Precursor Radiographic Findings in Patients With Medication-Related Osteonecrosis of the Jaw.

BACKGROUND: Oral surgical treatment, such as tooth extraction, has been identified as a risk factor for the onset of medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may already be latent, and its manifestation may be triggered by extraction. PURPOSE: The purpose of this study was to examine the association between pre-extraction imaging and MRONJ. STUDY DESIGN, SETTING, SAMPLE: We performed a multicenter case-control analysis of patients receiving antiresorptive agents (ARAs) who underwent extraction between 2012 and 2016. We enrolled patients who had undergone tooth extraction in the setting of ARA exposure. PREDICTOR VARIABLES: The predictor variables comprised preoperative radiographic findings associated with MRONJ stage 0. These findings included alveolar bone loss, thickening or obscuring of the periodontal ligament, and osteosclerosis involving the alveolar bone. They were coded as present or absent before tooth extraction. MAIN OUTCOME VARIABLE: The primary outcome variable was MRONJ status coded as present or absent. COVARIATES: Sex, age, underlying diseases necessitating the administration of ARA, the type of ARA used, corticosteroid use, extraction region, and wound closure were analyzed. ANALYSES: Mann-Whitney U test, χ2 test, Fisher's exact test for univariate analysis, and multiple logistic regression analysis were performed. P values < .05 were significant. RESULTS: The subjects consisted of 26 patients and 110 controls (male: 8/36, female: 18/74). The mean ages of the MRONJ group and the control group were 77.0 ± 11.9 and 63.0 ± 15.8, respectively (P value = .001). The prevalence of osteosclerosis was significantly higher in the MRONJ group than in the control group (14/72, 53.9%/29.3%, P < .01). Multivariate analysis identified osteosclerosis (odds ratio: 8.4, 95% confidence interval: 2.133.9, P < .01) as a significant independent predictor associated with the development of MRONJ after extraction. CONCLUSION AND RELEVANCE: These findings suggest that a precursor to MRONJ is highly likely to be present in patients with osteosclerosis at the time of extraction. The majority of patients who developed MRONJ after extraction had imaging findings that suggested infection in the surrounding alveolar bone.

5-Hydroxytryptamine-3 receptor antagonist and dexamethasone as prophylaxis for chemotherapy-induced nausea and vomiting during moderately emetic chemotherapy for solid tumors: a multicenter, prospective, observational study.

BACKGROUND: Of patients receiving moderate emetic risk chemotherapy (MEC), 30-90% experience chemotherapy-induced nausea and vomiting (CINV); however, the optimal antiemetic treatment remains controversial. METHODS: In this multicenter, prospective, observational study of adults treated with MEC while receiving chemotherapy for various cancer types in Japan, the enrolled patients kept diaries documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. RESULTS: Of the 400 patients enrolled from May 2013 to January 2015, 386 were eligible for evaluation. The median age was 64 (range, 26-84). The overall complete response (CR; no emetic events and no antiemetic measures) rate was 64%. The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5) + etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). Total control (TC; no emetic events, no antiemetic measures, and no nausea) and complete control (CC; no emetic events, no antiemetic measures, and less than mild nausea) were achieved in 51 and 61% of patients, respectively. Logistic regression analysis revealed history of motion sickness, history of pregnancy-associated vomiting and CBDCA-based chemotherapy as risk factors for CR and history of motion sickness and history of pregnancy-associated vomiting as risk factors for TC. Additional, Ages ≥65 years is an independent predictive factor for achieving TC. CONCLUSIONS: Our data showed that two antiemetics were insufficient to control CINV in patients receiving CBDCA- or oxaliplatin-based chemotherapy. However, two antiemetics may be sufficiently effective for elderly male patients receiving CBDCA (AUC5) + ETP, CBDCA+PTX for lung cancer, or CAPOX. Additionally, we consider that three antiemetics are necessary for women with colorectal cancer receiving CAPOX. Risk factor analysis related to CR showed that CINV prophylaxis in patients treated with CBDCA-based chemotherapy was generally supportive of the guideline-recommended three antiemetics. However, the control of nausea in patients receiving non-CBDCA-based chemotherapy is a key point to note. The further individualization of antiemetic regimens for patients receiving MEC based on both types of chemotherapy regimens and sex is needed.

Construction and characterization of human oral mucosa equivalent using hyper-dry amniotic membrane as a matrix.

