Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy.

BACKGROUND: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. METHODS: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. RESULTS: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% (P = 0.092), 56.5% and 41.3% (P = 0.629), and 43.0% and 42.5% (P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. CONCLUSIONS: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer.

Phase I pharmacokinetic study of S-1 granules and nedaplatin for advanced head and neck cancer.

AIM: We performed a pharmacokinetic phase I trial of the combination of S-1 granules and nedaplatin for head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Patients were treated with both nedaplatin on day 1 at a dose starting at 80 mg/m(2) (level 1) escalating up to 90 mg/m(2) (level 2), and S-1 granules at a daily dose of 80 mg/m(2) on days 1 to 14 every three weeks. The primary end-point was determination of the recommended dose. RESULTS: Twenty patients were enrolled. Dose-limiting toxicities occurred in one out of six patients at dose level 1 (neutropenia) and in all three patients at level 2 (neutropenia and thrombocytopenia). The recommended dose was determined as level 1. Pharmacokinetic parameters of S-1 granule did not differ from the capsula formulation. The response rate was 42.1%. CONCLUSION: This combination was well-tolerated and manifested a promising activity against HNSCC.

A case of calcific retropharyngeal tendinitis: the significance of an early diagnosis.

The clinical presentation of calcific retropharyngeal tendinitis, a rare entity, can mimic more serious disorders. We describe the case of a 35-year-old man who was referred to us for evaluation of a suspected retropharyngeal abscess. At presentation, the patient reported severe cervical pain and stiffness. He exhibited mild fever, torticollis, and a moderately elevated white blood count; no swelling of the retropharyngeal wall was observed. Based on the results of plain radiography and computed tomography (CT), we diagnosed the patient with calcific retropharyngeal tendinitis. He was treated with a 7-day course of a nonsteroidal anti-inflammatory drug and a 3-day course of a steroid, and he recovered well. We suggest that the true incidence of calcific retropharyngeal tendinitis is actually higher than what is generally believed because this diagnosis is frequently missed. Contrast-enhanced CT can aid in diagnosing calcific retropharyngeal tendinitis. CT should be performed in patients who present with nonspecific symptoms such as severe neck pain, sore throat, odynophagia, and mild fever.

Conventional MRI findings for predicting submandibular pleomorphic adenoma.

BACKGROUND: Although pleomorphic adenomas account for over 90% of all benign submandibular gland tumors, the imaging features of submandibular pleomorphic adenomas have not been reported in a large number of cases. PURPOSE: To assess the conventional magnetic resonance imaging (MRI) findings for predicting the submandibular pleomorphic adenoma. MATERIAL AND METHODS: MR studies of 42 pleomorphic adenomas and 28 other types of tumor were reviewed. MR images were assessed for the presence of hyperintense areas on T2-weighted images (first sign), a well-defined margin (second sign), and presence of crescent-shaped compression of the ipsilateral normal submandibular gland (third sign). RESULTS: For identifying submandibular pleomorphic adenoma, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 97.6%, 50.0%, 74.5%, 93.3%, and 78.6% for the first sign, 95.2%, 46.4% 72.7%, 86.7%, and 75.7% for the second sign, and 23.8%, 100%, 86.7%, 46.7%, and 54.3% for the third sign, respectively. Combining the first and second findings achieved to 85.7% specificity and 90.9% accuracy. CONCLUSION: Although non-specific, submandibular pleomorphic adenomas usually have hyperintense areas on T2-weighted images and well-defined margins. In addition, crescent-shaped compression of the ipsilateral normal gland seems to represent a highly specific sign.

Human papillomavirus DNA and p16 expression in Japanese patients with oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) is a major etiologic factor for oropharyngeal squamous cell carcinoma (OPSCC). However, little is known about HPV-related OPSCC in Japan. During the study, formalin-fixed, paraffin-embedded OPSCC specimens from Japanese patients were analyzed for HPV DNA by the polymerase chain reaction (PCR) and for the surrogate marker p16 by immuno-histochemistry. For HPV DNA-positive, p16-negative specimens, the methylation status of the p16 gene promoter was examined by methylation-specific PCR. Overall survival was calculated in relation to HPV DNA and p16 status and was subjected to multivariate analysis. OPSCC cell lines were examined for sensitivity to radiation or cisplatin in vitro. The study results showed that tumor specimens from 40 (38%) of the 104 study patients contained HPV DNA, with such positivity being associated with tumors of the tonsils, lymph node metastasis, and nonsmoking. Overall survival was better for OPSCC patients with HPV DNA than for those without it (hazard ratio, 0.214; 95% confidence interval, 0.074-0.614; P = 0.002). Multivariate analysis revealed HPV DNA to be an independent prognostic factor for overall survival (P = 0.015). Expression of p16 was associated with HPV DNA positivity. However, 20% of HPV DNA-positive tumors were negative for p16, with most of these tumors manifesting DNA methylation at the p16 gene promoter. Radiation or cisplatin sensitivity did not differ between OPSCC cell lines positive or negative for HPV DNA. Thus, positivity for HPV DNA identifies a distinct clinical subset of OPSCC with a more favorable outcome in Japanese.

