Tomoko Kanda

Epidermal growth factor receptor gene mutations in papillary thyroid carcinoma.

Recent studies have indicated that somatic mutations in the epidermal growth factor receptor (EGFR) gene have been identified in a subset of patients with nonsmall‐cell lung cancer (NSCLC) and are associated with sensitivity to the EGFR‐tyrosine‐kinase inhibitors. These mutations have been reported to be almost exclusively found in a pulmonary adenocarcinoma subgroup of NSCLC, with a low frequency in other solid tumors. We describe a patient with advanced‐stage papillary thyroid carcinoma (PTC) whose disease had been diagnosed as pulmonary adenocarcinoma at first, and who had a marked response to the EGFR‐tyrosine‐kinase inhibitor, gefitinib. An in‐frame deletion in exon 19 that eliminated 4 amino acids at positions 746 through 750, which is one of the common drug‐sensitive mutations in pulmonary adenocarcinoma, and a serine‐to‐proline substitution at codon 752, were found in a tumor specimen of the patient. We subsequently searched for mutations in the EGFR tyrosine kinase domain in primary tumors from 23 patients with PTC, and drug‐sensitive mutations commonly observed in pulmonary adenocarcinoma were found in 7 of these patients. Our observation of a high frequency of the EGFR‐activating mutations in PTC suggests that the EGFR mutation may be an important event in the development of PTC. EGFR gene amplification, also considered to be a predictor of response to EGFR‐tyrosine‐kinase inhibitors, was evaluated by fluorescence in situ hybridization (FISH); however, only 1 FISH‐positive tumor was detected. Our data suggest that EGFR‐tyrosine‐kinase inhibitors may deserve consideration in the treatment of a subset of patients with PTC, just as with pulmonary adenocarcinoma.

Ten years single institutional experience of treatment for advanced hypopharyngeal cancer in Kyoto University

Abstract Conclusion: Treatment of advanced hypopharyngeal cancer has become more conservative and more multidisciplinary, and the prognosis has been improved. Induction chemotherapy has the potential to extend organ preservation therapy even in cases with locally advanced primary lesion. It is also important to develop a strategy to reduce distant metastasis and to keep track of second primary cancers. Objectives: To update the therapeutic outcome of advanced hypopharyngeal cancer. Methods: A total of 72 cases with stage III/IV hypopharyngeal cancer were treated at Kyoto University Hospital during 2000–2008. Surgery was performed in 56 cases; total pharyngolaryngoesophagectomy (TPLE) in 39 cases and partial pharyngectomy (PPX) preserving the larynx in 17 cases. Radiotherapy (RT) with or without concurrent chemotherapy was applied in 16 cases. Induction chemotherapy (ICT) has been applied for 14 cases since 2006 to achieve organ preservation and reduction of distant metastasis. The follow-up period varied from 12 months to 96 months (mean 32 months). Therapeutic outcomes were chart reviewed. Results: Five years cumulative overall and disease-specific survival (DSS) rates were 52.1% and 63.8%, respectively. DSS rates in cases treated with surgery and those with RT were 65.1% and 56.1%, respectively. N2c status showed the worst prognosis according to nodal disease classification. Local control rates for cases treated with TPLE, PPX, and RT were 97.3%, 100%, and 80.4%, respectively. The effective rate of ICT was 79%, and laryngeal preservation was achieved in 79% of the cases with ICT. Recurrence occurred in 20 cases. Approximately half of the recurrence was distant disease. In the end, 17 cases died of the primary disease, while 10 cases died of other causes, mainly second primary cancers.

