Früherkennung von Kopf-Hals-Tumoren

Andreas O. H. Gerstner

doi:10.1055/s-2007-995536

Laryngo-Rhino-Otologie, Inhaltsverzeichnis

Laryngorhinootologie 2008; 87: S1-S20
DOI: 10.1055/s-2007-995536

Früherkennung

Früherkennung von Kopf-Hals-Tumoren

Entwicklung, aktueller Stand und PerspektivenAndreas O. H. Gerstner¹

¹Klinik und Poliklinik für Hals-Nasen-Ohren-Heilkunde/Chirurgie, Universitätsklinikum Bonn

Abstract

Zusammenfassung

Überleben und Lebensqualität bei den Krebserkrankungen im Kopf-Hals-Bereich hängen direkt von der Größe bei Erstdiagnose ab. Zusätzlich zur Primärprävention, bei der weitere Anstrengungen erforderlich sind, müssen die Möglichkeiten der Früherkennung verbessert werden. Allerdings fehlt es zum einen in Deutschland an der für ein erfolgreiches Screening erforderlichen Infrastruktur, zum anderen haben die bisher etablierten Untersuchungsverfahren eine zu niedrige Sensitivität und Spezifität. Die Fortschritte, die aktuell im Bereich der Endoskopietechnik, der Nachweismethoden und der Probengewinnung erzielt wurden, eröffnen jedoch Perspektiven im Bereich der Sekundärprävention. Mittels Chromoendoskopie und Narrowband Imaging können Schleimhautveränderungen leichter erkannt werden, mittels konfokaler Endomikroskopie und optischer Kohärenztomografie lassen sich optische „Schnitte” durch das Gewebe legen, und das hyperspektrale Imaging erlaubt eine Gewebsklassifikation anhand spektraler Signaturen. Diese Verfahren ermöglichen somit eine „optische Biopsie”. Auch die Palette der quantitativen und objektiven Parameter, die an minimal-invasiv gewonnenen Proben gemessen werden können, wurde größer und könnte die Grundlage für eine verlässliche Klassifikation der Schleimhautveränderungen sein (multiparametrische Zytometrie, quantitative Histologie). Schließlich könnten Ansätze der Proteomics und der Lab-on-the-Chip-Technologie eine bessere Identifikation der Hochrisikopatienten gewährleisten. Sensitivität und Spezifität all dieser Verfahren wurden jedoch noch nicht geprüft. Vor diesem Hintergrund und angesichts des ungeklärten Nutzen-Risiko-Verhältnisses sowohl für den Einzelnen als auch für die Solidargemeinschaft ist es jedoch bis zu einem Bevölkerungs-basierten Screeningprogramm noch ein weiter Weg.

Schlüsselwörter

Quantitative Histologie - Human Cytome Project - Hyperspectral Imaging - Optische Kohärenztomografie OCT

