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.

Secretory IgA accumulated in the airspaces of idiopathic pulmonary fibrosis and promoted VEGF, TGF-ß and IL-8 production by A549 cells.

Secretory IgA (SIgA) is a well-known mucosal-surface molecule in first-line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non-IPF subjects. An in-vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß and interleukin (IL)-8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA-induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF-ß and IL-8.

Secretory immunoglobulin A induces human lung fibroblasts to produce inflammatory cytokines and undergo activation.

Immunoglobulin (Ig)A is the most abundant immunoglobulin in humans, and in the airway mucosa secretory IgA (sIgA) plays a pivotal role in first-line defense against invading pathogens and antigens. IgA has been reported to also have pathogenic effects, including possible worsening of the prognosis of idiopathic pulmonary fibrosis (IPF). However, the precise effects of IgA on lung fibroblasts remain unclear, and we aimed to elucidate how IgA activates human lung fibroblasts. We found that sIgA, but not monomeric IgA (mIgA), induced interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by normal human lung fibroblasts (NHLFs) at both the protein and mRNA levels. sIgA also promoted proliferation of NHLFs and collagen gel contraction comparable to with transforming growth factor (TGF)-ß, which is involved in fibrogenesis in IPF. Also, Western blot analysis and real-time quantitative polymerase chain reaction (PCR) revealed that sIgA enhanced production of α-smooth muscle actin (α-SMA) and collagen type I (Col I) by NHLFs. Flow cytometry showed that NHLFs bound sIgA, and among the known IgA receptors, NHLFs significantly expressed CD71 (transferrin receptor). Transfection of siRNA targeting CD71 partially but significantly suppressed cytokine production by NHLFs co-cultured with sIgA. Our findings suggest that sIgA may promote human lung inflammation and fibrosis by enhancing production of inflammatory or fibrogenic cytokines as well as extracellular matrix, inducing fibroblast differentiation into myofibroblasts and promoting human lung fibroblast proliferation. sIgA's enhancement of cytokine production may be due partially to its binding to CD71 or the secretory component.

MIB-1 index is unlikely to predict relapse-free survival in patients who underwent R0-esophagectomy for esophageal squamous cell carcinoma.

MIB-1 is a cell proliferation marker and has previously been investigated as a diagnostic or prognostic indicator of malignancy. Previous studies have investigated MIB-1 index and clinicopathological factors in relation to prognosis of patients with esophageal cancer, with conflicting results. The aim of this study is to assess the prognostic significance of MIB-1 index in patients with thoracic esophageal squamous cell carcinoma. A total of 78 patients who underwent R0-esophagectomy for thoracic esophageal squamous cell carcinoma were enrolled in this study. Preoperatively, 29 patients underwent chemotherapy, six underwent chemoradiotherapy, and the remaining did not undergo any preoperative therapy. The MIB-1 labeling index was reported by counting 500 tumor cells in the hot spots of nuclear labeling. Correlations between MIB-1 index, clinicopathological factors, and relapse-free survival (RFS) were investigated. The mean MIB-1 index was 39.3 ± 21.0 (range: 0-91.3). There was no significant correlation between clinicopathological factors and MIB-1 index in the study patients, irrespective of whether they underwent preoperative therapy. Univariate analysis revealed no significant association between MIB-1 index and RFS. However, depth of tumor invasion, lymph node metastasis and stage, all showed a significant correlation to RFS. Multivariate analysis of RFS revealed that stage was the only significant factor. Conversely, MIB-1 index was not significantly related to RFS (p = 0.41). In conclusion, MIB-1 index is unlikely to be a significant prognostic indicator for esophageal cancer.

Histopathological grading systems analysis of oral squamous cell carcinomas of young patients.

BACKGROUND: To analyze the clinicopathological profile of young patients (≤ 40 years) with oral SCC and correlate with a control group (≥ 50 years) by means of histopathological grading systems. MATERIAL AND METHODS: 14 young patients and 14 control patients were selected with similar clinical stage and tumor location. Demographic and clinical data were obtained from patient records and histological sections were evaluated according to four histopathological grading systems. Associations between categories of demographic and clinical data were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to the Kaplan-Meier method. RESULTS: The comparison between groups showed a greater association of treatment modalities in younger patients (p=0.022), they had a higher incidence of local recurrence and regional metastasis (p=0.018) and lower disease-free survival in 5 years (p=0.069). There was no difference in 5-year overall survival among the studied groups. There was no difference in histological grading between studied groups according to the four used systems. CONCLUSIONS: This study showed that, despite tumors had similar histological grade and more therapeutic modalities were used in the young group, tumors in young patients had a higher incidence of recurrence/metastasis, showing tendency to a more aggressive behavior.

Measurement of the zygomatic bone and pilot hole technique for safer insertion of zygomaticus implants.

