Mitsuhisa Fujimaki

Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosis

OBJECT Malignant cells show increased uptake, which is considered to be facilitated by glucose transporters (GLUTs). Increased GLUT-1 expression has been reported in many human cancers. We hypothesized that a oral squamous cell carcinoma, characterized by high frequency of lymph node metastasis, distant metastasis or local recurrences, was associated with GLUT-1 overexpression in invasion front. METHODS GLUT-1 immunostaining in invasion front was studied on 24 oral squamous cell carcinomas, and revealed the correlation with the clinical characteristics. RESULT The analysis showed that all oral squamous cell carcinoma patients and GLUT-1 expression correlated the depth of the tumors (P = 0.023 < 0.05). Furthermore the survival of patients who had overexpression of invasion front was significant shorter than that of patients with GLUT-1 weakly positive (P = 0.046 < 0.05). No significant association was noted between GLUT-1 immunostaining and either age, gender, subsites, tumor size, or lymph node status. CONCLUSION The present study shows that GLUT-1 served as a marker indicating that tumors with deep invasion tended to result in a worse prognosis in patients due to either lymph node metastasis, a recurrence of the primary lesion or distant metastasis.

A feasibility study of NIR fluorescent image-guided surgery in head and neck cancer based on the assessment of optimum surgical time as revealed through dynamic imaging

Background In order to minimize surgical stress and preserve organs, endoscopic or robotic surgery is often performed when conducting head and neck surgery. However, it is impossible to physically touch tumors or to observe diffusely invaded deep organs through the procedure of endoscopic or robotic surgery. In order to visualize and safely resect tumors even in these cases, we propose using an indocyanine green (ICG) fluorescence method for navigation surgery in head and neck cancer. Objective To determine the optimum surgical time for tumor resection after the administration of ICG based on the investigation of dynamic ICG fluorescence imaging. Methods Nine patients underwent dynamic ICG fluorescence imaging for 360 minutes, assessing tumor visibility at 10, 30, 60, 120, 180, and 360 minutes. All cases were scored according to near-infrared (NIR) fluorescence imaging visibility scored from 0 to 5. Results Dynamic NIR fluorescence imaging under the HyperEye Medical System indicated that the greatest contrast in fluorescent images between tumor and normal tissue could be observed from 30 minutes to 1 hour after the administration of ICG. The optimum surgical time was determined to be between 30 minutes to 2 hours after ICG injection. These findings are particularly useful for detection and safe resection of tumors invading the parapharyngeal space. Conclusion ICG fluorescence imaging is effective for the detection of head and neck cancer. Preliminary findings suggest that the optimum timing for surgery is from 30 minutes to 2 hours after the ICG injection.

A novel approach to translymphatic chemotherapy targeting sentinel lymph nodes of patients with oral cancer using intra-arterial chemotherapy - preliminary study

BackgroundRecent progress in ICG (indocyanine green) fluorescence imaging has provided a means by which we can detect sentinel lymph nodes (SLNs) without the risk of exposing patients to radiation. Neck metastasis is the most significant prognostic factor. It is imperative that early metastasis can be controlled. Intra-arterial chemotherapy is performed in order to preserve organs and to improve prognosis when treating oral cancer.ObjectiveEvaluate translymphatic chemotherapy targeting SLNs in patients with oral cancer using intra-arterial chemotherapy. Evaluation will be carried out through the measurement of CDDP concentrations in SLNs.MethodsFive patients with tongue cancer (T3N0M0) were treated by intra-arterial chemotherapy as neoadjuvant chemotherapy from November 2010 to June 2011. After a week of chemotherapy, patients underwent surgical treatment including the partial resection of the tongue and neck dissection. Intra-arterial chemotherapy was administered at 50 mg/m2 of CDDP either one or two times weekly. 5 mg of ICG was administered to the lingual artery at the beginning of surgery. SLNs were detected using ICG fluorescence imaging. 0.1 g of SLNs and non-SLNs were resected in order to measure CDDP concentrations. The rests of each of the SLNs were examined intraoperatively by routine frozen pathological examination. SLNs were also identified using radioactive injection the day prior to surgery.ResultsThe mean CDDP concentrations in the SLNs and non-SLNs were 1.2 μg/g and 0.35 μg/g, respectively. Our intra- arterial infusion revealed that all metastatic lymph nodes, including SLNs, were without false negative SLNs. However, of 7 metastatic lymph nodes, one was not identified by means of conventional method.ConclusionOur findings verified the possibility that intra-arterial chemotherapy may be effective not only for organ preservation therapy, but also efficient in translymphatic chemotherapy targeting SLNs in patients with oral cancer through the use of ICG fluorescence imaging.