Volltext

Referenzen

Literatur

1 Essener Erklärung, Nationale Onkologische Präventionskonferenz N.O.P. 2007. Essen; http://www.praevention-krebs.de/downloads/essener_erklaerung.pdf (letzter Zugriff am 20. 12. 2007)
2 Statistisches Bundesamt .DRG Statistik 2007. https://www-ec.destatis.de/csp/shop/sfg/bpm.html.cms.cBroker.cls?cmspath=struktur,vollanzeige.csp&ID=1021166 (letzter Zugriff am 20. 12. 2007)
3 Ahrens H J. Perspektiven der Prävention in Deutschland aus der Sicht der GKV. In: Kirch W, Badura B (Hrsg) Prävention. Berlin, Heidelberg; Springer 2006: 41-53
4 Sackett D L. The arrogance of preventive medicine. CMAJ. 2002; 167 263-264
5 Mühlhauser I. Ist Vorbeugen besser als Heilen?. Dtsch Ärztebl. 2007; 104 A1804-A1807
6 Gøtzsche P C, Nielsen M. Screening for breast cancer with mammography. Cochrane Database of Systematic Reviews. 2001; 4 Art. No.: CD001877. DOI: 10.1002/14651858.CD001877.pub2
7 Farmer E R, Gonin R, Hanna M P. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol. 1996; 27 528-531
8 Giersiepen K, Hense H W, Klug S J, Antes G, Zeeb H. Entwicklung, Durchführung und Evaluation von Programmen zur Krebsfrüherkennung - ein Positionspapier. ZaeFQ. 2007; 101 43-49
9 Beske F, Becker E, Krauss C, Katalinic A, Pritzkuleit R. Gesundheitsversorgung 2050. Kiel; Schmidt & Klaunig 2007
10 Rabatta S. Sorge vor dem Gesundheitsgau. Dtsch Ärztebl. 2007; 104 A2624
11 Howard B V, Manson J E, Stefanick M L. et al . Low-fat dietary pattern and weight change over 7 years - the Women’s Health Initiative dietary modification trial. JAMA. 2006; 295 39-49
12 Howard B V, Van Horn L, Hsia J. et al . Low-fat dietary pattern and risk of cardiovascular disease - the Women’s Health Initiative randomized controlled dietary modification trial. JAMA. 2006; 295 655-666
13 Prentice R L, Caan B, Chlebowski R T. et al . Low-fat dietary pattern and risk of invasive breast cancer - the Women’s Health Initiative randomized controlled dietary modification trial. JAMA. 2006; 295 629-642
14 Jackson R D, LaCroix A Z, Gass M. et al . Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006; 354 669-683
15 Petitti D. Commentary: Hormone replacement therapy and coronary heart disease: four lessons. Int J Epidemiol. 2004; 33 461-463
16 Steiner W. Krebsprävention und Früherkennung im oberen Aerodigestivtrakt - Ergebnisse und Konsequenzen zweier Erlanger Feldstudien. Fortschr Med. 1984; 102 529-533
17 Steiner W. Krebsfrüherkennung im Bereich der oberen Luft- und Speisewege. HNO. 1993; 41 360-367, 497 - 503
18 Ambrosch P. Screeninguntersuchungen zur Früherkennung von Karzinomen der oberen Luft- und Speisewege. HNO. 1996; 44 609-611
19 Smart R S. Screening for cancer of the aerodigestive tract. Cancer. 1993; 72 1061-1065
20 Barra S, Barón A E, Barzan L, Caruso G, Veronesi A, Talamini R, Comoretto R, Franceschi S. Patients compliance in an early detection program for upper aero-digestive tract tumours in north-eastern Italy. Soz Praeventivmed. 1990; 35 159-163
21 Talamini R, Barzan L, Franceschi S, Caruso G, Gasparin A, Comoretto R. Determinant in compliance with an early detection programme for cancer of the head and neck in north-eastern Italy. Eur J Cancer B Oral Oncol. 1994; 30B 415-518
22 Festinger L. A theory of cognitive dissonance. Evanston; Row, Peterson 1957
23 Brehm J W. Increasing cognitive dissonance by a fait accompli. J Abnorm Psychol. 1959; 58 379-382
24 Case D O, Andrews J E, Johnson J D, Allard S L. Avoiding versus seeking: the relationship of information seeking to avoidance, blunting, coping, dissonance, and related concepts. J Med Libr Assoc. 2005; 93 353-362
25 McMaster C, Lee C. Cognitive dissonance in tobacco smokers. Addict Behav. 1991; 16 349-353
26 Steckelberg A, Kasper J, Redegeld M, Mühlhauser I. Risk information-barrier to informed choice? A focus group study. Soz Praventivmed. 2004; 49 375-380
27 Deutsche Krebshilfe .Sachstandserhebung „Krebs-Früherkennung 2005”. http://www.krebshilfe.de/fileadmin/Inhalte/Downloads/PDFs/Sachstandsbericht-KFU.pdf (letzter Zugriff am 20. 12. 2007)
28 Nationale Onkologische Präventionskonferenz .http://www.praevention-krebs.de/index.php (letzter Zugriff am 20. 12. 2007)
29 GEKID in Zusammenarbeit mit dem RKI .Krebs in Deutschland, 5. Auflage. Saarbrücken; 2006. http://www.krebsregister.saarland.de/publikationen/PDF/KiD_2006_Internet-Version.pdf (letzter Zugriff am 20. 12. 2007)
30 Stewart B W, Kleihues P (Hrsg). WHO World Cancer Report 2003. Lyon; IARC Press 2003
31 Gourin C G, Podolksy R H. Racial disparities in patients with head and neck squamous cell carcinoma. Laryngoscope. 2006; 116 1093-1106
32 Dost P, Talanow D D, Kaiser S, Hirche H, Jahnke K. Zum Zeitintervall zwischen Symptom- und Behandlungsbeginn bei Kopf- und Halstumoren. HNO. 1996; 44 492-496
33 Koscielny S, Wagner C, Beleites E. Untersuchungen zum Intervall zwischen Erstsymptom und Behandlungsbeginn bei Patienten mit Kopf-Hals-Tumoren. HNO. 1999; 47 551-555
34 Pitiphat W, Diehl S R, Laskaris G, Cartsos V, Douglass C W, Zavras A I. Factors associated with delay in the diagnosis of oral cancer. J Dent Res. 2002; 81 192-197
35 Maier H, Sennewald E (Hrsg). Risikofaktoren für Plattenepithelkarzinome im Kopf-Hals-Bereich - Ergebnisse der Heidelberger Fallkontrollstudien. Sankt Augustin; HVBG 1994
36 Maier H, Dietz A, Gewelke U, Heller W D, Weidauer H. Tobacco and alcohol and the risk of head and neck cancer. Clin Invest. 1992; 70 320-327
37 Bundeszentrale für gesundheitliche Aufklärung .Förderung des Nichtrauchens bei Jugendlichen 2007. http://www.bmg.bund.de/nn_604 822/DE/Themenschwerpunkte/Drogen-und-Sucht/Tabak/bzga-ergebnisse;templateId=raw,property=publicationFile.pdf/bzga-ergebnisse.pdf (letzter Zugriff am 20. 12. 2007)
38 Grønbæk M, Becker U, Johansen D, Tønnesen H, Jensen G, Sørensen T IA. Population based cohort study of the association between alcohol intake and cancer of the upper digestive tract. BMJ. 1998; 317 844-848
39 Maier H, Tisch M, Conradt C, Tisch M, Pötschke-Langer M. Alkoholgenuß und Krebs des oberen Aerodigestivtraktes bei Frauen. Dtsch Med Wochenschr. 1999; 124 851-854
40 Luce D, Guenel P, Leclerce A, Brugere J, Point D, Rodriguez J. Alcohol and tobacco consumption in cancer of the mouth, pharynx, and larynx: a study of 316 female patients. Laryngoscope. 1988; 98 313-316
41 Bundeszentrale für gesundheitliche Aufklärung .Alkoholkonsum der Jugendlichen in Deutschland 2004 - 2007. http://www.bmg.bund.de/cln_041/nn_604240/DE/Themenschwerpunkte/Drogen-und-Sucht/Alkohol/bzga-bericht-11-6,templateId=raw,property=publicationFile.pdf/bzga-bericht-11-6.pdf (letzter Zugriff am 20. 12. 2007)
42 Rosenquist K, Wennerberg J, Schildt E B, Bladström A, Hansson B G, Andersson G. Oral status, oral infections and some lifestyle factors as risk factors for oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. Acta Oto-Laryngologica. 2005; 125 1327-1336
43 Maier H, Tisch M, Enderle G, Dietz A, Weidauer H. Berufliche Exposition gegenüber Farben, Lacken und Lösungsmitteln und Krebsrisiko im Bereich des oberen Aerodigestivtraktes. HNO. 1997; 45 905-908
44 Maier H, Tisch M, Dietz A, Conradt C. Arbeiter in der Bauindustrie - eine Höchstrisikogruppe für Krebserkrankungen des oberen Atmungs- und Verdauungstraktes?. HNO. 1999; 47 730-736
45 Maier H, Tisch M. Beruf und Krebs im Kopf-Hals-Bereich. HNO. 1999; 47 1025-1037
