Professional Oral Health Care at General Dental Clinic Reduces Postoperative Complications of Head and Neck Free-Flap Reconstruction Surgery.

Background: Extensive resection and free-flap reconstruction surgery has become the standard treatment for locally advanced head and neck cancer. Surgical site infection (SSI) is one of the serious complications of this treatment. This study aimed to investigate the risk factor for onset of SSI, particularly focusing on whether preoperative professional oral health care in cooperation with general dental clinics is effective in reducing the occurrence of SSI. Methods: From March 2003 to August 2011, 183 patients who underwent head and neck free-flap reconstructive surgery by the same plastic surgeon at Miyagi Cancer Center for Head and Neck Surgery were investigated retrospectively. Results: Of the 183 patients, 135 and 48 were men and women, respectively, with a mean age of 62 (range, 29-82) years. The tumor was located in the oral cavity (n = 76), hypopharynx (n = 55), oropharynx (n = 28), and others (n = 24). Clinical stages were stage I/II in 18, stage III/IV in 164 patients, and benign tumor in one patient, based on UICC classification. SSI occurred in 66 patients (36.1%). Based on multivariate analysis, professional oral health care [P = 0.0076, odds ratio (OR) = 0.39] and radiation therapy history (P = 0.0214, OR = 2.820) were shown as factors that are significantly related to SSI. Conclusion: This study identified history of radiation therapy as a significant risk factor for SSI from univariate and multivariate analysis and revealed that patients receiving preoperative professional oral health care at general dental clinics reduce the risk of SSI. Preoperative professional oral health care in cooperation with general dental clinics has been shown to reduce SSI of head and neck free-flap reconstructive surgery.

Laryngeal function-preserving operation for T4a laryngeal cancer with vocal cord paralysis - A case report.

For locally advanced laryngeal cancers, the standard treatment of choice is chemoradiotherapy if organ function needs to be conserved. Surgical treatment with larynx preservation is conducted only for limited cases. For locally advanced laryngeal cancers such as those with vocal cord fixation and/or cricoid cartilage destruction, there is no apparent standardized organ-preserving surgery keeping the essential laryngeal functions, viz. the airway, deglutition and articulation, uncompromized. Recently, our surgical team saw a patient with T4a advanced laryngeal cancer with vocal cord fixation who aspired to maintain his laryngeal function. Driven by his eagerness, we contrived novel techniques for laryngeal function preservation and performed a two-staged operation. In the first stage, extended vertical partial laryngectomy was conducted including resection of the affected thyroid, arytenoid, and cricoid cartilages, followed by local closure of the hypopharynx. Additionally, laryngeal suspension surgery and cricopharyngeal myotomy were performed in addition to suturing the epiglottis with the intact arytenoid cartilage to enhance swallowing function. In the second stage, airway reconstruction was performed using a local skin flap. As of 10 months after operation, there has been no tumor recurrence, and the reconstructed larynx has been working satisfactorily. In this report we describe an innovative operation that was especially contrived for laryngeal function preservation.

Retrospective observational study of occult cervical lymph-node metastasis in T1N0 tongue cancer.

Objective: Delayed neck metastasis is the most significant prognostic factor for early tongue cancer. The main strategies for controlling cervical lymph nodes in Japan are elective neck dissection or watchful waiting. Elective neck dissection offers significantly better survival, but adversely impacts patient quality of life; consequently, here we investigated how to identify high-risk patients warranting elective neck dissection. Methods: We retrospectively evaluated 67 patients with T1N0 oral tongue squamous cell carcinoma who underwent primary treatment in our department from April 2001 to March 2015. All the patients underwent watchful waiting alone for neck management. We investigated the rates of occult neck metastasis, prognosis and circumstances of recurrence, and associations with pathological tumor thickness, depth and muscle invasion by the primary tumor. Correlation between the thickness in pathological specimens and that at magnetic resonance imaging was additionally investigated. Results: Neck recurrence was evident in 20 patients, of which 19 developed within 1 year. Therefore, the rate of occult neck metastasis was 29.9%. Patients with muscle invasion, tumor thickness ≥2 mm or tumor depth ≥2 mm on surgical specimens were significantly more likely to develop delayed neck metastasis. Prognosis was significantly worse for patients with muscle invasion or tumor thickness ≥2 mm. Thickness using magnetic resonance imaging was well correlated with pathological thickness. Conclusions: Patients with tumors ≥2 mm in thickness or muscle invasion developed neck metastasis, suggesting that elective neck dissection may be warranted for patients with these findings. For preoperative assessment of the need for elective neck dissection, magnetic resonance imaging would be a potential modality for T1N0 tongue cancer.

