. Our study warrants further research on PNI in head and neck squamous cell carcinoma with special emphasis on the impact of tobacco consumption to identify suitable candidates for therapeutic interventions.

Influence of coupler size on revision rate and timing of revision after free flap tissue transfer in the head and neck.

OBJECTIVE: Microvascular coupler devices have been proven an effective alternative to standard hand-sutured anastomoses in reconstructive surgery. Until now, the influence of the coupler size on the revision rate after free flap tissue transfer in head and neck surgery has not been investigated. Neither has its influence on the timing of venous revisions. MATERIALS AND METHODS: A retrospective mono-center cohort study was performed in order to analyze the influence of coupler size on timing and revision rate of microvascular procedures. RESULTS: 437 patients who had undergone surgery between 2009 and 2015 were included. The statistical analysis of coupler size and revision rate due to venous complications showed a significant reduction of more than 40% in the revision rate for each additional mm in the coupler size. We observed revisions due to venous congestion until the fourth day postoperatively within our cohort. However, when the coupler size used was ≥ 3 mm, no venous congestion occurred later than 12 h after surgery. CONCLUSION: The quantitative effects of coupler size on the revision rate in head and neck reconstruction were demonstrated for the first time. We recommend spending extra time and effort on dissecting the largest possible vein in order to be able to choose the largest possible coupler size for the venous anastomosis. As a consequence of our findings, we limit our postoperative monitoring for patients with a coupler ≥ 3 mm to 24 h, as later venous congestions are very unlikely.

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status.

OBJECTIVE: Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system. METHODS: From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis. RESULTS: 137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143). CONCLUSION: The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

Total Glossectomy Without Laryngectomy for Advanced Squamous Cell Cancer of the Tongue: Functional and Oncological Results.

BACKGROUND/AIM: Total glossectomy without laryngectomy for large tongue carcinomas still remains controversial, as these defects may go along with dramatic effects on respiration, speech and swallowing. As a consequence, these procedures significantly impact quality of life. Therefore, larger case series are rare. Nevertheless, with the development of free tissue transfer, functional reconstruction has become increasingly popular and encouraging results are reported in the literature. PATIENTS AND METHODS: We present our experience with complete glossectomy without laryngectomy and free flap reconstruction. A retrospective monocenter cohort-study was conducted. Reconstructive principles, which in our view lead to optimal functional results, are presented. Oncologic, as well as functional results are reported. Functional results were assessed in terms of swallowing ability, decannulation and intelligible speech. RESULTS: A total of 14 patients met the inclusion criteria. All patients were reconstructed using an anterolateral thigh flap. Complications occurred in 4 patients, 3 of which developed fistula formation. Oral feeding without the need for a gastrostomy tube was resumed in 11 patients (78.6%), 12 patients (85.7%) were able to be permanently decannulated and speech was at least acceptable in 12 patients (85.7%). The three-year survival was 57.1%. CONCLUSION: Following meticulous reconstructive principles, as well as a proper patient selection, total glossectomy without laryngectomy is a feasible treatment option for advanced cancer of the tongue.

Head and neck reconstruction in the elderly patient: a safe procedure?

Demographic changes strongly affect industrialized countries. While free tissue transfer was initially believed to be beneficial only for younger patients, there is an increasing number of elderly patients requiring microvascular operations in our aging society. Medical and surgical risks for head and neck cancer patients over a certain age who undergo free tissue transfer has hardly been investigated. A retrospective mono-center cohort study was performed. All patients with the age 75 or higher undergoing microvascular operations were reviewed. Patient characteristics including the ASA-status, the ACE-27-score, flap survival and postoperative medical and surgical complications were evaluated. The Clavien-Dindo-classification system for postoperative complications was applied to assess the severity of the complications. A total of 31 patients with an average age of 78.8 years were included. 4 patients suffered from venous congestion and had to undergo revision surgery. All flaps could successfully be salvaged. Higher ASA-status and ACE-score were significantly associated with postoperative medical and surgical complications and a higher severity of the complications. However , neither age nor operating time had influence on the complication rate. Microvascular free tissue transfer can be performed with a high degree of security in selected elderly patients. However, serious medical complications remain a concern, correlating strongly with high ASA and ACE-score. Careful patient selection is mandatory to reduce complications to a minimum.

Venous anastomosis in free flap reconstruction after radical neck dissection: is the external jugular vein a feasible option?