The zygomaticus implant was developed for patients with severe bone resorption of the posterior maxilla. These may eliminate or minimize the need for bone grafting. Although the zygomaticus implant has shown a remarkable success rate in this difficult-to-treat patient population, the method requires an advanced surgical technique and carries an increased risk of complications. There have been few anatomical studies on the zygomatic bone in relation to the insertion of zygomaticus implants. The height and thickness of the zygomatic bone for the insertion were measured in this study. The thickness at the 90° angle point, where the upper margin of the zygomatic arch and the temporal margin of the frontal process of the zygomatic bone intersect and where the apex of the implant penetrates, was found to be 1.8±0.4 mm; this gradually increased inferiorly and anteriorly. Thus, the penetration point of the apex of the zygomaticus implant should be located more inferoanterior to the 90° angle point, as the thickness in this region is thinner than the diameter of the implant. Based on the results of this study, a newer and safer insertion method for the zygomaticus implant using a drill guide is proposed.

The prognostic value of histopathological grading systems in oral squamous cell carcinomas.

OBJECTIVE: This study evaluated the association of four histopathological grading systems (WHO grading system, malignancy grading of the deep invasive margins (MG), histological risk (HR) model, and tumor budding and depth of invasion (BD) model) with clinicopathological parameters and outcome of 113 oral squamous cell carcinomas to identify their roles in prognosis. METHODS: Demographic and clinical features were obtained from patients' records. Sections from all paraffin-embedded blocks were evaluated according to the four grading systems. Demographic and clinical associations were analyzed using chi-square test, and correlations between the grading systems were established with the Spearman's rank correlation test. Survival curves were performed with Kaplan-Meier method, and multivariate analysis based on Cox proportional hazard model was calculated. RESULTS: Significant associations with survival were observed for WHO grading system and BD model in the univariate analysis, but only the BD model was significantly associated with disease outcome as an independent prognostic marker. Age, tumor size, and presence of regional metastasis were also independent markers of reduced survival. CONCLUSION: A significant association between the BD model and outcome of OSCC patients was observed, indicating this new histopathological grading system as a possible prognostic tool.

Laparoscopic splenectomy using pneumoperitoneum or gasless abdominal wall lifting: a 15-year single institution experience.

INTRODUCTION: Laparoscopic splenectomy using pneumoperitoneum has been performed since 1992. The gasless abdominal wall-lifting method for laparoscopic splenectomy was introduced as an alternative. This retrospective study was undertaken to compare results using the two techniques. METHODS: Between 1995 and 2010, 54 patients underwent laparoscopic splenectomy at a single institution; 30 underwent the procedure using the gasless technique and 24 using pneumoperitoneum. There were no significant differences between the two groups regarding age, sex or BMI, but more patients underwent concurrent operations in the pneumoperitoneum group. The abdominal wall-lift system with subcutaneous K-wires was used for the gasless method. RESULTS: Intraoperative blood loss was similar in the two groups (193.0 ± 196.7 mL gasless, 217.3 ± 296.6 mL pneumoperitoneum; P > 0.05), but operative time (182.1 ± 92.1 min, 135.1 ± 46.1 min; P < 0.05), and resected spleen weight (306.1 ± 297.7 g, 138 ± 81.0 g; P < 0.05) were significantly different. In the gasless group, additional procedures included conversion (n = 1), mini-laparotomy (n = 2), and CO(2) insufflation (n = 2). Excluding the concurrent living-related kidney donor patients, hospital stay was similar (6.9 ± 2.5 days, 6.3 ± 2.0 days, P > 0.05). CONCLUSION: Although gasless laparoscopic splenectomy is feasible, there are disadvantages, particularly the restricted operative working space in some patients. These results suggest that either technique may be used on an individual basis in patients undergoing laparoscopic splenectomy.

Localised right upper-lobe pulmonary oedema caused by extension of giant cell carcinoma to the mitral valve.

Giant cell carcinoma of the lung is a very rare primary malignant tumour and localised right upper-lobe pulmonary oedema is also unusual. We report a case of giant cell carcinoma, which invaded the left atrium through the left pulmonary vein and caused localised right upper-lobe pulmonary oedema.

Correlation of autoantibodies and CD5+ B cells in ocular adnexal marginal zone B cell lymphomas.