Carcinoma ex pleomorphic adenoma of the parotid gland: a multi-institutional retrospective analysis in the Northern Japan Head and Neck Cancer Society.

CONCLUSION: The 3-year progression-free survival rate of non-invasive salivary duct carcinoma (SDC) or adenocarcinoma not otherwise specified (NOS) was significantly better than that of invasive SDC or adenocarcinoma NOS in Carcinoma ex pleomorphic adenoma (CXPA). The presence of invasion is an important prognostic factor for SDC and adenocarcinoma NOS in CXPA. OBJECTIVES: CXPA is a rare parotid gland malignant tumor for which therapy is not yet standardized. The purpose of this study was to review the characteristics of CXPA patients and to analyze their outcomes in the Northern Japan Head and Neck Cancer Society. METHOD: The medical records of 33 patients who had been provided initial treatment in 12 institutes of northern Japan from 2002-2011 were reviewed as a multi-institutional retrospective study. RESULTS: The 3-year overall and progression-free survival rate of all patients was 79.9% and 76.8%, respectively. Both the 3-year overall and progression-free survival rates were 87.5% for patients with non-invasive SDC or adenocarcinoma NOS. The 3-year overall and progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS were 60.4% and 30.5%, respectively. The progression-free survival rates for patients with invasive SDC or adenocarcinoma NOS was significantly poor (p < 0.05).

Late-onset dysphagia caused by severe spastic peristalsis of a free jejunal graft in a case of hypopharyngeal cancer.

Free jejunal transfer is the main technique used for reconstructing a circumferential defect caused by total pharyngo-laryngo-cervical-esophagectomy in certain cancer cases. We report a rare case of severe late-onset dysphagia caused by autonomous spastic peristalsis, which led to complete obstruction of the free jejunal route. A 70-year-old man underwent treatment for hypopharyngeal cancer involving total pharyngolaryngectomy with free jejunal transfer. After uneventful peri- and postoperative recovery, he developed sudden-onset severe dysphagia 22 months later. Gastrografin fluoroscopy revealed abnormal peristalsis and contraction of the transferred jejunum, leading to complete obstruction. Nutritional treatment, application of depressants of peristalsis, and xylocaine injection into the outer space of the jejunal mucosa all failed to alleviate the dysphagia. Surgical treatment involving a longitudinal incision of the jejunal graft, and interposing a cutaneous flap, as a fixed wall, between the incised jejunal margins to prevent obstruction was performed. After further reconstructive surgery involving using a pectoralis major musculocutaneous flap and a split-thickness skin graft to close a refractory jejunum-skin fistula, the dysphagia was permanently alleviated. To our knowledge, this is the first report of severe dysphagia caused by peristalsis of a free jejunal graft.

Clear cell carcinoma of the nasal cavity: A case report from histopathological viewpoint.

We report an extremely rare case of primary clear cell carcinoma (CCC), not otherwise specified (NOS) of the nasal cavity. An 80-year-old woman was referred to our hospital with left nasal obstruction caused by a nasal cavity tumor. The tumor was resected completely with lateral rhinotomy approach. Histopathological examination revealed CCC. CCC metastasis from renal cell carcinoma (RCC), which is at the top of differential diagnosis, was ruled out by the absence of renal tumor at computed tomography (CT). Also, immunohistochemical results of the specimen with vimentin negative and CK7 focally positive excluded the possibility of RCC metastasis. The patient is free from recurrence 1 year after the surgery, and there is no evidence of RCC. In this report histopathological characteristics, especially immunohistochemical properties of primary CCC, NOS of the nasal cavity are presented together with some clinical features of this rare tumor. Also, we refer to histopathogenesis of primary CCC of nasal cavity in relation to myoepithelial carcinoma. Histopathological discussion is further extended to include other CCC and CCC-resembling histologies to confirm the uniqueness of the present case.

Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis.