Vestibular system changes in sudden deafness with and without vertigo: a human temporal bone study.

OBJECTIVE: To investigate the vestibular system changes in sudden deafness with vertigo (SDwV) and sudden deafness without vertigo (SDwoV) and the cause of persistent canal paresis (CP) in SDwV patients. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: Four temporal bones from the affected ear in 4 patients with unilateral sudden deafness (SD), 2 SDwV and 2 SDwoV, were selected. Four contralateral temporal bones with normal-hearing ears were defined as the control. Morphologic findings of the labyrinth, the number of Scarpa's ganglion cells, and the density of vestibular hair cells were investigated in all temporal bones. Clinical data and the results of vestibular tests of 11 patients with unilateral SD, as a separate group, also were investigated. RESULTS: Atrophic change of the organ of Corti, tectorial membrane, and stria vascularis in cochlea, and deposits and atrophic otoconial membrane in vestibular sense organs were seen on affected ears more than control ears. The density of Type I hair cells seemed to decrease on the saccular macula and the posterior semicircular canal crista on affected ears, and there was no remarkable difference between SDwV and SDwoV. In 1 patient with SDwoV who died 10 months after the onset of SD, there were large amount of deposits on the cupula, the atrophied otoconial membrane was peeling off from the saccular macula, and the saccular membrane collapsed to the saccular macula in the affected ear. In the clinical data, all SDwV who were examined within 2 years from the onset had CP, and all SDwV had profound hearing loss. CONCLUSION: There is no remarkable difference between SDwV and SDwoV in the number of Scarpa's ganglion cells and the density of vestibular hair cells. The damage of the extracellular superstructure is seen in SD with or without vertigo. The damage of extracellular superstructure is potentially one of the causes of persistent CP in patients with SD.

Marrow-middle ear connections: a potential cause of otogenic meningitis.

HYPOTHESIS: We hypothesize that the connections between the hematopoietic bone marrow and middle ear is a potential cause of childhood otogenic meningitis. BACKGROUND: Although it is known that there is a causal relationship between otitis media and bacterial meningitis, the relationship has never been satisfactorily established. Human fetal and infant temporal bones prepared for light microscopic evaluation revealed direct connections between the hematopoietic bone marrow and middle ear. We noted this difference in anatomy between the infant middle ear and the adult middle ear. METHODS: We studied 10 temporal bones from 5 infants in each group: meningitis group with otitis media who died of meningitis, control Group 1 without otitis media, and control Group 2 with otitis media who died of diseases other than meningitis. A quantitative analysis of the frequency of connections between the hematopoietic bone marrow and middle ear was performed. The correlation between unabsorbed mesenchyme and otitis media also was investigated. RESULTS: The frequency of connections was significantly higher in order of the meningitis group, control Group 2, and control Group 1. The degree of unabsorbed mesenchyme tended to be more severe in order of the meningitis group, control Group 2, and control Group 1. CONCLUSION: The prevalence of connections between the hematopoietic bone marrow and middle ear in patients with meningitis and otitis media is high. A higher prevalence of connections in infants with otitis media could increase the risk for otogenic meningitis in them.

Cochlear changes in presbycusis with tinnitus.

OBJECTIVES: The pathophysiology of tinnitus is obscure and its treatment is therefore elusive. Significant progress in this field can only be achieved by determining the mechanisms of tinnitus generation, and thus, histopathologic findings of the cochlea in presbycusis with tinnitus become crucial. We revealed the histopathologic findings of the cochlea in subjects with presbycusis and tinnitus. MATERIAL AND METHODS: The subjects were divided into 2 groups, presbycusis with tinnitus (tinnitus) group and presbycusis without tinnitus (control) group, with each group comprising 8 temporal bones from 8 subjects. We quantitatively analyzed the number of spiral ganglion cells, loss of cochlear inner and outer hair cells, and areas of the stria vascularis and spiral ligament. RESULTS: There was a significantly greater loss of outer hair cells in the tinnitus group compared with the control group in the basal and upper middle turns. The stria vascularis was more atrophic in the tinnitus group compared with the control group in the basal turn. CONCLUSIONS: Tinnitus is more common in patients with presbycusis who have more severe degeneration of outer hair cells and stria vascularis.

