[Show abstract][Hide abstract] ABSTRACT: Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current optimal protocols.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 09/2014;
[Show abstract][Hide abstract] ABSTRACT: We recently reported frequent detection of antibiotic-resistant bacteria on the oral mucosa during the period of hematopoietic cell transplantation (HCT) and suggested an association between oral mucositis and antibiotic-resistant bacterial infection. Methicillin-resistant Staphylococcus spp. were frequently detected, and the oral cavity may be a reservoir of the gene mediating methicillin resistance, mecA. Here, we examined the frequency of mecA carriers in patients undergoing HCT.
Fifty-nine patients (male (M) = 37, female (F) = 22, 47.3 ± 11.0 years) receiving HCT were enrolled in this study. Buccal swab samples were obtained four times from day -7 to day +20 (once/week), and mecA was detected by PCR. Fifty-two subjects without systemic disease, who completed dental treatment, especially periodontal treatment (M = 21, F = 31, 55.4 ± 14.2 years), were also enrolled as controls and checked for mecA on the oral mucosa.
Seventy-six percent (45/59) of the HCT patients carried mecA at least once in the study period (days -7 to +20), while no control subjects had mecA. The frequency of mecA carriers was 19.2 % from days -7 to -1, while it was significantly increased on days +7 to +13 and +14 to +20, with frequencies of 60.9 and 63.2 %, respectively (P < 0.01, ANOVA).
mecA was detected in oral mucosa of patients undergoing HCT. The high detection frequency of staphylococci resistant to penicillin and beta-lactams in our recent report was supported.
Supportive Care in Cancer 02/2014; · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eosinophil cationic protein (ECP) was reported previously to be involved in allergic inflammation with cytotoxic activity. On the other hand, recent studies showed that ECP did not induce cell death but inhibited the growth of cancer-derived cells. Our previous study indicated that human ECP enhanced differentiation of rat neonatal cardiomyocytes and stress fiber formation in Balb/c 3T3 mouse fibroblasts, while the effects of human ECP on human fibroblasts are unknown.
The present study was performed to determine the effects of human ECP on cytokine expression in human fibroblasts by protein array.
The effects of recombinant human ECP (rhECP) on normal human dermal fibroblasts (NHDF) were examined by assaying cell growth. Furthermore, cytokine expression of NHDF stimulated by ECP, which could influence cell growth, was evaluated by protein array.
ECP was not cytotoxic but enhanced the growth of NHDF. The peak rhECP concentration that enhanced the cell counts by 1.56-fold was 100 ng/mL, which was significantly different from cultures without ECP stimulation (ANOVA/ Scheffe's test, P < 0.05). Array analyses indicated that ciliary neurotrophic factor (CNTF), neutrophil-activating peptide (NAP)-2, and neurotrophin (NT)-3 were significantly upregulated in NHDF stimulated with 100 ng/mL ECP compared to those without stimulation.
ECP is not cytotoxic but enhances the growth of NHDF. CNTF, NAP-2, and NT-3 were suggested to be involved in enhancing the growth of NHDF. These findings will contribute to determination of the role of ECP in allergic inflammation.
Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 12/2013; 31(4):271-6. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. RESULTS: Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 μg/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence. CONCLUSIONS: Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional well-designed research is needed on other cytokine and growth factor interventions and in other cancer treatment settings.
Supportive Care in Cancer 09/2012; · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.
[Show abstract][Hide abstract] ABSTRACT: Coagulase-negative staphylococci (CoNS) are frequently isolated from blood cultures of hematopoietic cell transplantation (HCT) patients. Generally, the use of central venous catheters is recognized as a significant risk factor for CoNS infection, while the impact of CoNS infection from oral ulcerative mucositis, which occurs frequently in HCT, may be underestimated. Here, we examined the bacteria on the buccal mucosa after HCT.
Sixty-one patients were examined for bacteria on the buccal mucosa routinely once a week from 1 week before to 3 weeks after allogeneic HCT. Subjects were divided into groups with short and long periods of antibiotic use, and differences in bacterial substitution were evaluated. The relationships between type of HCT (conventional HCT or RIST) and bacterial substitution were also evaluated.
The changes in detection frequencies of CoNS and α-streptococci from before to 3 weeks after HCT were significant (P < 0.05, χ (2) test): 14.5-53.3% and 92.7-53.1%, respectively. Significant bacterial substitution of CoNS for streptococci was observed in the long-term antibiotic use group (P < 0.05, χ (2) test), but also occurred in cases with short-term or no antibiotic use. No relationships between type of HCT (conventional HCT or RIST) were observed.
