Takashi Shigeta

Clinical evaluation of Lugol's iodine staining in the treatment of stage I–II squamous cell carcinoma of the tongue

Oral squamous cell carcinoma (OSCC) is often surrounded by epithelial dysplasia; leaving it unresected can result in local recurrence. Staining with Lugols iodine solution detects epithelial dysplasia in oral mucosa, but whether it decreases local recurrence after OSCC surgery is unknown. This study investigated local recurrence rates in patients with early tongue cancer who underwent surgery using Lugols staining. 93 patients with T1-2N0 tongue SCC underwent partial glossectomy using Lugols staining during surgery. Resection was performed at least 5mm from the margin of the unstained area. Patients were investigated retrospectively for local recurrence status. Postoperative histology revealed negative surgical margins for SCC or epithelial dysplasia in 81 patients, close margins for SCC in 5, positive margins for mild epithelial dysplasia in 6, and a positive margin for SCC in one. Those with a positive or a close margin for SCC underwent additional resection 2-4 weeks after surgery; one was proved histologically to have residual SCC. No patients developed local recurrence, but 2 died of neck metastasis and 2 of distant metastasis. The 5-year disease specific survival rate was 93.8%. Lugols staining during surgery can reduce local recurrence and improve survival in patients with early tongue SCC.

Risk factors associated with inferior alveolar nerve injury after extraction of the mandibular third molar—a comparative study of preoperative images by panoramic radiography and computed tomography

In this study we investigated the relationships among the risk factors for inferior alveolar nerve injury (IANI), and the difference between preoperative imaging findings on panoramic radiographs and computed tomography (CT), by univariate and multivariate analyses. We determined the following to be significant variables by multivariate analysis: panoramic radiographic signs, such as the loss of the white line of the inferior alveolar canal or the diversion of the canal; excessive haemorrhage during extraction; and a close relationship of the roots to the IAN (type 1 cases) on CT examination. CT findings of type 1 were associated with a significantly higher risk (odds ratio 43.77) of IANI. In addition, many panoramic findings were not consistent with CT findings (275 of 440 teeth; 62.5%). These results suggest that CT findings may be able to predict the development of IANI more accurately than panoramic findings. Panoramic radiography alone did not provide sufficiently reliable images required for predicting IANI. Therefore, when the panoramic image is suggestive of a close relationship between the impacted tooth and the IAN, CT should be recommended as a means of conducting further investigations.

The observational study of delayed wound healing after tooth extraction in patients receiving oral bisphosphonate therapy.

INTRODUCTION In this study, we investigated whether such a discontinuation of oral bisphosphonate (BP) for 3 months might influence the incidence of BP-related osteonecrosis of the jaw (BRONJ) and wound healing after tooth extraction in patients receiving oral BP therapy. MATERIAL AND METHODS There were a total of 434 teeth in 201 patients (18 males and 183 females). The patients were divided into two groups depending on whether or not they underwent a 3-month discontinuation of BP therapy (BP- and BP+) before tooth extraction. In this observational study investigated delayed wound healing after tooth extraction in patients receiving oral BP therapy. RESULTS In all cases of the BP- group, there were no BRONJ although there was delayed wound healing in two cases. However, in one case of the BP+ group, oral BP was continued because it was deemed high risk to discontinue treatment by the patients physician. In this case, an intraoral fistula was still present with bone exposure at 120 weeks after extraction (BRONJ stage 1). CONCLUSION This study supports the idea of a drug holiday and encourages further clinical research on this topic of tooth extraction in patients receiving oral BP therapy.

Treatment and prognosis of malignant melanoma of the oral cavity: preoperative surgical procedure increases risk of distant metastasis

OBJECTIVE Many authors have reported that oral melanoma patients showed much worse prognosis than those with cutaneous melanoma. We investigated treatment method and prognosis of patients with oral malignant melanoma. STUDY DESIGN Twenty-one patients with oral melanoma treated at our hospital were investigated, with special reference to the influence of preoperative surgical procedures such as biopsy, incision, or tooth extraction on the prognosis. RESULTS All patients underwent surgery followed by immuno-chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC), ninustine hydrochloride (ACNU), vincristine (VCR), and biologic response modifier OK-432. Local control was obtained in 20 of 21 patients. Lymph node metastasis appeared in 13 patients, but neck failure was not detected in any patients. Distant metastasis occurred in 9 patients in spite of loco-regional control. Five-year survival rate of 12 patients with no preoperative surgical procedure was 91.7%, while that of the 9 patients who had undergone surgical procedures before treatment was 25.9% (P < .05). CONCLUSIONS Oral melanoma patients can obtain a prognosis as good as that for cutaneous melanoma patients, when the above-mentioned therapy is used without any preoperative surgical procedures.