46 Becher H, Ramroth H, Ahrens W, Risch A, Schmezer P, Dietz A. Occupation, exposure to polycyclic aromatic hydrocarbons and laryngeal cancer risk. Int J Cancer. 2005; 116 451-457
47 Wills J H. Nasal carcinomas in wood workers: a review. J Occup Med. 1982; 24 526-530
48 Pesch B, Pierl C B, Gebel M. et al . Occupational risks for adenocarcinoma. Occup Environ Med. 2007; epub ahead of print
49 Donhuijsen K, Hattenberger S, Schroeder H G. Sinunasale Karzinome nach Holzstaubbelastung - morphologisches Spektrum an 160 Fällen. Pathologe. 2004; 25 14-20
50 Shiboski C H, Schmidt B L, Jordan R CK. Tongue and tonsil carcinoma. Cancer. 2005; 103 1843-1849
51 Dahlstrom R K, Little J A, Zafereo M E, Margaret Lung M, Wie Q, Sturgis E M. Squamous cell carcinoma of the head and neck in never smoker-never drinkers: a descriptive epidemiologic study. Head Neck. 2007; epub ahead of print
52 Wight R, Paleri V, Arullendran P. Current theories for the development of nonsmoking and nondrinking laryngeal carcinoma. Curr Opin Otolaryngol Head Neck Surg. 2003; 11 73-77
53 León X, Rinaldo A, Saffiotti U, Ferlito A. Laryngeal cancer in non-smoking and non-drinking patients. Acta Otolaryngol. 2004; 124 664-669
54 Dahlstrom R K, Adler-Storthz K, Etzel C J, Liu Z, Dillon L, El-Naggar A K, Spitz M R, Schiller J T, Wie Q, Sturgis E M. Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. Clin Cancer Res. 2003; 9 2620-2626
55 zur Hausen H. Papillomaviruses and cancer: from basic science to clinical application. Nature Rev Cancer. 2002; 2 342-350
56 Löning T, Ikenberg H, Becker J, Gissmann L, Hoepfer I, zur Hausen H. Analysis of oral papillomas, leukoplakias, and invasive carcinomas for human papilloma virus type related DNA. J Invest Dermatol. 1985; 84 417-420
57 Syrjänen S, Syrjänen K, Mäntyjärvi R, Collan Y, Kärjä J. Human papillomavirus DNA in squamous cell carcinomas of the larynx demonstrated by in situ DNA hybridization. ORL J Otorhinol Relat Spec. 1987; 49 175-186
58 Hammarstedt L, Lindquist D, Dahlstrand D, Romanitan M, Onelöv Dahlgren L, Joneberg J, Creson N, Lindholm J, Ye W, Dalianis T, Munck-Wikland E. Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer. Int J Cancer. 2006; 119 2620-2623
59 D’Souza G, Kreimer A R, Viscidi R, Pawlita M, Fakhry C, Koch W M, Westra W H, Gillison M L. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007; 356 1944-1956
60 Klussmann J P, Weissenborn S J, Wieland U, Dries V, Kolligs J, Jungehuelsing M, Eckel H E, Dienes H P, Pfister H J, Fuchs P G. Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer. 2001; 92 2875-2884
61 Ritchie J M, Smith E M, Summersgill K F, Hoffman H T, Wang D, Klussmann J P, Turek L P, Haugen T H. Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer. 2003; 104 336-344
62 Kreimer A R, Clifford G M, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005; 14 467-475
63 Boeing H, Dietrich T, Hoffmann K. et al . Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study. Cancer Causes Control. 2006; 17 957-969
64 Perry C F, Stevens M, Rabie I, Yarker M E, Cochrane J, Perry E, Traficante R, Coman W. Chemoprevention of head and neck cancer with retinoids - a negative result. Arch Otolaryngol Head Neck Surg. 2005; 131 198-203
65 van Zandwijk N, Dalesio O, Pastorino U, de Vries N, van Tinteren H. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. J Natl Cancer Inst. 2000; 92 977-986
66 Hansemann D. Über asymmetrische Zelltheilung in Epithelkrebsen und deren biologische Bedeutung. Arch Pathol Anat Physiol Klin Medicin. 1890; 119 299-326
67 Boveri T. Ergebnisse über die Konstitution der chromatischen Substanz des Zellkerns. Jena; Fischer 1904
68 Boveri T. Zur Frage der Entstehung maligner Tumore. Jena; Fischer 1914
69 Hardy P A, Zacharias H. Reappraisal of the Hansemann-Boveri hypothesis on the origin of tumors. Cell Biology International. 2005; 29 983-992
70 Feulgen R, Rosenbeck H. Mikroskopisch-chemischer Nachweis einer Nucleinsäure vom Typus der Thymonucleinsäure und die darauf beruhende elektive Färbung von Zellkernen in mikroskopischen Präparaten. Hoppe-Seyler’s Zeitschr Physiol Chem. 1924; 135 203-248
71 Caspersson T, Lomakka G, Svensson G, Säfström R. A versatile ultramicrospectrograph for multiple-line and surface scanning high resolution measurements employing automatized data analysis. Exp Cell Res. 1955; 3 40-51
72 Atkin N B, Richards B M. Deoxyribonucleic acid in human tumours as measured by microspectrophotometry of Feulgen stain: a comparison of tumours arising at different sites. Brit J Cancer. 1956; 10 769-786
73 Capersson O. Quantitative cytochemical studies on normal, malignant, pre-malignant and atypical cell populations from the human uterine cervix. Acta Cytol. 1964; 8 45-60
74 Steinbeck R G, Auer G U, Zetterberg A D. Reliability and significance of DNA measurements in interphase nuclei and division figures in histological sections. Eur J Cancer. 1999; 35 787-795
75 Pitot H C, Goldsworthy T, Moran S. The natural history of carcinogenesis: implications of experimental carcinogenesis in the genesis of human cancer. J Supramol Struct Cellul Biochem. 1981; 17 133-146
76 Oshimura M, Barrett J C. Chemically induced aneuploidy in mammalian cells: mechansims and biological significance in cancer. Environ Mutagen. 1986; 8 129-159
77 Walch A, Bink K, Gais P, Stangl S, Hutzer P, Aubele M, Mueller J, Hofler H, Werner M. Evaluation of c-erbB-2 overexpression and Her-2/neu gene copy number heterogeneity in Barrett’s adenocarcinoma. Anal Cell Pathol. 2000; 20 25-32
78 Vogelstein B, Kinzler K W. The multistep nature of cancer. Trends Genet. 1993; 9 138-141
79 Pollack J R, Sorlie T, Perou C M, Rees C A, Jeffrey S S, Lonning P E, Tibshirani R, Botstein D, Borresen-Dale A L, Brown P O. Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci USA. 2002; 99 12 963-12 968
80 Vogel F, Motulsky A G. Human genetics: problems and approaches. New York; Springer Verlag 1986
81 Lengauer C, Kinzler K W, Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997; 386 623-627
82 Tomlinson I, Bodmer W. Selection, the mutation rate and cancer: insuring that the tale does not wag the dog. Nature Med. 1999; 5 11-12
83 Cairns J. The origin of human cancers. Nature. 1981; 289 353-357
84 Stock R P, Bialy H. The sigmoidal curve of cancer. Nature Biotech. 2003; 21 13-14
85 Meijer G A. Chromosomes and cancer, Boveri revisited. Cell Oncol. 2005; 27 273-275
86 Duesberg P, Li R. Multistep carcinogenesis: a chain reaction of aneuploidizations. Cell Cycle. 2002; 2 202-210
87 Duesberg P, Li R, Fabarius A, Hehlmann R. The chromosomal basis of cancer. Cell Oncol. 2005; 27 293-318
88 Barnes L, Eveson J W, Reichart P, Sidransky D (Hrsg). WHO Classification of Tumours, Pathology and Genetics of Head and Neck Tumours. Lyon; IARC Press 2005
89 O’Shaughnessy J A, Kelloff G J, Gordon G B. et al . Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res. 2002; 8 314-346
90 Neville B M, Day T A. Oral cancer and precancerous lesions. CA Cancer J Clin. 2002; 52 195-215
91 Schwimmer E. Die idiopathischen Schleimhautplaques der Mundhöhle (Leukoplakia buccalis). Arch Dermat Syph. 1877; 9 570-611
92 Kramer I R, Lucas R B, Pindborg JJ, Sobin L H. WHO collaborating centre for oral precancerous lesions - definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol. 1978; 46 518-539
93 Queyrat L. Erythroplasie de gland. Bull Soc Franc Derm Syph. 1911; 22 378-382
94 Shafer W G, Waldron C A. Erythroplakia of the oral cavity. Cancer. 1975; 36 1021-1028
