Evenly Distributed Protein Intake over 3 Meals Augments Resistance Exercise-Induced Muscle Hypertrophy in Healthy Young Men.

BACKGROUND: Although daily protein intake (PI) has been reported to be essential for regulating muscle mass, the distribution of daily PI in individuals is typically the lowest at breakfast and skewed toward dinner. Skewed protein intake patterns and inadequate PI at breakfast were reported to be negative factors for muscle maintenance. OBJECTIVES: This study examined whether a protein-enriched meal at breakfast is more effective for muscle accretion compared with the typical skewed PI pattern. METHODS: This 12-wk, parallel-group, randomized clinical trial included 26 men (means ± SEs; age: 20.8 ± 0.4 y; BMI: 21.8 ± 0.4 kg/m2). The "high breakfast" (HBR) group (n = 12) consumed a protein-enriched meal at breakfast providing a PI of 0.33 g/kg body weight (BW); their PI at lunch (0.46 g/kg BW) and dinner (0.48 g/kg BW) provided an adequate overall daily PI (1.30 g/kg BW/d). The "low breakfast" (LBR) group (n = 14) consumed 0.12 g protein/kg BW at breakfast; intakes at lunch (0.45 g/kg BW) and dinner (0.83 g/kg BW) yielded the same daily PI as in the HBR group. The participants performed supervised resistance training (RT) 3 times per week (75-80% 1-repetition maximum; 3 sets × 10 repetitions). DXA was used to measure the primary outcome variable, that is, total lean soft tissue mass (LTM). RESULTS: The total LTM at baseline did not differ between the HBR (52.4 ± 1.3 kg) and LBR (53.4 ± 1.2 kg) groups. After the intervention, increases in total LTM were significant in both groups, with that in the HBR group (2.5 ± 0.3 kg) tending to be greater than that in the LBR group (1.8 ± 0.3 kg) (P = 0.06), with a large effect size (Cohen d = 0.795). CONCLUSIONS: For RT-induced muscle hypertrophy in healthy young men, consuming a protein-enriched meal at breakfast and less protein at dinner while achieving an adequate overall PI is more effective than consuming more protein at dinner.This study was registered at University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000037583 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042763).

Descending musculospinal branch of the ascending pharyngeal artery as a feeder of carotid body tumors: Angio-architecture and embryological consideration.

INTRODUCTION: Although the ascending pharyngeal artery (APhA) is known as a main feeder of carotid body tumors (CBTs), its detailed architecture and embryological consideration have not been described. The objective of this study was to describe the architecture of a descending feeder of the APhA and to consider its origin embryologically through a review of our CBT embolizations. METHODS: We retrospectively analyzed data from patients with CBTs who underwent transarterial embolization or angiographic examination-only between July 2010 and February 2017. The arterial supply of the tumors, the number of feeder pedicles, the mean tumor size, embolization materials, complication of embolization, and extent of tumor removal were assessed. The embryological origin of feeding artery was considered based on the literature. RESULTS: Eighteen patients with 20 CBTs underwent preoperative embolization or angiographic examination. The number of feeder pedicles was significantly related to the size of the CBT (P = 0.0002). The main feeding artery was the descending branch of APhA, which was hypertrophied and tortuous (18/20, 90%). Embryologically, this artery originated from the musculospinal branch and is termed the "descending musculospinal branch". CONCLUSION: The main feeder of the CBTs was the "descending musculospinal branch" of the APhA and needs special consideration such as dangerous anastomosis for embolization.

VEGF-C/Flt-4 axis in tumor cells contributes to the progression of oral squamous cell carcinoma via upregulating VEGF-C itself and contactin-1 in an autocrine manner.

