Head-and-neck squamous cell carcinoma risk in smokers: no association detected between phenotype and AHR, CYP1A1, CYP1A2, or CYP1B1 genotype.

BACKGROUND: Head-and-neck squamous cell carcinoma (HNSCC) differs between smokers and nonsmokers in etiology and clinical presentation. Because of demonstrated unequivocal involvement in smoking-induced cancer in laboratory animals, four candidate genes--AHR, CYP1A1, CYP1A2, and CYP1B1--were selected for a clinical genotype-phenotype association study of HNSCC risk in smokers. Thirty-six single-nucleotide variants (mostly tag-SNPs) within and near these four genes [16 (AHR), 4 (CYP1A1), 4 (CYP1A2), and 12 (CYP1B1)] were chosen. METHODS: Extreme discordant phenotype (EDP) method of analysis was used to increase statistical power. HNSCC patients--having smoked 1-40 cigarette pack-years--represented the "highly-sensitive" (HS) population; heavy smokers having smoked ≥80 cigarette-pack-years without any type of cancer comprised the "highly-resistant" (HR) group. The vast majority of smokers were intermediate and discarded from consideration. Statistical tests were performed on N = 112 HS and N = 99 HR DNA samples from whole blood. CONCLUSIONS: Among the four genes and flanking regions--one haploblock, ACTTGATC in the 5' portion of CYP1B1, retained statistical significance after 100,000 permutations (P = 0.0042); among our study population, this haploblock was found in 36.4% of African-American, but only 1.49% of Caucasian, HNSCC chromosomes. Interestingly, in the 1000 Genomes Project database, frequency of this haplotype (in 1322 African and 1006 Caucasian chromosomes) is 0.356 and 0.003, respectively. This study represents an excellent example of "spurious association by population stratification". Considering the cohort size, we therefore conclude that the variant alleles chosen for these four genes, alone or in combinations, are not statistically significantly associated with risk of cigarette-smoking-induced HNSCC.

Perineural extension to the skull base from early cutaneous malignancies of the midface.

OBJECTIVE: To document the clinical progression of four patients with a past history of complete removal of early midface cutaneous malignancies that presented years later with isolated recurrence along the distribution of the infraorbital nerve, and to discuss the diagnostic role of early imaging to identify perineural invasion. STUDY DESIGN: The study is a retrospective chart review, review of radiographic findings, and review of the literature. RESULTS: The authors report four cases of isolated perineural invasion along the infraorbital nerve resulting from previously excised cutaneous malignancies. CONCLUSIONS: Pain followed by anesthesia in the distribution of second division of the trigeminal nerve should alert the practitioner about possible perineural recurrence that may require imaging and open exploration to establish the diagnosis.

A multidisciplinary approach to carotid paragangliomas.

The surgical management of carotid paragangliomas can be problematic. A multidisciplinary approach was used to include vascular surgery, otolaryngology, and neuroradiology to treat these patients over 9 years. From January 1992 to July 2001, a multidisciplinary team evaluated patients with carotid paragangliomas. Analyzed patient data included age, gender, diagnostic evaluation, tumor size, preoperative tumor embolization, operative exposure, need for extracranial arterial sacrifice/reconstruction, postoperative morbidity including cranial nerve dysfunction, and long-term follow-up. Twenty-five carotid paragangliomas in 20 patients underwent multidisciplinary evaluation and management. Average age was 51 years (range, 28-83 years), and 52% were male. Diagnostic evaluation included computed tomography in 76%, magnetic resonance imaging/magnetic resonance angiography in 52%, catheter angiography in 60%, and duplex ultrasonography in 16%. An extended neck exposure was required in 11 cases (44%), mandibulotomy was used once (4%), and mandibular subluxation was never required. The external carotid artery (ECA) was sacrificed in 8 cases (32%). The carotid bifurcation was resected in 1 patient (4%) requiring interposition reconstruction of the internal carotid artery. Preoperative tumor embolization was performed for 13 tumors (52%). Operative blood loss for patients undergoing preoperative embolization (Group I) was comparable to the nonembolized group (group II): group I lost 365 +/-180 mL versus 360 +/- 101 mL for group II (P = .48). This occurred despite larger tumors (group I - 4.2 cm versus group II - 2.1 cm, P = .03) and a higher mean Shamblin class (group I - 2.5 versus group II - 1.45, P = .001) for group I. There were no perioperative mortalities. Transient cranial nerve dysfunction occurred in 13 CBTs (52%), 2 (8%) of which remained present after 4 months. Patients with carotid paragangliomas benefit from a multidisciplinary team approach. Neuroradiology has been used for selective preoperative embolization, which has decreased estimated blood loss during excision of larger complex tumors. A combined surgical team of otolaryngology and vascular surgery provides for exposure of the distal internal carotid artery as high as the skull base, limited permanent cranial nerve dysfunction, and selective early division and excision of the external carotid artery for complete tumor resection.

