A Case of Nonocclusive Mesenteric Ischemia During Bioradiotherapy With Cetuximab.

Nonocclusive mesenteric ischemia (NOMI) causes mesenteric ischemia and intestinal necrosis despite the absence of organic obstruction, such as thrombi and emboli in mesenteric blood vessels, and it has an extremely poor prognosis. We report a case of NOMI developed during bioradiotherapy (BRT) with cetuximab for cervical lymph node metastasis of tongue cancer. The patient was a 73-year-old man who underwent right radical neck dissection for neck lymph node metastasis after tongue cancer surgery. Postoperatively, the patient received BRT with cetuximab. On the 34th day after BRT, the patient had abdominal distension and a decreased level of consciousness. Contrast-enhanced computed tomography revealed mesenteric ischemia without thrombi and extensive intestinal emphysema. The patient was diagnosed with NOMI. Furthermore, he had septic shock and was treated with vasopressors and antibacterial agents; however, the condition of the patient did not improve, and he died on the same day.

Prognostic Significance of Serum Interleukin-6 Levels in Oral Squamous Cell Carcinoma.

Introduction The prognosis of oral squamous cell carcinoma (OSCC) is often poor despite standard treatments. Additionally, no useful prognostic markers are available. Therefore, we aimed to investigate the relationship between serum Interleukin-6 (IL-6) levels and prognosis and explore its local and systemic effects in patients with OSCC. Methods Ninety-five new cases of OSCC were included, and the prognosis was compared between high and low serum IL-6 groups. The localization of IL-6 in OSCC tissues was examined. Furthermore, a comprehensive gene expression analysis was performed in OSCC tissues and compared between the two groups. Results A significant difference in overall survival and disease-free survival was observed. Furthermore, a substantial expression of IL-6 was localized in the stroma. Comprehensive gene expression analysis of tumor localization showed increased expression of genes related to oxidoreductase and lipid metabolism in the primary tissues of the group with high serum IL-6 levels. Regarding the correlation between blood tests and serum IL-6 levels, a strong positive correlation was observed between inflammatory responses and nutritional factors. Conclusion These results suggest that serum IL-6 may be a prognostic factor for metabolic abnormalities in patients with OSCC and that aggressive nutritional interventions may contribute to prognosis.

KRT13 and UPK1B for differential diagnosis between metastatic lung carcinoma from oral squamous cell carcinoma and lung squamous cell carcinoma.

Oral squamous cell carcinomas unusually show distant metastasis to the lung after primary treatment, which can be difficult to differentiate from primary squamous cell carcinoma of the lung. While the location and number of tumor nodules is helpful in diagnosing cases, differential diagnosis may be difficult even with histopathological examination. Therefore, we attempted to identify molecules that can facilitate accurate differential diagnosis. First, we performed a comprehensive gene expression analysis using microarray data for OSCC-LM and LSCC, and searched for genes showing significantly different expression levels. We then identified KRT13, UPK1B, and nuclear receptor subfamily 0, group B, member 1 (NR0B1) as genes that were significantly upregulated in LSCC and quantified the expression levels of these genes by real-time quantitative RT-PCR. The expression of KRT13 and UPK1B proteins were then examined by immunohistochemical staining. While OSCC-LM showed no KRT13 and UPK1B expression, some tumor cells of LSCC showed KRT13 and UPK1B expression in 10 of 12 cases (83.3%). All LSCC cases were positive for at least one of these markers. Thus, KRT13 and UPK1B might contribute in differentiating OSCC-LM from LSCC.

Positive impact of perioperative oral management on the risk of surgical site infections after abdominal surgery: Sixteen universities in Japan.

Surgical site infections (SSI) are associated with increased morbidity and mortality rates. This study aimed to investigate the ability of perioperative oral management (POM) to reduce the risk of SSI in abdominal surgery Real-world data collected from 16 university hospitals in Japan were reviewed. The medical records of consecutive 2782 patients (1750 men and 1032 women) who underwent abdominal surgery under general anesthesia at 16 university hospitals were retrospectively reviewed. Detailed information about SSI was assessed and compared between patients with and without POM in univariate and multivariate analyses. SSI were observed in 275 patients (incidence rate:9.9%), and POM was administered to 778 patients (28.0%). Univariate analyses revealed that diabetes mellitus, Eastern Cooperative Oncology Group performance status, American Society of Anesthesiologists classification, surgical site, preoperative Prognostic Nutritional Index score, POM, extent of surgery, operation time, and intraoperative blood loss were significantly associated with postoperative SSI (Chi-square or Mann-Whitney U test, P < .01). Multivariate analysis revealed that POM had significant preventive effects against postoperative SSI (estimate: -0.245, standard error: 0.080, P < .01). Surgical site, American Society of Anesthesiologists classification, and operation time were also significant and independent clinical predictors of SSI. The analysis of real-world data from 16 university hospitals revealed that, regardless of the content and degree of the problem, the addition of POM has significant beneficial effects in reducing the risk of SSI in patients who undergo abdominal surgery. Medical records from each hospital and data from the Health Care Payment Fund were collected and analyzed retrospectively.