Ten years single institutional experience of treatment for advanced laryngeal cancer in Kyoto University

Abstract Conclusion: It is important to suppress lymph node recurrence and distant metastasis to achieve better survival of advanced laryngeal cancer, especially supraglottic cancer. Objective: The therapeutic outcomes of 33 cases with advanced laryngeal cancer treated at Kyoto University Hospital between 2000 and 2008 were reviewed. Methods: Thirty-one males and two females were involved. Their ages ranged from 49 to 81 years (average 65.6 years). All tumors were squamous cell carcinoma, arising at the glottis in 21 cases and the supraglottis in 12 cases. Most glottic cancers (90.5%) and supraglottic cancers (83.3%) were classified as T3 or T4. Total laryngectomy with neck dissection was performed in the treatment of T3 or T4 cases. Two cases of T2 cancers were treated by radiotherapy (66–72 Gy) with neck dissection, and one case of T2 cancer was treated by radiotherapy (66 Gy). Partial laryngectomy with neck dissection was performed in one T3 case. Results: Five-year overall survival rates for stage III of glottic cancer, stage IV of glottic cancer, stage III of supraglottic cancer, and stage IV of supraglottic cancer were 100%, 40.9%, 100%, and 24.2%, respectively. Five-year disease-specific survival rates for stage III of glottic cancer, stage IV of glottic cancer, stage III of supraglottic cancer, and stage IV of supraglottic cancer were 100%, 56.3%, 100%, and 28.1%, respectively. No local recurrence occurred. Regional lymph node recurrence occurred in two cases– one patient with glottic cancer and one with supraglottic cancer. Both of them died of disease despite undergoing chemotherapy. One case initially had lung metastasis, and post-treatment distant metastasis occurred in the lung in four cases, in the skin in one, and in multiple organs in one case.

Pyogenic spondylodiscitis after transoral surgery for oropharyngeal cancer

We report the case of a patient with pyogenic spondylodiscitis after transoral surgery for oropharyngeal cancer. The patient was a 66-year-old man with a history of hepatic cell carcinoma, alcoholic cirrhosis, and chronic pancreatitis. The tumor was resected via a transoral approach with concurrent bilateral elective neck dissections. Although the initial postoperative course was uneventful, the patient experienced severe cervical pain because of which he revisited the hospital. The patient was diagnosed with pyogenic spondylodiscitis, according to the results of magnetic resonance imaging. Continuous treatment with parenteral antibiotics and a cervical brace was required for 2 months before all his symptoms and signs diminished. To the best of our knowledge, this is the first reported case of pyogenic spondylodiscitis as a complication of transoral resection for head and neck cancer.

Organ preservation surgery for advanced hypopharyngeal cancer

Abstract Conclusion: Organ preservation surgery with partial pharyngectomy preserving the larynx is feasible for the treatment of advanced hypopharyngeal cancer with comparable local control and preservation of function. Objectives: To examine the feasibility and therapeutic effects of organ preservation surgery for advanced hypopharyngeal cancer. Methods: Fourteen patients with stage III/IV hypopharyngeal cancer were treated by partial pharyngectomy with or without partial laryngectomy to preserve the larynx. Ten cases were T1/2 primary while four cases had T3/4 tumors. Reconstruction of the pharyngolarynx was completed by primary mucosal suture in six, while free forearm flap was used in eight cases. Induction chemotherapy was administered for six cases including three with T3/4 tumors. Results: Five-year overall survival and disease-specific survival rates were 57.1% and 66.7%, respectively. The 5-year locoregional control rate was 66.7% and the larynx preservation rate was 100%. No patients presented with local recurrence at the pharyngolaryngeal segment, while two cases showed nodal recurrence, from which they died. Tracheal stoma was closed in 9 of 14 cases. Vocal function was excellent in five cases, moderate in five, and poor in three. Swallowing function was excellent to moderate in eight cases and poor in six.