Tumor cell-derived vascular endothelial growth factor (VEGF)-C has been primarily implicated in promoting lymphangiogenesis by activating Flt-4 (VEGFR-3) expressed on lymphatic endothelial cells via a paracrine mechanism. Flt4 has also been shown to be expressed selectively in subsets of cancer cells. However, little is known about the functional role of VEGF-C/Flt4 signaling via an autocrine mechanism, as well as the clinicopathological implication of the VEGF-C/Flt4 axis and its downstream effector molecules, in head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC). In the present study, we detected Flt-4 expression selectively in several HNSCC cell lines by quantitative PCR, and its internalization reflecting receptor activation was confirmed by immunocytochemistry in SAS and HO1U1 cells. Flt-4 stimulation upregulated the expression of contactin-1 (CNTN-1, a neural cell adhesion molecule) and VEGF-C itself in SAS cells, while Flt-4 inhibition downregulated the expression of CNTN-1 in both SAS and HO1U1 cells and that of VEGF-C itself in SAS cells. In vitro cell proliferation and migration assays using SAS cells demonstrated that both cell proliferation and migration were promoted by Flt-4 stimulation, while those were suppressed by Flt-4 inhibition. Clinicopathological factors and immunohistochemical expression of Flt-4, VEGF-C, and CNTN-1 in tumor cells were evaluated using surgical specimens from patients with tongue squamous cell carcinoma. We found a significant correlation of CNTN-1 expression with both VEGF-C and Flt-4 expression, but not between VEGF-C and Flt-4. Multivariate logistic regression analysis revealed that T classification (P = 0.003), lymphatic invasion (P = 0.024), and Flt-4 expression in tumor cells (P = 0.046) were independently predictive of neck lymph node metastasis. These results suggest that the VEGF-C/Flt-4 axis in tumor cells enhances tumor cell proliferation and migration via upregulating the expression of VEGF-C itself and CNTN-1 in an autocrine manner, thereby contributing to cancer progression of OSCC, including neck metastasis. Hence, targeting the VEGF-C/Flt-4 axis in tumor cells can be an attractive therapeutic strategy for the treatment of cancer.

Clinical diagnosis and treatment outcomes for parapharyngeal space schwannomas: A single-institution review of 21 cases.

BACKGROUND: Because the incidence of schwannoma arising from the parapharyngeal space (PPS) is very low, no studies have analyzed extirpation methods and postoperative neurological complications exclusively in PPS schwannomas. METHODS: The preoperative diagnosis and clinical outcomes of surgical treatment in 21 patients with PPS schwannoma who underwent surgery were investigated. RESULTS: Neurological deficit of the involved nerve developed in all patients regardless of the extirpation method used. However, the incidence of first bite syndrome in sympathetic chain schwannoma was significantly lower after intracapsular enucleation (40%) than after total resection (100%; P = .045). Furthermore, the incidence of postoperative complications unrelated to the involved nerve was lower after intracapsular enucleation (0%) than after total resection (42.9%; P = .055). CONCLUSION: Although postoperative neurological deficit of the involved nerve was unavoidable in PPS schwannoma, intracapsular enucleation could be beneficial by reducing its severity and the incidence of complications unrelated to the involved nerve.

Clinical outcomes of transoral videolaryngoscopic surgery for hypopharyngeal and supraglottic cancer.

BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) was developed as a new distinct surgical procedure for hypopharyngeal cancer (HPC) and supraglottic cancer (SGC) staged at up to T3. However, long-term treatment outcomes of TOVS remain to be validated. METHODS: Under a straight broad intraluminal view provided by combined use of a distending laryngoscope and a videolaryngoscope, we performed en bloc tumor resection via direct bimanual handling of the ready-made straight-form surgical instruments and devices. We retrospectively analyzed functional and oncologic outcomes of 72 patients with HPC (n = 58) or SGC (n = 14) whose minimum follow-up was 24 months or until death. RESULTS: The cohort comprised nine patients of Tis, 23 of T1, 33 of T2, and 7 of T3. Among 36 patients (50%) who underwent neck dissection simultaneously, all but one were pathologically node-positive. Twelve patients underwent postoperative concurrent chemoradiation (CCRT) as adjuvant treatment, and another four patients underwent radiation or CCRT for second or later primary cancer. The endotracheal tube was removed in an operation room in all but two patients who underwent temporary tracheostomy. Pharyngeal fistula was formed transiently in two patients. The median time until patients resumed oral intake and could take a soft meal was 2 and 5 days, respectively. Eventually, 69 patients (96%) took normal meals. The 5-year cause-specific survival (CSS), overall survival (OS), larynx-preserved CSS, and loco-regional controlled CSS were 87.3%, 77.9%, 86.0%, and 88.0%, respectively. Multivariate analysis revealed N2-3 as an independent prognostic factor in both CSS (hazard ratio [HR] = 25.51, P = 0.008) and OS (HR = 4.90, P = 0.022), which indirectly reflected higher risk of delayed distant metastasis. CONCLUSIONS: Considering its sound functional and oncological outcomes with various practical advantages, TOVS can be a dependable, less invasive, and cost-effective surgical option of an organ-function preservation strategy for HPC and SGC.

Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists.

AIM: This study aimed to assess the efficacy of endoscopic endonasal surgery, conducted by a team of neurosurgeons and otolaryngologists. MATERIAL AND METHODS: We studied 40 patients who were undergoing surgery for primary non-functional pituitary adenomas with Knosp grades 1 to 3, at Keio University Hospital between 2005 and 2012. We compared the endoscopic endonasal transsphenoidal approach (team-eTSS; T-eTSS), with a microscopic transsphenoidal approach (mTSS). Analyses were conducted for differences between the two groups in tumor resection rates, operating durations, and complications from the non-functional pituitary adenomas. We also compared the heminostril and binostril approaches for T-eTSS. RESULTS: Tumor resection rates were higher when the surgeries were conducted by T-eTSS than mTSS. In particular, when the maximum tumor diameter was more than 25 mm, resection rates were significantly higher for T-eTSS than for mTSS. There were no unexpected complications in either group. There was no significant difference in resection rates between the heminostril and binostril approaches when T-eTSS was performed. CONCLUSION: T-eTSS is an efficacious surgical option for non-functional pituitary adenomas, particularly when the adenoma is of large size. Benefits of the heminostril approach are evident.

[Usefulness and Limitation of Thyroglobulin Measurement in Fine Needle Aspirates (FNA-Tg) for Diagnosis of Neck Lymph Node Metastasis from Thyroid Carcinoma].

BACKGROUND: Preoperative diagnosis of lymph node metastasis from thyroid carcinoma is usually confirmed by using fine needle aspiration cytology (FNAC) when thyroid carcinoma is suspected based on the clinical findings. However, the result of FNAC sometimes leads to a false negative, especially in cases of hypocellular lesions such as metastases with cystic change. Thyroglobulin measurement in fine needle aspirates (FNA-Tg) has been shown to be a useful technique to detect the protein specifically secreted by thyroid follicular cells. Elevated FNA-Tg levels in an extra-thyroidal lesion means that the lesion comprises thyroid-originated tissue, most of which suggests the metastasis from thyroid carcinoma. Thus, FNA-Tg is expected to improve the sensitivity of FNAC for the aforementioned purpose. PATIENTS AND METHODS: From 2008 to 2012, 49 extra-thyroidal lesions from 43 patients with thyroid carcinoma were examined using both FNAC and FNA-Tg, followed by surgical resection with a histopathological diagnosis. The results were retrospectively reviewed and analyzed. RESULTS: Among 49 lesions, 47 were metastatic lymph nodes from thyroid carcinoma (46 papillary carcinoma and one follicular carcinoma), one was a metastatic lymph node from submandibular gland adenocarcinoma, and one was an ectopic thyroid gland. In the 47 cases of thyroid carcinoma, the sensitivity of FNAC was 57.4% (27/47), whereas that of FNA-Tg was 76.6% (36/47). When both methods were combined, the sensitivity increased to 93.6% (44/47). Metastasis from submandibular gland adenocarcinoma was considered to be an example of a false positive from FNAC, whereas an ectopic thyroid gland was an FNA-Tg false positive. Three lesions were negative for both FNAC and FNA-Tg, although metastases were suspected by imaging studies and confirmed by histopathological diagnosis, which were consistent with examples of a false negative from both FNAC and FNA-Tg findings. CONCLUSIONS: FNAC reflects whether the lesion has malignant cells, whereas FNA-Tg reflects whether the lesion has thyroid-originated tissue that specifically secrets thyroglobulin. Therefore, FNAC and FNA-Tg are considered to be complementary to each other for the preoperative diagnosis of lymph node metastasis from thyroid carcinoma. FNA-Tg was validated to improve the preoperative diagnostic sensitivity especially when combined with FNAC, however, it is attended with the possibility of a false positive or negative finding, which requires caution in interpretation of the findings.

