Morimasa Kitamura

Histologic characterization of human scarred vocal folds.

Vocal fold scarring remains a significant problem. Although several animal models have been developed to improve our understanding of the histopathology, the histologic features of scarred human vocal folds have rarely been reported. The present case studies aimed to define the histologic changes of scarred human vocal folds caused by cordectomy or cordotomy. Ten patients with the scarred vocal folds were involved in this study. Nine patients with early glottic cancer underwent endoscopic cordectomy, and one patient underwent superficial cordotomy for idiopathic scar. The postcordectomy or cordotomy scar was biopsied or resected 3-13 months after the original procedure. After confirming absence of any tumor in cancer patients, the remaining specimens were used in the present study. Histologic examination investigated deposition of extracellular matrix (ECM) including collagen, elastin, hyaluronic acid (HA), fibronectin, and decorin in the lamina propria of the scarred vocal folds. There was a wide range of variation in the deposition of ECM in scarred vocal folds. Excessive and disorganized collagen deposition was observed in most cases that had undergone deep resection of the lamina propria, whereas deposition of collagen was mild and well organized after superficial resection. Decorin was retained in all cases after superficial cordectomy or cordotomy, but varied after deep resection. Deposition of elastin, HA, and fibronectin varied regardless of depth of injury. Histology of scarred vocal folds may vary with degree of injury and individual healing mechanism.

Increased Expression of Phosphatidylcholine (16:0/18:1) and (16:0/18:2) in Thyroid Papillary Cancer

A good prognosis can be expected for most, but not all, cases of thyroid papillary cancer. Numerous molecular studies have demonstrated beneficial treatment and prognostic factors in various molecular markers. Whereas most previous reports have focused on genomics and proteomics, few have focused on lipidomics. With the advent of mass spectrometry (MS), it has become possible to identify many types of molecules, and this analytical tool has become critical in the field of omics. Recently, imaging mass spectrometry (IMS) was developed. After a simple pretreatment process, IMS can be used to examine tissue sections on glass slides with location information. Here, we conducted an IMS analysis of seven cases of thyroid papillary cancer by comparison of cancerous with normal tissues, focusing on the distribution of phospholipids. We identified that phosphatidylcholine (16:0/18:1) and (16:0/18:2) and sphingomyelin (d18:0/16:1) are significantly higher in thyroid papillary cancer than in normal thyroid tissue as determined by tandem mass (MS/MS) analysis. These distributional differences may be associated with the biological behavior of thyroid papillary cancer.

Photocoagulation of microvascular and hemorrhagic lesions of the vocal fold with the KTP laser.

Objectives: Ectasias and varices of the vocal fold are microvascular lesions that are often due to chronic abuse of the voice, and are occasionally encountered in association with other disorders such as polyps, Reinkes edema, and hematoma. The KTP laser can be used for photocoagulation of small vascular lesions, because the laser beam is well absorbed by hemoglobin, and damage to the epithelium is minimal. The present pilot study examined how the KTP laser could be used for microvascular lesions and their associated lesions. Methods: Twelve patients who had undergone phonomicrosurgery were enrolled in the present study. The microvascular lesions were treated by photocoagulation with the laser set at a low power of 1.5 W in the continuous mode, while preserving the epithelium, and associated lesions were then treated by microdissection with cold instruments. The postoperative phonatory function was assessed by maximum phonation time, a perceptual test rating (GRBAS scale), and stroboscopy. Results: The procedures were completed successfully in all cases. An exceptional case of a small hemorrhagic polyp allowed treatment with the laser only. The postoperative stroboscopic findings, maximum phonation time, and perceptual test rating all showed significant improvement compared with the preoperative state. No adverse effects, such as scarring or reduction of the mucosal wave, were observed in the current series. Conclusions: KTP laser photocoagulation is a relatively simple and safe procedure for treating microvascular lesions of the vocal fold. It is not recommended for photocoagulation of hemorrhagic polyps or hematomas, because such lesions have little blood flow inside and thus photocoagulation is usually impossible or requires too much laser energy. However, photocoagulation of perimeter or feeding vessels of such disorders may facilitate the following procedure by avoiding unnecessary bleeding, as well as preventing recurrence of hemorrhagic lesions.

Magnifying Endoscopy with Narrow Band Imaging to Determine the Extent of Resection in Transoral Robotic Surgery of Oropharyngeal Cancer

Transoral robotic surgery (TORS) is a less invasive treatment that is becoming popular all over the world. One of the most important factors for achieving success in TORS is the ability to determine the extent of resection during the procedure as the extent of resection in the laryngopharynx not only affects oncological outcomes but also directly affects swallowing and voice functions. Magnifying endoscopy with narrow band imaging (ME-NBI) is an innovative optical technology that provides high-resolution images and is useful in detecting early superficial pharyngeal cancers, which are difficult to detect by standard endoscopy. A 55-year-old male with superficial oropharyngeal cancer has been successfully treated by combining MB-NBI with TORS and MB-NBI was useful in determining the extent of resection. ME-NBI with TORS will make it possible to achieve a higher ratio of minimally invasive treatment in pharyngeal cancer.

