Auroral molecular-emission effects on the atomic oxygen line at 777.4 nm.

One of the representative auroral emission lines that radiates from F-region heights and is measurable on the ground is the 777.4 nm line from excited atomic oxygen. This line has been adopted, along with another E-region emission line, for example 427.8 nm, to estimate the mean energy and total energy flux of precipitating auroral electrons. The influence of emissions from part of the molecular nitrogen band, which mainly radiate from E-region heights, should be carefully evaluated because it might overlap the 777.4 nm atomic oxygen line in the spectrum. We performed statistical analysis of auroral spectrograph measurements that were obtained during the winter of 2016-2017 in Tromsø, Norway, to derive the ratio of the intensity of the 777.4 nm atomic oxygen line to that of the net measurement through a typically used optical filter with a full width at half maximum of a few nm. The ratio had a negative trend against geomagnetic activity, with a primary distribution of 0.5-0.7 and a minimum value of 0.3 for the most active auroral condition in this study. This result suggests that the 30-50% emission intensities measured through the optical filter may be from the molecular nitrogen band.

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.

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.

[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.

[Survival analysis and immunohistochemical study of HER-2 and AR (androgen receptor) expression in salivary duct carcinoma].

BACKGROUND: Because of its low incidence, the clinical characteristics of the salivary duct carcinoma (SDC) based on a statistical analysis with a large number of patients remain to be elucidated, and thus it has been impossible to standardize the optimal treatments of SDC including adjuvant systemic therapy. AIMS: The present study aimed to determine the prognostic factors along with the clinical outcomes of patients with SDC and to evaluate the expression of several receptor molecules as treatment targets. METHODS: We performed a statistical analysis and immunohistochemical examination of 16 patients with SDC who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine from 1996 to 2010. RESULTS: The 3-year disease-free survival (DFS) and cause-specific survival (CSS) rates were 29.2% and 72.7%, respectively. At the time of the analysis, 6 patients are alive without the disease, 2 patients are alive with distant metastasis, whereas 7 patients had died of distant metastasis, and 1 patient had died of another cause (pulmonary embolism). We examined the prognostic value of the clinico-pathological factors such as age, sex, T classification, N classification, clinical stage, primary site, histological pre-existence of pleomorphic adenoma. A univariate analysis revealed that DFS was significantly correlated with age (p = 0.049), T classification (p = 0.018), and clinical stage (p = 0.029), whereas no factor was found to be correlated with CSS. A multivariate analysis demonstrated that age (> or = 61 vs. < or = 60, risk ratio (RR) = 5.423, p = 0.042) and T classification (3, 4 vs. 1, 2, RR = 1.087, p = 0.020) were the independent prognostic factors for DFS. Positive expressions of HER2, ER (estrogen receptor), PR (progesterone receptor), AR (androgen receptor), and MIB-1 (index > 20%) were found in 50%, 6%, 13%, 100%, and 69%, respectively. However, none of them showed significant correlation with survival. CONCLUSION: Frequent expressions of HER-2 and AR in SDC suggest that these receptors can be suitable molecular targets of systemic therapy for patients with SDC in which distant metastasis seems to be the largest obstacle to improving survival. In order to assess the efficacy of anti-HER-2 therapy and anti-androgen therapy for each receptor-positive SDC, a multi-institutional joint research system should be organized.

Overexpression of SIP1 and downregulation of E-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy.

BACKGROUND: Patients with clinical stage I/II (T1-2N0M0) oral tongue squamous cell carcinoma (TSCC) usually undergo partial glossectomy alone. However, 14-48% of them develop delayed neck metastasis (DNM), which may lead to an unfavorable course. Recently epithelial-to-mesenchymal transition (EMT) has been thought to play a crucial role in cancer metastasis. The present study aimed to examine the associations of EMT-involved molecular factors and clinicopathological factors with DNM in stage I/II TSCC. METHODS: mRNA expression levels of E-cadherin and its transcriptional repressors (snail, SIP1, and twist) in 7 head and neck squamous cell carcinoma (HNSCC) cell lines were evaluated by quantitative real-time PCR. Clinicopathological parameters and immunohistochemical expressions of E-cadherin and its repressors were examined in surgical specimens of 37 stage I/II TSCC patients who underwent partial glossectomy alone. RESULTS: In HNSCC cells, E-cadherin expression was inversely correlated with SIP1 expression (P = 0.023). Univariate analysis of immunohistochemistry showed that overexpression of SIP1 and loss of E-cadherin were significantly correlated with DNM, although no inverse correlation was found between E-cadherin and its repressors. Multiple logistic regression analysis including clinicopathological and molecular factors revealed that overexpression of SIP1 (P = 0.005), loss of E-cadherin (P = 0.046), and vascular invasion (P = 0.024) were independently correlated with DNM. CONCLUSIONS: These results suggest that development of DNM in stage I/II TSCC is closely related to induction of EMT in primary tumor cells. Especially, SIP1 and E-cadherin are considered to be the possible markers for selecting patients at high risk of DNM.