AIM: To determine the clinicopathological properties of ocular adnexal marginal zone B cell lymphomas (MZBLs) with CD5+ B cells. METHODS: This study determined the clinicopathological properties of MZBL samples from 97 patients with ocular adnexal MZBLs and searched for hallmarks of systemic autoimmunity in these patients. RESULTS: Two elderly female patients were found to have ocular adnexal MZBLs with CD5+ B cells; flow cytometry analysis suggested that one of these MZBLs had CD5+ B cell clonal proliferation. The levels of anti-single stranded (SS)-DNA and anti-SS-A/Ro antibodies in these two patients were significantly higher than those in controls that were matched for age, gender and disease (2/2 versus 0/14; p = 0.008) and controls without MZBL (2/2 versus 0/30; p = 0.002). The genes from the immunoglobulin heavy-chain variable region for one of the patients showed a V3-21 segment. In addition, another patient with ocular adnexal reactive lymphoid hyperplasia with CD5+ B cells also had anti-SS-DNA antibodies. CONCLUSION: Patients with ocular adnexal MZBLs with CD5+ B cells may have a background of systemic conditions with CD5+ B-cell-related autoantibodies.

Human CYP3A4-introduced HepG2 cells: in vitro screening system of new chemicals for the evaluation of CYP3A4-inhibiting activity.

1. The aims were to attest whether HepG2-GS-3A4, a cell line into which the human CYP3A4 gene was introduced, can be used for a screening of chemicals that will inhibit CYP3A4 activity. 2. The capacity of the cells for metabolizing CYP3A4 substrates in vitro was evaluated. Also determined was the effect of CYP3A4 inhibitors and non-inhibitors on nifedipine hydroxylation. Western blot, immunohistochemostry and determination of beta-nicotinamide adenine dinucleotide phosphate (NADPH)-reductase activity were performed. 3. HepG2-GS-3A4 selectively metabolized substrates of CYP3A4 (diazepam, nordiazepam, lidocaine, atorvastatin, and nifedipine) to a greater degree than control. The metabolites were easily detected in the culture medium. Values of V(max) of HepG2-GS-3A4 were about 30- to 100-fold higher than those of the control, while values of K(m) were comparable. Pre-incubation of cimetidine and ketoconazole significantly inhibited nifedipine hydroxylation, while addition of inhibitors specific to other isoforms of CYPs had no substantial effect. The HepG2-GS-3A4 expressed a higher amount of CYP3A4 protein and mRNA than control. Most NADPH reductase activity was detected in microsomal fractions. 4 In conclusion, HepG2-GS-3A4 sufficiently and selectively metabolize substrates of CYP3A4, and inhibitors of CYP3A4 reduced the metabolism. Because the metabolites were easily detected in the culture medium, this cell might be useful for the new and easy screening of new drugs for the evaluation of CYP3A4-inhibiting activity in vitro.

A new operative technique for the resection of gastric tube cancer by means of lifting the anterior chest wall and videoscope-assisted surgery.

The prolonged survival of patients receiving surgery for esophageal cancer has led to an increased incidence of adenocarcinoma arising in the gastric tube used for reconstruction (gastric tube cancer). In patients with advanced gastric tube cancer, resection of the gastric tube should be considered, but currently available procedures are very invasive. In patients undergoing curative surgery for gastric tube cancer that has developed after reconstruction through the retrosternal route, the gastric tube is usually resected through a median sternotomy, followed by reconstruction with the colon. However, postoperative complications often occur and treatment outcomes remain poor. We developed a new surgical technique for gastric tube resection without performing a sternotomy in patients with gastric tube cancer who had previously undergone reconstruction through the retrosternal route. Our technique was used to treat two patients. Two Kirschner wires were passed subcutaneously through the anterior chest; the chest was lifted to extend the retrosternal space and secure an adequate surgical field. The stomach was separated from the surrounding tissue under videoscopic guidance. Total resection of the gastric tube was done. The retrosternal space was used to lift the jejunum. Roux-en-Y reconstruction was performed. Neither patient had suture line failure or surgical site infection. Their recovery was uneventful. Our surgical technique has several potential advantages including (i) reduced surgical stress; (ii) the ability to use the retrosternal space for reconstruction after gastric tube resection; and (iii) a reduced risk of serious infections such as osteomyelitis in patients with suture line failure. Our findings require confirmation by additional studies.

Pulmonary Mycobacterium avium complex infection associated with the IVS8-T5 allele of the CFTR gene.

BACKGROUND: The T5 allele in intron 8 (IVS8) on specific haplotype backgrounds (e.g., long TG repeats) causes abnormal splicing in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and is also known to be associated with chronic airway diseases. OBJECTIVE: To investigate the role of CFTR variations for susceptibility to pulmonary Mycobacterium avium complex (MAC) infection. PARTICIPANTS: Three hundred patients with pulmonary MAC infection (72 males, 228 females; mean age at onset 61.6 + or - 12.4 years) took part in this study. Diagnosis of MAC infection was based on American Thoracic Society criteria. Clinical profiles were collected and blood samples were genotyped for TG repeats, poly-T and M470V polymorphisms. RESULTS: We found significantly higher T5 frequency in MAC patients than in healthy controls from our own study (0.035 and 0.005, respectively, P = 0.023) and other reports. Homozygote for the T5 allele was found in two MAC patients. All T5 alleles were associated with longer TG repeats, the TG12 or TG13 allele. Seventeen of the 21 T5 alleles appeared to be associated with the V470 allele. Other polymorphisms did not show any significant differences in frequency. CONCLUSIONS: These findings suggest that the IVS8 5T allele might be involved in susceptibility to pulmonary MAC infection.