The effects of perioperative oral management on perioperative serum albumin levels in patients treated surgically under general anesthesia: A multicenter retrospective analysis in Japan.

ABSTRACT: The purpose of the present study was to investigate the efficacy of perioperative oral managements (POMs) on perioperative nutritional conditions in patients undergoing surgery with general anesthesia. Medical records were retrospectively reviewed and the effects of POMs were investigated based on a large number of cases using a multicenter analysis. The profile of serum albumin levels was assessed and compared between patients with and without POMs using the multivariate analysis. Seventeen Eleven thousand and one hundred sixty patients (4,873 males and 6,287 females) were reviewed. Of these, 2710 patients (24.3%) had undergone POMs. The results of a multivariate analysis revealed the significant positive effect of POMs on perioperative serum albumin level (change between at admission and discharge, (Estimate: 0.022, standard error: 0.012, P < .0001). Patient gender, age, surgical site, performance status, the American Society of Anesthesiologists (ASA) physical status classification, operation time, amount of blood loss, and serum albumin level at admission were also significant predictors. Adjusted multivariate analysis of the effects of POMs on perioperative change of serum albumin level in all subjects reveled the significance of POMs intervention (estimate: 0.022, standard error: 0.012, P < .0001). These results suggest that POMs exerts significant positive effects on perioperative serum albumin levels in patients underwent surgery under general anesthesia.

Distribution of dendritic cell subtypes in primary oral squamous cell carcinoma is inconsistent with a functional response.

Dendritic cell (DC) function will likely be important for immunological cancer therapies, but our knowledge of the roles of DCs in tumors is limited, in part because most studies were performed before DC subtypes were defined. We studied the distributions of immature epidermal, immature dermal, mature, and plasmacytoid DCs in 63 primary tumors and eight lymph node metastases from oral squamous cell carcinoma patients without evidence of distant metastasis. Immature CD207/Langerin+ and CD209/DC-SIGN+ DCs were present in the primary tumor region, but CD209/DC-SIGN+ cells rarely infiltrated the tumor. Mature DCs were rare, and presence of CD123+ plasmacytoid DCs was associated with poorer outcome. Unexpectedly, migration and maturation of DCs was associated with a worse outcome. Overall, the distribution of DC subtypes indicated that ineffective DC response to tumor is a failure of DC function rather than recruitment, suggesting that a strategy of shifting the balance of secreted factors in the tumor milieu may be more effective in restoring anti-tumor immune function than current methods restoring only one population of DCs to the immunosuppressive tumor region.

Prognostic impact of preoperative serum interleukin-6 levels in patients with early-stage oral squamous cell carcinoma, defined by sentinel node biopsy.

Failure to detect recurrence and lymph node metastasis early represents a fundamental barrier to the improvement of survival rate in early stage oral squamous cell carcinoma (OSCC). The present study evaluated the association between serum interleukin-6 (IL-6) level and clinical outcomes in patients with early stage OSCC patients defined by sentinel node biopsy (SNB). A total of 53 patients with clinical stage I/II OSCC who underwent SNB were enrolled. SNB was determined by a radioisotope method, and was evaluated by histopathological examination and genetic analysis. Preoperative sera were measured for IL-6 by ELISA. In the clinical stage I/II patients, disease-free survival (DFS) was demonstrated to be higher in patients with negative SNB compared with patients with positive SNB. In total, 13 patients were demonstrated to exhibit lymph node metastasis by SNB or were reclassified to pathological stage T4 subsequent to analysis of the surgically resected specimens. Thus, 40 patients were diagnosed with early stage OSCC. Of these 40 patients, DFS of the patients with low serum IL-6 was significantly higher compared with the patients with high serum IL-6 (P=0.012). In 19 patients with negative SNB and low serum IL-6, the disease-free rate was 100%. These findings suggested that SNB staging and serum IL-6 level have a high prognostic value in patients with early stage OSCC. Additional investigation and longer follow-up times are warranted to improve understanding of the group of patients that may benefit from this procedure.