[Statistical analysis of 32 patients with nasopharyngeal carcinoma].

UNLABELLED: In order to assess the clinical outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) who were initially treated in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1997 and 2006, statistical analyses were performed based on the patient medical records. Cause-specific survival (CSS) and disease-free survival (DFS) in all cases (stage I to IV, n = 32) and advanced cases (stage III and IV, n = 22) were estimated using the Kaplan-Meier method. The independent prognostic values of the clinical and therapeutic factors were determined using multivariate Cox proportional hazards models. RESULTS: The 5-year CSS/DFS were 43.4%/34.8% in all cases and 34.5%/29.8% in advanced cases. Multivariate analysis revealed that, in all cases, the independent prognostic factors for CSS were age (> or = 61 vs. < or = 60, risk ratio (RR) = 5.717, p = 0.006), T-stage (3/4 vs. 1/2, RR = 6.957, p = 0.004), and the use of platinum agents (unused vs. used, RR = 3.911, p = 0.012), whereas those for DFS were T-stage (3/4 vs. 1/2, RR = 3.499, p = 0.019) and the use of platinum agents (unused vs. used, RR = 2.947, p = 0.028). In advanced cases, the use of platinum agents alone was significant for both CSS (RR = 4.503, p = 0.023) and DFS (RR = 4.218, p = 0.014). The patients who received neoadjuvant chemotherapy (NAC) showed better CSS and DFS than the patients who did not (p = 0.066 and p = 0.025, respectively) in a univariate analysis (Log-rank test), although no significant difference was seen between these groups in the multivariate analysis. CONCLUSION: The advantage of the administration of platinum agents in the treatment of NPC was statistically corroborated even in our study with its small sample size. As agents combined with chemoradiotherapy, the efficacy of docetaxel alone did not seem comparable to that of platinum agents. The docetaxel-CDDP-5-FU regimen applied as NAC was suggested to be possibly beneficial for advanced cases of NPC.

Vascular calcification estimated by aortic calcification area index is a significant predictive parameter of cardiovascular mortality in hemodialysis patients.

BACKGROUND: Vascular calcification is a feature of arteriosclerosis. In hemodialysis (HD) patients, vascular calcification progresses rapidly. This study used the aortic calcification area index (ACAI), an index of vascular calcification, to evaluate vascular calcification factors in HD patients, to investigate correlations between ACAI and long-term prognosis and to assess correlations between various factors and long-term prognosis. METHODS: Subjects comprised 137 patients on maintenance HD. ACAI was measured as an index of vascular calcification as measured by abdominal plain computed tomography. The patients were divided into a high ACAI (H) group and a low ACAI (L) group according to whether the ACAI was below or above the mean value (21.4%) of ACAI, and long-term all-cause death and cardiovascular death rates were compared between groups. Risk factors for all-cause death and cardiovascular death were examined by Cox hazard analysis. RESULTS: During follow-up (mean follow-up period 95.3 ± 50.3 months), 76 patients died, including 46 cardiovascular deaths. Deaths included 51 of 70 patients (67.1%) in Group H and 25 of 67 patients (37.3%) in Group L. Cardiovascular death rates were 51.4 and 14.9%, respectively. On Kaplan-Meier analysis, the number of all-cause deaths was significantly higher in Group H (P < 0.001, log-rank test). Similarly, the number of cardiovascular deaths was significantly higher in Group H. Multivariate Cox proportional hazards analysis showed that ACAI (%) was a significant prognostic indicator for cardiovascular death (hazard ratio 1.03; 95% confidence interval 1.00-1.06, P = 0.03). CONCLUSION: High ACAI was clearly correlated with mortality rate in HD patients, particularly cardiovascular mortality rate. ACAI was a useful long-term prognostic indicator in HD patients.

[Thyroglobulin concentration measurement in fine-needle aspiration fluid from cystic cervical lymph node metastases of papillary thyroid carcinoma].