95 LiVolsi V A. Can we agree to disagree?. Hum Pathol. 2003; 34 1081-1082
96 Ackerman A B. Can we agree to disagree - reflexions. Hum Pathol. 2004; 35 643-644
97 Foucar E. Diagnostic precision and accuracy in interpretation of specimens from cancer screening programs. Semin Diagn Pathol. 2005; 22 147-155
98 Fischer D J, Epstein J B, Morton T H, Schwartz S M. Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions. J Oral Pathol Med. 2004; 33 65-70
99 Kujan O, Khattab A, Oliver R J, Roberts S A, Thakker N, Sloan P. Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation. Oral Oncol. 2007; 43 224-231
100 McLaren K M, Burnett R A, Goodlad J R. et al . Consistency of histopathological reporting of laryngeal dysplasia - the Scottish pathology consistency group. Histopathology. 2000; 37 460-463
101 Lessells A M, Burnett R A, Goodlad J R. et al . Comment on a recent paper and editorial on the subject of dysplasia classification. J Pathol. 2002; 198 131-132
102 Montgomery E. Is there a way for pathologists to decrease interobserver variability in the diagnosis of dysplasia?. Arch Pathol Lab Med. 2005; 129 174-176
103 Morgenroth K. Über die Früherkennung maligner Veränderungen der Mundschleimhaut. Zahnärztl Mitt. 1969; 59 341-344
104 Kränzl B, Sorgo E, Wutka P. Untersuchung zur Anwendbarkeit der Zytodiagnostik für die Früherkennung von Mundhöhlenkrebs an der Klinik für Mundchirurgie. Wien Klin Wochenschr. 1974; 86 648-650
105 Wächter R. Technik und Indikationen der Zytodiagnostik für die Krebsfrüherkennung. SSO Schweiz Monatsschr Zahnheilk. 1978; 88 829-836
106 McLeod N MH, Saeed N R, Ali E A. Oral cancer: Delays in referral and diagnosis persist. Br Dent J. 2005; 198 681-684
107 Mignogna M D, Fedele S, Lo Russo L, Ruoppo E, Lo Muzio L. Oral and pharyngeal cancer: lack of prevention and early detection by health care providers. Eur J Cancer Prev. 2001; 10 381-383
108 Kujan O, Glenny A M, Oliver R J, Thakker N, Sloan P. Screening programmes for the early detection and prevention of oral cancer. Cochrane Database of Systematic Reviews. 2006; 3 Art. No.: CD004150. DOI: 10.1002/14651858.CD004150.pub2
109 Sankaranarayanan R, Ramadas K, Thomas G, Muwonge R, Thara S, Mathew B, Rajan B. Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet. 2005; 365 1927-1933
110 Dalcq A. Vital staining with toluidine blue and its metachromatic manifestations. C R Seances Soc Biol Fil. 1952; 146 1408-1411
111 Little J W. Toluidine blue staining in the detection of oral precancerous and malignant lesions. Oral Surg Oral Med Oral Pathol. 1984; 57 379-382
112 Gupta A, Singh M, Ibrahim R, Mehrotra R. Utility of toluidine blue staining and brush biopsy in precancerous and cancerous oral lesions. Acta Cytol. 2007; 51 788-794
113 Du G F, Li C Z, Chen H Z, Chen X M, Xiao Q, Cao Z G, Shang S H, Cai X. Rose bengal staining in detection of oral precancerous and malignant lesions with colorimetric evaluation: a pilot study. Int J Cancer. 2007; 120 1958-1963
114 Farah C S, McCullough M J. A pilot case control study on the efficacy of acetic wash and chemiluminescent illumination (ViziLite®) in the visualisation of oral mucosal white lesions. Oral Oncol. 2007; 43 820-824
115 Oh E S, Laskin D M. Efficacy of the ViziLite® system in the identification of oral lesions. J Oral Maxillofac Surg. 2007; 65 424-426
116 Ram S, Siar C H. Chemiluminescence as a diagnostic aid in the detection of oral cancer and potentially malignant epithelial lesions. Int J Oral Maxillofac Surg. 2005; 34 521-527
117 Epstein J B, Silverman Jr S, Epstein J D, Lonky S A, Bride M A. Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue. Oral Oncol. 2007; epub ahead of print
118 Policard A. Etude sur les aspects offerts par des tumeurs experimentales examinées a la lumière de Wood. C R Soc Biol. 1924; 91 1423-1424
119 Lipson R L, Baldes J E, Olsen A M. Hematoporphyrin derivative: a new aid for endoscopic detection of malignant tissue. J Thorac Cardiovasc Surg. 1962; 42 623-629
120 Delank W, Khanavkar B, Nakhosteen J A, Stoll W. A pilot study of autofluorescent endoscopy for the in vivo detection of laryngeal cancer. Laryngoscope. 2000; 110 368-373
121 Arens C, Reussner D, Woenkhaus J, Leunig A, Betz C S, Glanz H. Indirect fluorescence laryngoscopy in the diagnosis of precancerous and cancerous laryngeal lesions. Eur Arch Otorhinolaryngol. 2007; 264 621-626
122 Svistun E, Alizadeh-Naderi E, El-Naggar A, Jacob R, Gillenwater A, Richards-Kortum R. Vision enhancement system for detection of oral cavity neoplasia based on autofluorescence. Head Neck. 2004; 26 205-215
123 Zengyk H, Weissz A, Clinex R, MacAulayy C E. Real-time endoscopic fluorescence imaging for early cancer detection in the gastrointestinal tract. Bioimaging. 1998; 6 151-165
124 Rasetti L, Rubino G, Drago W. Ferrochelatase, ALA-dehydrase and ALA-synthetase activity in human tumor tissue. Minerva Med. 1966; 57 2834-2837
125 Leunig A, Betz C S, Heinrich P, Janda P, Baumgartner R. Fluoreszenzdiagnostik von Karzinomen im Mund-Rachen-Kehlkopf-Bereich nach Applikation von 5-Aminolävulinsäure. Laryngo-Rhino-Otol. 2002; 81 807-814
126 Leunig A, Betz C S, Mehlmann M, Stepp H, Arbogast S, Grevers G, Baumgartner R. Detection of squamous cell carcinoma of the oral cavity by imaging 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. Laryngoscope. 2000; 110 78-83
127 Mao L, Lee J S, Fan Y H, Ro J Y, Batsakis J G, Lippman S, Hittelman W, Hong W K. Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment. Nature Med. 1996; 2 682-685
128 Rosin M P, Cheng X, Poh C. et al . Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res. 2000; 6 357-362
129 Ha P K, Pai S I, Westra W H, Gillison M L, Tong B C, Sidransky D, Califano J A. Real-time quantitative PCR demonstrates low prevalence of human papillomavirus type 16 in premalignant and malignant lesions of the oral cavity. Clin Cancer Res. 2002; 8 1203-1209
130 Herrero R, Castellsagué X, Pawlita M. et al . Human papillomavirus and oral cancer: the international agency for research on cancer multicenter study. J Natl Cancer Inst. 2003; 95 1772-1783
131 Hullmann M, Reichert T, Dahse R, von Eggeling F, Pistner H, Kosmehl H, Driemel O. Orale Zytologie - historische Entwicklung, aktueller Stand und Ausblick. Mund Kiefer Gesichts Chir. 2007; 11 1-9
132 Koburg E, Steinbach E. Toluidinblau-Vitalfärbung zur Früherkennung und Abgrenzung maligner Kehlkopftumoren. Eur Arch Otorhinolaryngol. 1969; 194 320-323
133 Olofsson J. Laryngeal carcinoma: problems in diagnosis and classification. J Otolaryngol. 1982; 11 167-177
134 Harries M L, Lam S, Macaulay C, Qu J A, Palcic B. Diagnostic imaging of the larynx: autofluorescence of laryngeal tumors using the helium-cadmium laser. J Laryngol Otol. 1995; 109 108-110
135 Arens C, Malzahn K, Dias O, Andrea M, Glanz H. Endoskopische Bildgebung in der Diagnostik von Kehlkopfkrebs und seiner Vorstufen. Laryngorhinootolgie. 1999; 78 685-691
136 Žargi M, Fajdiga I, Šmid L. Autofluorescence imaging in the diagnosis of laryngeal cancer. Eur Arch Otorhinolaryngol. 2000; 257 17-23
137 Malzahn K, Dreyer T, Glanz H, Arens C. Autofluorescence endoscopy in the diagnosis of early laryngeal cancer and its precursor lesions. Laryngoscope. 2002; 112 488-493
138 Arens C, Dreyer T, Glanz H, Malzahn K. Indirect autofluorescence laryngoscopy in the diagnosis of laryngeal cancer and its precursor lesions. Eur Arch Otorhinolaryngol. 2004; 261 71-76