A comparison of treatments of squamous cell carcinoma of the base of tongue: surgical resection combined with external radiation therapy, external radiation therapy alone, and external radiation therapy combined with interstitial radiation.

PURPOSE: The outcomes of patients treated at a single institution over a specific time frame using three different therapeutic approaches for cancer of the base of tongue were reviewed. METHODS AND MATERIALS: Between 1992 and 1998, 53 patients were treated with curative intent for base of tongue cancer. Seventeen patients underwent surgical resection with postoperative radiation therapy, 16 patients received definitive external radiation therapy only, and 20 patients were treated with external and interstitial radiation, with neck dissection in 16 of those patients. Local control, survival, and functional status were assessed with each approach. RESULTS: The 5-year actuarial local control and survival for the surgically treated patients were 74% and 44%, respectively. The patients treated with external radiation therapy alone had local control of 28% and 5-year survival of 24%. The patients treated with external and interstitial radiation with neck dissection as indicated had 5-year actuarial local control of 87% and survival of 33%. Survival was not statistically different between the three treatment approaches (p=0.0995) but local control was worse in the definitive external radiation group (p < 0.0001). Speech and swallowing function among the long-term survivors was superior in the definitively irradiated patients compared with the operated patients. CONCLUSION: In this retrospective analysis, survival and local control was lowest in the patients treated with external radiation alone, however, patient selection likely played an important role. Local control was far better with surgical treatment and with external combined with interstitial radiation but survival remains less than 50% with each approach. Surgical treatment was superior for patients with T4 disease. Functional status was higher in the long-term survivors treated nonsurgically.

Continuous laryngeal nerve integrity monitoring during thyroidectomy: does it reduce risk of injury?

OBJECTIVE: To determine if continuous laryngeal nerve integrity monitoring (NIM) during thyroidectomy is associated with a decreased risk of postoperative recurrent laryngeal nerve (RLN) injury. STUDY DESIGN AND SETTING: Retrospective cohort study of 165 patients who underwent thyroidectomy at a resident teaching institution between 1999 and 2002. The control group had 120 nerves at risk (NAR) whereas the NIM group consisted of 116 NAR. Primary outcome measures included postoperative RLN paralysis, paresis, and total injury rates. RESULTS: RLN paralysis occurred in 2.54% NAR in the control group and 0.86% in the NIM group [relative risk (RR) = 0.34, 95% confidence interval (CI95) = 0.04-3.27, P = 0.62]. Temporary RLN paresis occurred in 4.24% NAR in the control group and 3.45% in the NIM group (RR = 0.9, CI95 = 0.23-3.55, P = 0.89). Total RLN injury occurred in 6.78% NAR in the control group and 4.31% in the NIM group (RR = 0.66, CI95 = 0.21-2.09, P = 0.48). When compared to all other NAR, advanced T-stage malignancy was associated with a significantly increased risk of RLN paresis (T4 RR = 9.0, CI95 = 2.56-31.67, P = 0.0006; T3+T4 RR = 7.5, CI95 = 2.17-25.86, P = 0.0001) but not paralysis. NIM did not significantly reduce the risk of RLN paresis in the advanced T-stage subset (T3+T4 RR = 0.36, CI95 = 0.04-3.0, P = 0.59). CONCLUSION: There were no statistically significant differences in RLN paralysis, paresis, or total injury rates between control and NIM groups, even in subsets with advanced T-stage and increased baseline risk. Advanced T-stage is a significant predictor of RLN paresis in this cohort.