Regional lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) is a crucial event for its progression, associated with a high rate of mortality. Sialidase, a key enzyme for the regulation of cellular sialic acids through catalyzing the initial step of degradation of glycoproteins and glycolipids, has been implicated in cancer progression. To facilitate the development of novel treatments for HNSCC, we have investigated whether sialidase is involved in the progression of this cancer. We found plasma membrane-associated sialidase (NEU3) to be significantly upregulated in tumor compared to non-tumor tissues; particularly, an increase in its mRNA levels was significantly associated with lymph node metastasis. To understand the mechanisms, we analyzed the NEU3-mediated effects on the malignant phenotype using squamous carcinoma HSC-2 and SAS cells. NEU3 promoted cell motility and invasion, accompanied by the increased expression of MMP-9, whereas NEU3 silencing or the activity-null mutant did not. NEU3 enhanced phosphorylation of epidermal growth factor receptor (EGFR), and an EGFR inhibitor, AG1478, abrogated the NEU3-induced MMP9 augmentation. These findings identify NEU3 as a participant in HNSCC progression through the regulation of EGFR signaling and thus as a potential target for inhibiting EGFR-mediated tumor progression.

Effect of HMB/Arg/Gln on the prevention of radiation dermatitis in head and neck cancer patients treated with concurrent chemoradiotherapy.

OBJECTIVE: This prospective randomized Phase II study was designed to evaluate the preventive effect of an oral nutrition supplement composed of beta-hydroxy-beta-methylbutyrate, arginine and glutamine (beta-hydroxy-beta-methylbutyrate/arginine/glutamine) on radiation dermatitis in head and neck cancer patients. METHODS: Forty patients with histologically proven head and neck cancer, treated with concurrent chemoradiotherapy involving cisplatin were recruited. They were randomly assigned to the beta-hydroxy-beta-methylbutyrate/arginine/glutamine supplement treatment group (Group A) or the control group that received no supplement (Group B). The primary endpoint of this study was the percentage of patients developing ≥Grade 3 dermatitis. The secondary endpoints were the percentage of patients developing ≥Grade 2 dermatitis, and the duration of each grade of dermatitis relative to the observation period. RESULTS: The incidence of ≥Grade 3 dermatitis did not differ between the two groups. However, as secondary endpoints of this study, the incidence of ≥Grade 2 dermatitis was lower in Group A than B (62.6 vs. 94.4%; P < 0.05), and the duration of ≥Grade 1 dermatitis was shorter in Group A than B (44.8 vs. 56.7%; P < 0.01), as was the duration of ≥Grade 2 dermatitis (16.5 vs. 26.5%; P < 0.05). CONCLUSIONS: Our study indicated that beta-hydroxy-beta-methylbutyrate/arginine/glutamine supplementation was potentially effective in the prevention of radiation dermatitis in head and neck cancer patients.

CD271 defines a stem cell-like population in hypopharyngeal cancer.

Cancer stem cells contribute to the malignant phenotypes of a variety of cancers, but markers to identify human hypopharyngeal cancer (HPC) stem cells remain poorly understood. Here, we report that the CD271(+) population sorted from xenotransplanted HPCs possesses an enhanced tumor-initiating capability in immunodeficient mice. Tumors generated from the CD271(+) cells contained both CD271(+) and CD271(-) cells, indicating that the population could undergo differentiation. Immunohistological analyses of the tumors revealed that the CD271(+) cells localized to a perivascular niche near CD34(+) vasculature, to invasive fronts, and to the basal layer. In accordance with these characteristics, a stemness marker, Nanog, and matrix metalloproteinases (MMPs), which are implicated in cancer invasion, were significantly up-regulated in the CD271(+) compared to the CD271 (-) cell population. Furthermore, using primary HPC specimens, we demonstrated that high CD271 expression was correlated with a poor prognosis for patients. Taken together, our findings indicate that CD271 is a novel marker for HPC stem-like cells and for HPC prognosis.

miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis.

For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we analyzed RPMI2650 and its derived previously established cis-diamminedichloroplatinum resistant cell line RPMI2650CR. To identify resistant phenotype-related microRNAs, we compared microRNA expressions between RPMI2650CR and RPMI2650 by microarray. One of the microRNAs as downregulated, miR-34a, was further investigated. Decreased expression of miR-34a in RPMI2650CR was confirmed by quantitative reverse transcription-polymerase chain reaction, but introduction of the miR-34a precursor into RPMI2650CR or the inhibitor of miR-34a into RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24 patients with sinonasal squamous cell carcinomas treated with intra-arterial infusion of cis-diamminedichloroplatinum showed a significant association between decreased expression of miR-34a and poor disease specific survival (P = 0.0015), poor disease free survival (P = 0.0019), and poor local control rates (P = 0.017) (median follow-up period: 53 months). Furthermore, multivariate analyses demonstrated significant associations between miR-34a expression and the hazard ratios of disease free survival at 0.005 (95% confidence interval [CI] 0.00-0.29, P = 0.011) and local control rate at 0.008 (95% CI 0.00-0.44, P = 0.019), although other parameters such as age, gender, treatment method, T and N stages did not show any similar association. These results strongly suggest that miR-34a expression can be an independent prognostic biomarker in patients with sinonasal squamous cell carcinoma who are undergoing treatment with cis-diamminedichloroplatinum.