Anti-tumor effect of radiation response by combined treatment with angiogenesis inhibitor, TNP-470, in oral squamous cell carcinoma.

Blocking angiogenesis may enhance conventional anticancer treatments such as radiation therapy. In this study, we examined the effects of the angiogenesis inhibitor TNP-470 on human OSCC cell lines HSC2 and KB, with combining radiation therapy in the nude mouse. We evaluated cell-induced neovascularization with dorsal air sac assay, and selected two cells (HSC2: low, KB: high) with different level of cell-induced angiogenesis. The angiogenesis inhibitor TNP-470 was given 30 mg/kg s.c. daily on day 1-5, and irradiation, 8 Gy x 1, was administered on day 1 each week for 3 weeks. Significant inhibition of tumor growth relative to untreated controls was achieved in KB cells showing high induced angiogenesis with both TNP-470 (P < 0.01) and radiation (P < 0.01) and combining TNP-470 and radiation (P < 0.01). We saw little effect of TNP-470 either alone or in addition to the effect of radiation on the HSC2 cells showing low induced angiogenesis. These results suggested that TNP-470 significantly enhanced the effect of radiation on the cells with high neovascularization. These findings indicated that individual evaluation of each tumor neovascularization potential will be important before deciding the anti-angiogenesis treatment.

[Clinical trial of chemotherapy identified according to chemosensitivity assay for oral cancer patients with unresectable recurrent lesions].

Treatment of patients with unresectable recurrent oral cancer is quite difficult. In particular,there is no scientific evidence to select anti-cancer drugs for patients who were given previous radiation therapy. To select optional chemotherapy regimens, we have employed a new chemosensitivity testing method, a collagen gel droplet embedded culture sensitivity test (CD-DST) for patients with unresectable oral cancer. Six oral cancer patients with recurrence and/or metastatic disease were treated with the optional chemotherapy based on the results of CD-DST. No result was obtained due to a problem of poor growth of tumor cells in one case. In another case, we could not find a sensitive anti-cancer drug among the agents we examined. These 2 patients were treated with selected palliative pain control therapy. Optional chemotherapy based on the results of CD-DST was given to 4 patients showing sensitivity to the anti-cancer drugs examined. Tumor recession or tumor dormancy was observed clinically during a definite period. Toxicity was mild and the median survival was 10.9 months. We therefore conclude that the examination with CD-DST may provide important scientific evidence to determine a suitable chemotherapy for patients with advanced oral cancer.

Hydrogen desorption mechanism in a Li-N-H system by means of the isotopic exchange technique.

The hydrogen desorption mechanism in the reaction from LiH + LiNH2 to Li2NH + H2 was examined by thermal desorption mass spectrometry, thermogravimetric analysis, and Fourier transform IR analyses for the products replaced by LiD or LiND2 for LiH or LiNH2, respectively. The results obtained indicate that the hydrogen desorption reaction proceeds through the following two-step elementary reactions mediated by ammonia: 2LiNH2 --> Li2NH + NH3 and LiH + NH3 --> LiNH2 + H2, where hydrogen molecules are randomly formed from four equivalent hydrogen atoms in a hypothetical LiNH4 produced by the reaction between LiH and NH3 according to the laws of probability.

Mechanism of hydrogenation reaction in the Li-Mg-N-H system.

The Li-Mg-N-H system composed of 3 Mg(NH2)2 and 8 LiH reversibly desorbs/absorbs approximately 7 wt % of H2 at 120-200 degrees C and transforms into 4 Li2NH and Mg3N2 after dehydrogenation. In this work, the mechanism of the hydrogenation reaction from 4 Li2NH and Mg3N2 to 8 LiH and 3 Mg(NH2)2 was investigated in detail. Experimental results indicate that 4 Li2NH is first hydrogenated into 4 LiH and 4 LiNH2. At the next step, 4 LiNH2 decomposes into 2 Li2NH and 2 NH3, and the emitted 2 NH3 reacts with (1/2) Mg3N2 and produces the (3/2) Mg(NH2)2 phase, while the produced 2 Li2NH is hydrogenated into 2 LiH and 2 LiNH2 again. Such successive steps continue until all 4 Li2NH and Mg3N2 completely transform into 8 LiH and 3 Mg(NH2)2 by hydrogenation.

Quantitative estimation of NH3 partial pressure in H2 desorbed from the Li-N-H system by Raman spectroscopy.