BACKGROUND: Combining ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and fine-needle aspiration cytology (FNAC) usually results in the best preoperative diagnosis of cervical masses, including neoplasms. This may not be true, however, especially in occult papillary thyroid carcinoma (PTC) associated with single cystic cervical lymph node metastasis. We assessed the role of thyroglobulin measurement in FNA fluid (FNATg) in differentially diagnosing cystic cervical mass lesions, including PTC cystic lymph node metastasis. METHODS: We reviewed the records of 17 subjects with cervical cystic masses undergoing both FNATg measurement and surgery. FNA was done under ultrasonographic guidance. We also measured FNATg concentrations from extrathyroid lesions, consisting of cystic cervical lymph node metastases and benign cystic lesions. RESULTS: Pathological diagnosis involved 5 PTC lymph node metastases, 3 lateral cervical cysts, 7 thyroglossal duct cysts, and 2 squamous cell carcinoma (lung and oropharynx) lymph node metastases. FNATg of PTC lymph node metastasis was much higher than the reference range of blood serum thyroglobulin, although much lower for the lateral cervical cyst detection threshold. FNAC and FNATg measurement are thought to be mutually complementary in the differential diagnosis of PTC cystic lymph node metastasis. CONCLUSION: High concentrations of FNATg in a cystic cervical mass is considered specific to PTC lymph node metastasis, indicating its usefulness in distinguish PTC cystic metastasis from other cystic lesions. Including FNATg measurement with FNAC may thus improve preoperative diagnosis accuracy without additionally stressing subjects with PTC cystic lymph node metastasis.

Selective EP2 and Cox-2 inhibition suppresses cell migration by reversing epithelial-to-mesenchymal transition and Cox-2 overexpression and E-cadherin downregulation are implicated in neck metastasis of hypopharyngeal cancer.

Cyclooxygenase-2 (Cox-2) has been shown to promote cancer initiation and progression through pleiotropic functions including induction of epithelial-to-mesenchymal transition (EMT) via its predominant product prostaglandin E2 that binds to the cognate receptor EP2. Hence, pharmacological inhibition at the level of EP2 is assumed to be a more selective alternative with less risk to Cox-2 inhibition. However, little is known regarding the anti-cancer effect of an EP2 antagonist on the malignant properties of cancers including hypopharyngeal squamous cell carcinoma (HPSCC). The present study found that both the Cox-2 inhibitor celecoxib and the EP2 antagonist PF-04418948 upregulated CDH-1 expression, restored membranous localization of E-cadherin, and reduced vimentin expression, by downregulating the transcriptional repressors of E-cadherin in BICR6 and FaDu cells. Such Cox-2 or EP2 inhibition-induced EMT reversal led to repressed migration ability in both cells. Immunohistochemical analysis of surgical HPSCC specimens demonstrated an inverse relationship in expression between Cox-2 and E-cadherin both in the context of statistics (P = 0.028) and of reciprocal immunolocalization in situ. Multivariate logistic regression revealed that overexpression of Cox-2 (P < 0.001) and downregulation of E-cadherin (P = 0.016) were both independently predictive of neck metastasis. These results suggest that suppression of cell migration ability via reversing EMT by inhibiting the Cox-2/EP2 signaling may contribute to preventing the development and progression of lymphatic metastasis. Collectively, targeting Cox-2/EP2, especially using EP2 antagonist, can be a promising therapeutic strategy by exerting an anti-metastatic effect via EMT reversal for improving the treatment outcomes of patients with various cancers including HPSCC.

Mucoepidermoid carcinoma of the head and neck: clinical analysis of 43 patients.

OBJECTIVE: It is well known that mucoepidermoid carcinoma (MEC) displays a variety of biological behaviors. While the high-grade type is a highly aggressive tumor, its low-grade counterpart usually demonstrates a more benign nature and several systems have, therefore, been proposed to grade this neoplasm. METHODS: This report analyzes 43 patients suffering from head and neck MEC, who were treated in our department during the period from 1989 to 2005. The relationship between clinical and pathologic characteristics and survival rate was investigated. RESULTS: The 5-year overall and disease-free survival rate was 62.3 and 57.2%. Multivariate analysis demonstrated that the parameters that significantly affected survival were the patient's age (P = 0.040) and treatment method (P = 0.011). CONCLUSIONS: The patient's age and treatment method is the prognostic parameter in this study. Although complete surgical resection is the standard treatment for MEC, we should aggressively consider adjunctive radiotherapy in those cases that have a high risk of recurrence and poor prognosis.

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.

Various dietary protein intakes and progression of renal failure in spontaneously hypercholesterolemic Imai rats.