BACKGROUND: Human amniotic membrane(HAM) as a graft material has been used in various fields. Hyper-dry amniotic membrane (HD-AM) is a novel dried amniotic membrane that is easy to handle and can be preserved at room temperature without time limitation. The purpose of this study was to investigate the useful properties of HD-AM in reconstruction of the oral mucosa. METHODS: Human oral keratinocytes were isolated and seeded on HD-AM in serum-free culture system. Oral mucosa equivalent (OME) was developed and transplanted onto full-thickness wound on athymic mice. The wound healing was analyzed and the OME both before and after transplantation was analyzed with hematoxylin-eosin staining and immunohistochemical staining for Cytokines 10 (CK10), Cytokines 16 (CK16), and Ivolucrin (IVL). RESULTS: Oral keratinocytes spread and proliferated well on HD-AM. Two weeks after air-lifting, OME had formed with good differentiation and morphology. We confirmed immunohistochemically that the expression of CK10 was positive in all suprabasal layers, as was CK16 in the upper layers, while IVL was present in all cell layers. Three weeks after transplantation to athymic mice, the newly generated tissue had survived well with the smallest contraction. The epithelial cells of newly generated tissue expressed CK10 throughout in all suprabasal layers, IVL was mainly in the granular layer, and CK16 positive cells were observed in all spinous layer and granular layer but were not expressed in the mouse skin, all of which were similar to native gingival mucosa. CONCLUSIONS: The OME with HD-AM as a matrix revealed a good morphology and stable wound healing. This study demonstrates that HD-AM is a useful and feasible biomaterial for oral mucosa reconstruction.

[Retrospective analysis of clinical and pathological factors that influence patient survival in salivary gland cancer - could chemotherapy improve survival ?].

The purpose of this retrospective study was to evaluate the prognostic factors in salivary gland cancer using a multivariate analysis. In total, 45 consecutive patients who underwent planned radical resection for salivary gland cancer between 1985 and 2010 were analyzed. Univariate and multivariate analyses were performed to analyze the clinical and pathological factors that influence patient survival in salivary gland cancer(tumor location, T and N classification, histological grade, excision margin status, postoperative radiotherapy, and postoperative adjuvant chemotherapy). The results of the multivariate analysis showed that T classification(odds ratio[OR]: 2.93, 95%confidence interval[CI]: 1.47-5.82), and excision margin status(OR: 4.86, 95% CI: 1.76-13.44)had a significant impact on tumor-free survival time, suggesting that both are important prognostic factors in salivary gland cancer. Moreover, postoperative adjuvant chemotherapy showed a tendency to improve tumor free survival time(OR: 0.28, 95% CI: 0.07-1.11), thereby indicating its potential in improving prognosis in patients with salivary gland cancer.

Clinical significance of apoptosis-associated speck-like protein containing a caspase recruitment domain in oral squamous cell carcinoma.

OBJECTIVES: To assess apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression in oral squamous cell carcinoma (OSCC) and analyze its clinical and pathological significance. STUDY DESIGN: ASC expression was studied using immunohistochemistry in 119 OSCCs patients. The relationships between ASC expression and clinical and pathological parameters were statistically analyzed. In addition, the relationships between ASC expression and cell differentiation [IVL (involcrin) expression] and apoptosis (TUNEL [TdT-mediated dUTP nick end labeling] positive cell number) were investigated. RESULTS: ASC expression showed significant correlations with parameters including clinical tumor stage, mode of invasion, and histological differentiation, and had a significant impact on survival of OSCC. The distribution of ASC correlated well with that of IVL. ASC expression was significantly correlated with the TUNEL-positive cell number. CONCLUSIONS: Lower ASC expression correlates with clinical and pathological malignancy and, consequently, poor prognosis of OSCC. ASC has a close association with cell differentiation and apoptosis.

Vital staining with iodine solution in oral cancer: iodine infiltration, cell proliferation, and glucose transporter 1.

