• Neuroendocrine neoplasms of the larynx: diagnosis, treatment and prognosis.

• Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer.

• Supraglottic carcinoma: patterns of failure and salvage treatment after curatively intended radiotherapy in 410 consecutive patients.

• Chondrosarcoma of the larynx: a clinicopathologic study of 111 cases with a review of the literature.

• Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ

• Intralesional cidofovir therapy for laryngeal papilloma in an adult cohort.

• Human papillomavirus in larynx.

• Polymorphisms of arylamine N-acetyltransferase (NAT1 and NAT2) and larynx cancer susceptibility.

• Exclusive surgery versus postoperative radiotherapy for supraglottic cancer.

• Proliferation of myofibroblasts in the stroma of epithelial hyperplastic lesions and squamous carcinoma of the larynx.

• Tumor angiogenesis as a predictive marker for organ preservation in patients with advanced laryngeal carcinoma.

• Management of supraglottic carcinoma.

• Prognostic significance of p16INK4a alterations and 9p21 loss of heterozygosity in locally advanced laryngeal squamous cell carcinoma.

• Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by

• Arterial baroreflex and peripheral chemoreflex function after radiotherapy for laryngeal or pharyngeal cancer.

• Partial laryngectomy to treat early glottic cancer after failure of radiation therapy.

• Current concepts in imaging of laryngeal and hypopharyngeal cancer.

• Factors predictive of poor functional outcome after chemoradiation for advanced laryngeal cancer.

• The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk.

1
UI - 12021501
AU - Ferlito A; Shaha AR; Rinaldo A
TI - Neuroendocrine neoplasms of the larynx: diagnosis, treatment and prognosis.
SO - ORL J Otorhinolaryngol Relat Spec 2002 Mar-Apr;64(2):108-13
AD - Department of Otolaryngology-Head and Neck Surgery, University of Udine, Italy. a.ferlito@dsc.uniud.it
The authors discuss the terminology, classification, diagnosis, treatment and prognosis of neuroendocrine neoplasms of the larynx. Copyright 2002 S. Karger AG, Basel

2
UI - 12076435
AU - Dey P; Arnold D; Wight R; MacKenzie K; Kelly C; Wilson J
TI - Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer.
SO - Cochrane Database Syst Rev 2002;(2):CD002027
AD - Centre for Cancer Epidemiology, University of Manchester, Kinnaird Road, Withington, Manchester, UK, M20 4QL. paola.dey@cce.man.ac.uk
BACKGROUND: Radiotherapy, open surgery and endolaryngeal excision (with or without laser) are all accepted modalities of treatment for early stage glottic cancer. Case series suggest that they confer similar survival advantage. Opinions on optimal therapy vary across disciplines and between countries. OBJECTIVES: To compare the effectiveness of open surgery, endolaryngeal excision (with or without laser) and radiotherapy in the management of early glottic laryngeal cancer SEARCH STRATEGY: Register. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing open surgery, endolaryngeal resection and/or radiotherapy DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed RCTs identified from the electronic searches for eligibility and methodological quality. All authors of the review discussed the results of these assessments. MAIN RESULTS: Only one RCT was identified which compared open surgery and radiotherapy among a substantial number of patients with early glottic laryngeal cancer. REVIEWER'S CONCLUSIONS: There is currently insufficient evidence to guide management decisions on the most effective treatment. Interpretation of the only large scale RCT comparing open surgery and radiotherapy in patients with early glottic cancer is limited because of concerns about the adequacy of treatment regimens and deficiencies in the reporting of the study design and analysis. Endolaryngeal resection of early glottic tumours is becoming more common and a well designed multicentre RCT is warranted.