Shoulder mobility after spinal accessory nerve–sparing modified radical neck dissection in oral cancer patients

OBJECTIVE Radical neck dissection (RND), a standard surgical procedure for lymph node metastasis of head and neck cancer for decades, causes various dysfunctions, such as pain or limited abduction of the shoulder. Various RND modifications have been made to reduce these postoperative dysfunctions, but the effect of preservation of the spinal accessory nerve is still controversial. The aim of this study was to explain our surgical method of sparing the accessory nerve during neck dissection and to clarify the effect of preserving the nerve on reduction in shoulder dysfunction. STUDY DESIGN One hundred five neck dissections were performed in 90 patients with oral cancer: 4 RNDs and 101 modified radical neck dissections (mRNDs). The spinal accessory nerve was preserved in 96 neck dissections. Dysfunction of the trapezius muscle was evaluated by the limitation of shoulder lateral abduction at 3 months after the operation. RESULTS All 9 patients with resection of the spinal accessory nerve showed severe shoulder dysfunction, whereas 90 out of 96 with preservation of the nerve maintained normal shoulder function. CONCLUSION Spinal accessory nerve-sparing neck dissection can reduce postoperative shoulder dysfunction if careful operating procedures are used.

Metastasis to the lateral retropharyngeal lymph node from squamous cell carcinoma of the oral cavity: Report of three cases

Carcinoma of the oral cavity sometimes metastasizes to the lateral retropharyngeal lymph node (LRPLN), especially when posteriorly invading the soft palate or oropharynx. CT or MRI imaging has enabled detection of LRPLN metastasis in the early stage, but the prognosis of patients with metastasis to this node is extremely poor. The authors report three patients with squamous cell carcinoma of the oral cavity with no posterior invasion who developed metastasis to LRPLN during observation. The primary sites of these three cases were gingiva of the upper incisor region, gingiva of the lower premolar region, and maxillary bone of the upper incisor region. Each patient underwent surgery as their initial therapy, but a recurrent tumor in the LRPLN was detected by CT or MRI despite good loco-regional control. A salvage operation with postoperative radiation therapy was performed for two patients, but only one is still alive with no evidence of tumor 14 months after the last surgery. Management of LRPLN metastasis in oral cancer patients is a challenge for oral surgeons, but early detection by CT or MRI and surgery with postoperative radiation therapy is likely to yield the best local control.

Alteration of Cell–Cell Junctions in Cultured Human Lymphatic Endothelial Cells with Inflammatory Cytokine Stimulation

BACKGROUND To maintain normal function, the lymphatic endothelium is regulated by cell-cell junctions. There have been few studies of lymphatic endothelial cell junctions using standard cell biological methods. This study had two purposes: to characterize cell junctions in cultured lymphatic endothelial cells and to investigate the effects of the inflammatory cytokine TNF-α on altered cell-cell junctions. METHODS AND RESULTS Cultured human dermal lymphatic endothelial cells (HDLEC) were immunostained with the tight junction marker, ZO-1, and adherens junction markers, VE-cadherin and PECAM-1. In TNF-α-treated HDLEC, we evaluated changes in endothelial cell junctions by immunostaining and through the use of transendothelial electrical resistance (TER). Immunofluorescence staining of HDLEC revealed heterogeneity among the endothelial cell junctions, which could be classified into continuous and discontinuous junctions. In these cell junctions, ZO-1 and VE-cadherin were co-localized. Double immunofluorescence staining revealed the broad distribution of VE-cadherin at the cell periphery, where VE-cadherin and PECAM-1 were co-localized. TNF-α treatment decreased TER, caused a predominance in the appearance of discontinuous junctions with a reduction in the broad distribution of VE-cadherin at the cell periphery in HDLEC. CONCLUSIONS The results indicate a heterogeneous distribution of cell junctions in HDLEC involving continuous and discontinuous junctions. Our data also suggest that TNF-α alters the normal distribution of cell junctions and affects the endothelial barrier of cultured lymphatic endothelial cells. The broad distribution of VE-cadherin at the cell periphery may reflect the lymphatic permeability.

