Multicenter prospective trial of total gastrectomy versus proximal gastrectomy for upper third cT1 gastric cancer.

BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.

Hypophosphatasia: Evaluation of Size and Mineral Density of Exfoliated Teeth.

OBJECTIVE: Most cases of hypophosphatasia (HPP) exhibit early loss of primary teeth. Results of micro-computed tomography (micro-CT) analysis of teeth with HPP have not yet been reported. The purpose of the present study was to describe the size and mineral density distribution and mapping of exfoliated teeth with HPP using micro CT. STUDY DESIGN: Seven exfoliated teeth were obtained from a patient with HPP. Exfoliated teeth sizes were measured on micro CT images and mineral densities of the mandibular primary central incisors were determined. RESULTS: Partial dentures were fabricated for the patient to replace the eight primary teeth which had exfoliated. Most primary teeth sizes were within the normal range. The mean values of enamel and dentin mineral densities in teeth with HPP were 1.35 and 0.88 g/cm3, respectively, in the mandibular primary central incisors. CONCLUSION: Mineral density distribution and mapping revealed that the values in teeth with HPP were lower than the homonymous teeth controls in all regions from the crown to apex. Furthermore, it was demonstrated that the differences between HPP and controls were larger on the crown side and the differences tended to converge on the apex side. These results suggested that the present patient showed mild hypomineralization in the primary dentition.

Self-Esteem and Oral Condition of Institutionalized Abused Children in Japan.

OBJECTIVE: Abused children have been reported to have low self-esteem. The aim of this study was to investigate the effects of dental intervention on self-esteem, oral condition, and concern for oral health in abused children admitted to a child protection service facility. STUDY DESIGN: We examined the oral condition of 65 children (34 boys, 31 girls; aged 2-15 years), instructed them in tooth-brushing. Self-esteem was examined using Pope's five-scale test for children. Before discharge, the children completed questionnaires on concern about their oral health. RESULTS: The findings revealed the reasons for admission were child abuse and neglect (n=45), domestic violence against the mother (n= 20), special needs (n=11), delinquency (n=7), school refusal (n=2), and other reasons (n=3). Thirty-five of the 65 residents (54%) needed treatment for caries. Of these, 24 (69%) were abused children and 11 (31%) were admitted due to other reasons. Mean self-esteem score differed significantly between the resident children (n=43) and an outpatient control group (n=102) (59.16±14.54 vs 73.92±16.81, respectively; p<0.01). CONCLUSION: Although the abused children had low self-esteem, after dental intervention, positive answers regarding oral health were obtained. The findings suggest that dental interventions might be effective for helping to improve the self-esteem of abused children.

Effect of low-intensity pulsed ultrasound stimulation on callus remodelling in a gap-healing model: evaluation by bone morphometry using three-dimensional quantitative micro-CT.

We evaluated the effect of low-intensity pulsed ultrasound stimulation (LIPUS) on the remodelling of callus in a rabbit gap-healing model by bone morphometric analyses using three-dimensional quantitative micro-CT. A tibial osteotomy with a 2 mm gap was immobilised by rigid external fixation and LIPUS was applied using active translucent devices. A control group had sham inactive transducers applied. A region of interest of micro-CT was set at the centre of the osteotomy gap with a width of 1 mm. The morphometric parameters used for evaluation were the volume of mineralised callus (BV) and the volumetric bone mineral density of mineralised tissue (mBMD). The whole region of interest was measured and subdivided into three zones as follows: the periosteal callus zone (external), the medullary callus zone (endosteal) and the cortical gap zone (intercortical). The BV and mBMD were measured for each zone. In the endosteal area, there was a significant increase in the density of newly formed callus which was subsequently diminished by bone resorption that overwhelmed bone formation in this area as the intramedullary canal was restored. In the intercortical area, LIPUS was considered to enhance bone formation throughout the period of observation. These findings indicate that LIPUS could shorten the time required for remodelling and enhance the mineralisation of callus.

Host beta-globin gene fragments in crevicular fluid as a biomarker in periodontal health and disease.

