Postoperative delirium after reconstructive surgery for oral tumor: a retrospective clinical study.

The aim of this study was to perform a statistical evaluation of the risk factors for postoperative delirium after oral tumor resection and reconstructive surgery. The records of 69 consecutive patients who underwent major head and neck tumor resection and reconstructive surgery, and who received postoperative management in the high care unit (HCU) or intensive care unit (ICU) of Tsukuba University Hospital between January 2013 and December 2017, were analysed retrospectively. Delirium was diagnosed in 23 patients (33.3%) after surgery. There were significant differences in age, sex, history of diabetes mellitus and chronic obstructive pulmonary disease, recent hospitalization history, sedation period, duration of ventilator use, length of ICU/HCU stay, postoperative blood tests (haemoglobin and potassium), and postoperative medication with a major tranquilizer between those with and without delirium. Logistic regression analysis of selected independent variables revealed a hazard ratio (95% confidence interval) of 1.42 (1.09-1.86) for the sedation period. Delirium was hyperactive type in 15 cases, hypoactive type in five, and mixed type in three. There was no obvious difference in postoperative day of onset or delirium period according to subtype. In conclusion, a history of diabetes and the sedation period were found to be related to postoperative delirium. However, this study was small and retrospective, so further investigation is necessary.

Tumor vessel-injuring ability improves antitumor effect of cytotoxic T lymphocytes in adoptive immunotherapy.

Angiogenesis is required for normal physiologic processes, but it is also involved in tumor growth, progression and metastasis. Here, we report the development of an immune-based antiangiogenic strategy based on the generation of T lymphocytes that possess killing specificity for cells expressing vascular endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells, we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors (cTCR-CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2 linked to an intracellular signaling sequence derived from the CD3ζ chain of the TCR and CD28 by retroviral gene transduction methods. The cTCR-CTL exhibited efficient killing specificity against VEGFR2 and a tumor-targeting function in vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR-CTL strongly inhibited the growth of a variety of syngeneic tumors after adoptive transfer into tumor-bearing mice without consequent damage to normal tissue. In addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor regression due to enhanced tumor infiltration by the CTL and long-term antigen-specific function. These findings provide evidence that the tumor vessel-injuring ability improved the antitumor effect of CTLs in adoptive immunotherapy for a broad range of cancers by inducing immune-mediated destruction of the tumor neovasculature.

Reflux esophagitis after esophagectomy: impact of duodenogastroesophageal reflux.

Reflux esophagitis (RE) is a known complication disturbing patients' quality of life after esophageal resection. It is generally recognized that bile reflux as well as acid reflux cause RE. However, the clinical influence of acid and bile reflux, and Helicobacter pylori (H. pylori) infection on RE in the cervical esophagus after esophagectomy is not yet clarified. Sixty patients who underwent cervical esophagogastrostomy following esophagectomy were enrolled in this study. They underwent examination for H. pylori infection, endoscopic examination, and continuous 24-hour pH and bilirubin monitoring, at 1 month after surgery. The influence of acid and/or bile reflux, H. pylori infection, and others on the development of RE were investigated. RE was observed in 19 patients (32%) at 1 month after esophagogastrostomy, mild RE in 16 (27%), and severe RE in 3 (5%). The percentage of time duration of both acid and bile reflux into the cervical esophagus was higher in patients with RE than in those without (P = 0.027, P < 0.001). A significant difference in %time pH < 4 acid reflux was found between mild RE and severe RE (P = 0.014), and a statistical difference in %time abs. > 0.14 between non-RE and mild RE (P = 0.017). Acid and/or bile reflux was observed in 31 patients (52%), acid-only reflux in 6 (10%), bile-only reflux in 15 (25%), and acid-and-bile reflux in 10 (17%). Severe RE was observed only in patients having acid-and-bile reflux. On the univariate analysis, no infection of H. pylori, acid reflux, and bile reflux were determined to be the influencing factors to RE among the clinical factors including age, gender, route of esophageal reconstruction, H. pylori infection, and acid-and-bile reflux. In the subanalysis using the logistic model, there were significant correlations between bile reflux and RE irrespective of the presence of H. pylori infection (P = 0.016, P = 0.007). On the other hand, there was a significant correlation between acid reflux and RE only in patients without H. pylori infection (P = 0.039). In the early period after esophagogastrostomy, bile reflux could cause RE irrespective of H. pylori infection, while acid reflex could cause RE only in patients without H. pylori infection. There is a possibility that bile reflux plays an important role in the development of RE after esophagectomy.