3
UI - 12095562
AU - Johansen LV; Grau C; Overgaard J
TI - Supraglottic carcinoma: patterns of failure and salvage treatment after curatively intended radiotherapy in 410 consecutive patients.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):948-58
AD - Department of Experimental Clinical Oncology, Danish Cancer Society, Aarhus University Hospital, Aarhus, Denmark. larsvendelbo@dadlnet.dk
PURPOSE: In a series of consecutive patients with squamous cell carcinoma of the supraglottic larynx, in which almost all were treated by primary radiotherapy, the study describes the path from diagnosis to cure or death, and evaluates the patterns of failure and the treatment of recurrences. METHODS AND MATERIALS: The analysis included 410 patients, 104 females and 306 males, treated between 1963 and 1991. Most patients were in Stage I (33%), and the remaining were in Stage II (18%), III (23%), and IV (26%). Primary intended curative treatment was delivered in 398 (radiotherapy, 394; surgery, 4) of 410 cases (98%). RESULTS: Initial radical treatment resulted in 173 cured patients and 225 patients with a recurrence. Curatively intended salvage could be applied in 158 patients: surgery in 154 patients (74 cured) and radiotherapy in 4 (none cured). Overall, 247 patients (60%) obtained tumor control, 179 (44%) without a laryngectomy. Sixty-three patients had a total laryngectomy, and five had a partial laryngectomy. The 5-year locoregional tumor control, disease-specific survival, and overall survival rates were 43%, 61%, and 47%, respectively. With a follow-up of 20 years posttreatment, 91 new primary malignant tumors were detected. CONCLUSIONS: Radiotherapy is effective in the treatment of supraglottic laryngeal carcinoma, and the patients have a relatively good prognosis. Many patients retained their larynx intact. Recurrence after primary radiotherapy can be treated by surgery, with a high success rate even in advanced stages. Development of second primary cancer is a growing problem.

4
UI - 12131151
AU - Thompson LD; Gannon FH
TI - Chondrosarcoma of the larynx: a clinicopathologic study of 111 cases with a review of the literature.
SO - Am J Surg Pathol 2002 Jul;26(7):836-51
AD - Department of Endocrine and Otorhinolaryngic-Head & Neck Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA. thompson@afip.osd.mil
Chondrosarcomas of the larynx are rare tumors accounting for about 0.5% of all laryngeal primary tumors. A total of 111 laryngeal chondrosarcoma cases, diagnosed between 1970 and 1997, were retrieved from the Otorhinolaryngic-Head & Neck Tumor Registry of the Armed Forces Institute of Pathology. There was a 3.6:1 male/female ratio of patients 25-91 years of age (mean, 64.4 years). Patients presented most frequently with hoarseness (n = 72 patients) present for a mean of 28.2 months. The majority of tumors involved the cricoid cartilage (n = 77) with a mean size of 3.5 cm. All tumors were invasive and malignant by radiology and/or histology (into bone within the ossified laryngeal cartilages in 52 tumors). Most tumors were low-grade lesions: grade 1 (n = 51), grade 2 (n = 54); there were six grade 3 tumors. An associated benign chondroma with (n = 41 tumors) or without ischemia (n = 24 tumors) was noted. All patients had surgery and five had radiation therapy. Wide excision or voice-sparing surgery was used in 73 patients, whereas 37 patients had a laryngectomy. Recurrences occurred in 20 (18%) patients, 10 of whom underwent salvage laryngectomy. At the last follow-up, 102 patients had no evidence of disease (alive or dead, mean 11.2 years) and five patients had evidence of disease (alive, one patient, 6.5 years; dead, four patients, mean 6.4 years). The six patients with high-grade chondrosarcoma were all without disease at the last follow-up (mean, 15.1 years). There was no difference in clinical outcome based on grade (p = 0.210), location (p = 0.078), or treatment (p = 0.607) but was worse for patients with a myxoid-type chondrosarcoma (p = 0.044). Primary laryngeal chondrosarcomas are typically low- to moderate-grade lesions involving the cricoid cartilage, frequently associated with a chondroma. They usually portend an excellent overall long-term prognosis with initial conservative voice-sparing surgery.

