Shinpei Kada

Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea

Immune‐mediated inner ear disorder has been well established as a clinical entity; however, the innate immune system of the inner ear is a poorly understood area of research with high clinical and immunological importance. Although the presence of resident tissue macrophages in the inner ear has been suggested, there has been some controversy. In this study, we analyzed the origin of cochlear resident macrophages and the contribution of hematopoietic bone marrow (BM) to the recruitment of macrophages in the cochlea. To visualize the localization of BM‐derived cells, BM chimeric mice were made by transplantation of hematopoietic stem cells, which were genetically labeled with enhanced green fluorescent protein, into lethally irradiated C57BL/6 mice. The distribution and characteristics of BM‐derived cells in the mouse cochlea were studied immunohistochemically. We successfully identified the constitutive presence of tissue resident macrophages in the spiral ligament and spiral ganglion that are derived from BM in larger numbers than previously reported. Moreover, cochlear resident macrophages gradually turn over for several months during steady‐state replacement by BM‐derived cells, and the number of cochlear macrophages immediately increased in response to local surgical stress. The present findings demonstrate the hematopoietic origin of cochlear resident and infiltrating macrophages. Our study provides a novel anatomical and immunological basis for the inner ear and indicates that the cochlear resident macrophages would be a therapeutic target in inner ear disorders.

Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus.

OBJECT Hearing levels following microsurgical treatment gradually deteriorate in a number of patients treated for vestibular schwannoma (VS), especially in the subacute postoperative stage. The cause of this late-onset deterioration of hearing is not completely understood. The aim of this study was to investigate the possibility that reactive gliosis is a contributory factor. METHODS Mechanical damage to nerve tissue is a feature of complex surgical procedures. To explore this aspect of VS treatment, the authors compressed rat auditory nerves with 2 different degrees of injury while monitoring the compound action potentials of the auditory nerve and the auditory brainstem responses. In this experimental model, the axons of the auditory nerve were quantitatively and highly selectively damaged in the cerebellopontine angle without permanent compromise of the blood supply to the cochlea. The temporal bones were processed for immunohistochemical analysis at 1 week and at 8 weeks after compression. RESULTS Reactive gliosis was induced not only in the auditory nerve but also in the cochlear nucleus following mechanical trauma in which the general shape of the auditory brainstem response was maintained. There was a substantial outgrowth of astrocytic processes from the transitional zone into the peripheral portion of the auditory nerve, leading to an invasion of dense gliotic tissue in the auditory nerve. The elongated astrocytic processes ran in parallel with the residual auditory neurons and entered much further into the cochlea. Confocal images disclosed fragments of neurons scattered in the gliotic tissue. In the cochlear nucleus, hypertrophic astrocytic processes were abundant around the soma of the neurons. The transverse diameter of the auditory nerve at and proximal to the compression site was considerably reduced, indicating atrophy, especially in rats in which the auditory nerve was profoundly compressed. CONCLUSIONS The authors found for the first time that mechanical stress to the auditory nerve causes substantial reactive gliosis in both the peripheral and central auditory pathways within 1-8 weeks. Progressive reactive gliosis following surgical stress may cause dysfunction in the auditory pathways and may be a primary cause of progressive hearing loss following microsurgical treatment for VS.

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.

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.

Oncologic safety of cervical nerve preservation in neck dissection for head and neck cancer

Although the functional merits of preserving cervical nerves in neck dissection for head and neck cancer have been reported, the oncologic safety has not yet been determined. Therefore, the purpose of this study was to evaluate the safety of cervical nerve preservation.

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.

Sensory preservation in neck dissection: outcomes of a sub-sternocleidomastoid approach

Abstract Objective: Cutaneous anesthesia in early postoperative period is common after neck dissection even if the cervical nerve (CN) rootlets are preserved. The aim of this study was to evaluate if the preservation of the terminal branches of CNs using sub-sternocleidomastoid (SCM) approach combined with medially placed skin incision can prevent early postoperative anesthesia. Material and methods: A retrospective chart review was performed on 129 neck dissections in 87 head and neck cancer patients. Results: The early postoperative sensory preservation rates for the ear tab, submandibular, lateral neck, and sub-clavicular areas of CN rootlet-preserved necks (n = 86) were 75.6%, 20.9%, 74.4%, and 86.0%, respectively, compared with 37.2%, 2.3%, 2.3%, and 4.7%, respectively, in CN rootlet-resected necks (n = 43). In CN rootlet-preserved necks, the sub-SCM approach (n = 54) showed 81.5%, 27.8%, 92.6%, and 94.4% preservation rates, respectively, compared with 65.6%, 9.4%, 43.8%, and 71.9%, respectively, using the conventional subplatysmal approach (n = 32). The rates were significantly better in the submandibular, lateral neck, and sub-clavicular areas after sub-SCM approach. Conclusions: Preservation of CN rootlets is a required element for sensory preservation in neck dissection. The sub-SCM approach can effectively prevent early postoperative cutaneous anesthesia following CN-preserving neck dissection.