Kenji Okami

Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma

We have identified a new human p53 homologue, p40 (p51/p63). This gene was mapped to the distal arm of 3q and was found to be essential for normal epithelial development. We used microsatellite and FISH analyses to search for genetic alterations of p40 in primary HNSCC. A more precise localization of p40 was completed using 6 known markers on 3q and a newly isolated microsatellite marker within the p40 gene. We also determined the genomic organization of the p40 gene using human YAC and BAC clones. Microsatellite analysis revealed that 14 of 26 (54%) primary HNSCC had allelic imbalance in at least 1 of the 7 microsatellite loci. However, FISH analysis with a p40 probe showed that a majority of HNSCC had an increased copy number of the locus regardless of allelic status. Thus, overrepresentation of the p40 locus may play an important role in the development of HNSCC. Int. J. Cancer 86:684–689, 2000.

Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck

BackgroundA phase I/II trial of concurrent docetaxel and radiation for head and neck cancer was conducted to estimate the recommended dose schedule of docetaxel, and then to evaluate the therapeutic benefit.MethodsPatients received radiation in 2.0-Gy single daily fractions to a total dose of 60 Gy. Docetaxel was administered weekly for 6 consecutive weeks.ResultsDocetaxel 15 mg/m2 was considered the maximum tolerated dose (MTD). The recommended dose was decided as 10 mg/m2. The phase II study was conducted using docetaxel at 10 mg/m2. Thirty-nine patients were enrolled. The overall response rate was 96.9%. The prognosis of the complete response (CR) patients was significantly better than that of the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia, stomatitis, and anorexia. Thirty-two of the 35 eligible patients showed high compliance, of over 90%, and their toxicities were manageable.ConclusionEven low-dose docetaxel shows a strong effect in combination with radiation, with a high survival rate in CR patients. The effect on survival will be assessed by further follow-up.

Platinum-based Chemotherapy Plus Cetuximab for the First-line Treatment of Japanese Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck: Results of a Phase II Trial

Objective To assess the efficacy and safety of cetuximab in combination with cisplatin and 5-fluorouracil for first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Methods In this open-label, single-arm, multicenter, Phase II study conducted in Japan, patients with confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck received weekly cetuximab (week 1, 400 mg/m2; subsequent weeks, 250 mg/m2) plus a maximum of six three-weekly cycles of cisplatin (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2/day, 24-h infusion, days 1–4). The primary endpoint was the best overall response assessed by an independent review committee according to the modified World Health Organization criteria. Results In total, 33 patients received treatment. The most frequent primary tumor site was the hypopharynx (42%), and most patients had metastatic disease (85%). The best overall response rate as assessed by the independent review committee was 36% (95% confidence interval: 20, 55) and was significantly greater (P = 0.002) than the protocol-specified threshold of 15% at the one-sided 5% level. The disease control rate was 88%. The median progression-free survival and overall survival were 4.1 and 14.1 months, respectively. There were no unexpected safety concerns. Grade 3 or 4 adverse events were experienced by nearly all patients (32, 97%). No adverse events were fatal. Conclusions The demonstrated efficacy and safety of cetuximab in combination with cisplatin and 5-fluorouracil for the first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck justify the further use of this combination treatment in this patient population (ClinicalTrials.gov number, NCT00971932).

New techniques to detect unknown primaries in cervical lymph node metastasis

Various methods have been reported for the detection of unknown primaries in cervical lymph node metastasis. Recently, we applied new optical devices and modifications of endoscopic techniques for the detection of primary lesions, and obtained excellent results. The detection rate of the new method was compared with that of previous methods.

Prevention of wound complications in salvage pharyngolaryngectomy by the use of well-vascularized flaps

Abstract Conclusions: We successfully reduced the incidence of pharyngocutaneous fistulas (PCFs) in high-risk patients undergoing surgery by using pectoralis major myocutaneous flaps (PMMCFs) and deltopectoral flaps (DPFs) to cover suture lines. Objectives: We used coverage of suture lines with PMMCFs and DPFs in patients with high risk of PCFs undergoing total laryngectomy (TL) or total pharyngolaryngectomy (TPL) to determine whether coverage of suture lines during salvage surgery can reduce the incidence of PCFs. Methods: This retrospective study was based on a review of 52 patients who underwent salvage TL or TPL between 2001 and 2011; we have been using PMMCFs or DPFs during salvage surgery since 2008. Details of postoperative complications including PCFs were analyzed. Results: The incidence rate of PCF was lower in the flap group (7.7%) than that in the non-flap group (30.1%). No carotid ruptures were observed in the flap group (0%) as contrasted with patients in the non-flap group (7.7%).

Transoral en bloc resection of superficial laryngeal and pharyngeal cancers

The objective of this study was to evaluate the efficacy and safety of minimally invasive transoral en bloc resection of superficial pharyngeal and laryngeal cancers.

Clinical features and treatment strategy for HPV-related oropharyngeal cancer

Among head and neck squamous cell carcinoma (HNSCC), the incidence of oropharyngeal SCC (OPSCC) is increasing in contrast to carcinoma with origin in other subsites. Human papillomavirus (HPV) is now recognized as a significant risk factor of the carcinogenesis of OPSCC. The HPV-related OPSCC patients tend to be relatively young, less exposed to tobacco and alcohol, and have a relatively high socioeconomic status and education level, which is distinct from HPV-unrelated classical OPSCC. The neck metastases tend to be aggressive and cystic. The better response to treatment resulting in improved prognosis of HPV-related OPSCC led to reconsidering the clinical staging and treatment approaches. Clinical trials of treatment deintensification to reduce the acute and late toxicity without compromising efficacy have been conducted. This review of HPV-related OPSCC focuses on current and generally accepted facts regarding the biology, epidemiology, and therapeutic strategy of this new disease entity.

Sonographic Appearance of the Submandibular Glands in Patients With Immunoglobulin G4-Related Disease

Swelling of the salivary glands is often an initial sign of immunoglobulin G4 (IgG4)‐related disease or IgG4‐related sclerosing/autoimmune disease. We encountered 2 patients with IgG4‐related disease who showed swollen submandibular glands with a unique characteristic sonographic pattern. Bilateral submandibular glands of both patients were enlarged with a smooth contour. The internal echo texture indicated multiple hypoechoic foci scattered against a heterogeneous background, which characteristically appeared with a mottled or irregular netlike appearance. A histopathologic examination of a resected section showed multiple foci of dense infiltrated lymphoplasmacytic cells and lymph follicles encircled by fibrous bands. A mottled appearance in the sonographic findings of the submandibular glands suggests the characteristic of IgG4‐related disease and can be helpful in the differential diagnosis at the initial manifestation.

Tortuosity of the internal carotid artery — report of three cases and MR-angiography imaging

Three cases of a tortuous internal carotid artery bulging the lateral pharyngeal wall that caused a persistent throat abnormal sensation were presented. Magnetic resonance angiography was non-invasive and useful for establishing its diagnosis. Otolaryngologists should recognize this anomaly, because it may cause a fatal hemorrhage during surgical procedures on the pharynx.

Effect of local extension sites on survival in locally advanced maxillary sinus cancer.

We analyzed the effects of local extension sites on survival in patients with locally advanced maxillary sinus cancer.