Tsutomu Minamikawa

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.

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.

Prognostic Value of FDG PET Imaging in Patients with Laryngeal Cancer

Background and Purpose To investigate the prognostic value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with laryngeal cancer. Materials and Methods The study included 51 patients of whom 30 underwent definitive radiotherapy with or without chemotherapy and 21 underwent radical surgery with or without adjuvant chemoradiation therapy. FDG uptake by both the primary lesion and the neck node was measured using the maximum standardized uptake value (SUVmax). The effects of clinicopathological factors including primary tumor SUVmax and nodal SUVmax on progression-free survival, local control, nodal progression-free survival, and distant metastasis-free survival were evaluated using the log-rank test and Cox method. Results The median duration of follow-up was 48.6 months (range 8 to 82.1 months). Univariate analysis showed that nodal SUVmax, N status, and tumor TNM stage were significantly associated with recurrence, whereas primary tumor SUVmax, age, treatment strategy and T status were not. Multivariate analysis demonstrated that only the nodal SUVmax was a significantly unfavorable factor for progression-free survival (p = 0.029, hazard ratio 0.54, 95% CI 0.38-0.87) and nodal progression-free survival (p = 0.023, hazard ratio 0.51, 95% CI 0.34-0.81). ROC curve analysis and log-rank test showed that patients with a high nodal SUVmax (≧4) had a significantly lower progression-free survival rate than those with a low SUVmax (<4; p<0.0001). Conclusions The pretreatment SUVmax of nodal disease in patients with laryngeal cancer is prognostic for recurrence.

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.

Risk Factors Associated with Distant Metastasis in Patients with Oral Squamous Cell Carcinoma

Objective The purpose of this study was to retrospectively evaluate the incidence of distant metastasis (DM) after curative surgical treatment and assess the multivariate relationships among various risk factors for DM in patients with oral squamous cell carcinoma (OSCC). Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods The medical records of all patients with OSCC without DM who underwent curative surgery with or without postoperative adjuvant chemoradiation between January 2001 and February 2014 at our institution were retrospectively reviewed. There were a total of 451 patients, including 271 men and 180 women, with a mean age of 65.9 ± 13.5 years. Results Of these patients, 30 (6.7%) developed DM. During the follow-up period, the 5-year overall survival rate was 76.2%. Sites of DM comprised the lungs (80.0%), skin (13.3%), liver (10.0%), bone (6.7%), and brain (3.3%). We found the T classification and N classification as well as the histologic grade to be significant risk factors associated with the development of DM in the univariate analysis only (P = .003), whereas locoregional failure (odds ratio [OR], 4.03), multiple lymph node metastases (more than 4 positive nodes; OR, 3.32) and positive extracapsular spread (OR, 3.06) were identified to be significant risk factors associated with the development of DM in the multivariate analysis. Conclusion We demonstrated multivariate relationships among various risk factors for DM in OSCC patients. Clinicians should consider these risk factors and pay special attention to detecting DM early during the postoperative management of OSCC patients with these risk factors.

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.

Risk factors associated with postoperative delirium after surgery for oral cancer

OBJECTIVE The purpose of this study was to retrospectively investigate the multivariate relationships among the various risk factors for postoperative delirium in patients undergoing oral cancer surgery. MATERIAL AND METHODS The medical records of all patients with oral cancer who underwent curative head and neck surgery between April 2011 and March 2013 at our institution were retrospectively reviewed. There was a total of 188 patients, including 110 males and 78 females. RESULTS We found that older age, extensive surgical procedure, longer operation, excessive hemorrhage, blood transfusion, longer postoperative management in the intensive care unit, longer postoperative hospital stay, lower albumin level in the preoperative blood test, and lower total protein, albumi, n and hemoglobin levels and a higher C-reactive protein (CRP) level in the postoperative blood tests were significant variables in the univariate analysis (p < 0.05). We also determined that an older age (odds ratio [OR] = 6.83), intraoperative lower hemoglobin levels (OR = 6.82), and excessive hemorrhage (OR = 3.62) during surgery were significant variables in the multivariate analysis. CONCLUSION Clinicians should pay special attention to preventing delirium during the postoperative management of older patients with these risk factors. Furthermore, increasing the hemoglobin levels during surgery may be able to prevent postoperative delirium.

Incidence of Venous Thromboembolism After Oral Oncologic Surgery With Simultaneous Reconstruction

PURPOSE Patients with oral cancer who undergo resection with simultaneous reconstruction are presumed to be at high risk for developing venous thromboembolism (VTE) according to current criteria. The primary purpose of this retrospective study was to report the incidence of VTE after oral cancer surgery requiring primary reconstruction and to identify the potential risk factors for VTE in this population. MATERIALS AND METHODS This retrospective study evaluated 133 consecutive patients who had undergone oral cancer resection with simultaneous reconstruction from April 2007 through December 2014. Bilateral lower-extremity venous duplex ultrasonography (VDUS) was routinely performed 2 days after surgery. Pulmonary embolism was confirmed with computed tomography. The Caprini risk score (CRS) was obtained for each patient. Patients with and without VTE were compared using the χ2 test and Student t test with some variables. Univariate predictors associated with VTE were entered into a multivariate logistic regression analysis. A P value less than .05 was regarded as indicating statistical significance. RESULTS The incidence of VTE after oral oncologic surgery with simultaneous reconstruction was 26.3% (35 of 133 patients): deep vein thrombosis (DVT) and pulmonary embolism occurred in 2.3% (3 of 133) and DVT alone was found in 24.0% (32 of 133). Multivariate logistic regression analysis showed that only a high CRS was statistically relevant to VTE occurrence. CONCLUSIONS Because a high incidence of VTE was found after major oral and maxillofacial surgery, lower-extremity VDUS should be undertaken in patients who undergo oral cancer surgery with simultaneous reconstruction, especially those with a high CRS.

Transcutaneous Carbon Dioxide Induces Mitochondrial Apoptosis and Suppresses Metastasis of Oral Squamous Cell Carcinoma In Vivo

Squamous cell carcinoma (SCC) is the main histological type of oral cancer. Its growth rate and incidence of metastasis to regional lymph nodes is influenced by various factors, including hypoxic conditions. We have previously reported that transcutaneous CO2 induces mitochondrial apoptosis and decreases lung metastasis by reoxygenating sarcoma cells. However, previous studies have not determined the sequential mechanism by which transcutaneous CO2 suppresses growth of epithelial tumors, including SCCs. Moreover, there is no report that transcutaneous CO2 suppresses lymphogenous metastasis using human cell lines xenografts. In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts. Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis. They also showed that transcutaneous CO2 significantly inhibits SCC tumor growth and affects expressions of HIF-1α, VEGF, MMP-2 and MMP-9, which play essential roles in tumor angiogenesis, invasion and metastasis. In conclusion, transcutaneous CO2 suppressed tumor growth, increased mitochondrial apoptosis and decreased the number of lymph node metastasis in human SCC by decreasing intra-tumoral hypoxia and suppressing metastatic potential with no observable effect in vivo. Our findings indicate that transcutaneous CO2 could be a novel therapeutic tool for treating human SCC.

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.