The effect of oral management on the severity of oral mucositis during hematopoietic SCT.

Oral mucositis (OM) is a frequent adverse effect of allogenic or autologous hematopoietic SCT. It results from direct toxic injury to the mucosal epithelial cells by the immunosuppressive regimen. Here, we compared the incidence and severity of OM between a group of 24 patients who received proper oral management during hematopoietic SCT and a group of 24 who did not. The oral management group received pre-hematopoietic SCT instruction on oral care and an oral examination in the clean room. Differences in the incidence and severity of OM between the two groups were examined statistically. OM was observed in 14 (58.3%) patients in the oral management group and 22 (91.6%) in the control group. The median of the OM score was 1 for the oral management group (range 0 to 3) and 2 for the control group (range 0 to 3). There was a significant difference in the OM score (P<0.05) and in the incidence of OM between the two groups (P<0.01). This study shows that oral management may decrease the occurrence of OM. Our results also suggest that it is important to include an oral management provider on the hematopoietic SCT team.

What influences the acidity in the gastric conduit in patients who underwent cervical esophagogastrostomy for cancer?

The aim of this study was to determine the factors influencing acidity in the gastric conduit after esophagectomy for cancer. Acidity and bile reflux in the stomach and in the gastric conduit were examined by 24-h pH monitoring and bilimetry in 40 patients who underwent transthoracic subtotal esophagectomy followed by esophageal reconstruction using a gastric conduit, which was pulled up to the neck through a posterior mediastinal route in 17 patients, through a retrosternal route in 10 patients, and through a subcutaneous route in 13 patients. They were examined at 1 week before surgery, at 1 month after surgery, and at 1 year after surgery. Helicobacter pylori infection was examined pathologically and using the (13) C-urea breath test. The factors influencing acidity of the gastric conduit were analyzed using the stepwise regression model. Gastric acidity assessed by percentage (%) time of pH < 4 was reduced after surgery and was significantly less in patients with H. pylori infection compared with those without H. pylori infection throughout the period from 1 week before surgery to 1 year after surgery. Duodenogastric reflux (DGR) assessed by % time absorbance > 0.14 into the lower portion of the gastric conduit was significantly increased after surgery throughout the period from 1 month after surgery to 1 year after surgery. Multivariate analysis showed that the acidity in the gastric conduit was influenced by H. pylori infection and DGR at 1 month after surgery, and by H. pylori infection and the route for esophageal reconstruction at 1 year after surgery. Acidity in the gastric conduit was significantly decreased after surgery. Acidity in the gastric conduit for esophageal substitutes is influenced by H. pylori infection and surgery. DGR influences the gastric acidity in the short-term after surgery, but not in the long-term after surgery.

Pharmacokinetic individualization of high-dose methotrexate chemotherapy for the treatment of localized osteosarcoma.