Malignant melanoma of the head and neck: a multi-institutional retrospective analysis of cases in northern Japan.

BACKGROUND: Mucosal melanoma of the head and neck is rare and is associated with a poor prognoses because of locoregional failure and distant metastasis. The aim of our study was to review the characteristics of these patients in northern Japan and to analyze their outcomes. METHODS: The medical records of 94 patients who had been provided initial treatment in 12 institutes from 1998 to 2007 were reviewed. RESULTS: When the 5-year overall survival rates of patients were evaluated, we found that the survival rates of patients treated by chemotherapy were significantly lower than those of patients treated by surgery or radiation. The survival rates of the single-treatment modality, 2-modality, and ≥3-modality groups were 23.4%, 38.0%, and 33.6%, respectively. CONCLUSION: Our results suggest that patients who underwent combined treatment had better prognoses. However, we found that chemotherapy had no additional survival benefits.

Surgical treatment is recommended for advanced oral squamous cell carcinoma.

Oral squamous cell carcinoma is one of the most frequent types of head and neck cancers in Japan. Although recent reports have shown positive results of non-surgical treatment for advanced head and neck squamous cell carcinoma, including tongue cancer, no clear treatment strategies have been established for oral cancers, except for tongue cancer. To assess appropriate therapies, we conducted a retrospective chart review of 114 Japanese patients with oral cancers that were pathologically diagnosed as squamous cell carcinoma, excluding tongue cancers. The overall and the disease specific 5-year survival rates were 53% and 61%, respectively. Univariate and multivariate analyses revealed a lower stage (I, II, or III) and non-surgical treatment as good and poor prognostic factors of oral squamous cell carcinoma, respectively, based on their hazard ratios of 0.17 (95% CI 0.045-0.60, p = 0.0061) and 5.3 (95% CI 2.7-11, p < 0.0001). Furthermore, impact of surgery was well documented in the operable stage IVa cancers (p = 0.00015). The surgical treatment consisted of the wide resection of the primary tumor and the neck dissection for stage III or IV tumors. The present data also suggest that adjunctive therapy, such as post-operative radiation therapy or post-operative chemo-radiation therapy, shows no survival benefit compared to the surgery alone. We therefore recommend the surgical treatment for advanced oral squamous cell carcinoma in Japanese patients. These results would be helpful in future clinical trials, especially in non-surgical treatment studies of oral squamous cell carcinoma in Japan.

Familial cervical paragangliomas with lymph node metastasis expressing somatostatin receptor type 2A.

We report a case of familial, bilateral cervical paragangliomas (PGs) with lymph node metastasis. Patient I-1 is a 56-year-old man with a right carotid body tumor and a left vagal PG. Patient II-1 is a 29-year-old woman and the daughter of Patient I-1; she had a left carotid body tumor with regional lymph node metastasis. Histology of all the tumors showed the typical pattern of PGs, i.e., a zellballen pattern composed of chief cells positive for chromogranin A, and sustentacular cells positive for S100 protein. The Ki-67 labeling index was 1% to 3% in these PGs in both the primary and the metastatic tumors. Immunohistochemical analysis showed expression of somatostatin receptor (sstr) type 2A, but was negative for sstr type 5. Genomic mutation in succinate dehydrogenase type D was confirmed in both patients. Here, we present a case of familial PGs, and discuss the cases with special reference to pathologic diagnosis, genetics, and treatment.

Survival of a free jejunal graft after the resection of its nutrient vessels.

We herein report a new patient with hypopharyngeal squamous cell carcinoma (SCC) who presented with recurrent metastasis in the mesenteric lymph nodes of a transplanted jejunum with resections of the anastomotic artery by means of definitive surgery. Our findings indicate that a path of collateral blood circulation had formed, at least in the mesentery, and although it is usually not predominant, the blood flow predominantly followed the path of collateral blood circulation due to the ligation of the nutrient vessels. The clinical presentation and clinical course are described with a review of the literature.