5
UI - 12150516
AU - Trask DK; Wolf GT; Bradford CR; Fisher SG; Devaney K; Johnson M;
TI - Singleton T; Wicha M Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation.
SO - Laryngoscope 2002 Apr;112(4):638-44
AD - Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, USA.
OBJECTIVES/HYPOTHESIS: Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy. STUDY DESIGN: Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome. METHODS: To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X(L), and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival. RESULTS: The Bcl-2 protein was expressed at high levels in only 15% of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bcl-X(L) (74%). Reduced expression of Bcl-X(L) was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation. CONCLUSIONS: The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X(L). Prospective studies of larger numbers of patients are under way to determine whether Bcl-X(L) expression will be a useful marker predicting larynx preservation.

6
UI - 12150526
AU - Bielamowicz S; Villagomez V; Stager SV; Wilson WR
TI - Intralesional cidofovir therapy for laryngeal papilloma in an adult cohort.
SO - Laryngoscope 2002 Apr;112(4):696-9
AD - Division of Otolaryngology-Head and Neck Surgery, George Washington University, Washington, DC 20037, USA. sursxb@gwumc.edu
OBJECTIVES: To confirm the safety and efficacy of intralesional cidofovir in the management of laryngeal papilloma and to identify variables that correlate with number of injections needed to achieve remission. STUDY DESIGN: An open-trial prospective evaluation of the efficacy of intralesional cidofovir in subjects with laryngeal papilloma. METHODS: Fourteen adult subjects with biopsy-proven laryngeal papilloma were enrolled in a treatment study of intralesional cidofovir. Preprotocol disease duration ranged from 1 to 30 years with a mean duration of 7 years. Subjects received monthly injections of cidofovir with a maximum dose of 37.5 mg per injection in 6 cc saline (6.25 mg/mL). Injections were repeated until no papilloma could be visually identified during an intraoperative evaluation. After disease remission was achieved, subjects received an additional injection. All injections occurred during suspension microlaryngoscopy. RESULTS: All subjects have achieved disease remission using an injection-only treatment protocol. No additional laryngeal scarring or systemic toxicity was identified. On average, 6 injections were required to achieve remission. Preprotocol disease duration and anatomical staging correlated positively with the number of injections required for disease remission. CONCLUSIONS: Intralesional injection of cidofovir is an excellent treatment option with limited local and systemic toxicities. The injection therapy regimen requires perseverance from both patient and surgeon. Remission of disease can be achieved in adults with laryngeal papilloma.

7
UI - 12150527
AU - Aaltonen LM; Rihkanen H; Vaheri A
TI - Human papillomavirus in larynx.
SO - Laryngoscope 2002 Apr;112(4):700-7
AD - Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Central Hospital, Finland. Leena-Maija.Aaltonen@helsinki.fi
OBJECTIVES: The core of the present clinical and basic research knowledge of laryngeal human papillomavirus (HPV) infection is described. STUDY DESIGN: Review. METHODS: A computer-aided search of MEDLINE database supplemented by hand searches of key journals was conducted. RESULTS: One of the tumor-promoting factors in the larynx is the HPV found both in normal laryngeal epithelium and in laryngeal tumors. The most important manifestation of laryngeal HPV infection is laryngeal papillomatosis, a rare disease caused by HPV types 6 and 11. In laryngeal carcinogenesis, the role of HPV remains uncertain. The means of transmission of HPV are partly unknown, and the course of laryngeal HPV infection is unpredictable and variable. Treatment of laryngeal papillomatosis is based on surgery, especially on CO2 laser and shaver. Alpha-interferon is the drug of choice in patients whose response to surgery is poor. However, neither interferon nor other antiviral drugs are able to eradicate the virus from laryngeal mucosa. Little is known about immunological mechanisms involved in laryngeal HPV infection, but in defense against HPV cellular immunity is considered a more important mechanism than humoral immunity. A good experimental model of HPV infection is lacking in which the entire viral life cycle can take place. Organotypic cell cultures (collagen rafts) are useful, but the rate-limiting step in this method is the difficulties in culturing HPV-positive epithelial cells. CONCLUSIONS: Although laryngeal papillomatosis is clinically well defined, the mechanisms and treatment modalities of laryngeal HPV infection need further investigations.