Sigmoid incision rescue nasoseptal flap technique for endoscopic endonasal skull base surgery.

Conclusion The sigmoid-incision (S-I) rescue flap technique has the advantage of both reduced-invasiveness and providing a sufficient surgical corridor for endoscopic endonasal skull base surgery (EESBS). Objective Skull base reconstruction with nasoseptal flap (NSF) is critically important in managing post-operative cerebrospinal fluid (CSF) leakage after tumor removal by EESBS. The NSF needs to be elevated before sphenoidotomy and posterior septectomy to preserve the pedicle. However, most extradural surgery without CSF leakage does not require NSF and, therefore, NSF preparation is often futile. As a result, a rescue flap technique to overcome this problem has been developed, whereby a new S-I rescue flap method is used that enables wide exposure of the sphenoidal rostrum and smooth manipulation of surgical instruments to preserve the NSF pedicle. Materials and methods Starting in April 2014, 19 cases underwent EESBS with S-I rescue flap. Results All patients underwent tumor resection under an adequate operative field with smooth manipulation of surgical instruments. Two complications were experienced. One patient had CSF leak after removal of the nasal packing, but the leakage was successfully closed by conventional NSF. Another patient had epistaxis from the septal wall, but this was controlled by electrocautery.

Vascularized middle turbinate flap for the endoscopic endonasal reconstruction of the anterior olfactory groove.

A vascularized middle turbinate flap (MTF) might be useful in the repair of lesions in the anterior olfactory groove. The sizes of the MTF and inferior turbinate flap (ITF) and these distances up to the frontal base were analyzed by computed tomography (CT) using a picture archiving and communication system (PACS) in 20 patients. The minimum flap measurement to reconstruct the skull base was defined as the distance from the basal plate to the medial slope or lateral slope edge of the MTF and the ITF on the coronal view. Next, we reviewed clinical data from three patients with dural deficits who underwent endoscopic vascularized MTF reconstruction. The distance to the frontal base from the ITF was significantly longer than that from the MTF. The minimum length of the MTF measured by coronal CT was similar to the distance to the frontal base. In contrast, the minimum length of the ITF was shorter than the distance to the frontal base. These results suggest that the MTF might be superior to the ITF for coverage of the anterior frontal base. Three patients who underwent MTF reconstruction for a defect in the anterior olfactory groove had good outcomes and no complications. The MTF is a good option for reconstruction of defects in the anterior part of the olfactory groove.

Expression of Oct3/4 and Nanog in the head and neck squamous carcinoma cells and its clinical implications for delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma.