Ten years single institutional experience of treatment for oral cancer in Kyoto University

Abatract Conclusions: The prognosis of patients was related to the initial stage at diagnosis. These results suggest that early diagnosis and treatment are the most important factors to improve the prognosis in oral cancer patients. Adjuvant treatment is also warranted to improve locoregional control of advanced cases. Objectives: To update the therapeutic outcome of oral cancer. Methods: In all, 129 cases with oral cancer were treated at Kyoto University Hospital during 2000–2008. Surgery with/without irradiation was performed for 34 cases in stage I, 27 in stage II, 15 in stage III, 42 in stage IVa, and 1 case in stage IVb. Brachytherapy was performed for three cases in stage II. Definitive radiotherapy was performed for three cases in stage III and five cases in stage IV. The follow-up period varied from 12 to 96 months (mean 30 months). Results: The 5-year cumulative overall and disease-specific survival (DSS) rates were 74.5% and 75.3%. DSS was 86.2% in stage I, 91.6% in stage II, 70.7% in stage III, 60.2% in stage IVa, and 0% in stage IVb. DSS shows worse prognosis with advanced nodal status. Locoregional recurrence occurred in 32 of 129 cases, including local recurrence in 8 cases, nodal recurrence in 18, retropharyngeal node metastasis in 1, and local and nodal recurrence in 5 cases. Salvage operation with/without postoperative radiotherapy was performed for 22 cases with locoregional recurrence and 7 of them have survived.

Management and pitfalls of stage I/II glottic cancer

Abstract Conclusions: Once-daily radiotherapy for stage I glottic cancer and hyperfractionated radiotherapy for stage II glottic cancer achieved satisfactory results in terms of prognosis and laryngeal preservation. The treatment strategy for stage II glottal cancer with subglottal invasion needs to be reconsidered to further improve the outcome. Objectives: Although early glottic carcinomas are highly curable by radiation therapy, the laryngeal preservation rate is not always sufficient. We reviewed the stage I/II glottal cancer treated in our institute during a recent 15-year period to improve the outcome and prognosis. Methods: In all, 113 cases of stage I/II glottic cancer (81 stage I cases and 32 stage II cases) were treated in Kyoto University hospital from 1994 to 2008. In 81 cases with stage I glottic cancer, radiation was performed for 66 cases, transoral laser excision (TLE) was performed for 14 cases, and hyperfractionated radiotherapy was done for one case. Among 32 cases with stage II glottic cancer, 24 cases were treated with hyperfractionated radiotherapy, 6 cases were treated with radiation, and one case with partial laryngectomy. Total laryngectomy was performed for one patient who suffered mixed connective tissue disease. Kaplan–Meier estimates were used for the analysis of survival rate and laryngeal preservation rate. Results: The 5-year overall survival rates were 88.4% in stage I cases and 89.1% in stage II cases. The 5-year disease-specific survival rates were 100% in stage I cases and 93% in stage II cases. The 5-year laryngeal preservation rates were 99% in stage I cases and 90% in stage II cases. Two cases of stage II glottal cancer with subglottal invasion failed to be controlled and the patients died from local recurrence and mediastinum lymph node metastasis, respectively.

Management of stage I/II hypopharyngeal cancer.

Abstract Conclusions: It is suggested that radiotherapy might be the first choice for stage I/II hypopharyngeal cancer, and that adjuvant treatment might be necessary for stage II patients to prevent distant metastasis. Objectives: To update the therapeutic outcome of early hypopharyngeal cancer. Methods: Twenty-eight patients with stage I/II hypopharyngeal cancer (8 in stage I, 20 in stage II) were treated at Kyoto University Hospital between 1995 and 2007. Of 8 cases in stage I, radiotherapy was applied for 4 cases, and surgical treatment for another 4, while 13 of 20 cases in stage II underwent radiotherapy and the remaining 7 cases underwent surgery. Results: The 5-year cumulative disease-specific survival and larynx preservation rates were 74.6% and 73.2%, respectively. Recurrent tumors were found in two cases in stage I treated by surgery and in five cases in stage II treated with radiotherapy. Two of five recurrent cases in stage II were rescued by salvage surgery. Distant metastasis to the lung appeared in two cases in stage II after initial treatment.