BACKGROUND/AIM: Dietary protein restriction is known to be beneficial in the preservation of the renal function in patients with chronic renal failure. Recently, the effect of varying quantity and quality of dietary protein intakes was also studied. This study investigates the effects of different dietary animal proteins on renal function in spontaneously hypercholesterolemic Imai rats that exhibit renal lesions similar to human focal and segmental glomerulosclerosis. The sources of proteins were from casein, pork, and fish. Primary concern was the effect of fish meat protein, because the effects of fish oil are well reported. To examine whether remnants of fish oil affect the experimental results, semi-defatted fish meat and fully defatted fish meat were prepared for these experiments. METHODS: Forty-two Imai rats were placed on diets containing casein, defatted pork meat, semi-defatted fish meat, or defatted fish meat as a protein sources from 10 to 22 weeks of age. Twenty-four hour urine collections were obtained along with measurements of systolic blood pressure and drawing blood from the tail artery every 4 weeks. Finally, the kidneys were removed and prepared for histological study. RESULTS: The semi-defatted fish meat diet retarded the rise of plasma cholesterol, virtually completely prevented the development of hypertriglyceridemia, and slowed the progression of proteinuria, renal function failure, and glomerular injury as compared with the control casein diet. However, the fully defatted fish meat diet led to renal failure at the same rate as the casein diet. The defatted pork diet group exhibited a higher creatinine clearance at the end of the experiments as compared with the casein and the fully defatted fish meat diet groups. CONCLUSIONS: These data suggest that an important determinant of the protective effects of the semi-defatted fish meat diet was related to the prevention of hypercholesterolemia and hypertriglyceridemia by the remaining fish oil. Fish meat protein itself did not indicate superior beneficial effects in the regression of the renal function in Imai rats as compared with casein protein, and defatted pork showed better results than casein and fully defatted fish meat.

[Planned neck dissection after weekly docetaxel and concurrent radiotherapy for advanced oropharyngeal cancer].

Small oropharyngeal carcinomas with advanced neck metastases (stage N2 or greater) are common. Patients with small T with large N oropharyngeal carcinoma have high rates of local control but lower rates of regional control when treated with chemoradiotherapy. Clinical assessment after chemoradiotherapy cannot ensure the absence of neck disease. In the last 5 years, we have treated patients with T1-2 with N2-3 oropharyngeal carcinoma with weekly docetaxel radiotherapy followed by planned neck dissection (PND). Our objectives were to clarify the pathologically complete response (CR) rate of neck metastasis after weekly docetaxel radiotherapy, to identify the clinical predictor of residual neck disease, and to determine the mobidity of planned neck dissection. After chemoradiotherapy, all 12 patients had a complete response at the primary site. We conducted 15 neck dissections. Of these, 6 (40%) had positive nodes. The pathological CR rate of neck metastasis was 58.3%, whereas overall 2-year neck control rate was 91.7%. These findings lend support to the role of PND after chemoradiotherapy in N2-3 neck disease. After chemoradiotherapy, clinical parameters including TN status, feasibility of chemoradiotherapy, largest lymph node size or size reduction in MRI, did not identify patients with residual neck disease. We conducted selective neck dissection (SND) in 80% of patients. SNI) as PND appears to be appropriate in this group of patients because of the low incidence of complications. A further cohort study including the comparison of PND nonenforcement group is necessary to clarify the validity of the addition of PND in weekly docetaxel radiotherapy.

[Long-term suppressive effect of falecalcitriol on parathyroid hormone secretion in secondary hyperparathyroidism in hemodialysis patients].

Alfacarcidol and calcitriol are widely used to treat secondary hyperparathyroidism associated with chronic renal failure, but it is often not possible to administer doses high enough to sufficiently inhibit parathyroid hormones because of the risk of hypercalcemia and hyperphosphatemia. We administered falecalcitriol (Hornel) Tablets) to patients with poorly controlled secondary hyperparathyroidism. The usefulness of falecalcitriol was demonstrated by the fact that control of intact-PTH was maintained for up to 24 months without a clear increase in serum Ca x serum inorganic phosphorus (iP), iP, and ALP levels.

[Levels of serum ascorbate and its metabolites in hemodialysis patients].