Individualization of high-dose methotrexate (MTX) dosing is important to achieve therapeutic levels (700-1,000 microM) for osteosarcoma. Therefore we developed a pharmacokinetically (PK) individualized dosage regimen to maintain MTX concentrations of 700 microM (1 h bolus followed by 5 h maintenance infusion) and evaluated its safety and efficacy. Loading and maintenance doses were calculated by the PK parameters based on 2-compartment model analysis. Thirty-two courses of chemotherapy were performed in 9 patients with osteosarcoma. The maximum concentrations during maintenance infusion in 31 courses (97%) were above 700 microM. Only 1 patient developed severe hepatotoxicity as adverse effect. Total body clearance of MTX decreased in 4 patients when weekly MTX chemotherapy was performed for 3 consecutive weeks. Although the clearance was changed, the average MTX concentrations were maintained at about 700 microM by the PK individualization. The 5-year survival rate was 77.8% (7 of 9 patients), and all of them have survived for more than 9 years. This PK individualization is safe and useful for tailoring high-dose MTX therapy to achieve therapeutic levels.

Role of 2-deoxy-2-[F-18] fluoro-D-glucose positron emission tomography in the management of bone and soft-tissue metastases.

We retrospectively reviewed 71 histopathologically-confirmed bone and soft-tissue metastases of unknown origin at presentation. In order to identify the site of the primary tumour all 71 cases were examined with conventional procedures, including CT, serum tumour markers, a plain radiograph, ultrasound examination and endoscopic examinations, and 24 of the 71 cases underwent 2-deoxy-2-[F-18] fluoro-D-glucose positron emission tomography (FDG-PET). This detected multiple bone metastases in nine patients and the primary site in 12 of the 24 cases; conventional studies revealed 16 primary tumours. There was no significant difference in sensitivity between FDG-PET and conventional studies. The mean maximal standardised uptake value of the metastatic tumours was significantly higher than that of the primary tumours, which is likely to explain why FDG-PET did not provide better results. It was not superior to conventional procedures in the search for the primary site of bone and soft-tissue metastases; however, it seemed to be useful in the staging of malignancy.

Pharyngolaryngeal reflux in patients who underwent cervical esophago-gastrostomy following esophagectomy.

Pharyngolaryngeal reflux has been generally accepted as a cause for pharyngolaryngitis, hoarseness, aspiration pneumonia, chronic cough, and nocturnal asthma. Although patients who have undergone gastric conduit reconstruction after esophagectomy are at a high risk to pharyngolaryngeal reflux disease (PLRD), PLRD after esophagectomy is still unknown. The aim of this study is to investigate the correlation between reflux pharyngolaryngitis and acid reflux into the hypopharynx and into the cervical esophagus in patients who have undergone cervical esophagogastrostomy. We enrolled 62 patients who received follow-up endoscopy and 24-h pH monitoring after cervical esophagogastrostomy. These included 26 at 1 month after surgery and 36 at 1 year or more after surgery. We investigated: (i) the correlation between the extent of reflux pharyngolaryngitis and that of reflux esophagitis based on endoscopic findings; and (ii) the correlation between the extent of reflux pharyngolaryngitis and that of acid exposure -'% time pH < 4' measured by 24-h pH monitoring - in the hypopharynx and in the cervical esophagus, and of acidity in the gastric conduit. There was no difference in acid exposure between the hypopharynx and the cervical esophagus according to time after surgery. However, the acidity in the gastric conduit was significantly more at one year or more after surgery compared with acidity at 1 month after surgery (P= 0.001). There was a significant correlation between acid exposure in the hypopharynx and that in the cervical esophagus (P < 0.001), although acid exposure in the hypopharynx was significantly less than that in the cervical esophagus (P < 0.001). A significant correlation between reflux pharyngolaryngitis and reflux esophagitis was observed (P < 0.001). There was a significant correlation between reflux pharyngolaryngitis and acid exposure in the hypopharynx (P= 0.021), and also that in the proximal esophagus (P= 0.001). The correlation between the extent of reflux pharyngolaryngitis and the acidity in the gastric conduit was not observed. These findings are consistent with pharyngolaryngitis being caused by gastro-esophago-pharyngolaryngeal reflux in patients after cervical esophagogastrostomy, despite the upper esophageal sphincter strongly preventing acid reflux from the cervical esophagus into the hypopharynx.

