Akihiro Terada

MECT1-MAML2 Fusion Transcript Defines a Favorable Subset of Mucoepidermoid Carcinoma

Purpose: Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. Mucoepidermoid carcinoma translocated gene 1-mastermind-like gene family (MECT1-MAML2) gene fusion was identified from a recurring t(11;19)(q21;p13) translocation, which is often the sole cytogenetic alteration in this disease. This fusion transcript has been frequently detected in mucoepidermoid carcinoma and shown to be involved in the transformation of epithelial cells. However, its clinicopathologic significance remains unclear. Experimental Design: Seventy-one cases of mucoepidermoid carcinoma and 51 cases of nonmucoepidermoid carcinoma salivary gland tumors (including 26 Warthin tumor cases) were retrospectively analyzed. RNA was extracted from archival materials: histologic paraffin specimens in all cases and cytologic specimens in 10 mucoepidermoid carcinoma cases. The MECT1-MAML2 fusion transcript was detected by a reverse transcription-PCR assay, which can be applied to both histologic and cytologic specimens. The presence of the fusion transcript was correlated with relevant clinicopathologic and survival data of the mucoepidermoid carcinoma patients. Results: The MECT1-MAML2 fusion transcript was detected in 27 of the 71 (38%) mucoepidermoid carcinoma cases but not in any case of nonmucoepidermoid carcinoma tumors. The reverse transcription-PCR results showed no difference between histologic and cytologic specimens. Detection of the MECT1-MAML2 fusion transcript was associated with a less advanced clinical stage and a low-grade tumor histology. The presence of the transcript was associated with longer disease-free and overall survivals on univariate analysis and emerged as an independent prognostic factor for longer overall survival on multivariate analysis. Conclusions: The MECT1-MAML2 fusion transcript may be specific to mucoepidermoid carcinoma and associated with a distinct mucoepidermoid carcinoma subset that exhibits favorable clinicopathologic features and an indolent clinical course.

Sentinel lymph node radiolocalization in clinically negative neck oral cancer

The sentinel node concept has become one of the most interesting topics in the treatment of head and neck cancer. The aim of this article is to report the results of our feasibility study and clinical application of sentinel lymph node (SLN) radiolocalization and biopsy in patients with clinically negative neck oral cancer.

FDG-PET predicts survival and distant metastasis in oral squamous cell carcinoma.

High [(18)F]-2-fluorodeoxyglucose (FDG)-uptake of primary tumor, assessed by pretreatment positron emission tomography (PET), shows poor overall survival of patients after several therapies in various cancers. An association between FDG-uptake and distant metastasis-free survival in oral squamous cell carcinoma (OSCC) has not been assessed so far. An objective of this study is to investigate an association between FDG-uptake and overall survival of OSCC patients, and to ask whether FDG-uptake is related with distant metastasis-free survival in OSCC. Twenty-four patients who underwent both pretreatment FDG-PET and radical surgery without preoperative therapy were enrolled. We used the maximum standardized uptake value (SUVmax) as FDG-uptake. Overall survival, locoregional recurrence-free survival and distant metastasis-free survival were analyzed by Kaplan-Meier method. In univariate survival analysis, patients with SUVmax>or=12 exhibited significance in both shorter 3-year overall survival (p<0.01) and distant metastasis-free survival (p<0.04) than patients with SUVmax<12. Moreover, by Cox proportional hazards model of multivariate analysis, SUVmax>or=12 was found to be independent of clinical T and N categories, and exhibited significance in both shorter 3-year overall survival (p<0.02) and distant metastasis- free survival (p<0.05) than patients with SUVmax<12. These results suggest that pretreatment FDG-PET is able to provide both non-invasive and effective information for identifying a high- or low-risk group of OSCC patients with distant metastasis.

Intraoperative diagnosis of cancer metastasis in sentinel lymph node of oral cancer patients

Sentinel lymph node (SLN) biopsy in the head and neck region is attracting attention. If intraoperative frozen section and/or cytology of SLN is available, one can select an appropriate patient who must undergo neck dissection in a one-stage procedure. We began intraoperative diagnosis of SLN biopsy in patients who underwent oral cancer surgery in 2003. From August 2003 to December 2006, 44 previously untreated patients were accumulated. All patients underwent SLN biopsy prior to the resection of primary cancer. Intraoperative diagnosis of SLN biopsy was performed by multislice frozen section analysis. Patients with positive SLN underwent immediate neck dissection in the same session. Imprint cytology specimen was prepared at the same time. The results of frozen section analysis and imprint cytology were compared with postoperative pathologic diagnosis of permanent specimens. The sensitivity, specificity, overall accuracy, positive and negative predictive value of intraoperative multislice frozen section analysis in lymph node basis were 90.9%, 100%, 99.1%, 100% and 99.0%, respectively. On the other hand, the indexes of imprint cytology were 27.3%, 99.0%, 92.0%, 75.0% and 92.6%, respectively. All indexes of intraoperative frozen section analysis were superior to imprint cytology. In our experience, multislice frozen section analysis surpasses imprint cytology in intraoperative diagnosis of SLN biopsy.