Combined therapy after superselective arterial cisplatin infusion to treat maxillary squamous cell carcinoma.

OBJECTIVE: We sought to assess the efficacy of combined therapy after superselective arterial cisplatin infusion (SACI) therapy to treat the maxillary squamous cell carcinoma. STUDY DESIGN: We conducted a retrospective chart review of 50 patients. After completion of two courses of SACI, 25 of the patients were successively treated by concurrent SACI and radiotherapy (AR), while the other 25 patients were treated by surgery with postoperative radiotherapy (ASR). RESULTS: Patients with surgery (ASR) had an 88% local control rate with 75% disease-free survival rate at 60 months by Kaplan-Meier analysis, compared with 62% disease-free survival rate for patients with AR treatment. A particularly good outcome was obtained in T4 cases of the ASR group (n=8) whose 5-year survival rate was 87% and local control rate was 100%. CONCLUSION/SIGNIFICANCE: Combined SACI therapy is very effective for the treatment of maxillary squamous cell carcinomas and contributes to the improving prognoses of patients and organ preservation rates.

A novel G106D alteration of the SDHD gene in a pedigree with familial paraganglioma.

Head and neck paragangliomas are tumors derived from parasympathetic paraganglia. Familial cases account for 10% or more of these tumors, and mutations of the genes encoding subunits for the mitochondrial respiratory chain complex II, SDHD, SDHB, and SDHC, have been reported. We analyzed mutations in the all four SDH genes, SDHA through SDHD, in a Japanese family with cervical paraganglioma that include a father with bilateral tumors and his daughter with a malignant left carotid body tumor with nodal metastasis. This pedigree harbored a germline G106D alteration in exon 4 of the SDHD gene that has not previously been reported to date. The tumors of the father expressed biallelic SDHD, but the SDHD expression was highly suppressed by an unknown mechanism(s) in tumors of his daughter, and the wild-type allele was predominantly suppressed in the metastatic node. These results suggest that the missense dysfunction of SDHD prepares neoplastic condition and that expressional silencing, particularly of the wild-type allele, plays an important role in the malignant transformation of the paragangliomas. Our results may lead to a better understanding of this disease and to the development of methods for prevention of this disease.

Plasma-membrane-associated sialidase (NEU3) differentially regulates integrin-mediated cell proliferation through laminin- and fibronectin-derived signalling.

We have found previously that human plasma-membrane-associated sialidase (NEU3), a key glycosidase for ganglioside degradation, was markedly up-regulated in human colon cancers, with an involvement in suppression of apoptosis. To elucidate the molecular mechanisms underlying increased NEU3 expression, in the present study we investigated its role in cell adhesion of human colon cancer cells. DLD-1 cells transfected with NEU3 exhibited increased adhesion to laminins and consequent cell proliferation, but decreased cell adhesion to fibronectin and collagens I and IV, compared with control cells. When triggered by laminins, NEU3 clearly stimulated phosphorylation of FAK (focal adhesion kinase) and ERK (extracellular-signal-regulated kinase), whereas there was no activation on fibronectin. NEU3 markedly enhanced tyrosine phosphorylation of integrin beta4 with recruitment of Shc and Grb-2 only on laminin-5, and NEU3 was co-immunoprecipitated by an anti-(integrin beta4) antibody, suggesting that association of NEU3 with integrin beta4 might facilitate promotion of the integrin-derived signalling on laminin-5. In addition, the promotion of phosphorylation of integrin beta1 and ILK (integrin-linked kinase) was also observed on laminins. G(M3) depletion as the result of NEU3 overexpression, assessed by TLC, appeared to be one of the causes of the increased adhesion on laminins and, in contrast, of the decreased adhesion on fibronectin - NEU3 probably having bimodal effects. These results indicate that NEU3 differentially regulates cell proliferation through integrin-mediated signalling depending on the extracellular matrix and, on laminins, NEU3 did indeed activate molecules often up-regulated in carcinogenesis, which may cause an acceleration of the malignant phenotype in cancer cells.

Management of the patients with hypopharyngeal cancer: eight-year experience of Miyagi Cancer Center in Japan.