139 Mehlmann M, Betz C S, Stepp H, Arbogast S, Baumgartner R, Grevers G, Leunig A. Fluorescence staining of laryngeal neoplasms after topical application of 5-aminolevulinic acid: preliminary results. Lasers Surg Med. 1999; 25 414-420
140 Franco Jr R A. Aminolevulinic acid 585nm pulsed dye laser photodynamic treatment of laryngeal keratosis with atypia. Otolaryngol Head Neck Surg. 2007; 136 882-887
141 Hoffman H AT, Karnell L H, Shah J P, Ariyan S, Brown G S, Fee W E, Glass A G, Goepfert H, Ossoff R H, Fremgen A M. Hypopharyngeal cancer patient care evaluation. Laryngoscope. 1997; 107 1005-1017
142 Zhou L, Cheng L, Tao L, Jia X, Lu Y, Liao P. Detection of hypopharyngeal squamous cell carcinoma using serum proteomics. Acta Oto-Laryngologica. 2006; 126 853-860
143 Eckel H E, Staar S, Volling P, Sittel C, Damm M, Jungehülsing M. Surgical treatment for hypopharynx carcinoma: feasibility, mortality, and results. Otolaryngol Head Neck Surg. 2001; 124 561-569
144 Watanabe A, Hosokawa M, Taniguchi M, Tsujie H, Sasaki S. Impact of endoscopic screening on early detection of hypopharyngeal cancer. Head Neck. 2006; 28 350-354
145 Pinkston J A, Cole P. Incidence rates of salivary gland tumors: results from a population-based study. Otolaryngol Head Neck Surg. 1999; 120 834-840
146 Belsky J L, Takeichi N, Yamamoto T, Cihak R W, Hirose F, Ezaki H, Inoue S, Blot W J. Salivary gland neoplasms following atomic radiation: additional cases and reanalysis of combined data in a fixed population, 1957-1970. Cancer. 1975; 35 555-559
147 Mihailescu D, Shore-Freedman E, Mukani S, Lubin J, Ron E, Schneider A B. Multiple neoplasms in an irradiated cohort: pattern of occurrence and relationship to thyroid cancer outcome. J Clin Endocrinol Metab. 2002; 87 3236-3241
148 Hoffman D A, McConahey W M, Fraumeni Jr J F, Kurland L T. Cancer incidence following treatment of hyperthyroidism. Int J Epidemiol. 1982; 11 218-224
149 Auvinen A, Hietanen M, Luukkonen R, Koskela R S. Brain tumors and salivary gland cancers among cellular telephone users. Epidemiology. 2002; 13 356-359
150 Horn-Ross P L, Ljung B M, Morrow M. Environmental factors and the risk of salivary gland cancer. Epidemiology. 1997; 8 414-419
151 Milham Jr S. Cancer mortality pattern associated with exposure to metals. Ann N Y Acad Sci. 1976; 271 243-249
152 Dietz A, Barme B, Gewelke U, Sennewald E, Heller W D, Maier H. Zur Epidemiologie der Parotistumoren - eine Fallkontrollstudie. HNO. 1993; 41 83-90
153 Swanson G M, Burns P B. Cancers of the salivary gland: workplace risks among women and men. Ann Epidemiol. 1997; 7 369-374
154 Muscat J E, Wynder E L. A case/control study of risk factors for major salivary gland cancer. Otolaryngol Head Neck Surg. 1998; 118 195-198
155 Droese M, Haubrich J, Tute M. Stellenwert der Punktionszytologie in der Diagnostik der Speicheldrüsentumoren. Schweiz Med Wochenschr. 1978; 108 933-935
156 Knapp I, Mann W, Wachter W. Stellenwert der ultraschallgesteuerten Feinnadelbiopsie in der Diagnostik unklarer Halstumoren. Laryngo Rhino Otol. 1989; 68 683-689
157 Siegert R, Schrader B, Barreton G. Die ultraschallgeführte Feinnadelpunktion pathologischer Raumforderungen im Kopf-Halsbereich. HNO. 1990; 38 287-291
158 Schoengen A, Binder T, Krause H R, Stussak G, Zeelen U. Der Wert der Feinnadelaspirationszytologie bei tumorverdächtigen Speicheldrüsenschwellungen. HNO. 1995; 43 239-243
159 Zbären P, Schar C, Hotz M A, Loosli H. Value of fine-needle aspiration cytology of parotid gland masses. Laryngoscope. 2001; 111 1989-1992
160 Schröder U, Eckel H E, Rasche V, Arnold G, Ortmann M, Stennert E. Wertigkeit der Feinnadelpunktionszytologie bei Neoplasien der Glandula parotis. HNO. 2000; 48 421-429
161 Driemel O, Kraft K, Hemmer J. DNA-Ploidie und proliferative Aktivität bei Speicheldrüsentumoren. Mund Kiefer GesichtsChir. 2007; 11 139-144
162 Driemel O, Kraft K, Hemmer J. Flow cytometric S-phase fraction contributes to diagnosis of diploid malignant salivary gland tumours. Int J Oral Maxillofac Surg. 2006; 35 947-950
163 Driemel O, Maier H, Kraft K, Haase S, Hemmer J. Flow cytometric DNA ploidy in salivary gland tumors. Oncol Rep. 2005; 13 161-165
164 Slaughter D P, Southwick H W, Smejkal W. „Field cancerization” in oral stratified squamous epithelium - clinical implications of multicentric origin. Cancer. 1953; 6 963-968
165 Hao S P. Six primary squamous cell carcinomas of the head and neck. Auris Nasus Larynx. 1998; 25 101-104
166 Braakhuis B JM, Brakenhoff R H, Leemans C R. Second field tumors: a new opportunity for cancer prevention?. Oncologist. 2005; 10 493-500
167 Warren S, Gates O. Multiple primary malignant tumors. A survey of the literature and a statistical study. Am J Cancer. 1932; 16 1358-1414
168 Shikhani A H, Matanoski G M, Jones M M, Kashima H K, Johns M E. Multiple primary malignancies in head and neck cancer. Arch Otolaryngol Head Neck Surg. 1986; 112 1172-1179
169 Shaha A R, Hoover E L, Mitrani M, Marti J R, Krespi Y P. Synchronicity, multicentricity, and metachronicity of head and neck cancer. Head Neck Surg. 1988; 10 225-228
170 Panosetti E, Luboinski B, Mamelle G, Richard J M. Multiple synchronous and metachronous cancers of the upper aerodigestive tract: a nine-year study. Laryngoscope. 1989; 99 1267-1273
171 Schwartz L H, Ozsahin M, Zhang G N, Touboul E, de Vafaire F, Andolenko P, Lacau-Saint-Guily J, Lnugier A, Schlienger M. Synchronous and metachronous head and neck carcinomas. Cancer. 1994; 74 1933-1938
172 Jäckel M C, Martin A, Steiner W. Lokale und regionäre Rezidive von laserchirurgisch behandelten Plattenepithelkarzinomen des oberen Aerodigestivtrakts - Häufigkeit, Latenz und Prognose sowie Einfluss der initialen Tumorparameter. HNO. 2007; epub ahead of print
173 Gao X, Fisher S G, Mohideen N, Emami B. Second primary cancers in patients with laryngeal cancer: a population-based study. Int J Radio Oncol Biol Phys. 2003; 56 427-435
174 Gleich L L, Ryzenman J, Gluckman J L, Wilson K M, Barrett W L, Redmond K P. Recurrent advanced (T3 or T4) head and neck squamous cell carcinoma: is salvage possible?. Arch Otolaryngol Head Neck Surg. 2004; 130 35-38
175 Glanz H. Late recurrence of radiation induced cancer of the larynx. Clin Otolaryngol Allied Sci. 1976; 1 123-129
176 Martin G, Glanz H, Kleinsasser O. Ionisierende Strahlen und Kehlkopfkrebse. Laryngo Rhino Otol. 1979; 58 187-195
177 Roostaeian J, Suh J D, Sercarz J A, Abemayor E, Lee J T, Blackwell K E. Factors affecting cancer recurrence after microvascular flap reconstruction of the head and neck. Laryngoscope. 2005; 115 1391-1394
178 Scherübl H, Steinberg J, Schwertner C, Mir-Salim P, Stölzel U, de Villiers E M. „Field cancerization” im oberen Aerodigestivtrakt - Überwachungsempfehlungen für Risikopersonen. HNO. 2007; epub ahead of print
179 Watanabe A, Hosokawa M, Taniguchi M, Sasaki S. Periodic pharyngolaryngoscopy detects early head and neck cancer and improves survival in esophageal cancer. Ann Thorac Surg. 2003; 76 1699-1705
180 Möschler O, Spahn T W, Middelberg-Bisping C, Grosse-Thie W, Christoph B, Kloeppel G, Mueller MK. Chromoendoscopy is a valuable tool for screening of high-risk patients with head and neck cancer for early detection of esophageal cancer. Digestion. 2006; 73 160-166