Minimum leakage rate (0.5%) of stapled esophagojejunostomy with sacrifice of a small part of the jejunum after total gastrectomy in 390 consecutive patients.

BACKGROUND: The development of new surgical instruments and devices has facilitated the performance of esophagojejunostomy after total gastrectomy. However, total prevention of dehiscence of anastomoses remains difficult. We introduced a new procedure for esophagojejunostomy using a circular stapler, requiring sacrifice of only a small part of the jejunum. METHODS: The study group comprised 390 consecutive patients who underwent reconstruction by Roux-en-Y esophagojejunostomy, performed with a circular stapler, sacrificing a small part of the jejunum after total gastrectomy. We assessed anastomotic leakage and anastomotic stenosis after surgery. RESULTS: Only 2 patients (0.5%) had leakage and 4 (1.0%) had anastomotic stenosis after reconstruction. All the patients were cured by conservative therapy. CONCLUSIONS: Esophagojejunostomy performed with a circular stapler after total gastrectomy, with sacrifice of only a small part of the jejunum, is a useful and easy procedure, with a leakage rate of 0.5%.

p21 provides stage specific DNA damage control to preimplantation embryos.

The early stage embryogenesis of higher eukaryotes lacks some of the damage response pathways such as G1/S checkpoint, G2/M checkpoint and apoptosis. We examined here the damage response of preimplantation stage embryos after fertilization with 6 Gy irradiated sperm. Sperm-irradiated embryos developed normally for the first 2.5 days, but started to exhibit a developmental delay at day 3.5. p21 was activated in the delayed embryos, which carried numerous micronuclei owing to delayed chromosome instability. Apoptosis was observed predominantly in the inner cell mass of the day 4.0 embryos. Sperm-irradiated p21-/- embryos lacked the delay, but chromosome instability and apoptosis were more pronounced than the corresponding p21 wild-type embryos. We conclude from the result that damage responses come in a stage-specific manner during preimplantation stage development; p53-dependent S checkpoint at the zygote stage, p21-mediated cell cycle arrest at the morula/blastocyst stages and apoptosis after the blastocyst stage in the inner cell mass.

Intraoperative localization of early-stage upper gastrointestinal tumors using a magnetic marking clip-detecting system.

BACKGROUND: Intraoperative tumor localization often is difficult during laparoscopic surgery for early-stage upper gastrointestinal tumors. METHOD: This study enrolled 15 patients undergoing laparoscopic gastrectomy. A magnetic marking clip-detecting system was used to apply a marking clip to the tumor site during preoperative gastroscopy, and to detect a marking magnetic body. RESULTS: In a basic ex vivo study, the mean permeance rate on the gastric wall serosal surface was 0.97 +/- 0.01. Magnetic flux densities required for exploration were 52.6 mT on the gastric wall serosal surface and 312.4 mT 10 mm away from the surface. In a clinical study, the mean distance between the detected tumor site and the clip along the longitudinal axis was 8.3 +/- 3.2 mm. The mean detection time was 5.7 +/- 2.3 min. CONCLUSION: The magnetic marking clip-detecting system may be useful for tumor site detection during laparoscopic gastrectomy.

CLCP1 interacts with semaphorin 4B and regulates motility of lung cancer cells.

We previously established a highly metastatic subline, LNM35, from the NCI-H460 lung cancer cell line, and demonstrated upregulation of a novel gene, CLCP1 (CUB, LCCL-homology, coagulation factor V/VIII homology domains protein), in LNM35 and lung cancer specimens. In this study, we focused on the potential roles of that gene in cancer metastasis. First, we established stable LNM35 RNAi clones, in which CLCP1 expression was suppressed by RNAi, and found that their motility was significantly reduced, although growth rates were not changed. Next, in vitro selection of a phage display library demonstrated that a phage clone displaying a peptide similar to a sequence within the Sema domain of semaphorin 4B (SEMA4B) interacted with LNM35. Immunoprecipitation experiments confirmed interaction of CLCP1 with SEMA4B, regulation of CLCP1 protein by ubiquitination and proteasome degradation enhanced in the presence of SEMA4B. These results are the first to indicate that CLCP1 plays a role in cell motility, whereas they also showed that at least one of its ligands is SEMA4B and that their interaction mediates proteasome degradation by CLCP1. Although the physiological role of the interaction between CLCP1 and SEMA4B remains to be investigated, this novel gene may become a target of therapy to inhibit metastasis of lung cancers.