Itaru Nagai

Phase I clinical trial of survivin‐derived peptide vaccine therapy for patients with advanced or recurrent oral cancer

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is abundantly expressed in most malignancies, but is hardly detectable in normal adult tissues. Previously we have identified a human leukocyte antigen (HLA)‐A24‐restricted antigenic peptide, survivin‐2B80‐88 (AYACNTSTL), recognized by CD8+ cytotoxic T lymphocytes (CTL). Survivin‐2B80‐88‐specific CTL were induced efficiently from peripheral blood mononuclear cells (PBMC) of oral cancer patients after stimulation with the peptide in vitro. We conducted a phase I clinical study to evaluate the safety and the efficacy of survivin‐2B80‐88 peptide vaccination in HLA‐A24‐positive patients with advanced or recurrent oral cancer. The vaccines were given subcutaneously or intratumorally six times at 14‐day intervals. Eleven patients were enrolled and 10 patients completed the vaccination protocol. No adverse events were observed in any patients. In two patients, the levels of serum squamous cell carcinoma (SCC) antigen decreased transiently during the period of vaccination. Tumor regression that was compatible with a partial response (PR) was noted in one patient. The remaining nine patients experienced progressive disease (PD). Immunologically, an increase of the peptide‐specific CTL frequency was detected in six of the eight patients evaluated by HLA‐A24/peptide tetramer analysis. The present clinical trial revealed that survivin‐2B peptide vaccination was safe and had therapeutic potential for oral cancer patients. However, subsequent clinical trials in combination with various adjuvant drugs will be required to improve the immunological and therapeutic efficacy. This trial was registered with University Hospital Medical Information Network (UMIN) number UMIN000000976. (Cancer Sci 2011; 102: 324–329)

Combined expression of p53, cyclin D1 and epidermal growth factor receptor improves estimation of prognosis in curatively resected oral cancer

p53, cyclin D1 and epidermal growth factor receptor (EGFR) are molecular markers that regulate the cell cycle or cell growth and play important roles in tumor development and progression. In this study, we examined the impact of immunohistochemical expression of these markers on tumor progression in 140 oral cancers. p53, cyclin D1 and EGFR were expressed in 64 cases (46%), 54 cases (39%) and 54 cases (39%), respectively, but there was no inter-relationship between any two of these markers. In the association of these markers with clinicopathological features, EGFR expression alone was significantly associated with poor differentiation (P=0.0008) and invasive growth pattern (P=0.0003). Any of these markers, including EGFR, had no significant impact on survival. Coexpression of all these markers, however, was significantly associated with invasive growth pattern (P=0.0149) and shortened survival (P=0.0181), and was a significant and independent unfavorable prognostic factor (P=0.0002), along with tumor size (P=0.0040), nodal metastasis (P=0.0137) and growth pattern (P=0.0017) in a multivariate analysis. Simultaneous coexpression of these markers in oral cancers might prove to be a useful indicator for identification of low- or high-risk patients.

Oral malignant melanoma: long-term follow up in three patients

Three patients with oral malignant melanoma, who survived for at least ten years after initial examination, are presented. The depth of tumor invasion was 5 mm or less in all patients. The first patient received surgery and postoperative immunotherapy and she had no recurrence more than 18 years after treatment. The second patient underwent surgery but had local recurrence after 11 years. He underwent resection and postoperative chemotherapy and was still alive more than 14 years after initial examination. The third patient received radiotherapy and had metastasis nine months after treatment. Resection and radiotherapy were performed and the patient was alive more than 14 years after first presentation.

Relationship Between Mandibular Ramus Height and Masticatory Muscle Function in Patients With Unilateral Hemifacial Microsomia.

Objective To clarify the relationship between mandibular ramus height and function of masticatory muscles in patients with hemifacial microsomia. Design Retrospective study of imaging and physiological data. Setting Images and physiological data were obtained from the records of Sapporo Medical University Hospital. Patients A total of 29 patients with hemifacial microsomia who showed Pruzansky grades I, II deformity. Main Outcome Measures Mandibular ramus height and masticatory muscle volume were evaluated with multi-detector row computed tomography. The electromyographic value was measured by the K7 Evaluation System. The hemifacial microsomia patients were classified into three groups based on the mandibular ramus height ratio of the affected and unaffected sides: group 0, > 1.00; group 1, 1.00 to 0.85; group 2, < 0.85. The Tukey-Kramer method and Games-Howell method were used to determine correlations between parameters. Results Decreased mandibular ramus height was significantly correlated with both reduced electromyographic values of the masseter muscle (P < .05) and the amount of mandibular lateral deviation at the time of maximum opening (P < .05) on the affected side. These differences were prominent in unilateral hemifacial microsomia patients classified as group 2. Conclusions Decreased mandibular ramus height may cause dysfunction of the masseter muscles but not the temporal muscle on the affected side in patients with hemifacial microsomia.