Oncocytic mucoepidermoid carcinoma of the parotid gland with CRTC1-MAML2 fusion transcript: report of a case with review of literature

Oncocytic mucoepidermoid carcinoma is a very rare variant of mucoepidermoid carcinoma, composed predominantly of oncocytic cells. Most previously reported cases described the difficulty in histologic differentiation from other oncocytic tumors. Here we report a case of oncocytic mucoepidermoid carcinoma of parotid gland diagnosed by the detection of CRTC1-MAML2 fusion. A 53-year-old man had a left superficial parotidectomy conducted for 3-cm-sized mass. The resected tumor was composed almost exclusively of oncocytic tumor cells. With detailed histologic evaluation, scarce vacuolated tumor cells, suggestive of mucous cell of mucoepidermoid carcinoma, and one focus of tumor embolism in a vein were found, suggesting the possibility of oncocytic mucoepidermoid carcinoma. Immunohistochemically, oncocytic cells were diffusely positive for p63. Reverse transcriptase polymerase chain reaction and direct sequencing revealed CRTC1-MAML2 translocation of this tumor. To our knowledge, this report describes the first case of oncocytic mucoepidermoid carcinoma confirmed with CRTC1-MAML2 fusion. Identification of this fusion gene may help in distinguishing oncocytic mucoepidermoid carcinoma from its mimics.

Significant preservation of swallowing function in chemoradiotherapy for advanced head and neck cancer by prophylactic swallowing exercise

Dysphagia is a serious complication of chemoradiotherapy (CRT) in patients with head and neck cancer. Approximately 20% to 30% of patients who have dysphagia require feeding tubes. The purpose of this study was to evaluate the impact of prophylactic swallowing exercises on swallowing function.

Relationship between insulin-like growth factor-1 receptor and human papillomavirus in patients with oropharyngeal cancer

Human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (SCC) is associated with better prognosis than HPV‐negative oropharyngeal SCC. The purpose of this study was to assess the expression of insulin‐like growth factor‐1 receptor (IGF‐1R) in patients with oropharyngeal SCC, its relationship to HPV status and various clinical parameters, and its relationship with clinical outcome.

Problems of primary T-cell lymphoma of the thyroid gland -A case report

In the following report we discuss a very rare case of malignant T-cell lymphoma of the thyroid gland that developed in a 70-year-old woman with a past history of hypothyroidism due to chronic thyroiditis. The chief complaint was a rapidly growing neck mass. CT and ultrasonographic examination revealed a diffuse large thyroid gland without a nodule extending up to 13 cm. Although presence of abnormal lymphoid cells in the peripheral blood was not found, the sIL-2 Receptor antibody and thyroglobulin measured as high as 970 U/ml and 600 ng/mL respectively. Fine needle aspiration cytology diagnosed chronic thyroiditis. A preoperative diagnosis of suspicious malignant lymphoma of the thyroid gland accompanied by Hashimoto’s thyroiditis was made, and a right hemithyroidectomy was performed to definite diagnosis. Histological examination revealed diffuse small lymphocytic infiltration in the thyroid gland associated with Hashimoto’s thyroiditis. Immunohistochemical examination showed that the small lymphocytes were positive for T-cell markers with CD3 and CD45RO. The pathological diagnosis was chronic thyroiditis with atypical lymphocytes infiltration. However, Southern blot analysis of tumor specimens revealed only a monoclonal T-cell receptor gene rearrangement. Finally, peripheral T cell lymphoma was diagnosed. Therefore, the left hemithyroidectomy was also performed one month later. No adjuvant therapy was performed due to the tumor stage and its subtype. The patient is well with no recurrence or metastasis 22 months after the surgical removal of the thyroid. As malignant T-cell lymphoma of the thyroid gland with Hashimoto’s thyroiditis was difficult to diagnose, gene rearrangement examination needed to be performed concurrently.