Free microvascular tissue transfer has become a reliable and wellestablished technique in reconstructive surgery. Success rates greater than 95% are constantly reported in the literature. End-to-end anastomosis to the external jugular vein (EJ) is supposed to be equally successful as anastomosis to the internal jugular vein (IJ) in patients treated with selective neck dissection. No data has been published so far when the IJ had to be resected during neck dissection. The purpose of this study was to evaluate the success rate and complications of end-to-end anastomosis to the EJ in cases of (modified) radical neck dissection with resected IJ. A retrospective mono-center cohort study was performed. All patients with end-to-end anastomosis to either the IJ or EJ-system were reviewed. 423 free-tissue transfers performed between 2009 and 2016 were included. The overall success rate was 97.0% with an anastomotic revision rate due to venous thrombosis of 12.3%. In patients when the IJ had to be resected and the venous anastomosis was performed at the ipsilateral side to the EJ (n = 53), overall flap loss was significantly higher (5/53; 9.4%). The revision rate in these cases was 22.6%. Success rate of anastomosis to the EJ when the ipsilateral IJ was still intact was 100% (n = 20). Success rate when the anastomosis was performed at the contralateral side was 100%. End-to-end anastomosis to the EJ in cases with resected IJ is more likely to result in free flap loss. Furthermore, it is associated with a higher revision rate. Therefore, in cases with resected IJ, we suggest to plan the operation beforehand with anastomosis at the contralateral side whenever possible.

Impact of comorbidity and anemia in patients with oropharyngeal cancer primarily treated with surgery in the human papillomavirus era.

BACKGROUND: Comorbidity and anemia strongly influence treatment and outcome of oropharyngeal squamous cell carcinomas (SCCs), but respective data are frequently lacking in clinical studies. We evaluated 149 cases of oropharyngeal SCC primarily treated with surgery regarding the impact of these factors on disease-free survival (DFS) and overall survival (OS). METHODS: Data were recorded during treatment and follow-up visits. Human papillomavirus (HPV) association of oropharyngeal SCC was detected by p16 immunohistochemistry. RESULTS: Patients with p16-positive disease were significantly less comorbid and anemic, and treated more aggressively. Comorbidity and anemia, but not p16 status, significantly influenced DFS and had more impact on OS than p16 status. CONCLUSION: In our study, p16-positive seems a good surrogate marker for healthier patients. Patients with p16-positive disease showed improved survival, but this was limited to none/mild comorbid and/or nonanemic individuals in this group. On the basis of our results, we strongly suggest the inclusion of these factors in risk stratification for clinical studies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 7-16, 2017.

A noninvasive procedure for early-stage discrimination of malignant and precancerous vocal fold lesions based on laryngeal dynamics analysis.

About two thirds of laryngeal cancers originate at the vocal cords. Early-stage detection of malignant vocal fold alterations, including a discrimination of premalignant lesions, represents a major challenge in laryngology as precancerous vocal fold lesions and small carcinomas are difficult to distinguish by means of regular endoscopy only. We report a procedure to discriminate between malignant and precancerous lesions by measuring the characteristics of vocal fold dynamics by means of a computerized analysis of laryngeal high-speed videos. Ten patients with squamous cell T1a carcinoma, ten with precancerous lesions with hyperkeratosis, and ten subjects without laryngeal disease underwent high-speed laryngoscopy yielding 4,000 images per second. By means of wavelet-based phonovibrographic analysis, a set of three clinically meaningful vibratory measures was extracted from the videos comprising a total number of 15,000 video frames. Statistical analysis (ANOVA with post hoc two-sided t tests, P < 0.05) revealed that vocal fold dynamics is significantly affected in the presence of precancerous lesions and T1a carcinoma. On the basis of the three measures, a discriminating pattern was extracted using a support vector machine-learning algorithm performing an individual classification in respect to the different clinical groups. By applying a leave-one-out cross-validation strategy, we could show that the proposed measures discriminate with a very high performance between precancerous lesions and T1a carcinoma (sensitivity, 100%; specificity, 100%). Although a large-scale study will be necessary to confirm clinical significance, the set of vibratory measures derived in this study may be applicable to improve the accuracy and reliability of noninvasive diagnostics of vocal fold lesions.

Surgically treated oropharyngeal cancer: risk factors and tumor characteristics.