181 Merkx M AW, van Gulick J JM, Marres H AM, Kaanders J HAM, Bruaset J, Verbeek A, de Wilde P CM. Effectiveness of routine follow-up of patients treated for T1 - 2 N0 oral squamous cell carcinomas of the floor of mouth and tongue. Head Neck. 2006; 28 1-7
182 de Visscher A V, Manni J J. Routine long-term follow-up in patients treated with curative intent for squamous cell carcinoma of the larynx, pharynx, and oral cavity - does it make sense?. Arch Otolaryngol Head Neck Surg. 1994; 120 934-939
183 Rassekh C H, Johnson J T, Eibling D E. Circulating markers in squamous cell carcinoma of the head and neck: a review. Eur J Cancer B Oral Oncol. 1994; 30B 23-28
184 Tannapfel A, Weber A. Tumor markers in squamous cell carcinoma of the head and neck: clinical effectiveness and prognostic value. Eur Arch Otorhinolaryngol. 2001; 258 83-88
185 Brown J J, Xu H, Nishitani J, Mohammed H, Osborne R, Teklehaimanot S, Gill G, Liu X. Potential biomarkers for head and neck squamous cell carcinoma. Laryngoscope. 2003; 113 393-400
186 Nagler R M, Barak M, Peled M, Ben-Aryeh H, Filatov M, Laufer D. Early diagnosis and treatment monitoring roles of tumor markers Cyfra 21 - 1 and TPS in oral squamous cell carcinoma. Cancer. 1999; 85 1018-1025
187 Doweck I, Barak M, Uri N, Greenberg E. The prognostic value of the tumour marker Cyfra 21 - 1 in carcinoma of head and neck and its role in early detection of recurrent disease. Br J Cancer. 2000; 83 1696-1701
188 Arlt A, Luckhaupt H, Hildmann H. Diagnostik von Kopf-Hals-Karzinom-Rezidiven mit dem Tumormarker SSC-Antigen. Laryngo Rhino Otol. 2000; 79 207-212
189 Welkoborsky H J, Bernauer H S, Riazimand H S, Jacob R, Mann W J, Hinni M L. Patterns of chromosomal aberrations in metastasizing and nonmetastasizing squamous cell carcinomas of the oropharynx and hypopharynx. Ann Otol Rhinol Laryngol. 2000; 109 401-410
190 Beyer T, Townsend D W, Brun T, Kinahan P E, Charron M, Roddy R, Jerin J, Young J, Byars L, Nutt R. A combined PET/CT scanner for clinical oncology. J Nucl Med. 2000; 41 1369-1379
191 Gordin A, Daitzchman M, Doweck I, Yefremov N, Golz A, Keidar Z, Bar-Shalom R, Kuten A, Israel O. Fluorodeoxyglucose-positron emission tomography/computed tomography imaging in patients with carcinoma of the larynx: diagnostic accuracy and impact on clinical management. Laryngoscope. 2006; 116 273-278
192 Brouwer J, Senft A, de Bree R, Comans E F, Golding R P, Castelijns J A, Hoekstra O S, Leemans C R. Screening for distant metastases in patients with head and neck cancer: is there a role for (18) FDG-PET?. Oral Oncol. 2006; 42 275-280
193 Schöder H, Yeung H WD, Gonen M, Kraus D, Larson S M. Head and neck cancer: clinical usefulness and accuracy of PET/CT image fusion. Radiology. 2004; 231 65-72
194 Basu D, Siegel B A, McDonald D J, Nussenbaum B. Detection of occult bone metastases from head and neck squamous cell carcinoma - impact of positron emission tomography-computed tomography with fluorodeoxyglucose F 18. Arch Otolaryngl Head Neck Surg. 2007; 133 801-805
195 Fakhry N, Lussato D, Jacob T, Giorgi R, Giovanni A, Zanart M. Comparison between PET and PET/CT in recurrent head and neck cancer and clinical implications. Eur Arch Otorhinolaryngol. 2007; 264 531-538
196 Ha P K, Hdeib A, Goldenberg D. et al . The role of positron emission tomography and computed tomography fusion in the management of early-stage and advanced-stage primary head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2006; 132 12-16
197 Roh J L, Yeo N K, Kim J S, Cho K J, Choi S H, Nam S Y, Kim S Y. Utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography and positron emission tomography/computed tomography imaging in the preoperative staging of head and neck squamous cell carcinoma. Oral Oncol. 2007; 43 887-893
198 Ritoe S C, Bergman H, Krabbe P FM, Kaanders J HAM, van den Hoogen F JA, Verbeek A LM, Marres H AM. Cancer recurrence after total laryngectomy: treatment options, survival, and complications. Head Neck. 2006; 28 383-388
199 Weaver B AA, Cleveland D W. Does aneuploidy cause cancer?. Curr Opin Cell Biol. 2006; 18 658-667
200 Hanson J, Bruchmüller W, Nischwitz A S. Krebsvorstufen und die Früherkennung von Pharynx- und Larynx-Karzinomen. Arch Geschwulstforschung. 1989; 59 99-105
201 Böcking A, Stockhausen J, Meyer-Ebrecht D. Towards a single cell cancer diagnosis - multimodal and monocellular measurements of markers and morphology (5M). Cell Oncol. 2004; 26 73-79
202 Tárnok A, Gerstner A. Clinical applications of laser-scanning cytometry. Cytometry (Clin Cytometry). 2002; 50 133-143
203 Patente: DE 1 815 352 (1968), GB 1 300 585, US 3,738,759.
204 Göhde W, Dittrich W. Simultane Impulsfluorimetrie des DNS- und Proteingehaltes von Tumorzellen. Z Anal Chem. 1970; 252 328-330
205 Kraus H, Bremke U, Wedding C. Ultraschnelle Messungen der DNS-Fluoreszenz an normalen Geweben, Entzündungen und Tumoren von Kopf und Hals. Archiv klin. exp. Ohren-, Nasen-, und Kehlkopfheilk. 1972; 202 698-699
206 Holm L E. Cellular DNA amount of squamous cell carcinomas of the head and neck region in relation to prognosis. Laryngoscope. 1982; 92 1064-1069
207 Wang X L, Chen R M, Wang Z S, Chen W L, Zuo L F. Flow cytometric DNA-ploidy as a prognostic indicator in oral squamous cell carcinoma. Chin Med J. 1990; 103 572-575
208 Hemmer J, Kreidler J. Flow cytometric DNA ploidy analysis of squamous cell carcinoma of the oral cavity - comparison with clinical staging and histologic grading. Cancer. 1990; 66 317-320
209 Bueno P R, Gias L N, Delgado R G, Cebollada J D, Díaz González F J. Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the oral cavity and tongue base. Head Neck. 1998; 20 232-239
210 Hemmer J, Kraft K, Kreidler J. The significance of DNA flow cytometry in predicting survival and delayed clinical manifestation of occult lymph node metastasis to the untreated neck in patients with oral squamous cell carcinoma. J Cranio Maxillofac Surg. 1998; 26 405-410
211 Ruá S, Comino A, Fruttero A, Cera G, Semeria C, Lanzillotty L, Boffetta P. Relationship between histologic features, DNA flow cytometry, and clinical behavior of squamous cell carcinomas of the larynx. Cancer. 1991; 67 141-149
212 Walter M A, Peters G E, Peiper S C. Predicting radioresistance in early glottic squamous carcinoma by DNA content. Ann Otol Rhinol Laryngol. 1991; 100 523-526
213 Golusinski W, Olofsson J, Szmeja Z, Biczysko W, Krygier-Stojatowska A, Kulczynski B. A comprehensive analysis of selected diagnostic methods with respect to their usefulness in evaluating the biology of neoplastic cells in patients with laryngeal cancer. Eur Arch Otorhinolaryngol. 1999; 256 306-311
214 Höfken F, Welkoborsky H J, Jacob R, Mann W. DNA-zytometrische Untersuchungen von Mund- und Rachenspülflüssigkeit als Screening-Verfahren zur Diagnose von Malignomen der Mundhöhle und der Oropharynx. Laryngo Rhino Otol. 1995; 74 678-683
215 Remmerbach T W, Weidenbach H, Pomjanski N, Knops K, Mathes S, Hemprich A, Böcking A. Cytologic and DNA-cytometric early diagnosis of oral cancer. Anal Cell Pathol. 2001; 22 211-221
216 Gerstner A OH, Thiele A, Tárnok A, Tannapfel A, Weber A, Bootz F. Prediction of upper aerodigestive tract cancer by slide-based cytometry. Cytometry Part A. 2006; 69A 582-587
217 Gerstner A OH, Müller A K, Machlitt J, TaŽrnok A, Tannapfel A, Weber A, Bootz F. Slide-based cytometry for predicting malignancy in solid salivary gland tumors by fine needle aspirate biopsies. Cytometry Part B (Clin Cytometry). 2003; 53B 20-25
