Hideoki Uryu

Aggressive invasive micropapillary salivary duct carcinoma of the parotid gland.

The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60‐year‐old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein‐15 (GCDFP‐15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP‐15 and AR. Immunohistochemical staining for D2‐40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP‐15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor.

Correlations between thymidylate synthase expression and chemosensitivity to 5-fluorouracil, cell proliferation and clinical outcome in head and neck squamous cell carcinoma

Background: 5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). Thymidylate synthase (TS), which is the target enzyme of 5-FU, has been demonstrated to be a key regulatory enzyme. In this study, we examined whether TS expression is correlated with chemosensitivity to 5-FU, cell proliferation and clinical outcome in HNSCC. Methods: An antisense TS cDNA was constitutively expressed in the HNSCC cell line. The effects of TS expression on in vitro cell growth and 5-FU cytotoxicity were examined. We also evaluated the association between TS expression and cell proliferation in surgical specimens, and prognosis in HNSCC patients. Results: Antisense TS transfection increases the cytotoxicity of 5-FU and inhibits cell proliferation in HNSCC cellsin vitro. Immunohistochemical expression of TS may have prognostic value in patients with HNSCC. Conclusions: These results indicate that TS expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy.

The role of dihydropyrimidine dehydrogenase expression in resistance to 5-fluorouracil in head and neck squamous cell carcinoma cells

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs to treat cancer patients. However, the presence of drug resistant tumor cells may cause a poor response to 5-FU based chemotherapy. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and is also responsible for the degradation of 5-FU. In this study, we examined whether DPD expression affects the cytotoxic activity of 5-FU against head and neck squamous cell carcinoma (HNSCC) and the role of DPD in the biological regulation of HNSCC. We constitutively expressed the DPD cDNA in a HNSCC cell line. The effect of DPD expression on in vitro cell growth, cell cycle and 5-FU cytotoxicity was examined. In addition, we also evaluated the association between DPD expression and the proliferation of tumor cells in surgical specimens, and prognosis of the patients with HNSCC. DPD overexpression decreases the cytotoxicity of 5-FU. CDHP, a strong DPD inhibitor, enhances the cytotoxic effect of 5-FU in HNSCC cells in vitro. DPD expression level does not effect cell proliferation and does not seem to have prognostic value in HNSCC. The present results strongly indicate that DPD expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy, suggesting the possibility of personalized chemotherapy including the prediction of response and adverse effects.

Tracheal reconstruction with a modified infrahyoid myocutaneous flap

Reconstruction of a tracheal defect is a challenge because it often requires invasive surgery associated with relatively high morbidity. We recently invented a less‐invasive method using a modified infrahyoid myocutaneous (IHMC) flap for the reconstruction of a tracheal defect in an 83‐year‐old male. A tracheal defect, the right half of the cricoid cartilage plus the right three quarters of the I‐IV tracheal cartilage (about 3 × 4 cm), was reconstructed with a modified IHMC flap composed of the sternohyoid and platysma muscles and a skin pedicle. Considering the age of patient, we avoided rigid reconstruction and used a soft silicone tracheal opening retainer (Koken Co., Ltd., Tokyo, Japan) as an anterior wall dilator after surgery and waited for the scarring of the flap until it become rigid enough. The postoperative course was uneventful and the trachea was reconstructed safely. Tracheal reconstruction with an IHMC flap is a useful and less‐invasive alternative compared to end‐to‐end anastomosis or reconstruction with a forearm flap, which is currently used as a mainstay.

Roles of Therapeutic Selective Neck Dissection in Multidisciplinary Treatment

In the treatment of head and neck squamous cell carcinoma (HNSCC), management of cervical lymph nodal metastases has a crucial impact on the prognosis of patients. The “radical neck dissection (RND)”, which was proposed by Crile (Crile, 1906) in 1906, had long been played a role of standard treatment for neck metastases due to its high curability. However, during the last two to three decades, modified neck dissection (MND), also called as “functional neck dissection”, which preserves non-lymphatic structures, has replaced the position of RND, because patients as well as surgeons have become more aware of the significance of the quality of life. In addition, it has become apparent that under current multimodality treatment protocols, MND can achieve improved functional results without compromising oncological outcomes, compared to the conventional RND (Ferlito et al., 2003). Of note, in this study, MND implies the comprehensive (I-V) ND that is generally termed as “modified radical neck dissection (MRND)”, unless described otherwise. Moreover, the detailed studies on the patterns of potential neck metastases clearly demonstrated that the laryngeal and pharyngeal cancers seldom metastasize to the level I and V, while the oral cavity cancers to the level IV and V (Lindberg, 1972; Shah, 1990). These data have strongly encouraged the application of selective neck dissection (SND) that spares the dissection of at least one level in the treatment of clinically N0 neck as “elective” SND (ESND). It is now widely accepted that ESND can achieve similar regional control rates compared to comprehensive neck dissection (CND) (i.e., RND or MRND) in this N0 clinical setting with improved functional outcomes as summarized in a comprehensive review (Ferlito et al., 2006). Recent remarkable advancements in chemoradiation have further extended the application of SND to clinically N+ cases as “therapeutic” SND (TSND) instead of therapeutic CND (TCND). Efficacy of TSND performed either as an initial treatment or as a planed ND (PND) in the course of multidisciplinary treatments has been reported by an increasing number of studies (Ambrosch et al., 2001; Byers et al., 1999; Ferlito et al., 2009; Lohuis et al., 2004; Muzaffar, 2003; Patel et al., 2008; Shepard et al., 2010). Moreover, a recent study by Robins et. al., (Robbins et al., 2005) demonstrated that super selective (i.e., only two levels) neck dissection can achieve quite favorable outcomes, when performed as a PND after RADPLAT. In view of these observations, neck dissection (ND)