PURPOSE: To assess risk factors of patients with oropharyngeal squamous cell carcinoma in the Munich area of Southern Germany in relation to human papillomavirus (HPV) association of the tumors. To demonstrate differences in tumor characteristics and their impact on adjuvant treatment. METHODS: Between November 2010 and July 2013, patients were prospectively interviewed for risk factors before they underwent surgical resection of their tumors. HPV association was evaluated by p16 immunohistochemistry; tumor characteristics and type of adjuvant treatment were recorded. Follow-up data were collected after a median follow-up of 12.1 month. RESULTS: In contrast to many recent studies, we could not detect any difference in overall age and age at sexual debut between p16-positive and p16-negative patients. P16-negative patients are characterized by a more intensive tobacco and alcohol use, a more abusive way of consumption, less nonoral and less oral sex partners. P16-positive patients had a significantly higher risk of lymph node metastases, but nevertheless a significant lower risk to recur or to die. No difference in the incidence of synchronous second primary tumors was seen. P16-positive patients generally received a more aggressive adjuvant treatment because of more frequently involved lymph nodes. CONCLUSION: Lifestyle risk factors such as smoking, drinking, and sexual habits were independent from age, but showed marked differences between the p16-positive and p16-negative group. Since p16-positive patients were treated more aggressively, it is not possible to distinguish whether the better outcome of HPV-positive patients is a result of less aggressive cancers or more aggressive treatment. With regard to the ongoing debate about treatment deintensification, we should keep in mind that the survival of HPV-positive cancer patients is not 100 %.

Chemoprevention by celecoxib and mutagen sensitivity of cyclin d1 in patients with oropharyngeal carcinoma.

UNLABELLED: The head and neck region is one of the most important locations predisposed for tobacco-associated cancer. Chemoprevention might offer a chance to decrease the risk for this type of disease. MATERIALS AND METHODS: Mini-organ cultures (MOC) of macroscopically-healthy pharyngeal tissues from 20 patients with oropharyngeal squamous cell carcinoma (SCC) and from 20 controls were employed in the study. MOC were firstly incubated with Celecoxib, and DNA damage was induced by incubation with Benz[a]pyren-7,8-diol-9,10-epoxid (BPDE), a major representative of tobacco-associated carcinogens. DNA damage was evaluated with the alkaline single-cell microgel electrophoresis (Comet assay). Furthermore, fragmentation of the cyclin D1 gene, a gene of special importance in head and neck carcinogenesis was examined by the Comet-FISH assay. Finally, the chemoprotective potential of Celecoxib was analyzed after incubation with MOC. RESULTS: As expected, BPDE caused significant DNA fragmentation in tumor compared to negative control tissues. No enhanced damage was observed in the cyclin D1 gene. DNA fragmentation was significantly reduced when MOC were incubated with Celecoxib in the tumor group. Surprisingly, these effects were also observed in the group without cancer of the oropharynx, although COX-2 is not expressed in macroscopically-healthy mucosa. CONCLUSION: Celecoxib showed considerable chemoprotective effeciency against BPDE in both groups and this effect seems to be independent of COX-2 expression. No evidence for higher mutagen sensitivity in the Cyclin D1 gene was observed.

Vacuum assisted closure in the management of wound healing disorders in the head and neck: a retrospective analysis of 23 cases.

BACKGROUND: Since the middle of the 1990s vacuum-assisted closure (VAC) has been used in many areas of surgery to manage complex wounds and impaired wound healing. Until recently, little attention has been paid to this treatment modality in the field of head and neck surgery. The evaluation of its efficacy in wound healing disorders of the head and neck was the aim of this study. MATERIAL AND METHODS: Patients with complex wounds and impaired healing treated with VAC therapy between 2008 and 2011 were included into the study. VAC dressings were changed every 3 days and improvements in wound healing were documented. RESULTS: 23 patients were treated with VAC therapy, in 18 cases (78%) closure of the defect could be reached without any further surgical procedure. 5 patients needed subsequent regional flap reconstruction to close the remaining defect. All of these patients had undergone salvage surgery in a previously irradiated neck before. CONCLUSION: Vacuum assisted closure is an effective treatment in the management of wound healing disorders and complex wounds in the head and neck. It offers a useful, non-invasive modality to close even large defects in the area. Previous irradiation seems to have a significant negative influence on the outcome of the therapy, but more data are required to assess these effects.

Reduction of DNA damage by curcumin and celecoxib in epithelial cell cultures of the oropharynx after incubation with tobacco smoke condensate.