218 Gerstner A OH, Thiele A, Tárnok A, Machlitt J, Oeken J, Tannapfel A, Weber A, Bootz F. Preoperative detection of laryngeal cancer in mucosal swabs by slide-based cytometry. Eur J Cancer. 2005; 41 445-452
219 Gerstner A OH, Machlitt J, Welkoborsky H J, Bootz F, Tárnok A. Analysis of ploidy in hypopharyngeal cancer by laser scanning cytometry on fine needle aspirate biopsies. Anal Cell Pathol. 2003; 25 51-62
220 Gerstner A OH, Gutsche M, Bücheler M, Machlitt J, Emmrich F, Sommerer F, Tárnok A, Bootz F. Eosinophilia in nasal polyposis: its objective quantification and clinical relevance. Clin Exp Allerg. 2004; 34 65-70
221 Remmerbach T W, Weidenbach H, Hemprich A, Böcking A. Earliest detection of oral cancer using non-invasive brush biopsy including DNA-image-cytometry: report on four cases. Anal Cell Pathol. 2004; 25 159-166
222 Leoni-Parvex S, Mihaescu A, Pellanda A, Monnier P, Bosman F T. Esophageal cytology in the follow-up of patients with treated upper aerodigestive tract malignancies. Cancer. 2000; 90 10-16
223 Hutchinson M L, Cassin C M, Ball H G. The efficacy of an automated preparation device for cervical cytology. Am J Clin Pathol. 1991; 96 300-305
224 Klinkhamer P JJM, Meerding W J, Rosier P FWM, Hanselaar A GJM. Liquid-based cervical cytology - a review of the literature with methods of evidence-based medicine. Cancer (Cancer Cytopathol). 2003; 99 263-271
225 Bollmann R, Bankfalvi A, Griefingholt H, Trosic A, Speich N, Schmitt C, Bollmann N. Validity of combined cytology and human papillomavirus (HPV) genotyping with adjuvant DNA-cytometry in routine cervical screening: results from 31 031 women from the Bonn-region in West Germany. Oncol Rep. 2005; 13 915-922
226 Bollmann M, Heller H, Bánkfalvi A, Griefingholt H, Bollmann R. Quantitative molecular urinary cytology by fluorescence in situ hybridization: a tool for tailoring surveillance of patients with superficial bladder cancer?. Br J Urol. 2005; 95 1219-1225
227 Gerstner A OH, Trumpfheller C, Racz P, Osmancik P, Tenner-Racz K, Tárnok A. Quantitative histology by multicolor slide-based cytometry. Cytometry Part A. 2004; 59A 210-219
228 Rubin M A, Zerkowski M P, Camp R L, Kuefer R, Hofer M D, Chinnaiyan A M, Rimm D L. Quantitative determination of expression of the prostate cancer protein α-Methylacyl-CoA racemase using automated quantitative analysis (AQUA) - a novel paradigm for automated and continuous biomarker measurements. Am J Pathol. 2004; 164 831-840
229 Taylor C R, Levenson R M. Quantification of immunohistochemistry - issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006; 49 411-424
230 de Solórzano C O, Costes S, Callahan D E, Parvin B, Barcellos-Hoff M H. Applications of quantitative digital image analysis to breast cancer research. Microscop Res Tech. 2002; 59 119-127
231 Ludwig J A, Weinstein J N. Biomarkers in cancer staging, prognosis and treatment selection. Nature Rev Cancer. 2005; 5 845-856
232 Issaq H J, Veenstra T D, Conrads T P, Felschow D. The SELDI-TOF MS approach to proteomics: protein profiling and biomarker identification. Biochem Biophys Res Comm. 2002; 292 587-592
233 Wadsworth J T, Somers K D, Stack B C, Cazares L, Malik G, Adam B L, Wright G L, Semmes O J. Identification of patients with head and neck cancer using serum protein profiles. Arch Otolaryngol Head Neck Surg. 2004; 130 98-104
234 Gourin C G, Xia Z S, Han Y, French A M, O’Rourke A K, Terris D J, Adam B L. Serum protein profile analysis in patients with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2006; 132 390-397
235 Kopf E, Zharhary D. Antibody arrays - an emerging tool in cancer proteomics. Int J Biochem Cell Biol. 2007; 39 1305-1317
236 Hudelist G, Pacher-Zavisin M, Singer C F, Holper T, Kubista E, Schreiber M, Manavi M, Bilban M, Czerwenka K. Use of high-throughput protein array for profiling of differentially expressed proteins in normal and malignant breast tissue. Breast Cancer Res Treat. 2004; 86 281-291
237 Hathaway B, Landsittel D P, Gooding W, Whiteside T L, Grandis J R, Siegfried J M, Bigbee W L, Ferris R L. Multiplexed analysis of serum cytokines as biomarkers in squamous cell carcinoma of head and neck patients. Laryngocope. 2005; 115 522-527
238 Linkov F, Lisovich A, Yurkovetsky Z. et al . Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling. Cancer Epidemiol Biomarkers Prev. 2007; 16 102-107
239 Ziober B L, Mauk M G, Falls E M, Chen Z, Ziober A F, Bau H H. Lab-on-a-chip for oral cancer screening and diagnosis. Head Neck. 2008; 30 111-121
240 Virchow R. Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre - 20 Vorlesungen. Berlin; August Hirschwald 1858
241 Valet G, Leary J F, Tárnok A. Cytomics - new technologies: towards a human cytome project. Cytometry Part A. 2004; 59A 167-171
242 Valet G, Valet M, Tschöpe D, Gabriel H, Rothe G, Kellerman W, Kahle H. White cell and thrombocyte disorders - standardized, self-learning flow cytometric list mode data classification with the CLASSIF1 program system. Ann N Y Acad Sci. 1993; 20 233-251
243 Valet G. Cytomics, the human cytome project and systems biology: top-down resolution of the molecular biocomplexity of organisms by single cell analysis. Cell Prolif. 2005; 38 171-174
244 van Driel B EM, Valet G K, Lyon H, Hansen U, Song J Y, van Noorden C JF. Prognostic estimation of survival of colorectal cancer patients with the quantitative histochemical assay of G6PDH activity and the multiparameter classification program CLASSIF1. Cytometry (Comm Clin Cytometry). 1999; 38 176-183
245 Valet G, Repp R, Link H, Ehninger A, Gramatzki M. SHG-AML study group . Pretherapeutic identification of high-risk acute myeloid leukemia (AML) patients from immunophenotypic, cytogenetic, and clinical parameters. Cytometry Part B (Clinical Cytometry). 2003; 53B 4-10
246 Valet G. Cytomics: an entry to biomedical cell systems biology. Cytometry Part A. 2005; 63A 67-68
247 Valet G. Cytomics as a new potential for drug discovery. Drug Discov Today. 2006; 11 785-791
248 Bloching M, Stephan D, Agha-Mir-Salim P, Berghaus A, Lautenschläger C, Grummt T. Der Ames-Test als Biomarker. HNO. 2001; 49 440-446
249 Righini C A, de Fraipont F, Timsit J F, Faure C, Brambilla E, Reyt E, Favrot M C. Tumor-specific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence. Clin Cancer Res. 2007; 13 1179-1185
250 Bloching M, Hofmann A, Berghaus A, Lautenschläger C, Grummt T. Mikrokerne als Biomarker zum Nachweis der Feldkanzerisierung im oberen Aerodigestivtrakt. HNO. 2000; 48 444-450
251 Kamboj M, Mahajan S. Micronucleus - an upcoming marker of genotoxic damage. Clin Oral Invest. 2007; 11 121-126
252 Hsu T C, Johnston D A, Cherry L M, Rmakissoon D, Schantz S P, Jessup J M, Winn R J, Shirley L, Furlong C. Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to enviromental carcinogenesis. Int J Cancer. 1989; 43 403-409
253 Kleinsasser N H, Schmid K, Sassen A W, Harréus U A, Staudenmaier R, Folwaczny M, Glas J, Reichl F X. Cytotoxic and genotoxic effects of resin monomers in human salivary gland tissue and lymphocytes as assessed by the single cell microgel electrophoresis (COMET) assay. Biomaterials. 2006; 27 1762-1770
254 Kleinsasser N H, Wallner B C, Kastenbauer E R, Muenzenrieder R K, Harréus U A. Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay. Mutation Res. 2000; 467 21-30