Follow-up after intraoperative sentinel node biopsy of N0 neck oral cancer patients

The objective of the study was to evaluate the validity of sentinel node (SN) biopsy in early oral cancer patients focusing on the accuracy of intraoperative diagnoses of SN status, recurrences in follow-up and impact on patient survival. Previously untreated N0 oral cancer patients were candidates for the study. Using a radioisotope method, an intraoperative SN biopsy was performed. Patients with a positive frozen section of SN underwent immediate neck dissection as a single-stage procedure; they were followed in our outpatient clinic. Forty-five cT1-2N0 patients with squamous cell carcinoma were analyzed. There were seven patients with positive SN, five of whom were detected by intraoperative frozen section analysis. The sensitivity, specificity and accuracy of the intraoperative frozen section analysis of SN were 71.4, 100 and 95.6%, respectively. There were 13 recurrences in the course of all patients treated. Those with positive SN showed a tendency toward recurrence. Three patients with negative SN suffered from delayed ipsilateral neck recurrence. These were considered false negatives at a rate of 7.9%. The 5-year overall survival rate of all patients was 91.1%. SN-positive patient survival was significantly poorer than that of SN-negative patients. Positive SN had a negative impact on the survival. SN biopsy was shown to be a valuable method for determining the neck status of early oral cancer patients. The concordance rate of intraoperative multislice frozen section analysis of SN and patient neck status at the time of operation was 95.6%. SN-positive patients exhibited a tendency toward cancer recurrence. There were three cases of false negatives not conforming to the SN concept and their rate was 7.9%. Positive SN had a negative impact on patient survival.

En bloc petrosectomy for malignant tumors involving the external auditory canal and middle ear: surgical methods and long-term outcome

OBJECTIVESnThe aim of this study was to describe a method for resecting malignant tumors originating in the external auditory canal or middle ear and requiring en bloc resection of the petrous bone.nnnMETHODSnBetween 1995 and 2005, the authors performed en bloc petrosectomy for 18 malignant tumors in 9 male and 9 female patients, ranging in age from 15 to 74 years. Fourteen tumors originated in the external ear, 2 in the middle ear, and 2 in the parotid gland. The pathological entities included 15 squamous cell carcinomas, 2 adenoid cystic carcinomas, and 1 rhabdomyosarcoma. Through an L-shaped temporosuboccipital craniotomy, a medial osteotomy was created through the inner ear for tumors without extension into the inner ear (14 cases) and through the tip of the petrous bone for tumors reaching the inner ear (4 cases). Temporal dura mater in 3 patients and the base of the temporal lobe in 2 patients were included in the en bloc resection.nnnRESULTSnSurgical complications occurred in 5 patients (28%) with no deaths. During a mean follow-up period of 45 months, 3 patients died of tumor recurrence. Overall, 2- and 5-year survival rates were 86 and 78%, respectively. Two of three patients with dural extension and 1 of 2 with brain invasion remain alive. Two of four patients with tumor extension into the inner ear died.nnnCONCLUSIONSnEn bloc petrosectomy is recommended for malignant tumors of the ear. It is safe and effective for lesions limited to the middle ear and may be the procedure of choice for tumors reaching the inner ear and those with dural or brain invasion.

Prediction of Chemosensitivity Using Multigene Analysis in Head and Neck Squamous Cell Carcinoma

Aims: The main purpose of the current study was to find predictive biomarkers that can be routinely used for the response to chemotherapy in head and neck squamous cell carcinoma (HNSCC). Methods: From this standpoint, we selected the histoculture drug response assay (HDRA) to assess in vitro chemosensitivity, and real-time reverse transcription polymerase chain reaction to investigate the gene expression profile of individual tumors as available predictive biomarkers. Using both surgery and biopsy specimens, we analyzed their gene expression profiles using the 18 markers that we thought were likely predictors of the response to anti-cancer agents. Results: Statistically significant associations were found between 5-fluorouracil (5-FU) sensitivity in HDRA and HER-2 mRNA expression level (p = 0.0030). Moreover, HER-2 expression was significantly associated with cisplatin sensitivity (p = 0.0089). Cisplatin sensitivity in HDRA was also demonstrated to have a significant association with epidermal growth factor receptor (EGFR) expression in which the group with cisplatin resistance tended to have a higher expression level than the sensitive group (p = 0.0385). Conclusion: HER-2 and EGFR may be possible reliable predictive biomarkers for anti-cancer therapy, and might help in the decision-making process for individual patients with HNSCC.