The status of ascorbic acid (AA) in dialysis patients is the subject of debate. Some reports have found AA to be deficient in dialysis patients, while others have found that AA is not deficient. In an attempt to confirm AA serum concentrations in dialysis patients, we analyzed the concentrations of AA as well as its metabolites using the specific determination of AA with chemical derivatization and the HPLC method. We studied 131 patients under maintenance hemodialysis therapy (HD), 23 patients with chronic renal failure (CRF) and 48 healthy controls (C). Serum concentrations of AA and the AA metabolites dehydroascorbic acid (DHA) and 2, 3-diketogulonate (DKG) were measured by HPLC. Nine HD patients were taking AA supplements. Seventy-six (62.3%) of the 122 HD patients not taking AA supplements exhibited deficient levels of AA (< 20 microM), while 13 (56.5%) of the 23 CRF patients and 9 (18.8%) of the 48 C showed deficient levels of AA. Analysis of AA metabolites in the normal-range AA (20-80 microM) group revealed that the DHA/AA ratio in HD patients was significantly higher than in C (3.3 +/- 2.6% and 1.2 +/- 2.2%, respectively). The DKG/AA ratio in HD patients was higher than in CRF patients (3.6 +/- 5.2% vs. 0.9 +/- 1.9%), whereas DKG was not detected in C. When compared to serum levels before the start of dialysis, serum AA, DHA and DKG concentrations at the end of the dialysis session decreased by an average of 74.2, 84.0 and 78.8% respectively. In HD patients, serum levels of thiobarbituric reactive substances (TBARS) were significantly lower in the higher AA (> 80 microM) group than in the deficient and normal-range AA groups. In 12 AA-deficient patients, after 1 month of taking AA supplements (200 mg/day), serum AA levels rose to 79.9 microM, while serum TBARS level declined when compared with levels before supplementation. In conclusion, the frequency of AA deficiency in dialysis patients is extremely high. AA deficiency in HD patients may result in high TBARS levels, which reflect increased oxidative stress. Adequate AA supplementation should therefore be considered in such patients.

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.

Improved assessment of aortic calcification in Japanese patients undergoing maintenance hemodialysis.

OBJECTIVE: Vascular calcification is a feature of arteriosclerosis and in hemodialysis (HD) patients it may be severe, even at a relatively young age, and is closely related to the overall prognosis. We used the aortic calcification area index (ACAI), derived from the aortic calcification index (ACI), to evaluate and analyze the risk factors for abdominal aortic calcification in HD patients. PATIENTS AND METHODS: Subjects comprised 137 patients on maintenance HD. ACAI was measured on abdominal plain computed tomography: 10 slices of the abdominal aorta were obtained at 1-cm intervals from the bifurcation of the common iliac artery and the area of the aortic cross-section and calcification was measured using image software. The calcification area was divided by the cross-sectional area and expressed as a percentage (%). The mean value for the 10 slices was also calculated. Patients were divided into 2 groups according to ACAI being lower or higher than the mean value and the risk factors in each group were compared by multivariate analysis. Results Group comparison showed significant differences in age, systolic blood pressure, serum calcium, and lipoprotein(a). On multiple regression analysis, age, systolic blood pressure, and serum calcium were independent risk factors. On logistic regression analysis, age, duration of dialysis, systolic blood pressure, and serum calcium were independent risk factors. CONCLUSION: Risk factors for abdominal aortic calcification in HD patients include age, systolic blood pressure, and serum calcium, according to ACAI evaluation. The ACAI was accurate and useful for evaluating abdominal calcification.

Renal protective effects of pitavastatin on spontaneously hypercholesterolaemic Imai Rats.

BACKGROUND: Independent of their lipid-lowering effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have renal protective effects on various models of progressive renal diseases, therefore, additional therapeutic advantages have been considered. In the present study, using spontaneously hypercholesterolaemic Imai rats, we examined the protective effects of pitavastatin on renal injuries and the oxidative modification of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL), since oxidized lipoproteins are speculated to be involved in the mechanism of this rat strain's renal injuries. METHODS: Male Imai rats were treated with pitavastatin (n = 11) at a dose of 100 mg/kg diet or received no specific therapy as controls (n = 11) from 10 to 22 weeks of age. Body weight, urinary protein excretion and serum constituents were evaluated every 4 weeks. At the end of the study, the effects of pitavastatin on the susceptibility of serum LDL and HDL to oxidation, and renal histology were examined. RESULTS: Pitavastatin treatment did not affect hyperlipidaemia, but significantly reduced proteinuria and preserved creatinine clearance deterioration. At the end of the study, lag times for LDL and HDL oxidation were prolonged by the treatment of pitavastatin to 126 and 153%, respectively, compared with the controlled group. The glomerulosclerosis index (SI) for untreated controlled rats was significantly higher than that for the pitavastatin-treated group. An immunohistochemistry study showed significantly lower numbers of ED-1 positive macrophages in the glomeruli and interstitium in pitavastatin-treated rats compared with those controlled. CONCLUSION: Pitavastatin treatment prevented renal injuries in Imai rats independent of lipid-lowering effects. Prevention of oxidative modification of LDL and HDL may play an important role on the beneficial effects of pitavastatin treatment.