Esophagectomy for cancer: clinical concerns support centralizing operations within the larger hospitals.

Esophagectomy needs experienced surgical techniques and a well-trained perioperative care team. There are now many reports that the mortality rate after esophagectomy is higher in those hospitals with a low volume of esophagectomy and/or low surgeon's volume. The purpose of this study is to decide the respective numbers of esophagectomy operations per year to define low-volume and high-volume hospitals in Japan. If medical policy aims to further reduce mortality and morbidity associated with esophagectomy, then esophagectomy operations should be further centralized, away from low-volume hospitals, into high-volume hospitals. The Japanese Association for Thoracic Surgery has accumulated the surgical outcomes from 31 380 esophagectomy operations, registered from 709 institutes during the period from 2001 to 2006. These institutes are here classified into six groups according to the number of esophagectomy operations per year as 4 or less, 5-9, 10-19, 20-39, 40-79, and 80 or more. Using a statistical model-selection procedure by information criteria, these six groups are then classified into three categories as low-volume, medium-volume, and as high-volume hospitals. Among the 31 380 patients registered, overall, 390 patients (1.2%) died within 30 days, and 1187 patients (3.8%) died during the primary hospital stay. The odds ratio of the greatest volume group to the minimum volume group was 0.307 for the 30-day mortality rate, and 0.288 for the in-hospital mortality rate. For both the 30-day mortality rate and the in-hospital mortality rate, a hospital with less than five esophagectomy operations per year was classified as a low-volume hospital. A hospital with 40 or more esophagectomy operations per year was classified as a high-volume hospital. Concerning the number of esophagectomy operations performed per year in Japan, low-volume hospitals are defined as those where esophagectomy is performed less than five times per year, and high-volume hospitals are defined as those where esophagectomy is performed 40 or more times per year. If medical policy in Japan aims to further decrease the mortality after esophagectomy, then esophagectomy operations should be limited in these identified low-volume hospitals.

Cochlear protection from acoustic injury by inhibitors of p38 mitogen-activated protein kinase and sequestosome 1 stress protein.

This study evaluated the protective role of p38 mitogen-activated protein kinase (p38 MAPK) inhibitors and sequestosome 1 (Sqstm1/A170/p62), a stress-induced signal modulator, in acoustic injury of the cochlea in mice. Two weeks after the exposure of mice to acoustic stress, threshold shifts of the auditory brainstem response (ABR) from the pre-exposure level and hair cell loss were evaluated. The activation of p38 MAPK was observed in cochlea by immunostaining 4 h after acoustic stress. To examine the role of p38 MAPK in tissue injury, its inhibitors were i.p. injected into male wild-type C57BL mice before the acoustic overexposure. The inhibitors SB202190 and SB203580 but not the inactive analogue SB202474 dose-dependently decreased the auditory threshold shift and outer hair cell loss induced by acoustic overexposure, suggesting the involvement of p38 MAPK in ototoxicity. We found that acoustic overexposure induced the up-regulation of Sqstm1 mRNA expression in the cochlea of wild-type mice and that SQSTM1-deficient mice exhibited an enhanced ABR threshold shift and hair cell loss, suggesting a role of SQSTM1 in the protection of tissue from acoustic stress.

Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer.