Combined transcervical and orbitozygomatic approach for the removal of a nasopharyngeal adenocarcinoma.

OBJECTIVE In some cases, the exposure and safeguarding of the internal carotid artery (ICA) are not easy by the maxillary swing approach that is used as a mainstay for the removal of nasopharyngeal tumors. To address this issue, we have developed a new combined transcervical and orbitozygomatic approach. METHODS A nasopharyngeal adenocarcinoma arose in a 52-year-old patient and occupied the right middle skull base extending to the ICA. We first identified and dissected the ICA from the posterolateral part of the tumor using a transcervical approach. Then, the tumor was approached and removed by an orbitozygomatic technique with hemifacial dismasking. The surgical defect was filled using a temporal muscle flap, which was divided into two parts according to the blood supply from either the anterior or the posterior deep temporal artery. RESULTS The postoperative course was uneventful and favorable cosmetic results were obtained. The patient has been free of carcinoma for more than 40 months after the surgery. CONCLUSION Our new combined approach might be a good option for selected patients with nasopharyngeal tumors.

Single-cycle induction chemotherapy for resectable advanced hypopharyngeal cancer

BackgroundThe role of induction chemotherapy (IC) in the treatment of resectable advanced head and neck squamous cell carcinoma has not been elucidated, and the most effective IC regimen for chemoselection is still unknown. At our institute we have not used the triple combination of docetaxel, cisplatin, fluorouracil (TPF) for chemoselection, but rather the double combination of docetaxel + cisplatin (TP). The aim of this study is to report the outcome of patients with advanced hypopharyngeal cancer treated by single cycle of IC with TP followed by chemoradiation (CRT) or surgery.MethodsA total of 29 patients with resectable advanced hypopharyngeal cancer who were treated with a single cycle of IC were entered into the study. Responders were treated by CRT while nonresponders underwent surgery. Outcomes were analyzed using the Kaplan–Meier method.ResultsA single cycle of IC with TP achieved response in 21 of the 29 patients. The major side effect was neutropenia which could be managed without delaying the sequential treatment. The 2-year overall survival and disease-specific survival were both 74.0% (stage III 100%, stage IVA 69.1%). The cumulative 2-year laryngeal preservation rate was 100% for stage III and 53.6% for stage IVA.ConclusionA single cycle of IC with the combination of docetaxel + cisplatin may be sufficient to select advanced hypopharyngeal cancer patients with radio-sensitivity. IC intended for organ preservation strategies should be low toxic. Our strategy may be a useful for providing the benefits of IC and the opportunity for curative surgery without delay.

Morphological reconstruction of the neoepiglottis after hyo-sub-glosso-epiglottectomy (anteriorly extended supraglottic laryngectomy)

INTRODUCTION Primary closure (PC) has been used as the standard surgical technique for defects after supraglottic laryngectomy (SL). In the head and neck cancer surgery textbooks and literature, this relatively simple method has also been recommended for the closure of surgical defects after hyo-sub-glosso-epiglottectomy (HSE) or anteriorly extended supraglottic laryngectomy, in which the base of the tongue is removed with supraglottic structures during SL. However, this closing method ignores the original three-dimensional morphology of the supraglottic space that plays a critical functional role in phonation, respiration, and swallowing. Consequently, even after simple SL, patients who undergo PC suffer from frequent postoperative complications, including unclear voice, insufficient airway, and aspiration pneumonia, which often require placement of permanent tracheal stoma, gastric tube, and gastrostomy. These unfavorable outcomes become more prominent in patients with HSE due to the reduced volume of the base of the tongue. In particular, the enhanced risks of acute and persistent postoperative aspiration pneumonia occasionally require the sacrifice of the preserved larynx to save the life of the patient. In addition, this reconstruction method imposes excessive tension between sutured tissues, causing frequent postoperative leakage, infection, and fistula formation, especially in cases of salvage surgery. To overcome these critical problems, we reconstructed the supraglottic space after HSE with a rectus abdominis myocutaneous (RAMC) flap in a series of three patients including one salvage case. The purpose of this method was to create a sufficient convex shape that hangs over the remaining larynx expecting that it might function as a neoepiglottis. This method worked well, and all three patients demonstrated quite satisfactory functional results compared to the PC method. Surgical techniques of this novel reconstruction method are described herein.