Pathologic correlations of otologic symptoms in acute lymphocytic leukemia.

OBJECTIVES: To assess the clinicopathologic correlations of otologic complaints in patients with acute lymphocytic leukemia. DESIGN: Otologic complaints and histologic findings were evaluated in 25 temporal bones of 13 acute lymphocytic leukemia patients. RESULTS: Nine patients had a history of otologic complaints, including hearing loss, otalgia, otorrhea, and vertigo in 5, 3, 3, and 2 patients, respectively. Hemorrhage was most commonly observed in the middle ear (6 patients, 9 temporal bones) and was also observed in cochlea (4 patients, 4 temporal bones), and vestibule (6 patients, 6 temporal bones). Leukemic infiltration was observed in the petrous apex (13 patients, 24 temporal bones), middle ear (7 patients, 14 temporal bones), cochlea (3 patients, 4 temporal bones), vestibule (3 patients, 4 temporal bones), and internal auditory canal (5 patients, 8 temporal bones). Inflammatory changes were observed in the cochlea (5 patients, 8 temporal bones) and vestibule (5 patients, 8 temporal bones). Middle ear effusion containing floating tumor cells was observed in 4 temporal bones of 3 patients. Irreversible histopathologic changes of the middle ear, such as the destruction of the ossicles, perforation of the tympanic membrane, and granulation tissues were observed in 5 temporal bones of 4 patients. CONCLUSIONS: Ear involvement is common in acute lymphocytic leukemia patients. With prolonged survival due to the progress of treatment, the diagnosis and treatment of nonhematopoietic system symptoms, such as ear problems due to acute lymphocytic leukemia, have become more important.

Cochlear otosclerosis adjacent to round window and oval window: a histopathological temporal bone study.

HYPOTHESIS: The purpose of this histopathological study is to examine temporal bones of patients with cochlear otosclerosis adjacent to the round window or adjacent to the oval window as compared with healthy controls. BACKGROUND: It is unclear if the extent and site of otosclerosis affects the extent of damage to cochlear structures and hearing loss. METHODS: Twelve temporal bones from 10 patients with cochlear otosclerosis adjacent to the round window, 11 temporal bones from 8 patients with cochlear otosclerosis adjacent to the oval window, and 12 bones of healthy age-matched controls were selected for study. We calculated the number of spiral ganglion cells, changes in cochlear structures, the extent and site of cochlear otosclerosis, and audiometric data. RESULTS: The loss of spiral ganglion cells and the absence of outer hair cells in patients with cochlear otosclerosis adjacent to the round window were significantly higher than those in patients with cochlear otosclerosis adjacent to the oval window and healthy controls. The area of the spiral ligament in patients with cochlear otosclerosis adjacent to the oval window was significantly smaller than that in healthy controls. However, no significant difference was found in the spiral ligament of patients with cochlear otosclerosis adjacent to the round window and healthy controls. There was no significant difference between patients with cochlear otosclerosis and age-matched controls in audiometric data. CONCLUSION: Cochlear otosclerosis adjacent to the round window caused significantly more damage to spiral ganglion cells and outer hair cells than cochlear otosclerosis adjacent to the oval window without loss of spiral ligament.

[Adjuvant chemotherapy with S-1 for head and neck carcinoma].

Combined chemotherapy is considered essential for further improvement of the cure rate of head and neck carcinoma. Chemotherapy in cases of head and neck carcinoma is administered with one of two objectives: as adjuvant therapy to increase the survival rate after radical treatment in the early stage of the disease, and to prolong the survival rate in cases with advanced or recurrent carcinoma. There is, however, no clear answer to the question of how these objectives can be accomplished. In our department, we use S-1 chemotherapy to achieve these goals. Our modified S-1 administration method until 2005 consists of a 3-week drug administration period followed by a 2-week drug-free period (3w-2w), or a 2-week administration period followed by a 2-week drug-free period (2w-2w). We determined the usefulness of the optimum administration method by examining the rate of completion of the treatment, and its safety and therapeutic efficacy. S-1 administration was used in 68 cases of head and neck carcinoma until 2005. As a result, the rate of completion of the treatment and its safety were high. Further randomized controlled trials with a high degree of accuracy are needed to confirm whether or not our treatment method would improve the survival rate/ prolong the duration of survival in these patients.