BACKGROUND: Vital staining with iodine solution has been used to distinguish dysplastic/malignant oral epithelium from normal mucosa. However, little is known about its critical mechanism. The purpose of this study was to visualize how iodine infiltrates the oral epithelium and reacts with glycogen. In addition, we tested the hypothesis that higher cell proliferation requires increased energy consumption, and consequently exhausted glycogen may lead to a failure to be stained by iodine solution. METHODS: Fifteen frozen tissue samples of iodine-stained and -unstained mucosa were obtained from 15 cases of oral squamous cell carcinoma (OSCC). Serial frozen sections were cut and examined with hematoxylin and eosin and periodic acid-Schiff methods and immunohistochemical staining for p53, Ki67 and glucose transporter 1 (GLUT 1). RESULTS: Iodine solution was able to penetrate normal epithelium to a maximum depth neighboring the parabasal layer, but iodine-stained areas were completely consistent with glycogen distribution only in the upper superficial layer. Iodine-negative epithelium presented significantly higher immunoreactions for P53 and GLUT 1 in basal, parabasal, and superficial layers, respectively, whereas the reaction for Ki67 in the superficial layer was higher than that in iodine-positive epithelium (Wilcoxon signed-rank test, P < 0.05). CONCLUSIONS: Iodine infiltrated and reacted with glycogen mainly in the upper superficial layer of the nonkeratinized epithelium. Both histological and molecular margins can be confirmed by iodine vital staining in OSCC. It is also suggested that high cell proliferation induced elevated glycolysis, resulting in an intraepithelial glycogen degradation and consequent failure to be stained by iodine solution.

Effectiveness of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa.

The purpose of this retrospective study was to assess the effect of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa. The historical control group had dysplastic or malignant mucosal lesions resected solely on the evidence of direct inspection and palpation. In the vital staining group tissue was resected only after vital staining with iodine solution. Seven of 25 patients in the conventional group developed recurrent dysplastic or cancerous oral mucosa around the primary site, while no patient among 23 reported recurrence in the vital staining group (p<0.01). Kaplan-Meier assessment showed that the 5-year primary control rate was 100% in the vital staining group and 75% in the conventional group. Although this retrospective study has some limitations, the results suggest that vital staining with iodine may be useful in reducing the incidence of recurrence of dysplastic or cancerous epithelium at a primary site. Further well-controlled study is essential.

Cultured epithelial grafting using human amniotic membrane: the potential for using human amniotic epithelial cells as a cultured oral epithelium sheet.

OBJECTIVE: Human amniotic cells are a valuable source of functional cells that can be used in various fields, including regenerative medicine and tissue engineering. The aim of this study was to investigate the utility of human amniotic epithelial (hAE) cells as a new cell source for culturing stratified epithelium sheets for intraoral grafting. METHODS: Enzymatically isolated hAE cells were submerged in a serum-free, low-calcium-supplemented MCDB 153 medium without a feeder layer. The hAE cells were seeded onto a Millicell cell culture plate insert and cultured while submerged in a high-calcium medium for 4 days. Then, they were cultured at an air-liquid interface for 3 weeks. Cultures of hAE cells proliferated at the air-liquid interface. RESULTS: After 3 weeks, the hAE cells cultivated using the air-liquid interface method lead to almost 10 continuous layers of stratified epithelium without parakeratinization or keratinization. It confirmed immunohistochemically that the presence of CK10/13 and Ki-67 positive cells were spread throughout almost all the epithelial layer, and that CK19 positive cells were expressed throughout the entire epithelial layer in the cultured hAE cell sheets. Cultured hAE cells sheets showed a staining pattern similar to that of uncultured oral mucosa: ZO-1 and occludin were located in the intercellular junctions throughout all the epithelial layers. It was suggested that the hAE sheets consisted of highly-active proliferating cells and undifferentiated cells, and had a barrier function. CONCLUSIONS: These results suggested that hAE cells may be a promising cell source for the development of stratified epithelium allograft sheets using a human cell strain.

Impact of different surgical margin conditions on local recurrence of oral squamous cell carcinoma.