BACKGROUND: The side population (SP) of cancer cells is reportedly enriched with cancer stem cells (CSCs), however, the functional role and clinical relevance of CSC marker molecules upregulated in the SP of head and neck squamous carcinoma (HNSCC) cells are yet to be elucidated. Patients with clinical stage I/II (T1-2N0M0) tongue squamous cell carcinoma (TSCC) typically undergo partial glossectomy; however, development of delayed neck metastasis (DNM) tends to reduce their survival. In the present study, we aimed to determine the CSC markers in the SP of HNSCC cells along with their functions in cellular behaviors, and to clarify the association of these markers with DNM. METHODS: Flow cytometry was applied to isolate SP from main population (MP) in HNSCC cells. The expression of the CSC markers was examined by semi-quantitative RT-PCR and immunocytochemistry. In vitro proliferation, migration, and invasion assays were performed to assess cellular behaviors. Clinicopathological factors and immunohistochemical expressions of Oct3/4 and Nanog were evaluated using surgical specimens from 50 patients with stage I/II TSCC. RESULTS: SPs were isolated in all three cell lines examined. Expression levels of Oct3/4 and Nanog were higher in SP cells than MP cells. Additionally, cell migration and invasion abilities were higher in SP cells than MP cells, whereas there was no difference in proliferation. Univariate analysis showed that expression of Oct3/4 and Nanog, vascular and muscular invasion, and mode of invasion were significantly correlated with DNM. Multivariate logistic regression revealed that Oct3/4 expression (risk ratio = 14.78, p = 0.002) and vascular invasion (risk ratio = 12.93, p = 0.017) were independently predictive of DNM. Regarding the diagnostic performance, Oct3/4 showed the highest accuracy, sensitivity, and NPV of 82.0 %, 61.5 %, and 86.8 %, respectively, while vascular invasion showed the highest specificity and PPV of 94.6 % and 71.4 %, respectively. CONCLUSION: These results suggest that Oct3/4 and Nanog represent probable CSC markers in HNSCC, which contribute to the development of DNM in part by enhancing cell motility and invasiveness. Moreover, along with vascular invasion, expression of Oct3/4 can be considered a potential predictor for selecting patients at high risk of developing DNM.

Petrous apex cholesterol granuloma: importance of pedicled nasoseptal flap in addition to silicone T-tube for prevention of occlusion of drainage route in transsphenoidal approach--a technical note.

Recently, petrous apex cholesterol granulomas (CGs) have been treated via the endoscopic endonasal transsphenoidal approach (EEA) using a silicone tube, to prevent drainage route occlusion. Occlusion of the drainage route has led to problems with recurrence. The aim of this report is to describe the use of a surgical technique to prevent drainage route occlusion. In surgical technique, the posterolateral wall of the sphenoid sinus was opened by EEA. After cyst debridement, a vascularized nasoseptal flap with a width of approximately 4 cm was inserted into the lumen with a silicone T-tube with a diameter of 7 mm. This technique was used in two patients: the first patient during the second operation after recurrence following occlusion of the drainage route, and the second patient during the first operation. Opening of the cyst wall was confirmed endoscopically in both patients 12-24 months after surgery, even after removal of the T-tube. In conclusion, the use of a pedicled nasoseptal flap with a silicone tube is useful to prevent CG recurrence, by paranasal cavitization of the cystic cavity.

Analysis of sphenoid sinus lateral pneumatization for endonasal endoscopic surgery.

BACKGROUND: The purpose of this study was to analyze sphenoid sinus lateral pneumatization (SSLP), especially in Asian populations, and to identify cautionary items when using the endoscopic endonasal approach (EEA) for parasellar/lateral lesions. METHODS: We analyzed SSLP and the width of SS (SSW) in 121 patients who had undergone EEA from 2008 to 2013 at the Division of Neurosurgery, Keio University Hospital. SSLP was defined as the distance between the SS lateral edge and the medial aspect of the pterygoid process on coronal reconstruction computed tomography. SSW was defined as the distance between the midline and lateral wall. We recorded SSLP and SSW for 242 sides. Further, we present two characteristic cases. RESULTS: The average SSLP and SSW were 7.0 mm (-10.0-25.8 mm) and 21.8 mm (6.0-40.2 mm), respectively. No correlation between pneumatization and age was observed at age 15 or more. Sphenoid pneumatization was significantly wider in male than in female patients. There was no relationship between lateral and sagittal plane pneumatization. In a patient with recurrent chordoma who had an undeveloped SSLP, the tumor was removed via the medial space in the internal carotid artery. In another patient who had a giant pituitary adenoma and average SSLP, the tumor was located in the middle cranial fossa and was removed via the lateral internal carotid space through the left SSLP. CONCLUSIONS: Wide variations were observed in SSLP and SSW. For EEA, pneumatization is an instrument corridor. Preoperative assessment of SSLP is important, especially for parasellar lesions.