8
UI - 12037388
AU - Varzim G; Monteiro E; Silva R; Pinheiro C; Lopes C
TI - Polymorphisms of arylamine N-acetyltransferase (NAT1 and NAT2) and larynx cancer susceptibility.
SO - ORL J Otorhinolaryngol Relat Spec 2002 May-Jun;64(3):206-12
AD - Molecular Oncology Unit, Portuguese Institute of Oncology, Porto, Portugal. gvarzim@hotmail.com
Our aim was to examine the role of NAT1 and NAT2 polymorphisms in human larynx cancer susceptibility. Genotype tests for NAT1 alleles *4, *10 and *11, and NAT2 alleles *4, *5, *6A and *7A, using PCR-RFLP analysis, were performed in 172 healthy Portuguese individuals and 88 patients with squamous cell carcinoma of the larynx. NAT1 and NAT2 genotype frequencies were correlated between patients and control groups, using the chi-square test. Odds ratios and 95% confidence intervals were calculated from 2 x 2 tables with the Fisher's exact model. The statistical analysis of NAT1 and NAT2 genotype frequencies revealed a significant difference of NAT1*10/*11 (p = 0.038) and NAT2*5/*7 (p = 0.003) genotype distribution between cases and controls. We also observed differences concerning tumor location, since NAT1*10/*11 genotype frequency was significantly different when comparing normal control individuals with the glottic subgroup of patients. The present data suggest that NAT1 and NAT2 polymorphisms may be correlated with an increased risk of larynx cancer. Copyright 2002 S. Karger AG, Basel

9
UI - 12037389
AU - Esposito E; Motta S; Motta G
TI - Exclusive surgery versus postoperative radiotherapy for supraglottic cancer.
SO - ORL J Otorhinolaryngol Relat Spec 2002 May-Jun;64(3):213-8
AD - ENT Department, Ospedale 'Santa Maria della Pieta', Nola, Rome.
AIM OF THE STUDY: To verify the effectiveness of prophylactic postoperative radiotherapy for supraglottic cancer. PATIENTS AND METHODS: 97 patients underwent supraglottic horizontal laryngectomy with bilateral neck dissection: 35 patients (group A) received postoperative radiotherapy (60-70 Gy, 2 Gy fractions daily); 62 patients (group B) received only surgery. RESULTS: Overall 5-year actuarial survival and corrected actuarial survival rates were 74 and 90% in group A and 61 and 80% in group B (p = 0.2 and 0.4, respectively). As for tumor extent, no significant differences were observed between the two groups. In N0 patients overall actuarial survival rate was significantly higher in group A as compared to group B (p = 0.01); most likely this difference was due to errors in clinical staging for the presence of reactive lymphadenitis and micrometastases. CONCLUSIONS: The present study did not document the effectiveness of postoperative radiotherapy. Radiation therapy should be avoided in those patients in whom surgery was proven to be curative while it could be considered in combination with surgery when the resection margins are dubious and/or inadequate. Copyright 2002 S. Karger AG, Basel

10
UI - 12138247
AU - Zidar N; Gale N; Kambic V; Fischinger J
TI - Proliferation of myofibroblasts in the stroma of epithelial hyperplastic lesions and squamous carcinoma of the larynx.
SO - Oncology 2002;62(4):381-5
AD - Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia. nina.zidar@mf.uni-lj.si
OBJECTIVES: The immunohistochemical phenotype, distribution and significance of proliferation of myofibroblasts in laryngeal epithelial hyperplastic lesions (EHL) and squamous carcinoma (SC) were analyzed. METHODS: Samples of 42 resected larynxes and 40 laryngeal biopsies of EHL and SC were included. Immunohistochemistry was performed using antibodies against vimentin, alpha-smooth muscle actin (SMA), desmin and leukocyte common antigen. RESULTS: Myofibroblasts were vimentin- and SMA-positive, and were found exclusively in SC, indicating that invasion beyond the basement membrane is necessary to evoke a myofibroblastic stromal reaction. We observed two patterns of stromal reaction in SC: one was characterized by a marked proliferation of myofibroblasts and desmoplasia, with scarce lymphocytic infiltration; this pattern tended to be associated with well- or moderately differentiated SC. The other was characterized by few myofibroblasts, weak desmoplasia, and dense lymphocytic infiltration; the latter pattern tended to be associated with moderately or poorly differentiated SC. The degree of myofibroblast proliferation was inversely related to the density of lymphocytic infiltration. Antibodies against SMA also stained stromal blood vessels, demonstrating a gradual increase of vessel density as the grade of EHL increased. CONCLUSIONS: Immunohistochemical analysis of myofibroblasts provides useful information on the phenotypic characteristics of the stroma in laryngeal EHL and SC, and can serve as an additional marker of invasion. Copyright 2002 S. Karger AG, Basel