The partial pressure of NH3 gas estimated by Raman spectroscopy indicates that approximately 0.1% NH3 inevitably contaminates the H2 desorbed from a hydrogen storage material composed of LiH and LiNH2 at any temperature up to 400 degrees C in a closed system.

Kinetic Modification on Hydrogen Desorption of Lithium Hydride and Magnesium Amide System.

Various synthesis and rehydrogenation processes of lithium hydride (LiH) and magnesium amide (Mg(NH2)2) system with 8:3 molar ratio are investigated to understand the kinetic factors and effectively utilize the essential hydrogen desorption properties. For the hydrogen desorption with a solid-solid reaction, it is expected that the kinetic properties become worse by the sintering and phase separation. In fact, it is experimentally found that the low crystalline size and the close contact of LiH and Mg(NH2)2 lead to the fast hydrogen desorption. To preserve the potential hydrogen desorption properties, thermochemical and mechanochemical rehydrogenation processes are investigated. Although the only thermochemical process results in slowing the reaction rate due to the crystallization, the ball-milling can recover the original hydrogen desorption properties. Furthermore, the mechanochemical process at 150 °C is useful as the rehydrogenation technique to preserve the suitable crystalline size and mixing state of the reactants. As a result, it is demonstrated that the 8LiH and 3Mg(NH2)2 system is recognized as the potential hydrogen storage material to desorb more than 5.5 mass% of H2 at 150 °C.

Identification of Akt1 as a potent therapeutic target for oral squamous cell carcinoma.

Oncogene addiction can provide therapeutic opportunities in human malignancies. In this study, we aimed to identify critical oncogenes for oral squamous cell carcinoma (OSCC) development and progression. We determined gene expression profiles in 10 primary OSCCs and 10 human OSCC cell lines using Applied Biosystems Human Genome Survey Arrays. Akt1 was the only gene identified that was expressed in all OSCC tissues and cultured cells, but not in non-neoplastic tissues and cells. Subsequently, western blot analysis showed that Akt1 protein was overexpressed in OSCC tissues and cell lines. Immunohistochemistry also showed Akt1 protein expression in 59 of 63 (94%) primary OSCCs. To clarify the oncogenic function of Akt1 in human OSCC cells, we used RNA interference. We designed and synthesized 5 small interfering RNAs specific for Akt1 (siAkt1). Transfecting human OSCC cells with siAkt1 in vitro markedly suppressed their expression of Akt1 protein and significantly reduced their growth rate. Furthermore, the growth of human OSCC tumors which had been subcutaneously xenografted in athymic nude mice lacking interferon responses was markedly inhibited by atelocollagen-mediated systemic siAkt1 administration. We also found that synthetic siAkt1 had an inhibitory effect on the growth of primary cultured OSCC cells. Finally, we investigated the molecular mechanisms involved in the growth inhibitory effect of Akt1 suppression using microarray analysis of human OSCC cells transfected with siAkt1. Knockdown of Akt1 induced the expression of CDKN2B, a tumor suppressor gene, and reduced the expression of TGFBR1, which supports malignant phenotypes. These results suggest that Akt1 functions as a critical oncogene in human OSCC cells and may therefore be an appropriate target for novel OSCC therapies.

Clinical implication of blood glucose monitoring in general dental offices: the Ehime Dental Diabetes Study.

OBJECTIVE: We examined whether general dentists can contribute to the detection of patients with undiagnosed diabetes and prediabetes by monitoring blood glucose in dental clinics. RESEARCH DESIGN AND METHODS: A total of 716 patients who visited clinics for dental treatment were enrolled and classified into 3 groups (mild, moderate, and severe) according to Kornman's criteria for periodontitis. The correlations between the casual blood glucose level, presence or absence of the history of diabetes, and/or severity of periodontitis were evaluated. RESULTS: 68 patients (9.5%) had hyperglycemia (blood glucose ≥200 mg/dL). Of these patients, 20 (29.4%) did not have a history of diabetes. Blood glucose tended to be higher with greater periodontitis severity. Of the 3 groups, the severe periodontitis group had the highest proportion of patients with hyperglycemia (p<0.0001). CONCLUSIONS: Patients with dental problems could be screened for diabetes, especially undiagnosed diabetes. General dentists could function as practitioners to screen for diabetes. TRIAL REGISTRATION NUMBER: UMIN-CTR 000014877.

Dysfunction of the p53 tumor suppressor pathway in head and neck cancer.