Recurrent advanced (T3 or T4) head and neck squamous cell carcinoma: is salvage possible?

BACKGROUND: Salvage surgery is often the only curative option for recurrent cancer. In patients whose initial tumor is stage T3 or T4, the primary therapy often makes salvage even more difficult. We therefore analyzed the outcome in patients who were originally treated for T3 or T4 squamous cell carcinoma of the oral cavity, larynx, oropharynx, or hypopharynx and who then had a recurrence and chose to undergo further therapy for cure. PATIENTS AND METHODS: From 1980 to 2000, a total of 940 patients were treated for stage T3 or T4 cancer. Forty-eight patients underwent salvage therapy for recurrence: 24 for primary site recurrence, 20 for regional recurrence, and 4 for locoregional recurrence. RESULTS: The mean time to recurrence was 14.0 months, and the mean survival time was 26.2 months. Among the 28 patients treated for primary site recurrence, the mean time to rerecurrence was 12.6 months, and the mean survival time was 27.3 months. Only 5 of the 28 patients had prolonged survival. The stage of the recurrent disease did not influence outcome. Among the 20 patients treated for neck recurrence, the mean time to recurrence was 14.0 months, and the mean survival time was 25.0 months. Six of the 20 patients had prolonged survival, but none had a recurrence in a previously dissected and irradiated neck. CONCLUSIONS: These results show the limited potential for survival in patients who have a recurrence after treatment for advanced primary site head and neck cancer. Patients who have not undergone all modalities of therapy have the potential for salvage, but even then the chances are limited. Given the morbidity of salvage therapy, and the limited chance for cure, physicians must cautiously counsel patients who are contemplating treatment of recurrent cancer after therapy for advanced disease.

Microsatellite instability as a predictor of survival in head and neck cancer -- is there a link with colon cancer?

OBJECTIVE: A reliable genetic marker to predict outcome for head and neck cancer is needed. In colon cancer, microsatellite instability (MSI) predicts response to therapy and improved prognosis. Colon cancer patients with MSI have a 60% improvement in survival as compared to patients without MSI. To assess whether MSI is a predictor of improved prognosis in head and neck cancer we used our tumor registry to find 8 patients treated between 1995 and 1998 with head and neck squamous cell carcinoma and either a history of colon cancer or a parent who had colon cancer. As a control, 15 T(2) or T(3) oral cavity cancers were used. METHODS: The tumor specimens were obtained and laser capture microdissected for analysis using the following microsatellite markers: BAT25, BAT26, BAT40, D1S2883, D2S123, D3S1611, D5S346, D7S501 and D8S25. RESULTS: All 8 patients with head and neck cancer and a colon cancer history exhibited MSI or loss of heterozygosity (LOH) at 1 or more of the markers tested. Three patients had 2 abnormal markers, 1 patient had 3 abnormal markers and 1 had 7 abnormal markers. Only 1 of the patients with a colon cancer history, all of whom had MSI, developed recurrent head and neck cancer. Of the 15 control patients, 5 had MSI or LOH and 1 had MSI or LOH at 2 markers. Three of the 5 patients with MSI or LOH had a recurrence; hence MSI and LOH at these markers were uncommon, and there was no relation between MSI and outcome in patients without a history of colon cancer. CONCLUSIONS: These results support a possible alternative mode of carcinogenesis in patients with head and neck cancer and a history of colon cancer and, most significantly, that these cancers are a subgroup of head and neck cancer that may have a better prognosis.

Radiation therapy for recurrent orbital hemangioma.