Analysis of Salvage Operation in Head and Neck Microsurgical Reconstruction

In this study, we examined salvage operations after reexploration in head and neck reconstruction and analyzed ways to solve problems. Free flap reconstruction of the head and neck lesion was carried out for 513 cases in our hospital over the past 12 years. Twenty‐one cases of reexploration were caused by postoperative thrombosis (4.1%). We could only salvage seven cases (33.3%) of 21 cases from flap thrombosis. All seven cases were included in the category of venous thrombosis, and they were undertaken within 3 days postoperatively. Our results have shown that once thrombosis occurs, there is little possibility of flap salvage, particularly 3 days after operation and in infectious cases. When no flow phenomena are observed and no flap salvage is deemed possible, aggressive treatment such as a second free flap or next pedicle flap should be chosen as soon as possible to avoid any delay in postoperative treatment.

Limitations of FDG-PET and FDG-PET With Computed Tomography for Detecting Synchronous Cancer in Pharyngeal Cancer

OBJECTIVEnTo analyze the ability of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and the fusion of FDG-PET with computed tomography (FDG-PET/CT) to detect synchronous upper gastrointestinal tract (UGI) cancer in newly diagnosed pharyngeal squamous cell carcinoma (SCC). Synchronous UGI cancer is a significant problem in treating pharyngeal SCC, particularly for Japanese populations reported to be at high risk. Good results have been reported from the use of FDG-PET and FDG-PET/CT in staging head and neck SCC (HNSCC). An additional advantage is that both techniques are expected to prove useful in detecting synchronous cancer.nnnDESIGNnRetrospective analysis of medical records.nnnSETTINGnAichi Cancer Center, Nagoya, Japan.nnnPATIENTSnForty-three Japanese patients with pharyngeal SCC were assessed for the ability of FDG-PET and FDG-PET/CT to detect synchronous UGI cancer via a comparison with UGI Lugol chromoendoscopy. The patients had undergone 17 FDG-PET and 26 FDG-PET/CT scans before treatment.nnnMAIN OUTCOME MEASUREnSensitivity of FDG-PET and FDG-PET/CT to detect synchronous UGI cancer.nnnRESULTSnPathologically, 6 patients with esophageal SCC (14%) and 4 with stomach adenocarcinoma (9%) were diagnosed on the basis of suspect lesions detected by UGI Lugol chromoendoscopy. One patient was found to have stage T2 esophageal cancer by FDG-PET/CT, but no patients had UGI cancer. The sensitivity of detecting T1 UGI cancer by FDG-PET and FDG-PET/CT was 0%.nnnCONCLUSIONSnThe choice of diagnostic technique must be based on the site and histologic characteristics of the synchronous tumor. Although FDG-PET and FDG-PET/CT are still the preferred techniques for staging HNSCC, neither replaces Lugol chromoendoscopy for detecting synchronous UGI cancer in high-risk populations.

Management of a total parotidectomy defect with a gastrocnemius muscle transfer and vascularized sural nerve grafting

Immediate facial nerve reconstruction is very demanding after total parotidectomy. Under such conditions, we reconstructed facial nerves using vascularized sural nerve with free lateral gastrocnemius muscle flap. The patient was a 14-year-old male diagnosed with mucoepidermoid carcinoma of the right parotid gland. We reconstructed zygomatic, buccal, and mandibular branches of facial nerve using 2 vascularized sural nerves, medial sural cutaneous nerve, and the lateral sural cutaneous nerve. The postoperative course was good, and there was no flap trouble. The reinnervated nerve recovered from 3 months after the operation. In 6 months after operation, almost normal animation was recovered, except for the corners of the patients mouth. The advantages of this flap are feasible harvesting in the supine position, feasible filling of the dead space, possible harvesting of 2 series of lateral sural cutaneous nerve and median sural cutaneous nerve, and less sacrifice of the donor site. The disadvantage of this method is that the diameter of the pedicle is smaller than that of the medial pedicle. But the diameters of the lateral sural artery and vein are suitable to anastomose the cervical artery and vein. This flap is one of the good options for reconstruction of facial nerves after total parotidectomy.