Transoral vs. endoscopic endonasal approach for clival/upper cervical chordoma.

The surgical results of 18 cases of clival/upper cervical chordoma treated in the last decade via the endoscopic endonasal approach (EEA, 9 cases) and the transoral-transpalatal approach (TO-TPA, 9 cases) were compared. Each group showed the same incidence of subdural invasion, with 5 cases each. The superior (frontal base) and lateral surgical fields were wider by EEA, but the inferior view lower than the cranio-vertebral junction (CVJ) was wider by TO-TPA. Gross total removal was achieved in 3 cases in the EEA group, but in only 1 case in the TO-TPA group. Differences in radicality might be due to the extent of the lateral and subdural overview. However for large tumors extending below the CVJ, TO-TPA was the only viable approach for surgical removal. Surgical complications were higher in the EEA (4 cases) than the TO-TPA group (1 case), and were mainly caused by aggressive management of subdural invasion in the EEA group. Post-operative oral intake was earlier and the operative time was shorter in the EEA group. The surgical results were more radical and less invasive in the EEA group than the TO-TPA group. However in tumors extending below the CVJ, the surgical field in EEA was limited, indicating the need to use the transoral route or a combination of routes. A higher complication rate following subdural management was a negative factor that requires improvement in the EEA group and two-staged EEA followed by a transcranial approach may be considered for the cases with subdural invasion.

Analysis of the bacterial flora in the nasal cavity and the sphenoid sinus mucosa in patients operated on with an endoscopic endonasal transsphenoidal approach.

The aim of this study was to analyze the bacterial flora in the nasal cavity and sphenoid sinus and evaluate the sensitivity of these bacteria to antibiotics that can be used to prevent postoperative meningitis. Bacteria of the preoperative nasal cavity and intraoperative sphenoid sinus mucosa were cultured and analyzed in 40 patients (20 men and 20 women; mean age, 52.2 years) who underwent endoscopic transsphenoidal surgery. The sensitivity of these bacteria to cephalosporin, a representative prophylactic antibiotic, was examined. Staphylococcus epidermidis was the most frequently detected species in both spaces; 24 (38.7%) of 62 isolates in the nasal cavity and 26 (37.1%) of 70 isolates in the sphenoid sinus. In contrast, Corynebacterium species were found mainly in the nasal cavity, and anaerobic bacteria were found only in the sphenoid sinus. Bacteria that were resistant to cephalosporin were found in the nasal cavity in 3.2% of patients and in the sphenoid sinus in 20% of patients. In conclusion, the composition of bacterial flora, including bacteria that are resistant to prophylactic antibiotics, differs between the nasal cavity and the sphenoid sinus.

Primary dural closure and anterior cranial base reconstruction using pericranial and nasoseptal multi-layered flaps in endoscopic-assisted skull base surgery.