BACKGROUND AND OBJECTIVE: Leukocytes and epithelium are the first line of defense in preventing bacterial invasion into periodontium. Some of these cells die in gingival crevicular fluid, whereupon their DNA is spilled out. The present study was designed to investigate the profile of host beta-globin gene fragments in the gingival crevicular fluid of various periodontal conditions. MATERIAL AND METHODS: Gingival crevicular fluid from 40 teeth with chronic periodontitis, 30 with gingivitis and 22 that were clinically healthy were centrifuged (3,000 g, 10 min). The supernatant (cell-free gingival crevicular fluid) was centrifuged again (13,000 g, 10 min), resulting in the pellet and the supernatant as debris and debris-free fractions, respectively. Specific primers for amplifying 110 bp, 536 bp and 2 kb amplicons of human beta-globin gene were used to investigate host DNA by quantitative and qualitative polymerase chain reaction. RESULTS: The periodontitis group showed the largest amount of host beta-globin gene fragments, while the healthy group had the lowest. In the debris and debris-free fractions, the 536 bp and 2 kb amplicons were more often detected in the periodontitis group than in the other groups. Interestingly, the presence of 2 kb amplicon in the debris fraction could be used to discriminate periodontitis from gingivitis and healthy groups because we found it in 85% of periodontitis samples but only in 13% of gingivitis samples, and it was absent in the healthy group. CONCLUSION: This study shows the different DNA profiles of cell-free gingival crevicular fluid in periodontal health and disease. It suggests that the quantity and quality of host DNA are dependent on the disease conditions. Therefore, the beta-globin gene fragments in cell-free gingival crevicular fluid may be a potential biomarker of periodontal disease progression.

Evaluation of clinical significance of 18F-fluorodeoxyglucose positron emission tomography in superficial squamous cell carcinomas of the thoracic esophagus.

(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used for pre-treatment staging and evaluation of response to pre-operative therapy in advanced thoracic esophageal cancers. To evaluate the clinical significance of PET diagnosis of superficial thoracic esophageal cancers, FDG-PET was conducted preoperatively in 41 patients with such cancers without pre-operative therapy. We compared the PET diagnosis with clinicopathological findings with respect to both the primary tumor and lymph node (LN) metastasis. Of the 41 superficial thoracic esophageal cancers, 21 (51.2%) were PET positive for primary tumors. Although tumor length and histological type did not correlate with FDG uptake by primary tumors, non-flat (elevated or depressed) tumors showed significantly stronger FDG uptake than flat ones. Of 28 tumors infiltrating the deep submucosal layer, 19 (67.9%) were PET positive, while only two (15.4%) of 13 tumors infiltrating only the mucosa or shallow submucosal layer were PET positive. Manova identified FDG uptake as the only independent risk factor for deep submucosal invasion (odds ratio, 7.407; P = 0.0279). In 13 patients with pathological LN metastasis, although no LN metastasis was detected by FDG-PET, FDG uptake by the primary tumors was the only risk factor for LN metastasis (P = 0.0318). PET-negative tumors tended to reflect longer disease-free survival than PET-positive tumors, although this was not significant. FDG-PET is useful for detecting tumors infiltrating the middle or deep submucosal layer (sm2/sm3), and for predicting LN metastasis in patients with superficial thoracic esophageal cancers. FDG-PET is helpful for decision-making regarding treatment of such patients.

A new method for measurement of bone deformation by echo tracking.

No method has been available to noninvasively detect bone deformation or strain under loading in vivo. We focused on ultrasonic measurement of the displacement at a certain point on a bone using the echo-tracking method (ET). To develop a method that can noninvasively detect bone deformation in vivo, a preliminary investigation was performed. We investigated the accuracy of measuring displacement with our echo tracking system by using a flat metal panel and found that the method could measure displacement with a precision of a few microns. A three-point bending test of a porcine tibia with both ends fully constrained was performed to measure bone surface displacement, and simultaneous measurement of the surface strain was done using two strain gauges. The correlation between the displacement measured by ET and the strain gauge readings was completely linear (r=0.999), showing that the method could precisely detect bone deformation. The loads versus displacement curves obtained with cyclic loading were typical hysteresis loops that showed viscoelastic properties of the measured bone. We also improved a multi-ET system capable of simultaneously tracking multiple points to detect deformation of the bone surface. Measurement by this echo tracking system was also compared with strain gauge readings during a three point bending test with both ends of the tibia supported. The linearity of both methods was very high (r=0.998). Our ET method might have considerable potential for noninvasive measurement of bone viscoelasticity and plasticity.

Effect of vascularity on canine distracted tibial callus consolidation.

In the consolidation period of distraction osteogenesis, mineralization occurs before corticalization. We hypothesized that the increased rate of bone mineral density correlates to the density of vascularity in the callus. We unilaterally lengthened the tibia in eight adult beagles. After a waiting period of 7 days, tibiae were lengthened for 30 days. After a consolidation period of an additional 60 days, all animals were euthanized. Just before euthanasia, blood vessels were perfused with 50% w/v barium sulfate solution, and soft radiographs of the distracted callus and the control tibiae were taken. Bone mineral density of the regenerated bones was measured preoperatively by quantitative computed tomography on Days 37, 68, and 98. Increases of the percent bone mineral density (from Day 37 to Day 98 and from Day 68 to Day 98) correlated with the blood vessel volume density ratios on Day 98. Our results suggest that preservation of the higher density of blood vessels in the consolidation period could lead to the better mineralization of the distracted callus.