Bacterial substitution of CoNS for streptococci occurred frequently on the buccal mucosa after HCT. In addition to antibiotic use, environmental factors may be involved in bacterial substitution. It is important to consider the presence of oral mucositis in CoNS infection after HCT.
Supportive Care in Cancer 07/2011; 19(7):995-1000. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic low-grade infection has been suggested to be associated with metabolic disorder such as diabetes. However, the molecular mechanism underlying this important association is largely unknown. The only clue established so far is that many subjects exhibit elevated levels of C-reactive protein as measured by highly sensitive assay. Here, we hypothesized that adipocyte-macrophage interaction plays a key role in amplifying such low grade infection to the level of influencing metabolic disorders. The presence of macrophages in abdominal adipose tissues was investigated by immunohistochemistry. To see whether molecules associated with acute phase protein, LPS signaling, and persistent recruitment of monocytes, are produced at higher amounts in adipocytes co-cultured with macrophages stimulated with low concentration of LPS (1 ng/ml), we measured serum amyloid A (SAA), LPS binding protein (LBP), soluble CD14 (sCD14), and RANTES levels in culture supernatant of co-cultures. Lastly, we investigated in vivo effect of low-grade LPS infusion on the production of these molecules using obese model mice. The macrophages were certainly identified in abdominal adipose tissues. Investigated molecules, especially LBP, SAA, and RANTES were produced at higher amounts in co-cultures stimulated with LPS compared with the cells without LPS. The ob/ob, and high-fat diet-induced obesity mice produced higher amounts of LBP, SAA, and RANTES one day after LPS infusion (1 ng/ml/g body weight) compared with ob/- and normal-fat fed control mice. Thus, adipocytes and infiltrated macrophages, and their interaction with low endotoxin stimulation appear to play an important role in amplifying and maintaining LPS-induced low-grade inflammation.
[Show abstract][Hide abstract] ABSTRACT: Methanobrevibacter oralis is an archaeal species frequently isolated from sites of severe periodontitis. However, its pathogenic roles remain unclear. Here, we aimed to isolate group II chaperonin from M. oralis and examine its antigenicity. The genes encoding two chaperonin subunits (Cpn-1 and Cpn-2) were cloned from M. oralis using polymerase chain reaction and genome walking procedures. Recombinant proteins Cpn-1 and Cpn-2 were generated, and the reactivities of sera from patients with periodontitis were examined by Western immunoblotting. The open reading frames of Cpn-1 and Cpn-2 genes consisted of 1641 and 1614 base pairs, respectively. Putative ATP-binding domains conserved among the chaperonin family were observed in both genes. The deduced amino acid sequences of the two genes showed 28.8-40.0% identity to each of the subunits of human CCT (CCT1-8). Thirty and 29 of 36 patients' sera reacted with the recombinant Cpn-1 and recombinant Cpn-2, respectively. Western immunoblotting using antiserum against human CCT subunits indicated that anti-CCT3 and anti-CCT8 antibodies recognized recombinant Cpn-1. In addition, anti-CCT1, CCT3, CCT6, and CCT8 antibodies recognized an antigen of approximately 60 kDa in M. oralis. The results suggested that the chaperonin subunits of M. oralis were antigenic molecules that were recognized by periodontitis patients and that may cross-react with human chaperonin CCT.
[Show abstract][Hide abstract] ABSTRACT: Oral health care providers may discover systemic diseases incidentally from signs observed in the oral cavity. Here, we report a case in which oral health care providers in a hospital discovered a patient with strongly suspected bullous pemphigoid (BP), which is a relatively rare but important disease, in a ward.
The patient was a 78-year-old Japanese woman admitted to our hospital because of severe Alzheimer's disease. We discovered recurrent ulcers in the oral mucosa and skin when performing oral care in her ward. Biopsy could not be performed safely because of involuntary biting. We performed blood tests for anti-BP180-NC16a antibody, which is autoantibody specific for BP.
The patient had a very high anti-BP180-NC16a antibody titre. We consulted a dermatologist regarding her clinical course and the clinical features of the oral mucosa and skin along with blood test results. BP was very strongly suspected.