BACKGROUND: Tobacco smoke, as the major risk factor for the development of squamous cell cancer of the head and neck (HNSCC), contains various xenobiotics, such as polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines and phenols. Chemoprevention either by artificial agents such as celecoxib, or natural compounds such as curcumin, might offer a chance to reduce the risk of developing malignant transformation. MATERIALS AND METHODS: In order to evaluate the DNA-damaging effects of smoke condensate towards human mucosa cells of the oropharynx, mini organ cultures (MOC) of macroscopically healthy pharyngeal tissue of 40 patients with oropharyngeal SCC were used. After incubation with smoke condensate DNA damage was evaluated with the alkaline single-cell microgel electrophoresis (comet assay). The chemoprotective potential of curcumin and celecoxib was analyzed after their incubation with the condensate-treated MOCs. As DNA-damaging and chemopreventive effects might not be equally distributed over the whole DNA, fragmentation of the epithelial growth factor receptor (EGFR) gene was additionally examined by Comet fluorescence in situ hybridization (FISH). RESULTS: As expected, tobacco smoke condensate caused significant DNA fragmentation compared to the negative control. No enhanced damage was observed on the EGFR gene. DNA fragmentation was significantly reduced when MOCs were incubated with celecoxib (p ≤ 0.001) and with curcumin (p ≤ 0.001). CONCLUSION: Both celecoxib and curcumin showed considerable chemoprotective effects towards the impact of smoke condensate. No evidence was found for higher susceptibility to damage in the EGFR gene.

Perioperative management of antithrombotic medication in head and neck reconstruction-a retrospective analysis of 137 patients.

PURPOSE: Various protocols exist to prevent thrombosis after free flap surgery in the head and neck. This study reviews the outcome and incidence of perioperative complications in patients undergoing head and neck reconstruction, simply using subcutaneous low-molecular-weight heparin. MATERIALS AND METHODS: A total of 137 free tissue transfers performed between 2007 and 2010 were reviewed. All patients received a general thrombosis prophylaxis with subcutaneous low-molecular-weight enoxaparin. No aspirin, dextran, or additional antithrombotic medication was administered. RESULTS: Overall flap survival was 97.1%. A total of 3 complete and 1 partial flap loss occurred, all due to venous thrombosis. Five cases of venous congestion were successfully revised. CONCLUSION: The free flap survival rate using simple subcutaneous heparin seems to be equivalent to other management regimens. Therefore, we suggest that no additional antithrombotic treatment is needed for patients who undergo head and neck reconstruction with free tissue transfer.

Curcumin and other polyphenolic compounds in head and neck cancer chemoprevention.

Despite clear results of observational studies linking a diet rich in fruits and vegetables to a decreased cancer risk, large interventional trials evaluating the impact of dietary micronutrient supplementation, mostly vitamins, could not show any beneficial effects. Today it has become clear that a single micronutrient, given in supernutritional doses, cannot match cancer preventive effects of whole fruits and vegetables. In this regard polyphenols came into focus, not only because of their antioxidant potential but also because of their ability to interact with molecular targets within the cells. Because polyphenols occur in many foods and beverages in high concentration and evidence for their anticancer activity is best for tissues they can come into direct contact with, field cancerization predestines upper aerodigestive tract epithelium for cancer chemoprevention by polyphenols. In this paper, we summarize cancer chemopreventive attempts with emphasis on head and neck carcinogenesis and discuss some methodological issues. We present data regarding antimutagenic effects of curcumin and epigallocatechin-3-gallate in human oropharyngeal mucosa cultures exposed to cigarette smoke condensate.

DNA repair and mutagen sensitivity of epithelial cells and lymphocytes in oropharyngeal cancer.

Tobacco-associated nitrosamines are known carcinogens causing DNA damage in epithelial cells of the head and neck. A matched case-control study was performed to evaluate the sensitivity of patients with squamous cell cancer (SCC) of the oropharynx, and controls to tobacco-associated nitrosamines. Quantitative DNA repair was evaluated following a period of 15 and 30 min. Fresh biopsies from 100 male donors of macroscopically healthy oropharyngeal cells and lymphocytes (50 SCC patients and 50 controls) were incubated with N-nitrosodiethylamine (NDEA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or N-nitrosonornicotine (NNN). DNA damage in epithelial cells and lymphocytes was assessed using the comet assay. Following incubation with NDEA, cells underwent a period of DNA repair. All of the nitrosamines caused equivalent genotoxic damage in mucosal cells and lymphocytes of the two groups. Lymphocyte DNA repair capacity in the control group (26.8 and 37.1% after 15 and 30 min) was comparable to the tumor group (23.6 and 40.6%). However, epithelial cell DNA repair capacity of carcinoma patients was significantly reduced to 17.1% (15 min) and 23% (30 min) compared to the DNA repair of the control group (36.2%, 15 min and 46.0%, 30 min). Mutagen sensitivity was comparable in patients and controls. Thus, reduced epithelial cell DNA repair capacity of tumor patients is a possible endogenous risk factor for the development of head and neck squamous cell cancer.