Role of women in medicine: a look at the history, the present condition and the future status of women in the surgical field, especially neurosurgery.

We have analyzed the historical background of women's progress in medicine in Japan and the role of female neurosurgeons as models for the next generation. Female neurosurgeons were asked to complete a questionnaire regarding their professional life in detail and the problems they are facing while managing their personal life after getting married and having a child. Some feel that there remain some constraints at work for being a female, due to their male colleagues who are not so understanding in nature. The younger generation is not so keen on joining the neurosurgical branch as their life career due to hard work and complete dedication demanded by neurosurgery. It is not easy for all to manage a neurosurgical career along together with a married life and children. Hence it is now time for those successful female neurosurgeons to become role models. Government can play an important role in these social reforms by coming up with programs to give social security to females and initiate programs for child care for married females pursuing such a demanding profession. Certain measures to encourage females to take up surgery are providing more time by arranging care for babies and families, flexibility in working hours, in addition to having a considerate husband and a considerate chief of department and senior staff. Departmental policies need to be completely impartial and should promote everyone based on their skills and knowledge. Women neurosurgeons need to get together and discuss all these issues so that the younger generation will not hesitate to take up this profession and become stalwarts of neurosurgery like their male counterparts.

Mucoepidermoid carcinoma of the esophagus treated by endoscopic mucosal resection.

Mucoepidermoid carcinoma is a mixed cell tumor with both adenocarcinomatous and squamous components. We report a rare case of superficial mucoepidermoid carcinoma of the esophagus with mucosal gastric cancer. Endoscopic mucosal resection was performed on a 67-year-old man with a slight but defined depressed lesion of the thoracic esophagus and two lesions of mucosal gastric cancer. Histological examination revealed that the lesion of the esophagus was a mucoepidermoid carcinoma and the two lesions of the stomach were well-differentiated adenocarcinoma. Since the mucoepidermoid carcinoma had only slightly invaded the submucosal layer, it was thought to arise from the ductal epithelium of the esophageal gland or the stratified squamous epithelium of the esophagus. Radiation therapy with a total dose of 60 Gy was performed and there has been no recurrence or metastasis to other organs during 36 months of follow-up.

Fermentation of five sucrose isomers by human dental plaque bacteria.

Sucrose has five structural isomers: palatinose, trehalulose, turanose, maltulose and leucrose. Although these isomers have been reported to be noncariogenic disaccharides, which cannot be utilized by mutans streptococci, there is no information about their fermentability by other bacteria in dental plaque. The purpose of the present study was to examine whether these isomers were fermented by predominant bacteria in human dental plaque. Clinical bacterial isolates obtained from dental plaque from 3 children aged 22 months to 50 months (146 strains) were inoculated into 3 ml of peptone-yeast extract (PY medium) containing glucose for 1 day, then an aliquot of 20 microl of culture medium was inoculated into 1 ml of PY medium containing 1% (w/v) of the respective test carbohydrates. After incubation for 1 day, the pH values and the optical density at 660 nm of the cultures were measured. Fermentation ability was measured by pH or=0.5. Of the clinical isolates, 33% fermented palatinose, and 69% of these were Actinomyces species. All of the palatinose-fermenting bacterial strains fermented trehalulose, 25% fermented turanose, 70% fermented maltulose and 23% fermented leucrose. We therefore conclude that, in human dental plaque, there are significant numbers of bacteria that are able to ferment sucrose isomers.

Identification of mutans streptococci by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified 16S ribosomal RNA genes.