AIMS: 5-Fluorouracil (5-FU) is one of the most widely used anticancer drugs; however, the activity of 5-FU is determined by the presence of several enzymes that limit its activation or degradation, and these include dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), thymidine kinase (TK), thymidine phosphorylase (TP) and deoxyuridine triphosphatase (dUTPase). The aim of this study was to compare the expression levels of these enzymes between the primary colorectal cancer of patients with and without distant metastases. Furthermore, there was a comparison of these expression levels between the primary tumour and the corresponding metastasis. METHODS: Of 55 patients with colorectal cancer, 20 had no metastasis and the other 35 had distant metastasis. A strong expression was classified as positive, while weak to moderate or no expression was negative by immunohistochemistry. RESULTS: Of the six 5-FU-related enzymes, the numbers of patients with expression of dUTPase (54% versus 15%; p = 0.005), TK (26% versus 0%; p = 0.019) and DPD (17% versus 45%; p = 0.033) were significantly different in those with primary tumours with metastasis compared with those with non-metastasis, respectively. The altered expression of OPRT (34.3%), TS (40.0%) and dUTPase (42.9%) was significantly greater from primary to metastasis among the 35 patients with metastasis. By contrast, the expression of OPRT, TS and dUTPase was decreased in 6, 5 and 7 patients, respectively, in metastatic sites. CONCLUSIONS: From this comparative study of the six 5-FU-related enzymes in colorectal cancer, the expression of dUTPase was most significantly different between primary tumours and their corresponding metastatic tumour. It is suggested that dUTPase may be a predictive biomarker for the metastatic potential of colorectal cancer.

Loss of cytokeratin 13 expression in squamous cell carcinoma of the tongue is a possible sign for local recurrence.

Cytokeratin (CK) 13 is an intermediate filament protein that is expressed in a cell-type-specific manner, in the tongue and occasionally in tongue squamous cell carcinoma (SCC). Correlations between the clinical features of patients with SCC and CK13 expression in the tumor are here investigated along with CK13's utility as a marker for tongue cancer status. Samples from 121 patients with SCC of the tongue were examined by immunohistochemistry with antibodies against CK13. Correlations between the expression level of CK13 in the tumor and the patients' clinical features were statistically analyzed by univariate and multivariate methods. Univariate analysis showed a more relevant number of local recurrence (P = 0.04) in CK13-negative staining patients. In addition, CK13-negative cases were associated with local recurrence by multiple logistic regression analysis (OR: 3.36; 95% CI: 1.044-10.78; P = 0.04). Our results suggest that the loss of CK13 expression indicates tumors with a high potential for recurrence, and thus CK13 could be useful for determining the best course of treatment.

Helicobacter pylori infection influences the acidity in the gastric tube as an esophageal substitute after esophagectomy.

It is commonly considered that acidity in a gastric tube used as an esophageal substitute after esophagectomy decreases due to truncal vagotomy. However, there have been few, if any, studies on the factors influencing the acidity in the gastric tube. It is well known that Helicobacter pylori (H. pylori) plays an important role in acid secretion of the stomach. The aim of this study was to investigate whether or not H. pylori infection also influenced the acidity in the gastric tube as an esophageal substitute. We investigated the changes in the levels of gastric acidity and the status of H. pylori infection from the preoperative period to 1 year after surgery. In 65 Japanese patients who underwent resection of esophageal cancer followed by reconstruction using a gastric tube, 24-h gastric pH monitoring and examination of H. pylori infection using the 13C-urea breath test and biopsy specimen obtained from the gastric mucosa under upper gastrointestinal endoscopy were performed pre- and postoperatively. Twenty-seven among the 65 patients underwent the same examinations at 1 year after surgery. The levels of postoperative gastric acidity and at 1 year after surgery were significantly lower than that of preoperative gastric acidity (P = 0.031, P = 0.001, respectively). There was no difference in the levels of gastric acidity between 1.5 months and 1 year after surgery (P = 0.282). The levels of gastric acidity in the stomach and in the gastric tube were significantly influenced by H. pylori infection, while age, gender, and past history of peptic ulcer showed no influence. The level of gastric acidity in patients who had H. pylori infection pre- and postoperatively were significantly lower than that in patients who had no H. pylori infection pre- and postoperatively (P < 0.0001). H. pylori infection was indicated to be an important factor influencing the levels of gastric acidity in the reconstructed esophagus as well as in the stomach before surgery.

Widely tunable 3.4 microm band difference frequency generation using apodized chi(2) grating.