11
UI - 12150616
AU - Teknos TN; Cox C; Barrios MA; Chepeha DB; Bradford CR; Fisher SG; Wolf
TI - GT Tumor angiogenesis as a predictive marker for organ preservation in patients with advanced laryngeal carcinoma.
SO - Laryngoscope 2002 May;112(5):844-51
AD - University of Michigan Health System, Department of Otolaryngology-Head and Neck Surgery, Ann Arbor 48109-0312, USA. teknos@umich.edu
BACKGROUND: The purpose of this study was to retrospectively investigate tumor angiogenesis as a predictive marker for response to neoadjuvant chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma. METHODS: A total of 332 patients with stage III (188 patients) or stage IV (144 patients) squamous cell carcinoma of the larynx were entered in the prospective trial conducted by the Department of Veteran Affairs Laryngeal Cancer Study Group. Of this patient population, 20 pretreatment biopsy specimens were available from the chemotherapy arm for immunohistochemical analysis of Factor VIII expression. Two blinded investigators determined microvessel density in each patient by manual inspection of 10 high-power (400 x) fields (HPF). RESULTS: The patients who had a partial response (>50% decrease in tumor volume) or complete response to chemotherapy had a mean value of 20.90 (+/- 8.09 standard deviation [SD]) blood vessels per HPF. Those who did not respond to chemotherapy and thus required a total laryngectomy had a mean value of 32.99 (+/- 10.10 SD) vessels per HPF. The difference of the means was statistically significant using a two-tailed t test (P < .0085). Kaplan-Meier survival curve analysis also revealed that patients with vessel counts above the mean tended to have poorer survival than those below the mean regardless of treatment selection. The most-vascular tumors, those greater than 1 SD above the mean, had a statistically significant difference in survival and laryngeal preservation (P = .0345). CONCLUSIONS: These results indicate that tumor angiogenesis, as measured by number of vessels per HPF, was associated with decreased responsiveness to chemotherapy and radiation for larynx preservation. The most-vascular tumors also were associated with poorer survival than those with lesser degrees of angiogenesis.

12
UI - 12095543
AU - Mendenhall WM; Hinerman RW; Morris CG; Amdur RJ
TI - Management of supraglottic carcinoma.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):793-4

13
UI - 12124774
AU - Bazan V; Zanna I; Migliavacca M; Sanz-Casla MT; Maestro ML; Corsale S;
TI - Macaluso M; Dardanoni G; Restivo S; Quintela PL; Bernaldez R; Salerno S; Morello V; Tomasino RM; Gebbia N; Russo A Prognostic significance of p16INK4a alterations and 9p21 loss of heterozygosity in locally advanced laryngeal squamous cell carcinoma.
SO - J Cell Physiol 2002 Sep;192(3):286-93
AD - Section of Molecular Oncology, University of Palermo, Italy.
The p16INK4a gene, localized within chromosome 9p21, has been identified as a cyclin-dependent kinase inhibitor and may negatively regulate the cell cycle acting as a tumor suppressor. Genetic alterations involving the 9p21 region are common in human cancers. A consecutive series of 64 untreated patients (median of follow up 53 months) undergoing surgical resection for locally advanced laryngeal squamous-cell carcinomas (LSCCs) has been studied prospectively. Our purpose was to investigate p16 alterations (9p21 allelic loss, hypermethylation and point mutations) and their possible association with clinico-pathological data and flow cytometric variables (DNA-ploidy and S-phase fraction (SPF)), and to determine the possible prognostic role of this gene in these tumors. PCR-based techniques were used for investigating 9p21 loss of heterozygosity (LOH) and methylation promoter status of the p16 gene. p16 mutations were detected by PCR-SSCP (single strand conformation polymorphism) and sequencing. 9p21 LOH was detected in 16/62 (26%) informative tumors, point mutations in 5% (3/64) and hypermethylation in 9% (6/64) of the cases. p16 alterations were significantly associated with high SPF and DNA-aneuploidy. By univariate analysis, poor histologic differentiation, stage IV, DNA-aneuploidy and p16 point mutations proved to be significantly related to quicker relapse, whereas these same factors, and in addition high SPF, 9p21 LOH and any p16 alterations were significantly related to shorter overall survival. By Cox proportional hazards analysis only histologic grade (G3) and p16 point mutations were independently related to both disease relapse and death. Our study has identified p16 point mutations as important biomolecular indicators in LSCCs. Copyright 2002 Wiley-Liss, Inc.