Mutans streptococci are frequently isolated from dental plaque and carious lesions. These bacteria have been identified by conventional methods such as biochemical and serologic tests followed by the isolation of colonies on the mitis-salivarius agar, which are sometimes inconsistent. Recently, species-specific polymerase chain reaction (PCR) has been reported to rapidly identify Streptococcus mutans and Streptococcus sobrinus. However, in the case of identification and classification into several species, e.g. within the group of mutans streptococci consisting of seven species, the identification using species-specific PCR seems somewhat inefficient because of need for the development and preparation of specific primers for each species. Therefore, in this study we developed a simple method using restriction fragment length polymorphism analysis of PCR-amplified 16S ribosomal RNA genes (16S rRNA genes PCR-RFLP) for the identification of seven different species included in the group of mutans streptococci. We amplified 16S rRNA gene sequences from genomic DNA samples by PCR using universal primers and digested the PCR products with the restriction endonucleases, HpaII and HaeIII. HpaII produced six RFLP patterns for eight reference strains, since the patterns for S. sobrinus, Streptococcus downei and Streptococcus ferus were similar. RFLP patterns produced with HaeIII could separate these three species. Furthermore, the RFLP patterns predicted from the 16S rRNA gene sequences in the GenBank database agreed with the actual RFLP patterns produced in the present study. The 16S rRNA sequence comparisons can be used to identify oral mutans streptococci; however, the identification by sequencing is sometimes difficult in large-scale studies and for small laboratories. Therefore, 16S rRNA genes PCR-RFLP, using HpaII and HaeIII, could be an alternative method for the identification of mutans streptococci, and may be applicable for large-scale studies on the cariogenicity of mutans streptococci.

Nested PCR for detection of mutans streptococci in dental plaque.

AIMS: Mutans streptococci such as Streptococcus mutans and Streptococcus sobrinus have been implicated in human dental caries. In an attempt to develop a rapid and sensitive method for detecting Strep. mutans and Strep. sobrinus in dental plaque, a nested PCR amplification based on the 16S rRNA gene was employed. METHODS AND RESULTS: A universal set of PCR primers for bacterial 16S rRNA gene was introduced for the first PCR, and then two sets of primers specific for the 16S rRNA gene sequences of either Strep. mutans or Strep. sobrinus were used for the second PCR. Eighteen plaque samples were analyzed, and a nested PCR was shown to be more sensitive for detecting Strep. mutans and Strep. sobrinus than direct PCR. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: The 16S rRNA gene-based nested PCR method is a rapid and sensitive method for the detection of mutans streptococci, and may also be suitable for carrying out large-scale studies on the cariogenicity of mutans streptococci.

Clinical features of symptomatic Rathke's cleft cyst.

To investigate the clinical features of Rathke's cleft cysts (RCCs), we retrospectively analyzed 15 cases with histologically confirmed RCCs. All patients underwent formal testing of visual field, endocrinological evaluation and magnetic resonance imagings. As overall presenting symptoms, endocrine disturbance was the most common symptoms, followed by visual disturbance and headache. Among the endocrine disturbances based on adenohypophysial dysfunction, hyperprolactinemia was most common. Considering the size of RCCs, RCCs could induce hyperprolactinemia only when the cysts became large enough to compress the infundibular system. Our series showed relative high incidence of pituitary dwarfism and diabetes insipidus (DI). These facts indicated that RCCs could evoke hyposecretion of growth hormone in young patients and DI in aged patients by direct compression of the pituitary gland in the early stage of progression. All cases who had headache had no other symptoms. We could not prove the evidence that RCCs could induce headaches in these cases. This might be suggested that headache could not be a sole symptom in cases of RCCs.

Binding characteristics of bovine lactoferrin to the cell surface of Clostridium species and identification of the lactoferrin-binding protein.

The binding characteristics of bovine lactoferrin (bLf) to cells of the Clostridium species were observed by using a horseradish peroxidase-bLf conjugate. A bLf-binding protein (BP) having a relative molecular mass of about 33 kDa was confirmed in the surface layer components from 7 strains of the Clostridium species. The binding of the conjugate to bLf-BP or C. perfringens was strongly blocked by intact Lfs, lysine or arginine residues modified bLf, and deglycosylated bLf, but was not by other milk proteins or by the constituent sugars of glycan. Bacterial growth was inhibited by bLf, but was slightly inhibited by lysine residues modified bLf or deglycosylated bLf. Lactoferricin B did not block the binding of the conjugate, but strongly inhibited the bacterial growth. This suggests that the lysine or arginine residues and glycan of bLf hardly participated in binding bLf to the bacterial cells, but that the amino acid residues and glycan played an important role in inhibiting the growth of bacteria.

Binding of lactoferrin to bacterial cells of the Clostridium species and their agglutination.

Cell agglutination in cell suspensions of 10 strains of Clostridium by lactoferrin (Lf) was observed by obtaining the ratio of increased absorbance (RIA) at 450 nm. The RIA values were very different among the species, being higher in the cell suspensions with bovine Lf (bLf) than in those with human Lf. The binding ability of bLf to the bacterial cells was also observed by an enzyme-linked ligand-binding assay, using the conjugate of iron-free or iron-saturated bLf with horseradish peroxidase (HRPO). The binding ability of bLf was very different among the 10 species, and showed a significant correlation with the cell agglutination of each strain. bLf formed a complex with the cells of C. perfringens, did not dissociate in 2 M NaCl or 4 M urea, but did dissociate in 1 M KSCN. These results suggest that the agglutination of cells of the Clostridium species by bLf is probably caused by the cooperative action of at least electrostatic and hydrophobic interactions between bLf and certain components of the cell surface.