The purpose of this study was to analyze the impact of different surgical margin conditions on local recurrence of oral squamous cell carcinoma (SCC) in 148 consecutive patients who underwent planned radical resection of oral SCC. The patients were classified into four categories according to the status of the surgical margin: clear (no SCC within 5mm, n=103), close (SCC within 5mm, n=21), dysplasia (dysplastic epithelium at margin, n=13), and involved (SCC at margin, n=11). Cox's proportional hazard model showed that the status of the surgical margin had a significant impact on local recurrence (p<0.003); hazard ratio was 3.79 (95%CI: 1.17-12.28) with a close and 7.89 (2.38-26.17) with an involved margin. The presence of mucosal dysplasia at the surgical margin was also a significant predictor of local recurrence (hazard ratio: 5.29, 95%CI: 1.31-21.29). Local recurrence was observed only with severe dysplasia, while no recurrence with mild and moderate dysplasia. In the patients with a clear and closed surgical margin, local recurrence was related with T4 tumor and an advanced mode of tumor invasion. The results of this study suggested that the presence of tumor cells at or close to the surgical margin increased the risk of local recurrence. The presence of dysplastic epithelium (especially severe dysplasia) at the mucosal surgical margin has a significant impact on local control. It was also suggested that not simply the width of the free margin but also clinical and histological risk factors should be included in deciding the necessity for adjuvant radiotherapy.

Usefulness of a commercial enzyme-linked immunosorbent assay kit for Candida mannan antigen for detecting Candida in oral rinse solutions.

OBJECTIVE: The aim was to test the performance of a commercial enzyme-linked immunosorbent assay (ELISA) kit for Candida mannan antigen for detecting Candida in oral rinse solutions. STUDY DESIGN: Forty-eight oral rinse solutions (38 from patients and 10 from healthy volunteers) were available. Mannan antigen was measured using a commercial sandwich ELISA kit, Unimedi Candida. The result of the mannan assay was compared with the result of conventional detection and identification by culture. RESULTS: The result of the mannan assay revealed that 31 of 38 clinical and 3 of 10 healthy volunteer samples were positive for Candida. Using the culture as a gold standard, the overall sensitivity and specificity of the mannan antigen detection were 90.9% and 46.2%, respectively. CONCLUSIONS: The results of this study suggested that mannan antigen detection might be a possible and sensitive technique for the detection of oral Candida. The conditions of the ELISA-based assay should be optimized for oral rinse solutions.

Highly dispersed ruthenium hydroxide supported on titanium oxide effective for liquid-phase hydrogen-transfer reactions.

Supported ruthenium hydroxide catalysts (Ru(OH)(x)/support) were prepared with three different TiO(2) supports (anatase TiO(2) (TiO(2)(A), BET surface area: 316 m(2) g(-1)), anatase TiO(2) (TiO(2)(B), 73 m(2) g(-1)), and rutile TiO(2) (TiO(2)(C), 3.2 m(2) g(-1))), as well as an Al(2)O(3) support (160 m(2) g(-1)). Characterizations with X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), electron spin resonance (ESR), and X-ray absorption fine structure (XAFS) showed the presence of monomeric ruthenium(III) hydroxide and polymeric ruthenium(III) hydroxide species. Judging from the coordination numbers of the nearest-neighbor Ru atoms and the intensities of the ESR signals, the amount of monomeric hydroxide species increased in the order of Ru(OH)(x)

Intraoperative tissue staining of invaded oral carcinoma.

The purpose of this study was to assess the ability of intraoperative tissue staining with consecutive application of 0.4% indigo carmine and 0.5% Congo red to demonstrate the extent and border of oral carcinoma invasion. Seventeen patients were included in the study. Once the oral tumor was resected, a vertical section of surgical specimen was taken from the central part of the tumor. The extent and border of the invaded carcinoma were assessed on digital microscopic examination with tissue staining. The results of assessments were compared with corresponding results of conventional histopathological analysis with HE staining, which is considered the gold standard. Tissue staining produced a brown-black stain on normal muscle, connective, and salivary tissues but not tumor and epithelial tissues. It clearly demonstrated the extent and border of tumor invasion in 13 of 17 patients (76.5%); however, detection of remnant vital tumor cells in scar tissue after neoadjuvant chemotherapy, and distinction between the tumor and adipose tissue scattered in the muscle tissue was difficult. The results of this study showed that intraoperative tissue staining was a possible method in demonstrating the extent and border of carcinoma deeply invaded in the soft tissue and selecting the site for additional frozen section analysis, although the method needed some refinement.

Synthetic scope of Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions: an application to reduction of allylic alcohols by a sequential process of isomerization/Meerwein-Ponndorf-Verley-type reduction.