In cases in which oral health care providers suspect their patients may have BP, appropriate examination and provision of information to the doctor are important. Oral health care providers should have knowledge about systemic diseases, the signs of which appear in oral cavity to avoid missing important systemic diseases.
International Journal of Dental Hygiene 03/2010; 9(2):159-62. · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral mucositis is a common symptomatic complication associated with hematopoietic stem cell transplantation (HCT). We use simple strategies aimed to reduce oral mucositis by keeping the oral cavity clean and moist. Here, we report on the progress of oral care and the changes in the degree of oral mucositis. The purpose of this pilot study is to evaluate the effects of our strategies on the prevalence and the severity of oral mucositis.
Fifty-three consecutive patients from 2003 to 2006 administered with conventional allogeneic HCT were enrolled in this study. The degree of oral mucositis was evaluated daily in all patients. Our oral care program was divided into two periods: "examination and trial period (2003 and 2004)" and "intensive oral care period (2005 and 2006)." In the latter, an oral care regimen was carried out systematically by a multidisciplinary team.
Using our oral care strategies, the prevalence of ulcerative oral mucositis was decreased significantly. The rate was reduced from 76% (10 of 13) of patients with ulcerative oral mucositis in 2003 to only 20% (3 of 15) in 2006.
Our pilot study suggests that oral mucositis in HCT patients can be alleviated by simple strategies aimed at keeping the oral cavity clean and moist.
Supportive Care in Cancer 02/2010; 19(2):303-7. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The commercial saliva substitute Oralbalance has been reported to alleviate symptoms of postradiotherapy xerostomia in head and neck cancer patients. Oralbalance may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are in a severely compromised condition, and saliva substitute must not promote infection. We reported previously that Oralbalance has antimicrobial effects against microbial species detected during HCT in vitro. This study was performed to determine the in vivo effects of Oralbalance on oral mucosal total bacterial counts in patients undergoing HCT.
A total of 18 neutropenic patients undergoing HCT were enrolled in this study. Before and after 1 week of Oralbalance use, bacterial samples were obtained from patients by wiping an area of varphi1 cm on the buccal mucosa with sterilized cotton swabs. Total bacterial counts of the obtained samples were examined by quantitative polymerase chain reaction amplification of the bacterial 16S ribosomal RNA gene. As controls, bacterial samples were also obtained from ten healthy subjects, and total bacterial counts were examined.
No significant increase in bacterial count was observed with use of Oralbalance. None of the patients showed bacterial counts above the range found in healthy controls after using Oralbalance.
In neutropenic patients undergoing HCT, Oralbalance did not increase the total counts of oral mucosal bacteria beyond the range found in healthy controls. Oral care using Oralbalance may alleviate the symptoms induced by hyposalivation without promoting infection.
Supportive Care in Cancer 12/2009; 18(3):395-8. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A genome-association study is a powerful tool for analyzing small gene effects in complex diseases such as chronic periodontitis (CP), although the cost of analysis is prohibitive. We designed a study using the DNA pooling method, which could be a breakthrough in lowering such costs. This study was conducted to assess the genetic association in severe CP in a Japanese population.
We adopted a DNA pooling method by genotyping 454 densely spaced microsatellite (MS) markers in chromosome 19 as a pilot study, with the possibility of future use in a whole-genome study. This can reduce the high cost and technical burden, which is generally unavoidable in a genomic association study. Pooled DNA samples from 300 case subjects, 300 control subjects, and 200 systemically healthy subjects were screened by genotyping MS markers. The case-control association in the candidate region was analyzed by individual typing of MS and single nucleotide polymorphisms (SNPs).
The single MS marker allele 17 of 1902G31 was isolated in association with severe CP (P = 0.0012 for 2 x 2; P <0.046 for 2 x m, where m refers to the number of polymorphic alleles observed in a population). No other SNP or MS polymorphism hypothesized to affect biologic functions in the critical region was found in the linkage disequilibrium block analysis.
We efficiently isolated the susceptible locus for severe CP in chromosome 19 and identified a useful marker to evaluate the risk for disease. This approach can be applied to a whole-genome study in severe CP.
Journal of Periodontology 05/2009; 80(4):663-71. · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe oral mucositis induced by allogeneic hematopoietic cell transplantation (HCT) is associated with intolerable pain and risk of systemic bacteremia infection. Differences between conventional HCT and reduced-intensity regimens for allogeneic HCT (RIST) may influence the occurrence and severity of oral mucositis. Here, we evaluated oral mucositis in patients undergoing RIST and compared the results with those in conventional allogeneic HCT patients to facilitate predictive measures for mucositis.