We achieved apodization in a quasi-phase-matched wavelength converter. The new design yields a large bandwidth and a flat phase-matching response with a high conversion efficiency. Using the method, we demonstrate widely tunable 3.4 microm band difference frequency generation in a LiNbO3 ridge waveguide.

Cotransduction of CCL27 gene can improve the efficacy and safety of IL-12 gene therapy for cancer.

Interleukin-12 (IL-12) is a potent antitumoral cytokine, but high doses are toxic. Herein, we demonstrate that combinational transduction of IL-12 and CC-chemokine ligand-27 (CCL27) genes into pre-existing murine OV-HM ovarian carcinoma and Meth-A fibrosarcoma, by using RGD fiber-mutant adenoviral vectors, could induce tumor regression and relieve systemic side effects more effectively than either treatment alone. The antitumor activity of the IL-12 and CCL27 combination treatment was T-cell-dependent, and development of long-term specific immunity was confirmed in rechallenge experiments. Immunohistochemical analysis of tumors transduced with CCL27 gene alone or cotransduced with IL-12 and CCL27 genes showed significant increases in numbers of infiltrating CD3(+) T cells, which included both CD4(+) and CD8(+) cells. Additionally, cotransduction with IL-12 and CCL27 genes could more efficiently activate tumor-infiltrating immune cells than transduction with CCL27 alone, as determined by the frequency of perforin-positive cells and expression levels of IFN-gamma. Furthermore, mice treated with the IL-12 and CCL27 combination compared with those treated with IL-12 alone showed milder pathological changes, for example, lymphocyte infiltration and extramedullary hematopoiesis, in lung, liver and spleen. Our data provide evidence that combinational in vivo transduction with IL-12 and CCL27 genes is a promising approach for the development of cancer immunogene therapy that can simultaneously recruit and activate tumor-infiltrating immune cells.

Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas.

To clarify the involvement of autocrine motility factor (AMF) in the phenotype and biological profiles of human lung carcinomas, we analysed protein and mRNA expression in a total of 180 cases. Immunohistochemistry revealed positive staining in 67.2%, with the highest frequency in squamous cell carcinoma (SCC; 90.8%) and the lowest in small cell carcinoma (SmCC; 27.8%). In SCC, the staining frequency and intensity correlated with the degree of morphological differentiation. Generally, the expression levels in immunoblotting analysis corresponded well with immunohistochemical positivity. However, there was less agreement between protein and mRNA levels: in SmCC and large cell carcinomas (LCCs), mRNA showed higher, but protein showed lower expression. Among non-small cell lung carcinomas (NSCLCs), AMF protein levels correlated inversely with tumour size, but tumours exhibiting lymph node metastasis showed higher mRNA expression. In cultured lung carcinoma cells which comprised all histological subtypes, AMF was detected in the lysates of all ten cell lines. Secreted AMF protein was detected in the conditioned media from six cell lines, most of which were SmCC or LCC. Thus, a particular subset of lung carcinomas secrete AMF, which may promote cell motility via autocrine stimulation through its cognate receptor and cause the biological aggressiveness seen in SmCC and LCC. Moreover, treatment by proteasome inhibitors resulted in increased cellular AMF in five cell lines, suggesting that intracellular AMF levels are regulated by both secretion and proteasome-dependent degradation. In conclusion, AMF was detected in a major proportion of lung carcinomas, and may play a part not only in proliferation and/or progression of the tumours, but also, possibly, in the differentiation of SCC. Furthermore, higher mRNA expression may be related to the high metastatic potential of NSCLC and increased protein secretion, leading to a more aggressive phenotype, such as the invasiveness of SmCC and LCC.

Nutritional support for head-injured patients.