BACKGROUND: Surgical resection and corticosteroid therapy have traditionally been the preferred methods of treatment for orbital hemangioma. Radiation therapy is not usually indicated because of the potential for ocular complications. With modern radiation techniques, however, patients may experience substantial clinical improvement without significant radiation-induced morbidity. METHODS: A case of unresectable, recurrent orbital hemangioma is described. The clinical presentation, management protocol using radiation therapy, and 5-year follow-up are reviewed. RESULTS: The patient was initially seen with left orbital pain, diplopia, proptosis, and conjunctival edema caused by a recurrent left orbital hemangioma after failed previous surgery. CT scan and angiogram revealed a large, irregular, multilocular mass in the left orbit consistent with hemangioma. The patient was treated with a total of 2000 cGy in 10 treatments. Five-year follow-up revealed a stable, regressed hemangioma with no radiation complications. CONCLUSIONS: Radiation therapy may be used if appropriately indicated for function-threatening orbital hemangioma.

Alloantigen gene therapy for head and neck cancer: evaluation of animal models.

BACKGROUND: Human trials of alloantigen gene therapy, using the class I major histocompatibility complex (MHC) HLA-B7, have demonstrated the potential efficacy of this treatment for head and neck cancer. Its mechanism remains unclear. An immune-competent mouse model of MHC gene therapy to test factors potentially important to the tumor response is needed. METHODS: Two cell lines were used, B4B8 cells that grow in Balb/c mice and SCC-VII cells that grow in C3H mice. The mouse MHC H2-K(b) was used as the therapeutic gene, because it is an alloantigen to both mice strains. Plasmids that encode the H2-K(b) cDNA were prepared, and the cell lines were transfected. Mice were injected subcutaneously with naive cells to determine the tumor kinetics and serve as controls. Mice were injected with H2-K(b) transfected cells and tumor growth was compared with controls. Mice that did not grow tumor were rechallenged with naive cells to assess for tumor immunity. Mice were injected with transfected and naive cells admixed to determine whether the concentration of the alloantigen is important. RESULTS: B4B8 tumors grew slowly, whereas SCC-VII tumors grew rapidly. Transfection with H2-K(b) plasmid prevented or inhibited tumor growth of both the B4B8 and SCC-VII tumors. This growth inhibition was independent of the number of cells injected. In the mice that did not grow tumor, tumor immunity was demonstrated after challenge with naive cells in both models. There was no relationship between induction of immunity and the timing of the challenge or initial cell quantity. The mice injected with a mixture of naive and transfected cells grew tumor, although growth was delayed in the B4B8 model. CONCLUSIONS: The results demonstrate that the two mouse models can serve as a rapid and slow growing tumor model of alloantigen gene therapy. In addition, it was noted that initial tumor cell number is not a significant factor for predicting tumor response and demonstrated that in both of these models alloantigen gene therapy results in significant antitumor immunity.

Therapeutic decision making in stages III and IV head and neck squamous cell carcinoma.