Oral squamous cell carcinoma with multiple neck metastases--cases with more than ten pathologically positive lymph nodes in the unilateral side.

PURPOSE The purpose of this study is to know an outcome of the treatment for oral squamous cell carcinoma having more than 10 unilateral pathologically positive lymph nodes (pN)s. PATIENTS AND METHODS We reviewed 212 primary cases of oral squamous cell carcinoma that visited our hospital from January 1999 to December 2011 and underwent resection of the primary tumor with neck dissection. The patients were classified into 3 categories of pN0, pN1-9, and pN ≥ 10 cases, and an outcome of pN ≥ 10 was studied specifically in comparison with the other categories. RESULTS Of the patients studied, 103 cases (48.6%) were pN0, 103 cases (48.6%) were pN1-9, and 6 cases (2.8%) were pN ≥ 10. The pN ≥ 10 group, which had positive nodes of 10 to 30 on the ipsilateral side, was predominantly male and had no cases of well-differentiated squamous cell carcinoma. Extracapsular spread (ECS) was found in all pN ≥ 10 cases, and postoperative distant metastasis occurred in cases with ECS, which was localized in levels higher than III. The proportion of distant metastasis was 0% (0 cases) in pN0, 8.7% (9 cases) in pN1-9, and 66.7% (4 cases) in pN10. Overall survival rate in pN ≥ 10 was 20.8%, whereas it was 89.0% in pN0, and 34.9% in pN1-9. CONCLUSION Oral squamous cell carcinoma having multiple neck metastases (pN ≥ 10) had a poor prognosis because the proportion of distant metastasis was higher in comparison with the other groups of pN0 and pN1-9.

Oral squamous cell carcinoma with microscopic extracapsular spread in the cervical lymph nodes.

The purpose of this study was to determine the detailed background of cases of oral squamous cell carcinoma (OSCC) with microscopic extracapsular spread (ECS) in the cervical lymph nodes. The cases of 78 patients with primary OSCC, who attended hospital from October 2007 to July 2011 and underwent resection of the primary tumour with neck dissection, were reviewed. The subjects were classified into three categories: pN0, pN+/ECS-, and pN+/ECS+; the outcomes of pN+/ECS+ patients were compared in detail with those of the other categories. Thirty-one cases (39.7%) were pN0, 25 cases (32.1%) were pN+/ECS-, and 22 cases (28.2%) were pN+/ECS+. The 3-year overall survival rate was 82.1% in pN0, 74.1% in pN+/ECS-, and 39.8% in pN+/ECS+ (pN0 vs. pN+/ECS+, P=0.0004; pN+/ECS- vs. pN+/ECS+, P=0.0086). The 3-year disease-specific survival rate was 96.2% in pN0, 77.2% in pN+/ECS-, and 39.8% in pN+/ECS+ (pN0 vs. pN+/ECS+, P<0.0001; pN+/ECS- vs. pN+/ECS+, P=0.0038). Patients with poorly differentiated carcinoma, those with three or more ECS+ nodes, and those with ECS+ node(s) located at levels III, IV, and V, had the worst prognosis among pN+/ECS+ subjects.

Effects of postoperative chemotherapy and radiotherapy on patients with squamous cell carcinoma of the oral cavity and multiple regional lymph node metastases

Nodal metastasis in oral squamous cell carcinoma (OSCC) is considered to be a predictor of a poor prognosis. The aim of this study was to investigate the relationship between the number of positive lymph nodes and the prognosis in OSCC patients with nodal metastases and to assess the effects of postoperative radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) on this patient group. A retrospective investigation of 98 patients with OSCC who underwent radical neck dissection and had at least three pathologically positive lymph nodes was performed. The 5-year disease-specific survival rate was 66.7% for patients with 3 positive nodes, while it was significantly lower for those with 4 positive nodes and those with ≥ 5 positive nodes (21.5% and 46.1%, respectively; P < 0.01). The loco-regional control and disease-specific survival rates for the surgery alone, surgery plus RT, and surgery plus CCRT groups were 46.2% and 40.5%, 66.3% and 54.4%, and 81.7% and 52.4%, respectively. For patients with ≥ 4 positive nodes, the loco-regional control rate after surgery plus CCRT was better than that observed after surgery alone (77.5% vs. 32.6%, P = 0.01). Postoperative RT and CCRT have positive impacts on the prognosis of OSCC patients with advanced stage neck disease.