255 Olive P L, Durand R E, le Riche J, Olivotto I A, Jackson S M. Gel electrophoresis of individual cells to quantify hypoxic fraction in human breast cancers. Cancer Res. 1993; 53 733-736
256 Singh N P, McCoy M T, Tice R R, Scheider E L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988; 175 184-191
257 McKelvey-Martin V J, Green M HL, Schmezer P, Pool-Zobel P L, DeMeo M P, Collins A. The single cell gel electrophoresis assay (Comet assay): a European review. Mutat Res. 1993; 288 47-63
258 Voegeli R. Die Schillersche Jodprobe im Rahmen der Ösophagusdiagnostik (Vorläufige Mitteilung). Pract Oto-Rhino-Laryngol. 1966; 28 230-239
259 Connor M J, Sharma P. Chromoendoscopy and magnification endoscopy for diagnosing esophageal cancer and dysplasia. Thorac Surg Clin. 2004; 14 87-94
260 Dawsey S M, Fleischer D E, Wang G Q, Zhou B, Kidwell J A, Lu N, Lewin K J, Roth M J, Tio L, Taylor F R. Mucosal iodine staining improves endoscopic visualization of squamous dysplasia and squamous cell carcinoma of the esophagus in Linxian, China. Cancer. 1998; 83 220-231
261 Muto M, Nakane M, Katada C, Sano Y, Ohtsu A, Esumi H, Ebihara S, Yoshida S. Squamous cell carcinoma in situ at oropharyngeal and hypopharyngeal mucosal sites. Cancer. 2004; 101 1375-1381
262 Voo I, Mavrofrides E C, Puliafito C A. Clinical applications of optical coherence tomography for the diagnosis and management of macular diseases. Ophthalmol Clin North Am. 2004; 17 21-31
263 Bibas A G, Podoleanu A G, Cucu R G, Bonmarin M, Dobre G M, Ward V MM, Odell E, Boxer A, Gleeson M J, Lackson D A. 3-D optical coherence tomography of the laryngeal mucosa. Clin Otolaryngol. 2004; 29 713-720
264 Armstrong W B, Ridgway J M, Vokes D E. et al . Optical coherence tomography of laryngeal cancer. Laryngoscope. 2006; 116 1107-1113
265 Kraft M, Lüerßen K, Lubatschowski H, Glanz H, Arens C. Technique of optical coherence tomography of the larynx during microlaryngoscopy. Laryngoscope. 2007; 117 950-952
266 Xie T, Xie H, Fedder G K, Pan Y. Endoscopic optical coherence tomography with a modified microelectromechanical systems mirror for detection of bladder cancers. Appl Optics. 2003; 42 6422-6426
267 Wang Z, Lee C S, Waltzer W C, Liu J, Xie H, Yuan Z, Pan Y. In vivo bladder imaging with microelectromechanical-systems-based endoscopic spectral domain optical coherence tomography. J Biomed Opt. 2007; 12 034 009
268 Pan Y T, Wu Z L, Yuan Z J, Wang Z G, Dub C W. Subcellular imaging of epithelium with time-lapse optical coherence tomography. J Biomed Opt. 2007; 12 050 504
269 Watanabe A, Tsujie H, Taniguchi M, Hosokawa M, Fujita M, Sasaki S. Laryngoscopic detection of pharyngeal carcinoma in situ with narrowband imaging. Laryngoscope. 2006; 116 650-654
270 Koenig F, González S, White W M, Lein M, Rajadhyaksha M. Near-infrared confocal laser scanning microscopy of bladder tissue in vivo. Urology. 1999; 53 853-857
271 Dickensheets D L, Kino G S. Micromachined scanning confocal optical microscope. Optics Letters. 1996; 21 764-766
272 Koenig F, Knittel J, Stepp H. Diagnosing Cancer in Vivo. Science. 2001; 292 1401-1403
273 Kiesslich R, Burg J, Vieth M. et al . Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology. 2004; 127 706-713
274 Hoffman A, Goetz M, Vieth M, Galle P R, Neurath M F, Kiesslich R. Confocal laser endomicroscopy: technical status and current indications. Endoscopy. 2006; 38 1275-1283
275 Just T, Stave J, Boltze C, Wree A, Kramp B, Guthoff R F, Pau H W. Laser scanning microscopy of the human larynx mucosa: a preliminary, ex vivo study. Laryngoscope. 2006; 116 1136-1141
276 Harris A T. Spectral mapping tools from the earth sciences applied to spectral microscopy data. Cytometry Part A. 2006; 69A 872-879
277 Farkas D L, Du C, Fisher G W, Lau C, Niu W, Wachman E S, Levenson R M. Non-invasive image acquisition and advanced processing in optical bioimaging. Comput Med Imaging Graphics. 1998; 22 89-102
278 Yang P, Farkas D L, Kirkwood J M, Abernethy J L, Edington HD, Becker D. Macroscopic spectral imaging and gene expression analysis of the early stages of melanoma. Mol Med. 1999; 5 785-794
279 Farkas D L, Becker D. Applications of spectral imaging: detection and analysis of human melanoma and its precursors. Pigment Cell Res. 2001; 14 2-8
280 McMurdy J W, Jay G D, Suner S, Trespalacios F M, Crawford G P. Diffuse reflectance spectra of the palpebral conjunctiva and its utility as a noninvasive indicator of total hemoglobin. J Biomed Opt. 2006; 11 014 019
281 Ecker R C, de Martin R, Steiner G E, Schmid J A. Application of spectral imaging microscopy in cytomics and fluorescence resonance energy transfer (FRET) analysis. Cytometry Part A. 2004; 59A 172-181
282 Chung A, Wachsmann-Hogiu S, Zhao T, Xiong Y, Joseph A, Farkas D L. Advanced optical imaging requiring no contrast agents - a new armamentarium for medicine and surgery. Current Surg. 2005; 62 365-370
283 Müller M G, Valdez T A, Georgakoudi I. et al . Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma. Cancer. 2003; 97 1681-1692
284 Chung A, Karlan S, Lindsley E, Wachsmann-Hogiu S, Farkas D L. In vivo cytometry: a spectrum of possibilities. Cytometry Part A. 2006; 69A 142-146
285 Lindsley E, Wachman E S, Farkas D L. The hyperspectral imaging endoscope: a new tool for in vivo cancer detection. Prog Biomed Opt Imaging. 2004; 5 75-82
286 Adams C L, Kobets N, Meiklejohn G R, Millington O R, Grierson A M, Rush C M, Smith K M, Garside P. Tracking lymphocytes in vivo. Arch Immunol Ther Exp. 2004; 52 173-187
287 Boutrus S, Greiner C, Hwu D, Chan M, Kuperwaser C, Lin C P, Georgakoudi I. Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells. J Biomed Opt. 2007; 12 020 507
288 Novak J, Puoris’haag M. Two-color, doulbe-slit in vivo flow cytometer. Opt Lett. 2007; 32 2993-2995
289 Zharov V P, Galanzha E I, Tuchin V V. In vivo photothermal flow cytometry: imaging and detection of individual cells in blood and lymph flow. J Cell Biochem. 2006; 97 916-932
290 Zharov V P, Galanzha E I, Shashkov E V, Khlebtsov N G, Tuchin V V. In vivo photoacustic flow cytometry for monitoring of circulating single cancer cells and contrast agents. Opt Lett. 2006; 31 3623-3625
291 He W, Wang H, Hartmann L C, Cheng J X, Low P S. In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry. Proc Natl Acad Sci USA. 2007; 104 11 760-11 765
292 Boissonnas A, Fetler L, Zeelenberg I S, Hugues S, Amigorena S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med. 2007; 204 345-356
293 Wessels J T, Busse A C, Mahrt J, Dullin C, Grabbe E, Mueller G A. In vivo imaging in experimental preclinical tumor research - a review. Cytometry Part A. 2007; 71A 542-549
294 Levenson R M, Mansfield J R. Multispectral imaging in biology and medicine: slices of life. Cytometry Part A. 2006; 69A 748-758
295 Shcherbo D, Merzlyak E M, Chepurnykh T V. et al . Bright far-red fluorescent protein for whole-body imaging. Nature Methods. 2007; 4 741-746
296 Sahai E. Illuminating the metastatic process. Nature Rev Cancer. 2007; 7 737-749
297 Kim S, Lim Y T, Soltesz E G. et al . Near-infrared fluorescence type II quantum dots for sentinel lymph node mapping. Nature Biotech. 2004; 22 93-97
298 Gao X, Cui Y, Levenson R M, Chung L WK, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nature Biotech. 2004; 22 969-976

PD Dr. Andreas O. H. Gerstner

Klinik und Poliklinik für Hals-Nasen-Ohren-Heilkunde/Chirurgie, Universitätsklinikum Bonn

Sigmund-Freud-Straße 25
53105 Bonn

eMail: gerstaoh@web.de