BACKGROUND: The best treatment for advanced head and neck cancer remains unclear. Proponents of various therapeutic regimens continue to debate this issue with inconclusive and frequently biased data and with carefully selected patients in controlled trials to support their approach. To assess the outcome of patients in a real-world situation, we reviewed a prospectively maintained database of patients with head and neck cancer. METHODS: We reviewed data from 591 consecutive patients with stage III or IV squamous cell carcinoma treated at a university medical center from January 1, 1992, through December 31, 2000, and analyzed survival using the Kaplan-Meier method. RESULTS: Overall survival was 48%, 40%, and 33% at 2, 3, and 5 years, respectively. We found a significant death rate due to comorbid conditions. The primary tumor was treated surgically (with or without postoperative radiation) in 363 patients, with survival of 55%, 46%, and 38% at 2, 3, and 5 years, respectively. The tumor was treated primarily with radiation therapy (with or without neck dissection) in 193 patients, with survival of 40%, 33%, and 27% at 2, 3, and 5 years, respectively. Overall survival in the surgical group was better than in the radiation group (P =.005, log-rank chi 2 test). The radiation group was subcategorized into those who underwent radiation because the tumor was so advanced as to be unresectable (n = 86), because they were too unhealthy to undergo radical surgery (n = 23), and because they elected radiation therapy (n = 84). Survival in each of the radiation subgroups at 2, 3, and 5 years was 28%, 20%, and 14%, respectively, in the unresectable group; 34%, 22%, and 11%, respectively, in the unhealthy group; and 57%, 53%, and 46%, respectively, in the elective group. Thus, survival in the elective radiation subgroup exceeded that of the surgical group, although not statistically. We analyzed data regarding T and N stages, age, race, surgical margin status, postoperative radiation therapy, chemotherapy, radiation dose, and tumor site. Multivariate analysis of the surgical group and elective radiation subgroup showed that N stage and age were the strongest predictors of survival and that the method of therapy was not significant. For oropharyngeal cancer, the patients in the elective radiation subgroup did as well as the surgical group. Many patients were noncompliant with portions of therapy, with a resulting reduction in survival. CONCLUSIONS: The data demonstrate the value of analyzing a consecutive series of patients with advanced head and neck cancer. By including patients with comorbidities and those who are noncompliant, we determined a realistic expectation of patient outcomes. By including all patients, the data dramatically show the impact of age, comorbidity, and advanced stage on survival. The survival of patients who underwent elective radiation therapy in combination with neck dissection was similar to that of patients treated with primary tumor surgery. This was particularly true for oropharyngeal tumors. The site and stage-specific data are useful in counseling patients with advanced head and neck cancer regarding treatment choices.

Immunohistochemical Expression of N-ras Oncogene is a Late Event in Head and Neck Carcinomas.

This study investigated the expression of the N-ras oncogene in routinely processed tissue sections from 133 patients with squamous cell carcinoma of the head and neck (SCCHN) by immunohistochemistry using anti-N-ras monoclonal antibody. N-ras expression was present in 67 of 133 (49.6%) cases. There was a highly significant correlation between N-ras expression and clinical stage of disease (P=0.003). This study confirmed that overexpression of the N-ras oncogene is common in SCCHN and that it may be an important event in the late stage of disease.

nm23-H1 Expression in Squamous Cell Carcinoma of the Head and Neck.

Archival material from 47 patients with primary squamous cell carcinoma of the head and neck (SCCHN) was studied immunohistochemically for the presence of nm23-H1 protein. Our data indicate that nm23-H1 protein expression is a common event in SCCHN and that there is a trend toward correlation of increased expression of nm23-H1 with increasing tumor size (p = 0.072). The results also show that when adjusting for age and cause of death, there tended to be an inverse relationship between overall survival and the expression of nm23-H1 gene in the primary tumor (p = 0.088).

What has changed in the management of oropharyngeal cancer in the past twenty years?

Novas técnicas de diagnóstico que permitem delimitaçäo mais precisa do tumor primátrio e das metástases regionais, exame sob anestesia e pan-endoscopia de rotina säo essenciais no planejamento terapêutico. Lesöes precoces podem ser tratadas com sucesso tanto pela cirurgia quanto pela radioterapia . Todavia lesäo avançadas requerem combinaçäo de trtamentos agressivos, para oferecer alguma esperança de cura. Com o objetivo de melhorar a resposta terapêutica as irradiaçöes, novas alternativas, tais como hiperfracionamento e hipertermia, têm sido investigadas. Todas essas técnicas permanecem näo comprovadas e controversas. Indubitavelmente, os avanços mais importantes ocorreram no tratamento cirúrgico destes cânceres. Além disso, as técnicas de reconstruçäo tornaram-se mais sofisticadas. O uso de agentes quimioterápicos como adjuvantes a cirurgia e radioterapia continua a ser objetivo de interesse, embora näo existam evidências definitivas de que possa influenciar os resultados a longo prazo. O estabelecimento de clínicas multidisciplinares foi o mais significante avanço obtido nas duas últimas décadas