14
UI - 12128119
AU - Rijpkema M; Kaanders JH; Joosten FB; van der Kogel AJ; Heerschap A
TI - Effects of breathing a hyperoxic hypercapnic gas mixture on blood oxygenation and vascularity of head-and-neck tumors as measured by magnetic resonance imaging.
SO - Int J Radiat Oncol Biol Phys 2002 Aug 1;53(5):1185-91
AD - Department of Radiology, University Medical Center Nijmegen, Nijmegen, The Netherlands. M.Rijpkema@rdiag.azn.nl
PURPOSE: For head-and-neck tumors, breathing a hyperoxic hypercapnic gas mixture and administration of nicotinamide has been shown to result in a significantly improved tumor response to accelerated radiotherapy (ARCON, Accelerated Radiotherapy with CarbOgen and Nicotinamide). This may be caused by improved tumor oxygenation, possibly mediated by vascular effects. In this study, both blood oxygenation and vascular effects of breathing a hyperoxic hypercapnic gas mixture (98% O2 + 2% CO2) were assessed by magnetic resonance imaging (MRI) in patients with head-and-neck tumors. METHODS AND MATERIALS: Tumor vascularity and oxygenation were investigated by dynamic gadolinium contrast-enhanced MRI and blood oxygen level dependent (BOLD) MRI, respectively. Eleven patients with primary head-and-neck tumors were each measured twice; with and without breathing the hyperoxic hypercapnic gas mixture. RESULTS: BOLD MR imaging revealed a significant increase of the MRI time constant of transverse magnetization decay (T2*) in the tumor during hypercapnic hyperoxygenation, which correlates to a decrease of the deoxyhemoglobin concentration. No changes in overall tumor vascularity were observed, as measured by the gadolinium contrast uptake rate in the tumor. CONCLUSION: Breathing a hyperoxic hypercapnic gas mixture improves tumor blood oxygenation in patients with head-and-neck tumors, which may contribute to the success of the ARCON therapy.