Reduction of allylic alcohols can be promoted efficiently by the supported ruthenium catalyst Ru(OH)x/Al2O3. Various allylic alcohols were converted to saturated alcohols in excellent yields by using 2-propanol without any additives. This Ru(OH)x/Al2O3-catalyzed reduction of a dienol proceeds only at the allylic double bond to afford the corresponding enol, and chemoselective isomerization and reduction can be realized under similar conditions. The catalysis is truly heterogeneous and the high catalytic performance can be maintained during at least three recycles of the Ru(OH)x/Al2O3 catalyst. The transformation of allylic alcohols to saturated alcohols consists of three sequential reactions: oxidation of allylic alcohols to alpha,beta-unsaturated carbonyl compounds; reduction of alpha,beta-unsaturated carbonyl compounds to saturated carbonyl compounds; and reduction of saturated carbonyl compounds to saturated alcohols.

Accuracy of intraoperative tissue staining in delineating deep surgical margins in oral carcinoma surgery.

The purpose of this study was to assess the accuracy of this tissue staining assessment of surgical specimens in delineating deep surgical margins in oral cancer surgery. Fifteen patients who underwent surgery for oral carcinoma were included in the study. Once the tumor was resected, a vertical section of the surgical specimen was taken from the central part of the tumor. The section was consecutively stained with 0.4% indigo carmine and 0.5% Congo red, and deep surgical margins were assessed using a digital microscope with a magnification power of 25-175x. The results of tissue staining analysis were compared with the corresponding results of conventional histopathological analysis with HE staining, which is considered the gold standard. The extent of carcinoma invasion could be visualized after the application of tissue staining solutions. Tissue staining analysis was accurate in 12 of the 15 patients (80%) in evaluating the closest deep surgical margin. There was no significant difference in the tumor-margin distance between tissue staining and histopathological assessment in these 12 patients (Wilcoxon signed-ranks test, P>0.63). The results of this study showed that intraoperative tissue staining of surgical specimens permitted visual inspection and assessment of tumor spread to surgical margin, although the method has some limitations. The method had a possible ability in controlling the deep surgical margin.

Retrospective analysis on prognostic impact of adjuvant chemotherapy in the patients with advanced and resectable oral squamous cell carcinoma.

PURPOSE: The effect of adjuvant chemotherapy on oral squamous cell carcinoma (SCC) is unclear mainly because there have been a few studies which evaluate the efficacy of adjuvant chemotherapy. The purpose of this retrospective study was to analyze the efficacy of adjuvant chemotherapy in the patients with advanced and resectable oral SCC. METHODS: 41 patients in whom advanced SCC (stage III and IV) was completely removed were included in this study. The impact of multiple variables including T-classification, degree of differentiation, mode of invasion, number and level of cervical metastatic node, pre-and post-operative radiation therapy, neoadjuvant chemotherapy, and adjuvant chemotherapy on survival and control of local relapse or distant metastasis was assessed using the stepwise Cox proportional hazards model. RESULTS: The level of neck node metastasis (p<0.02) was a significant independent predictor for cause-specific survival and adjuvant chemotherapy was of borderline significance (p=0.07). The number of neck node metastasis (p<0.01) and adjuvant chemotherapy (p<0.01) were significantly related with disease free survival. CONCLUSION: The results of this retrospective study suggested that adjuvant chemotherapy had a significant benefit in improving disease free survival.

Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells.

BACKGROUND: Interleukin (IL)-13 has recently been reported as the major T-helper 2 cytokine involved in mucus overproduction and oversecretion in allergic airways. However, the relationship between human calcium-activated chloride channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully investigated. OBJECTIVES: The present study examines whether IL-13 induces the expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also investigated the relationship between hCLCA1 and MUC5AC expression and the development of goblet cell hyperplasia (GCH). METHODS: NHBE cells were isolated from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC gene and protein expression, as well as GCH were examined in the cells after exposure to IL-13. RESULTS: Incubation with IL-13 for 14 and 21 days increased the total number of epithelial cells, the number of periodic acid-Schiff (PAS)-stained epithelial cells, the number of goblet cells, as well as expression of mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory granules also increased after 21 days of incubation with IL-13. Niflumic acid, a chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells exposed or not to IL-13 expressed IL-13 receptor alpha(1) (IL-13Ralpha(1)), and an antibody to IL-13 Ralpha(1) also reduced the number of PAS-positive cells after exposure to IL-13. CONCLUSIONS: IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic.