INTRODUCTION: Dural and anterior cranial base reconstruction is essential in the surgical resection of a craniofacial tumor that extends from the paranasal sinuses to the subdural space. Watertight reconstruction of vascularized tissue is essential to prevent postoperative liquorrhea, especially under conditions that prevent wound healing (e.g., postoperative irradiation therapy). METHOD: We successfully treated two cases of olfactory neuroblastoma by endoscopic-assisted craniotomy with primary dural closure and anterior cranial base reconstruction using a multi-layered flap technique. Dural defects were closed using temporal fascia or fascia lata in a conventional fashion, immediately after detaching the subdural tumor, in order to isolate and prevent contamination of subdural components and cerebrospinal fluid (CSF) from the tumor and nasal sinuses. Tumor removal and anterior cranial base reconstruction were performed without any concern of CSF contamination after dural closure by craniotomy and endoscopic endonasal approach (EEA). Vascularized pericranial flaps (PCF) and nasoseptal flaps (NSF) were used simultaneously as doubled-over layers for reconstruction. RESULTS: The tumor was completely removed macroscopically and the anterior cranial base was reconstructed in both cases. CSF leak and postoperative meningitis were absent. Postoperative and irradiation therapy courses were successful and uneventful. CONCLUSIONS: This multi-layered anterior cranial base reconstruction consisted of three layers: a fascia for dural plasty and double-layered PCF and NSF. This surgical reconstruction technique is suitable to treat craniofacial tumors extending into the subdural space through the anterior cranial base dura mater.

[Clinical outcome and clinicopathological prognostic factors in adenoid cystic carcinoma of the head and neck].

We retrospectively reviewed the records of the 30 patients with adenoid cystic carcinoma of the head and neck (ACCHN) who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1988 and 2007. The primary tumor site was the parotid gland in 10 patients and the submandibular gland in 4 patients, which account for about a half of the subjects. Thirty patients underwent surgical resection with curative intent as the primary treatment, of which 10 patients had post-operative radiotherapy. The 5-and 10-year disease-specific survival (DSS) was 73.9% and 62.4%, respectively, whereas the 5-and 10-year disease-free survival (DFS) was 64.3% and 59.7%, respectively. A univariate analysis revealed that DSS was significantly correlated with perineural invasion (p = 0.010) and lymphatic invasion (p = 0.036), while DFS was significantly correlated with higher T-stage (p = 0.044), a positive surgical margin (p = 0.012) and perineural invasion (p = 0.019). A multivariate analysis demonstrated that perineural invasion (p = 0.034, risk ratio = 9.530) was the independent prognostic factor for DSS, whereas for DFS it was a positive surgical margin (p = 0.038, risk ratio = 8.897). The histological grade classification, defined specifically for ACC, showed no correlation with the survival. Extended resection with wider margin and additional resection in cases with positive margin may improve treatment results, however, surgical resection alone can prevent neither the development of local recurrence mainly attributed to undetectable perineural invasion, nor that of delayed distant metastasis. Therefore, the roles of adjuvant radiotherapy and effective systemic therapies are also significant in ACCHN, although a reliable regimen for the latter has not yet been established. Development of a personalized strategy for the adjuvant therapy, which should be based on the accurate prediction of the long-term prognosis in combination with dependable molecular biomarkers, would be indispensable in the future to improve the clinical outcome of the patients with ACCHN.

Restoration of E-cadherin expression by selective Cox-2 inhibition and the clinical relevance of the epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma.