15
UI - 12128121
AU - Timmers HJ; Karemaker JM; Wieling W; Kaanders JH; Folgering HT; Marres
TI - HA; Lenders JW Arterial baroreflex and peripheral chemoreflex function after radiotherapy for laryngeal or pharyngeal cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Aug 1;53(5):1203-10
AD - Department of Internal Medicine, University Medical Center, Nijmegen, The Netherlands. H.Timmers@aig.azn.nl
PURPOSE: Denervation of the carotid sinus causes baroreflex and chemoreflex failure, resulting in labile hypertension and loss of hypoxic responsiveness. We investigated whether radiation therapy for laryngeal or pharyngeal cancer affects baroreflex and chemoreflex function. METHODS AND MATERIALS: Twelve patients were studied after radiation therapy for locally advanced laryngeal or pharyngeal cancer (11 male, 1 female, age: 56.0 +/- 7.9 years), 3.3 years (median; range 1.0-4.7) after radiotherapy and 15 healthy controls (11 male, 4 female, 53.4 +/- 9.2 years). We measured baroreflex sensitivity (phenylephrine), blood pressure level and variability (24-h Spacelabs and 5-h Portapres recordings), responses to cardiovascular reflex tests, and the ventilatory responses to normocapnic and hypercapnic hypoxia. RESULTS: Baroreflex sensitivity was lower in patients (9.7 +/- 7.8 ms/mm Hg) than in controls (17.5 +/- 10.3 ms/mm Hg, p = 0.011). Mean office blood pressure was significantly higher in patients (141.5 +/- 27.8/89.2 +/- 10.6 mm Hg, 63.3 +/- 12.3 bpm) than in controls (117.3 +/- 10.1/75.1 +/- 6.8 mm Hg, 61.8 +/- 10.8 bpm). Blood pressure variability was not different between groups, nor were the responses to reflex tests. The normo/hypercapnic ventilatory response to hypoxia was similar in patients (0.21 +/- 0.10/1.37 +/- 0.60 L/min/%) and controls (0.22 +/- 0.16/1.19 +/- 0.78 L/min/%). CONCLUSIONS: Radiation therapy for laryngeal or pharyngeal carcinoma does not affect chemoreflex function, but results in an attenuated baroreflex sensitivity. Clinically relevant blood pressure lability is absent however.

16
UI - 12162769
AU - Toma M; Nibu K; Nakao K; Matsuzaki M; Mochiki M; Yuge T; Terahara A;
TI - Sugasawa M Partial laryngectomy to treat early glottic cancer after failure of radiation therapy.
SO - Arch Otolaryngol Head Neck Surg 2002 Aug;128(8):909-12
AD - Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, University of Tokyo, Japan. makiko@jd5.so-net.ne.jp
OBJECTIVE: To evaluate the role of partial laryngectomy to treat glottic cancer after failure of radiation therapy. DESIGN: A 12-year retrospective outcome analysis. SETTING: University referral center. PATIENTS: A total of 19 patients who underwent partial laryngectomy to treat glottic cancer after failure of radiation therapy. RESULTS: The follow-up period in this group ranged from 31 to 144 months. After surgery, a laryngocutaneous fistula was observed in 4 cases, and flap necrosis occurred in 2, but these complications were successfully managed. Maximum phonation time after surgery ranged from 3 to 28 seconds (median phonation time, 10.2 seconds). Of these 19 patients, 3 developed local recurrence. These cases were successfully treated with total laryngectomy. A surgical margin of less than 1 mm was found to be a significant risk factor for local recurrence after partial laryngectomy. CONCLUSIONS: These results indicate that partial laryngectomy is a useful option for the treatment of irradiation failure in the treatment of stage I and stage II vocal cord carcinomas. However, careful follow-up is mandatory for patients with a small surgical margin.

17
UI - 12111057
AU - Keberle M; Kenn W; Hahn D
TI - Current concepts in imaging of laryngeal and hypopharyngeal cancer.
SO - Eur Radiol 2002 Jul;12(7):1672-83
AD - Department of Radiology, University of Wurzburg, Josef-Schneider-Strasse 2, Germany. marc.keberle@mail.uni-wuerzburg.de
In adjunct to direct laryngoscopy, CT and/or MRI are needed for an accurate staging of laryngeal and hypopharyngeal carcinomas because both cross-sectional imaging modalities are known to reliably evaluate deep tumor infiltration. Except for the clinical background, this article reviews technical aspects of CT and MRI, the pathologic appearance of laryngeal and hypopharyngeal carcinomas, and therapeutically relevant diagnostic aspects.