Significant improvement in superselective intra-arterial chemotherapy for oral cancer by using indocyanine green fluorescence

BACKGROUND Recent advances in indocyanine green (ICG) fluorescence imaging have enabled the visualization of the blood supply to tissues. For advanced head and neck cancer, intra-arterial chemotherapy has been applied for organ preservation and improvement of the prognosis. To identify the tumor-feeding artery, through which the intra-arterial chemotherapy should be administered, CT angiography has been shown to be useful. However, the precise evaluation for oral cancer patients depends on the oral environment, that is, whether they have been treated with dental metal. OBJECTIVES To assess the feasibility of the ICG fluorescence technique during intra-arterial chemotherapy for advanced oral cancer. MATERIAL AND METHOD Twenty-five patients with oral cancer who were treated by intra-arterial chemotherapy were included in this study. Conventional CT angiography followed by 5mg of ICG injection was performed to confirm the areas in which the drug had dispersed. Intra-arterial chemotherapy was administered at 75 mg/m(2) of CDDP. Additional information about the arteries feeding the tumors provided by ICG was evaluated. RESULTS Out of 25 cases, in 15 (56%) the blood supply to the cancer was clearly detected by CT angiography. Using the infrared ICG evaluation, the blood supply to the tumor was confirmed easily in all cases. The information obtained from fluorescence imaging was helpful for making decisions concerning the administration of chemo-agents for oral cancers. CONCLUSION ICG fluorescence imaging during intra-arterial chemotherapy compensated for the deficiencies of CT angiography, especially for oral cancer. ICG fluorescence provided us clearer and more useful information about the feeders to tumors.

Impact of intra-arterial chemotherapy including internal carotid artery for advanced paranasal sinus cancers involving the skull base

Background:The most significant problem of intra-arterial chemotherapy for advanced paranasal sinus carcinomas and residual cancers supplied by internal carotid artery (ICA) and involving the skull base is the lack of salvage therapies.Objective:The objective of the study was to evaluate the usefulness of intra-arterial chemotherapy including ICA infusion for treating advanced paranasal sinus carcinomas, which have invaded the skull base.Methods:Forty-six patients with advanced paranasal sinus carcinomas supplied by ICA were treated by intra-arterial chemotherapy using CDDP and sodium thiosulphate (STS) as a neutraliser of CDDP toxicity. After evaluating CT angiography, 150 mg m−2 of CDDP was superselectively administered weekly to each feeding artery including ICA four times.Results:The 10-year overall survival rate and progression-free survival rate were 70.7 and 60.2%, respectively. Compared with control group without infusing ICA, recurrences at anterior skullbase or anterior ethomoid sinus were significantly diminished. Of 32 patients in which the orbital apex had been invaded, 29 patients were treated with successful preservation of orbital contents. The CT angiography could efficiently determine all feeding arteries supplying the cancers. Consequently, chemotherapy could be administered on schedule, and side effects were minimal and acceptable.Conclusions:This new method has promising applications in the treatment of advanced paranasal sinus carcinomas involving the skull base.

Impact of middle and lower jugular neck dissection on supraclavicular lymph node metastasis from endometrial carcinoma

Supraclavicular lymph node metastasis from endometrial carcinoma is considerably rarer than metastasis from uterine cervical cancer. To date, there have been no reported cases regarding systematic neck dissection as a salvage treatment. In this report, we describe the neck dissection procedure carried out on a 74-year-old woman with supraclavicular lymph node metastasis. Our objective was to histologically determine the origin of the metastasis while simultaneously providing appropriate treatment. The patient’s past medical history included two prior cases of cancer: rectal cancer 7 years earlier and endometrial adenocarcinoma 4 years earlier. We determined that middle and lower jugular neck dissection was appropriate in treating this case based on the results of our preoperative FDG-PET and tumor markers. This surgery provided histological evidence that metastasis occurred from endometrial carcinoma. Middle and lower jugular neck dissection was expected to improve the patient’s prognosis without impacting the patient’s active daily life. We have continued to monitor the patient closely over an extended period.