The aim of this study is to evaluate the results of treatment for hypopharyngeal cancer and indicate the future prospect of the treatment. Seventy-four patients with squamous cell carcinoma of the hypopharynx admitted to Miyagi Cancer Center from 1993 through 2000 are reviewed. Sixty-four patients received radical treatment, and 10 patients received palliative treatment or no treatment. The cancer was advanced (stages III and IV) in 82% of all the patients. The overall 5-year survival rate of all the patients was 38%. The overall 5-year survival rate of 64 patients received radical treatment was 43%. The ten patients who received palliative treatment or no treatment died of cancer within 16 months. Fifty-two out of the 74 patients underwent neck dissection for the neck lymph node involvement; forty of the 52 patients underwent ipsilateral neck dissection and 12 underwent bilateral neck dissection. Four out of the 40 patients, who underwent ipsilateral neck dissection alone, developed late contralateral regional recurrence but were successfully treated by contralateral neck dissection at the time of recurrence. Twenty-three out of 74 patients had multiple primary cancers synchronously or metachronously (31%). Cause of the death of six patients out of 74 patients was confirmed to be primary cancers other than hypopharyngeal cancer, as judged by physicians in other department or other hospitals. Most of the patients died due to distant metastasis from hypopharyngeal cancer or other primary cancers. We therefore conclude that contralateral elective neck dissection which is frequently chosen for the treatment of hypopharyngeal cancer surgery is unnecessary. Even if locoregional control is accomplished, distant metastasis or multiple primary cancers emerge and make prognosis poor. To improve the prognosis, we should develop some strategy against hypopharyngeal cancer for each patient. New strategies including chemoprevention and surgery against distant metasistasis are necessary.

A multi-institutional survey of the effectiveness of chemotherapy combined with radiotherapy for patients with nasopharyngeal carcinoma.

BACKGROUND: Previous randomized trials have shown a survival advantage of concurrent platinum-based chemoradiotherapy with or without adjuvant chemotherapy for advanced nasopharyngeal cancer. Applicability of these data to a Japanese population is an important issue which remains to be solved. METHODS: A retrospective survey of treatment of patients with nasopharyngeal cancer in 17 institutions in Japan was done with special reference to the relationship between the type of chemotherapy and survival outcome. Chemotherapy used was classified according to: (i) whether > or =2 courses of platinum plus 5-fluorouracil (FP) was given; or (ii) whether platinum was administered concurrently with radiotherapy (RT). This resulted in three groups being produced consisting of (i)/(ii) = YES/YES, other miscellaneous (MISC) and RT alone. RESULTS: Of 333 evaluable replies, 67 patients (20%) corresponded to the YES/YES, 192 (58%) to the MISC and 74 (22%) to the RT alone group. The YES/YES group achieved a better overall survival than RT alone for patients with intermediate stage (T3N0 or T1-3N1, 81.9 versus 60.7% at 5 years, P = 0.042) and advanced stage (T4 or N2/3, 56.6 versus 31.5%, P = 0.017) disease. The MISC group achieved an almost identical survival rate to that in the YES/YES group for patients with intermediate stage disease (81.9% at 5 years, P = 0.968), whereas it was not significantly different from that of the RT alone group for patients with advanced stage disease (44.0%, P = 0.261). CONCLUSION: The results of this survey mirrored the data from previous randomized trials for patients with intermediate and advanced stage nasopharyngeal cancer in Japan. However, confirmatory prospective trials are required to test the efficacy of less toxic approaches for patients with intermediate stage disease.

Allelic loss correlated with tissue specificity in head and neck squamous cell carcinomas and the clinical features of patients.

Head and neck squamous cell carcinomas (HNSCC) manifest various clinical behaviors according to their origin, i.e., from various parts of the head and neck mucosa. However, genetic factors involved in the carcinogenesis of HNSCC in different tissues have not yet been studied and evaluated. Three hundred and two specimens of HNSCC were characterized for allelic loss of certain areas of the genome, i.e., 3p21, 9p21 and 17p13, and were examined for genetic factors that might correlate with the tissue specificity of HNSCC and influence their clinical features. Loss of heterozygosity (LOH) at 3p21, 9p21 and 17p13 was detected in 54.5%, 57.4% and 57.1% of the informative cases, respectively. The frequencies of LOH in hypopharyngeal and in laryngeal cancers were significantly higher than in oral cancers. There were significant correlations between LOH at 3p21 and lymph node involvement and between LOH at 17p13 and tumor size, resulting in positive correlations with clinical stage of HNSCC in the patients. These results indicate that not only the functions of tumor suppressor genes differ among HNSCC in various regions, but also that allelic loss plays a key role in the acquisition of a malignant phenotype of these tumors.