18
UI - 12161729
AU - Staton J; Robbins KT; Newman L; Samant S; Sebelik M; Vieira F
TI - Factors predictive of poor functional outcome after chemoradiation for advanced laryngeal cancer.
SO - Otolaryngol Head Neck Surg 2002 Jul;127(1):43-7
AD - Department of Otolaryngology-Head and Neck Surgery, University of Tennessee, Memphis, College of Medicine, USA.
OBJECTIVE: The study goal was to determine whether pretreatment parameters can be used to predict poor outcomes related to laryngeal function among survivors after organ preservation therapy for advanced laryngeal cancer. DESIGN: A retrospective analysis of patients treated in an ongoing chemoradiation trial. SETTING: Academic tertiary care referral medical center. PATIENDS AND METHODS: Among the 65 patients receiving concomitant intra-arterial cisplatin and radiation therapy for stage III and IV laryngeal cancer between 1993 and 1999, we identified 45 who were available for follow-up and were disease free 6 months after the completion of therapy. A nominal logistic regression analysis was performed to study the effect of age, gender, T and N classification, vocal cord fixation, massive cartilage destruction, and neck dissection on the likelihood of requiring a tracheostomy tube for breathing and/or a gastrostomy tube for feeding at 6 months after the completion of therapy. Main Outcome Measure: Persistent use of gastrostomy tube feedings and/or tracheostomy at 6 months after the completion of therapy. RESULTS: Sixteen patients (36%) required a feeding tube and/or a tracheostomy (tracheostomy 13, gastrostomy 13, both 10). Regression analysis of all pretreatment factors indicated vocal cord fixation as being the strongest predictor of a poor functional outcome (defined as the persistent need for a feeding tube and/or tracheostomy at 6 months after therapy). Among the 27 patients in this subset, 15 (56%) had a poor functional outcome. In contrast, only 1 (6%) of 18 patients without vocal cord fixation had poor laryngeal function. Although the history of pulmonary disease was not a significant parameter by itself, when combined with vocal cord fixation, 6 of 8 patients had a poor functional outcome. CONCLUSION: Pretreatment parameters may be used to predict a poor functional outcome after chemoradiation. Because of the high likelihood of poor function, laryngeal cancer patients seeking organ preservation therapy with chemoradiation should be cautioned if they present with a fixed vocal cord.

19
UI - 12117782
AU - Elahi A; Zheng Z; Park J; Eyring K; McCaffrey T; Lazarus P
TI - The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk.
SO - Carcinogenesis 2002 Jul;23(7):1229-34
AD - Divisions of Cancer Control and Molecular Oncology, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
The human OGG1 (hOGG1) gene encodes a DNA glycosylase that is involved in the excision repair of 8-hydroxy-2'-deoxyguanine (8-OH-dG) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in risk for orolaryngeal cancer, we screened normal orolaryngeal tissue specimens for hOGG1 expression and assessed the role of the hOGG1 Ser326Cys polymorphism in risk for orolaryngeal cancer. hOGG1 expression was determined by reverse transcription-polymerase chain reaction of total RNA from aerodigestive tract tissues, and hOGG1 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis of buccal cell DNA isolated from 169 Caucasian orolaryngeal cancer cases and 338 race-, sex- and age-matched controls. hOGG1 mRNA was detected in all aerodigestive tract tissues tested including tonsil, tongue, floor of mouth, larynx and esophagus. Significantly increased risk for orolaryngeal cancer was observed for both the hOGG1 326(Ser)/326(Cys) (odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.04-2.6) and hOGG1 326(Cys)/326(Cys) (OR = 4.1, 95% CI = 1.3-13) genotypes. Although no significant difference in risk for orolaryngeal cancer was observed for hOGG1 genotypes in never-smokers, increased risk for orolaryngeal cancer was observed for subjects with the homozygous polymorphic hOGG1 326(Cys)/326(Cys) genotype in smokers (>100 cigarettes lifetime; OR = 4.8, 95% CI = 1.3-18). Similarly, although no association was observed in never drinkers of alcohol, significantly increased risk was observed for the hOGG1 326(Cys)/326(Cys) genotype in alcohol drinkers (>1 shot/week; OR = 6.9, 95% CI = 1.6-29). These results suggest that hOGG1 may play an important role in the repair of 8-OH-dG adducts in the aerodigestive tract and that the hOGG1 Ser326Cys polymorphism plays an important role in risk for smoking- and alcohol-related orolaryngeal cancer.

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