BACKGROUND: Head injury increases the body's metabolic responses, and therefore nutritional demands. Provision of an adequate supply of nutrients is associated with improved outcome. The best route for administering nutrition (parenterally (TPN) or enterally (EN)), and the best timing of administration (for example, early versus late) of nutrients needs to be established. OBJECTIVES: To quantify the effect on mortality and morbidity of alternative strategies of providing nutritional support following head injury. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Injuries Group specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, National Research Register, Web of Science and other electronic trials registers. Reference lists of trials and review articles were checked. The searches were last updated in July 2006. SELECTION CRITERIA: Randomised controlled trials of timing or route of nutritional support following acute traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data and assessed trial quality. Information was collected on death, disability, and incidence of infection. If trial quality was unclear, or if there were missing outcome data, trialists were contacted in an attempt to get further information. MAIN RESULTS: A total of 11 trials were included. Seven trials addressed the timing of support (early versus delayed), data on mortality were obtained for all seven trials (284 participants). The relative risk (RR) for death with early nutritional support was 0.67 (95% CI 0.41 to 1.07). Data on disability were available for three trials. The RR for death or disability at the end of follow-up was 0.75 (95% CI 0.50 to 1.11). Seven trials compared parenteral versus enteral nutrition. Because early support often involves parenteral nutrition, three of the trials are also included in the previous analyses. Five trials (207 participants) reported mortality. The RR for mortality at the end of follow-up period was 0.66 (0.41 to 1.07). Two trials provided data on death and disability. The RR was 0.69 (95% Cl 0.40 to 1.19). One trial compared gastric versus jejunal enteral nutrition, there were no deaths and the RR was not estimable. AUTHORS' CONCLUSIONS: This review suggests that early feeding may be associated with a trend towards better outcomes in terms of survival and disability. Further trials are required. These trials should report not only nutritional outcomes but also the effect on death and disability.

A prospective study to evaluate a new dental management protocol before hematopoietic stem cell transplantation.

Pre-hematopoietic stem cell transplantation (HSCT) dental treatment is essential to prevent serious infections from oral sources during immunosuppression, in patients who undergo HSCT therapy. This study was planned to establish a dental management protocol for such patients. Forty-one patients scheduled for HSCT to treat hematological malignancies were consecutively enrolled in the prospective trial. The dental status of all patients was evaluated by clinical and radiographic examination at a median of 47 days before the commencement of HSCT therapy. Thirty-six patients had one or more dental diseases; the remaining five had none. Caries was found in 26 patients, apical periodontitis in 19, marginal periodontitis in 24 and a partially erupted third molar in 11. Our policy is to preserve patients' teeth whenever possible, and therefore minimal dental intervention was planned. Treatment was completed for all 36 patients with dental pathologies, before the conditioning regimen began. All patients received the scheduled HSCT therapy without alteration, interruption or delay, and did not show any signs or symptoms associated with odontogenic infection while they were immunosuppressed. This protocol, therefore, appears to be appropriate for the pre-HSCT dental treatment of patients with hematological diseases.

Motility and growth of human bone-marrow mesenchymal stem cells during ex vivo expansion in autologous serum.

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures. Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.

Peroxiredoxin I expression in tongue squamous cell carcinomas as involved in tumor recurrence.

Peroxiredoxin (Prx) I is an antioxidant protein expressed in proliferating cells. We investigated Prx I as marker for tongue cancer status by correlating clinical features with Prx I expression. Samples from 132 patients with squamous cell carcinoma in the tongue were examined by immunohistochemistry with an anti-Prx I antibody. Correlations between Prx I expression and the clinical features of tumors were statistically determined using univariate and multivariate analyses. Univariate analysis showed Prx I was significantly associated with local recurrence (P=0.033). By multiple logistic regression analysis, Prx I expression was associated with local recurrence (odds ratio: 2.84; 95% confidence interval: 1.09-7.43; P=0.034) and lymph node recurrence (odds ratio: 2.86; 95% confidence interval: 1.02-8.01; P=0.046). Our results suggested that Prx I expression indicates tumors with a high potential for recurrence. Prx I may be used clinically to guide treatment for squamous cell carcinoma of the tongue.