Synthetic scope and mechanistic studies of Ru(OH)x/Al2O3-catalyzed heterogeneous hydrogen-transfer reactions.

Three kinds of hydrogen-transfer reactions, namely racemization of chiral secondary alcohols, reduction of carbonyl compounds to alcohols using 2-propanol as a hydrogen donor, and isomerization of allylic alcohols to saturated ketones, are efficiently promoted by the easily prepared and inexpensive supported ruthenium catalyst Ru(OH)x/Al2O3. A wide variety of substrates, such as aromatic, aliphatic, and heterocyclic alcohols or carbonyl compounds, can be converted into the desired products, under anaerobic conditions, in moderate to excellent yields and without the need for additives such as bases. A larger scale, solvent-free reaction is also demonstrated: the isomerization of 1-octen-3-ol with a substrate/catalyst ratio of 20,000/1 shows a very high turnover frequency (TOF) of 18,400 h(-1), with a turnover number (TON) that reaches 17,200. The catalysis for these reactions is intrinsically heterogeneous in nature, and the Ru(OH)x/Al2O3 recovered after the reactions can be reused without appreciable loss of catalytic performance. The reaction mechanism of the present Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions were examined with monodeuterated substrates. After the racemization of (S)-1-deuterio-1-phenylethanol in the presence of acetophenone was complete, the deuterium content at the alpha-position of the corresponding racemic alcohol was 91%, whereas no deuterium was incorporated into the alpha-position during the racemization of (S)-1-phenylethanol-OD. These results show that direct carbon-to-carbon hydrogen transfer occurs via a metal monohydride for the racemization of chiral secondary alcohols and reduction of carbonyl compounds to alcohols. For the isomerization, the alpha-deuterium of 3-deuterio-1-octen-3-ol was selectively relocated at the beta-position of the corresponding ketones (99% D at the beta-position), suggesting the involvement of a 1,4-addition of ruthenium monohydride species to the alpha,beta-unsaturated ketone intermediate. The ruthenium monohydride species and the alpha,beta-unsaturated ketone would be formed through alcoholate formation/beta-elimination. Kinetic studies and kinetic isotope effects show that the Ru-H bond cleavage (hydride transfer) is included in the rate-determining step.

Dihydropyrimidine dehydrogenase expression predicts survival outcome and chemosensitivity to 5-fluorouracil in patients with oral squamous cell carcinoma.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-Fu) catabolism. The aim of this study was to evaluate the prognostic value of DPD expression and the correlation between DPD expression and efficacy of 5-Fu. Retrospective analysis of DPD expression was performed immunohistochemically in 103 patients with oral squamous cell carcinoma (OSCC), in which staining intensity of DPD expression and degree of heterogeneity of DPD expression were categorized. Expression of DPD correlated with lymph node metastasis, mode of invasion and differentiation. Expression of DPD was an independent significant factor for survival outcome and was more predictive than conventional clinical factors. Furthermore, heterogeneous expression of DPD was more effective than homogeneous expression of DPD in neoplastic cells when evaluated in patients treated with chemotherapy including tegafur/uracil (UFT). Expression of DPD is an independent predictor for clinical outcome. Furthermore, heterogeneity of DPD expression may be a clue for predicting sensitivity to 5-Fu in patients with OSCC.

Clinical predictors for contralateral neck lymph node metastasis from unilateral squamous cell carcinoma in the oral cavity.

The factors that predict contralateral (C-) lymph node metastasis (LNM) in patients with unilateral oral squamous cell carcinoma (SCC) were analyzed. One hundred and twenty-nine patients who had untreated SCC that originated from the lateral oral cavity, but not around the midline, were included. The impact of multiple clinicopathologic factors (sex, performance status, primary site, T-stage, number and level of ipsilateral LNM, growth type, histopathological grading, mode of invasion, extension across the midline, and systemic neoadjuvant/adjuvant chemotherapy) on time-to-C-LNM was assessed using the stepwise Cox proportional hazards model. The T-stage, number of ipsilateral LNM, and histopathological grading were independent and significant predictors for C-LNM. No C-LNM occurred in patients without ipsilateral LNM and in those with earlier cancers (T1 to T3) excepting tongue cancer. The results of this retrospective study suggested that patients with advanced tumors, multi-involvement of the ipsilateral neck nodes, or a higher degree of histopathological grading were at a higher risk for C-LNM.