It is important to examine the abnormality of the entire p53 tumor suppressor pathway in head and neck cancer. We examined the mRNA expressions of p53 regulatory factors, p33ING1 and p14ARF, and a p53-target gene, p21WAF1 in head and neck cancer. Nine of 14 benign pleomorphic adenomas (PAs) and 7 of 8 malignant salivary gland tumors (MSGTs) expressed p33ING1 mRNA. Thirteen of 14 PAs expressed p14ARF mRNA, however, only 1 of 8 MSGTs expressed p14ARF mRNA. Eight of 14 PAs and 7 of 8 MSGTs expressed p21WAF1 mRNA. In salivary gland tumors, there was clear correlation between the expression of p33ING1 and p21WAF1 (p<0.0001, r2=0.53). However, there was no correlation between the expression of p14ARF and p21WAF1 (p=0.6543, r2=0.009). Twenty-six of 28 oral squamous cell carcinomas (SCCs) expressed p33ING1 mRNA. Nineteen of 28 oral SCCs expressed p14ARF mRNA. All of the oral SCCs expressed p21WAF1 mRNA. In oral SCCs, the expressions of both p33ING1 (p=0.009, r2=0.181) and p14ARF (p=0.0009, r2=0.271) correlated with the expression of p21WAF1. Interestingly, 24 of 26 oral SCCs (92%) showed either abnormality of p53 itself or loss of expression of p53 regulatory factors, p33ING or p14ARF. These results suggest that head and neck cancer often involve the dysfunction of p53 tumor suppressor pathway.

Leucine zipper structure of TSC-22 (TGF-beta stimulated clone-22) markedly inhibits the anchorage-independent growth of salivary gland cancer cells.

Several investigators have demonstrated that TGF-beta stimulated clone-22 (TSC-22) regulates cell growth and differentiation, and cell death. TSC-22 is a putative transcriptional regulator containing a leucine zipper-like structure and a nuclear export signal. We previously showed the cytoplasmic localization of TSC-22 and the nuclear translocation of TSC-22 concomitant with induction of apoptosis in salivary gland cancer cells. In the present study, we attempted to identify the active domain of TSC-22 protein that regulated the biological functions of TSC-22. We constructed three mammalian expression vectors, which could produce full length TSC-22 only in cytoplasm, the leucine zipper structure of TSC-22 in both cytoplasm and nucleus, and the leucine zipper structure only in nucleus. Then, we transfected a salivary gland cancer cell line, HSG with these expression vectors, and investigated the growth profile of the transfectants. None of the TSC-22 constructs inhibited the monolayer growth and the anchorage-dependent colony formation of HSG cells. However, the leucine zipper structure of TSC-22 markedly inhibited the anchorage-independent colony formation of HSG cells (p<0.001; one way ANOVA). Full length TSC-22 also suppressed the anchorage-independent colony formation of HSG cells, although the effect of full length TSC-22 was much lower than those of the leucine zipper constructs. These observations suggest that the leucine zipper structure in TSC-22 protein is an active domain that negatively regulates the growth of salivary gland cancer cells.

[A case of advanced maxillary carcinoma with cervical lymph node metastases showing a complete response to the combination therapy of CDDP, TS-1 and radiation].

We report a case of right maxillary carcinoma with metastases to the cervical lymph nodes (T4N2cM0, Stage IV). A 76-year-old woman was administered preoperative chemoradiotherapy, followed by curative surgery. TS-1 (80 mg/day), CDDP (5 mg/m2/day) and concurrent radiation (total 40 Gy) induced a complete response. Grade 2 neutropenia, thrombocytopenia and stomatitis were observed. In the primary tumor and cervical metastatic lymph nodes, no viable carcinoma cells were detected and cancer nests were replaced with marked fibrous tissue.

[A clinical study of neoadjuvant radiochemotherapy with docetaxel and cisplatin for oral cancers].

Docetaxel is classified among the microtubule-inhibiting compounds called taxanes, which are currently used as agents to treat head and neck cancers. To investigate the efficacy and safety of a neoadjuvant radiation therapy combined with docetaxel/cisplatin, we used this combination to treat 6 patients with oral squamous cell carcinoma. The patients received a low-dose fraction of docetaxel (20 mg/m2/week; total dose: 123.0 +/- 35.0 mg) and cisplatin (5 mg/m2/day, 5 days a week; total dose: 160.0 +/- 42.1 mg) combined with simultaneous irradiation of 40 Gy. Of the 6 patients, 5 (83.3%) showed a partial response (PR) and 1 showed no response (NC). Pathological efficacy was revealed in 4 patients (66.7%). All patients experienced stomatitis over grade 2, and 4 experienced neutropenia.