Differentiation of oral Actinomyces species by 16S ribosomal DNA polymerase chain reaction-restriction fragment length polymorphism.

16S rDNA polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to generate restriction profiles of the reference strains, including the American Type Culture Collection type strains, of oral Actinomyces spp., i.e., A. israelii, A. gerencseriae, A. naeslundii genospecies 1 and 2, A. odontolyticus, A. meyeri and A. georgiae, and 23 Actinomyces strains isolated from human dental plaque. The 16S rRNA gene sequences from isolated genomic DNA samples were amplified by PCR. The PCR products were purified and characterized by single digestion with four restriction endonucleases, i.e., MnlI, HaeIII, CfoI, or HpaII. Among them, MnlI was found to discriminate the respective reference strains. The clinical isolates were assigned to one of the species, i.e., A. gerencseriae, A. naeslundii genospecies 1 and 2 and A. odontolyticus, on the basis of their restriction profiles by single digestion with MnlI. Thus, 16S rDNA PCR-RFLP, using MnlI, is a rapid and reliable method for the differentiation of oral Actinomyces spp.

Restriction fragment-length polymorphism analysis of 16S rDNA from oral asaccharolytic Eubacterium species amplified by polymerase chain reaction.

Restriction fragment-length polymorphism (RFLP) analysis of 16S rDNA amplified by polymerase chain reaction was used to generate restriction profiles of the type strains of oral asaccharolytic Eubacterium species, that is, Eubacterium brachy, Eubacterium exiguum, Eubacterium lentum, Eubacterium minutum, Eubacterium nodatum, Eubacterium saphenum, Eubacterium timidum and 33 asaccharolytic Eubacterium strains isolated from oral sites. The 16S rRNA gene sequences from isolated genomic DNA samples were amplified by polymerase chain reaction (PCR). PCR products were purified and characterized by single digestions with 7 restriction endonucleases. Among the 7 endonucleases, HpaII was found to discriminate the respective reference strains. Twenty-three isolates, out of 33, were assigned to one of the reference species, on the basis of their restriction profiles by digestion with HpaII. The remaining 10 isolates could not be assigned to any of the established species and constituted 4 distinct groups, each of which may be a new species.

PCR-restriction fragment length polymorphism analysis of genes coding for 16S rRNA in Veillonella spp.

Restriction fragment length polymorphism analysis of PCR-amplified 16S ribosomal DNA (16S rDNA PCR-RFLP) was used to generate restriction profiles of the American Type Culture Collection type strains of the genus Veillonella, i.e., V. atypica, V. caviae, V. criceti, V. dispar, V. parvula, V. ratti, and V. rodentium. Whole-cell protein profiles were obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for comparative purposes. The 16S rRNA genes were amplified by PCR, and RFLP analysis of the 16S rDNA was performed with MnlI and Sau3AI. MnlI produced six RFLP patterns for seven type strains, since the patterns for V. atypica and V. caviae were the same. RFLP patterns with Sau3AI could distinguish between V. atypica and V. caviae. The type strains of Veillonella species were easily distinguished by 16S rDNA PCR-RFLP.

Differentiation of Veillonella atypica, Veillonella dispar and Veillonella parvula using restricted fragment-length polymorphism analysis of 16S rDNA amplified by polymerase chain reaction.

Veillonella atypica, Veillonella dispar and Veillonella parvula cannot be reliably distinguished by conventional phenotypic tests, including the API ZYM test. In this study, restricted fragment-length polymorphism (RFLP) analysis of 16S rDNA amplified by polymerase chain reaction (PCR) was used to generate restriction profiles of the type strains of V. atypica, V. dispar and V. parvula and 20 Veillonella strains isolated from oral sites. 16S rRNA gene sequences from isolated genomic DNA samples were amplified by PCR. PCR products were purified and characterized by single digestion with 13 restriction endonucleases. Among them, Mn/I was found to discriminate the respective reference strains, and the clinical isolates were assigned to one of the three species on the basis of their restriction profiles by digestion with Mn/I. Thus, RFLP analysis of PCR-amplified 16S rDNA, using Mn/I, is a rapid and reliable method for the differentiation of V. atypica, V. dispar and V. parvula.