Pattern and Significance of Cervical Metastatic Disease in Oral Squamous Cell Carcinoma

Abstract Objective: This study describes the patterns of the cervical metastatic lymph nodes of patients with oral carcinoma who received unilateral neck dissection and their correlation with the clinical course. Patients and Methods: Clinical examination of 72 patients with tongue, floor of the mouth, and mandibular gingival squamous cell carcinoma who had received unilateral neck dissection during an 11-year period between 1987 and 1997 was performed. Results: The survival rates of patients with 3 or more metastatic lymph nodes, and/or extracapsular nodes, and/or a metastatic level of III or IV were all lower than for patients with less than 3 metastatic lymph nodes (p = 0.002) and/or intracapsular nodes (p = 0.0118), and/or metastasis of level I or II (p = 0.0067). Multivariate analysis revealed that the number of metastatic lymph nodes was the factor of greatest influence in terms of prognosis. Conclusion: The prognosis for patients with 3 or more metastatic lymph nodes and/or extracapsular nodes are poor, so postoperative therapy such as radiotherapy should be considered for these patients.

Clinical investigation of supraomohyoid neck dissection in N0 cases of oral squamous cell carcinoma

舌 (10例) , 口底 (10例) , 下顎歯肉 (4例) 原発のN0の扁平上皮癌症例で片側の肩甲舌骨筋上部郭清術を行った24例について臨床的検討を行った。病理学的に転移リンパ節は8例 (33.3%) にみられたが, それらの臨床経過は良好であった。病理学的に転移リンパ節がみられなかった16例中1例が術後にみられた頸部転移により死亡しているが, 他の15例は再発, 転移なく生存している。3個の転移リンパ節が1例で, 1個が7例で認められた。転移リンパ節はlevel 1に6例で, level 2に2例でみられた。被膜外転移巣はlevel 1に2例でみられた。検索症例の大半では, 原発巣の病理組織学的悪性度は比較的高度であつた。今回の検索より, 原発巣の病理組織学的悪性度を考慮すれば, 肩甲舌骨筋上部郭清術は診断的効果のみならず治療的効果があがることが示唆された。

Postoperative Evaluation of Maxillofacial Deformity According to Facial Form Classification. Patients Evaluation by Questionnaire.

Data from questionnaires consisting of 36 items which were sent to patients with prognathism were analysed, for self-evaluation on the postoperative release from various troubles that were suffered before surgery.The subjects were 77 patients (14 males and 63 females) out of 147 patients who had undergone sagittal splitting ramus osteotomy in our clinic from 1989 to 1994. The patients were divided into three groups with different facial profile, skeleton, and occlusion: prognathism group (28 patients with mandibular prognathism only), asymmetry group (27 patients with mandibular prognathism with asymmetry), and open bite group (22 patients with mandibular prognathism and open bite).The results were as follows:1) As for the preoperative particular troubles, those concerning occlusion and facial profile were noted in the prognathism group and those concerning mastication in the open bite group. The patients in the asymmetry group had the same troubles as noted in the above two groups, but suffered from multiple troubles, including temporomandibular joint disorder and others. Moreover, they were comparatively younger.2) In the open bite group, only a few patients evaluated the postoperative change in the facial profile, but much more patients evaluated the change in speech after surgery.3) Over 90 per cent of the evaluated patients from the three groups the improvement of occlusion after the operation, but it took more time for patients to eat an ordinary meal satisfacorily in the asymmetry group.4) Preoperative discomforts due to the temporomandibular joint syndrome were most remarkable in the asymmetry group, but less reduced in the prognathism group after surgery.5) As for the change in tongue and the numbness of lip or chin after surgery, there were no significant differences among the three groups.6) The difference between before and after surgery in the open bite group was move noticeable than the others.7) As for the motive of undergoing surgery, although many patients were recommended to undergo surgery by dentists among the three groups, more patients from the prognathism group decided to undergo it by themselves.8) As for the overall evaluation for the result of surgery, most patients in the three groups showed positive response to surgery. As the main reason, aesthetic improvement was evaluated in the prognathism group, that of occlusion and mastication in the open bite group, and that of the psychological aspect in the asymmetory group.

Two cases of squamous cell carcinoma of the oral tongue treated successfully with immuno-chemotherapy.

今回, 舌癌2症例に対して, 1症例はOK-432を腫瘍内及び腫瘍周囲に注射後, PBO療法を併用した。また他の1症例ではOK-423の局所投与前後にPP療法を併用した。その結果は良好であり両症例ともにCRであった。したがって免疫化学療法は上述した治療によって免疫能が増強を示す舌癌患者に対してより有効であると考えられた。