BACKGROUND: The epithelial-to-mesenchymal transition (EMT) accompanied by the downregulation of E-cadherin has been thought to promote metastasis. Cyclooxygenase-2 (Cox-2) is presumed to contribute to cancer progression through its multifaceted function, and recently its inverse relationship with E-cadherin was suggested. The aim of the present study was to investigate whether selective Cox-2 inhibitors restore the expression of E-cadherin in head and neck squamous cell carcinoma (HNSCC) cells, and to examine the possible correlations of the expression levels of EMT-related molecules with clinicopathological factors in HNSCC. METHODS: We used quantitative real-time PCR to examine the effects of three selective Cox-2 inhibitors, i.e., celecoxib, NS-398, and SC-791 on the gene expressions of E-cadherin (CDH-1) and its transcriptional repressors (SIP1, Snail, Twist) in the human HNSCC cell lines HSC-2 and HSC-4. To evaluate the changes in E-cadherin expression on the cell surface, we used a flowcytometer and immunofluorescent staining in addition to Western blotting. We evaluated and statistically analyzed the clinicopathological factors and mRNA expressions of Cox-2, CDH-1 and its repressors in surgical specimens of 40 patients with tongue squamous cell carcinoma (TSCC). RESULTS: The selective Cox-2 inhibitors upregulated the E-cadherin expression on the cell surface of the HNSCC cells through the downregulation of its transcriptional repressors. The extent of this effect depended on the baseline expression levels of both E-cadherin and Cox-2 in each cell line. A univariate analysis showed that higher Cox-2 mRNA expression (p = 0.037), lower CDH-1 mRNA expression (p = 0.020), and advanced T-classification (p = 0.036) were significantly correlated with lymph node metastasis in TSCC. A multivariate logistic regression revealed that lower CDH-1 mRNA expression was the independent risk factor affecting lymph node metastasis (p = 0.041). CONCLUSIONS: These findings suggest that the appropriately selective administration of certain Cox-2 inhibitors may have an anti-metastatic effect through suppression of the EMT by restoring E-cadherin expression. In addition, the downregulation of CDH-1 resulting from the EMT may be closely involved in lymph node metastasis in TSCC.

Transoral vs. endoscopic endonasal approach for clival/upper cervical chordoma.

The surgical results of 18 cases of clival/upper cervical chordoma treated in the last decade via the endoscopic endonasal approach (EEA, 9 cases) and the transoral-transpalatal approach (TO-TPA, 9 cases) were compared. Each group showed the same incidence of subdural invasion, with 5 cases each. The superior (frontal base) and lateral surgical fields were wider by EEA, but the inferior view lower than the cranio-vertebral junction (CVJ) was wider by TO-TPA. Gross total removal was achieved in 3 cases in the EEA group, but in only 1 case in the TO-TPA group. Differences in radicality might be due to the extent of the lateral and subdural overview. However for large tumors extending below the CVJ, TO-TPA was the only viable approach for surgical removal. Surgical complications were higher in the EEA (4 cases) than the TO-TPA group (1 case), and were mainly caused by aggressive management of subdural invasion in the EEA group. Post-operative oral intake was earlier and the operative time was shorter in the EEA group. The surgical results were more radical and less invasive in the EEA group than the TO-TPA group. However in tumors extending below the CVJ, the surgical field in EEA was limited, indicating the need to use the transoral route or a combination of routes. A higher complication rate following subdural management was a negative factor that requires improvement in the EEA group and two-staged EEA followed by a transcranial approach may be considered for the cases with subdural invasion.

Analysis of the bacterial flora in the nasal cavity and the sphenoid sinus mucosa in patients operated on with an endoscopic endonasal transsphenoidal approach.

The aim of this study was to analyze the bacterial flora in the nasal cavity and sphenoid sinus and evaluate the sensitivity of these bacteria to antibiotics that can be used to prevent postoperative meningitis. Bacteria of the preoperative nasal cavity and intraoperative sphenoid sinus mucosa were cultured and analyzed in 40 patients (20 men and 20 women; mean age, 52.2 years) who underwent endoscopic transsphenoidal surgery. The sensitivity of these bacteria to cephalosporin, a representative prophylactic antibiotic, was examined. Staphylococcus epidermidis was the most frequently detected species in both spaces; 24 (38.7%) of 62 isolates in the nasal cavity and 26 (37.1%) of 70 isolates in the sphenoid sinus. In contrast, Corynebacterium species were found mainly in the nasal cavity, and anaerobic bacteria were found only in the sphenoid sinus. Bacteria that were resistant to cephalosporin were found in the nasal cavity in 3.2% of patients and in the sphenoid sinus in 20% of patients. In conclusion, the composition of bacterial flora, including bacteria that are resistant to prophylactic antibiotics, differs between the nasal cavity and the sphenoid sinus.