Glottic regeneration with a tissue-engineering technique, using acellular extracellular matrix scaffold in a canine model†

Acellular extracellular matrix scaffold derived from porcine urinary bladder (UBM) is decellularized material that has shown success for constructive remodelling of various tissues and organs. The regenerative effects of UBM were reported for the tympanic membrane, oesophagus, trachea, larynx, pleura and pericardium in animal studies, with promising results. The aim of this study was to investigate the regenerative effects of UBM on hemilarynx, using a canine model. A left partial hemilaryngectomy was performed and the surgical defects were reconstructed by insertion of UBM scaffold. Although local infection was observed in one dog in 1 week after implantation of the scaffold, all dogs showed good re‐epithelialization with minimum complication in 1 month. The effect of regeneration of the larynx was evaluated 6 months after the operation. The excised larynx experiments were performed to measure phonation threshold pressure (PTP), normalized mucosal wave amplitude (NMWA) and normalized glottal gap (NGG). The results of the measurements showed that PTP was normal or near normal in two cases and NMWA was within normal range in three cases, although there were individual variations. Histological examination was completed to evaluate structural changes in the scaffold with the appearance of the new cartilaginous structure. However, the regenerated vocal fold mucosa was mostly scarred. The UBM scaffold has shown to be biocompatible, biodegradable and useful for tissue regeneration of the hemilarynx, with possible restoration of function of the vocal fold. The vocal fold mucosa was scarred, which is the next challenge to be addressed. Copyright

Magnifying endoscope with NBI to predict the depth of invasion in laryngo-pharyngeal cancer

To examine if macroscopic classification with a magnifying gastrointestinal endoscope with narrow band imaging (ME‐NBI) is useful in predicting pathological depth of tumor invasion in laryngo‐pharyngeal cancer.

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.

Upper Mediastinal Node Dissection for Hypopharyngeal and Cervical Esophageal Carcinomas

Objectives: Hypopharyngeal cancer (HPC) and cervical esophageal cancer (Ce) are aggressive tumors with a poor prognosis. Multiple lymph node metastases often occur in the upper mediastinum, as well as in the neck, and thus upper mediastinal dissection (MD) is crucial to improving the cure rate. However, excessive MD can increase postoperative morbidity and mortality, making it important to employ the proper technique and appropriate extent of dissection. In the present retrospective study we aimed to determine the proper extent of upper MD according to tumor site and stage. The benefit and risk of upper MD are also discussed. Methods: Chart review was completed for patients who underwent upper MD, including 64 patients with HPC, 21 patients with Ce, and 9 patients with Ce extending to involve the upper thoracic esophagus (Ce/Ut). The incidence and distribution of lymph node metastases in the upper mediastinum were assessed by postoperative histopathologic examination. Postoperative complications of upper MD, as well as the impact on survival and locoregional control, were also reviewed. Results: Upper mediastinal metastases were detected in 7.8% of HPC patients, 33.3% of Ce patients, and 55.6% of Ce/Ut patients. In HPC patients, mediastinal metastases were usually associated with T4 primary tumors (80%), whereas positive nodes in the upper mediastinum were detected regardless of T stage in both Ce and Ce/Ut. Only 1 Ce/Ut patient with a T4 tumor developed late nodal metastasis in the lower mediastinum. The 5-year disease-specific survival and locoregional control rates were 58.6% and 90.2% in HPC, 45.5% and 94.1% in Ce, and 38.9% and 77.7% in Ce/Ut, respectively. Rupture of the greater vessels after MD was observed in 5 cases (5.3%). Conclusions: The present results indicate excellent locoregional control rates following upper MD, while major complications such as arterial breakdown were rare. It is suggested that upper MD may be an essential and adequate procedure for patients with Ce or Ce/Ut tumors, and may also be required for cases of HPC with a T4 primary to improve locoregional control of the disease.

Recurrence patterns after postoperative radiotherapy for squamous cell carcinoma of the pharynx and larynx

Abstract Conclusions: Distant metastasis was a major pattern of recurrence after postoperative radiotherapy (PORT) for squamous cell carcinoma (SCC) of the oropharynx, hypopharynx, and larynx. PORT provided good loco-regional control, with tolerable toxicities. Advanced pT and pN were unfavorable prognostic factors. Objective: To determine the clinical outcomes, and the patterns and risk factors for recurrence of SCCs of the oropharynx, hypopharynx, and larynx treated with surgery and PORT. Methods: We retrospectively reviewed 84 patients who received PORT after definitive surgery for SCC of the oropharynx, hypopharynx, or larynx between 2000 and 2010. The primary sites were the oropharynx in 25 patients, hypopharynx in 47 patients, and larynx in 12 patients. Results: The 3-year overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC) rates were 64.9%, 56.7%, and 92.1%, respectively. Recurrences were observed in 27 patients: 6 patients had loco-regional recurrence and 23 patients developed distant metastasis. On multivariate analysis, pT4 and pN2c-N3 displayed significantly worse effects on OS (p = 0.02 and p < 0.01, respectively) and PFS (p = 0.02 and p < 0.001, respectively). In the acute phase, 12 patients experienced grade 3 or 4 toxicities. There were no grade 5 toxicities. Late grade 3 toxicity developed in six patients and no grade 4 or 5 toxicities were observed.