A total of 127 consecutive patients undergoing HCT (conventional, 63; RIST, 64) were included in this study. Severity of oral mucositis during HCT period was evaluated daily. Differences in severity of mucositis among HCT types were analyzed. Use of morphine to control pain due to oral mucositis was evaluated in each HCT method.
The severity of oral mucositis was reduced in patients undergoing RIST. Worsening of oral mucositis was delayed in patients receiving RIST. Use of morphine to control pain due to oral mucositis was significantly decreased in patients undergoing RIST compared with those receiving conventional allogeneic HCT.
The severity of oral mucositis was reduced and the peak day of oral mucositis was delayed in RIST patients compared with those receiving conventional HCT.
Supportive Care in Cancer 05/2009; 18(1):115-9. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral and systemic infections arising from the oral cavity are significant problems in clinical management of patients undergoing leukemia treatment. However, there is significant disparity in the reported incidences of development of periodontal infections. Evidence is limited to those showing the systemic influence of periodontal infection in neutropenic patients. This study indicated an association between febrile neutropenia (FN) and periodontitis in a case in which periodontal treatment in the intervals between chemotherapy cycles reduced FN in subsequent courses of chemotherapy and hematopoietic transplantation (HCT).
Periodontal treatment was performed in a 61-year-old man with advanced periodontitis, who received HCT following three cycles of chemotherapy. After recovery from neutropenia induced by initial chemotherapy, periodontal treatment was performed in each chemotherapy interval period. Following extraction of teeth with severe advanced periodontitis, all teeth were subjected to periodontal pocket curettage and root planning, which are common periodontal treatments to reduce periodontal pockets harboring anaerobic periodontal bacteria, before HCT.
Periodontal treatment successfully reduced periodontal pockets from 4.1 +/- 1.5 mm to 3.0 +/- 0.6 mm, which was almost within the healthy range (<3.0 mm), before HCT. The frequency of FN decreased significantly with increasing cycles of chemotherapy, and decreases in FN corresponded to progress of periodontal treatment. Blood cultures obtained a total of 12 times throughout leukemia treatment were all negative.
The observations reported here indicate the importance of periodontal treatment in clinical management of patients undergoing leukemia treatment to prevent FN, although all blood cultures were negative.
Supportive Care in Cancer 11/2008; 17(5):581-7. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have suggested that macrophages were integrated into adipose tissues to interact with adipocytes, thereby exacerbating inflammatory responses. Furthermore, both adipocytes and macrophages appear to express toll-like receptor-4 (TLR-4), and free fatty acids may stimulate cells through TLR-4. Herein, we analyzed genes differentially expressed in adipocytes when co-cultured with macrophages in the presence of a ligand for TLR-4, bacterial lipopolysaccharide (LPS). RAW264.7, a murine macrophage cell line and differentiated 3T3-L1 adipocytes were co-cultured using a transwell system. Genes differentially expressed in adipocytes were analyzed by the DNA microarray method following 4, 8, 12 and 24 h stimulation with 1 ng ml(-1) of Escherichia coli LPS. Randomly selected genes with high expressions were confirmed by quantitative methods at both the gene and the protein level. Co-culture of macrophages and adipocytes with a low LPS concentration (1 ng ml(-1)) markedly upregulated gene expressions associated with inflammation and/or angiogenesis, such as those of interleukin-6 (IL-6), MCP-1, RANTES and CXCL1/KC, in adipocytes. Furthermore, several genes associated with insulin resistance were differentially expressed. Upregulations of genes encoding MCP-1, RANTES and CXC/KC were confirmed by quantitative methods. These results suggest that ligands for TLR-4 stimulate both adipocytes and macrophages to upregulate the expressions of many genes associated with inflammation and/or angiogenesis.
International journal of obesity (2005) 10/2008; 32(11):1725-9. · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic cell transplantation (HCT) may lead to the development of xerostomia. However, there have been few reports of xerostomia in HCT patients based on objective data. We investigated moisture in the oral mucosa in patients undergoing HCT by the capacitance method using a convenient device, Moisture Checker for Mucus (MCM; Life Co., Ltd., Saitama, Japan).
Thirty-six patients undergoing HCT at Okayama University Hospital of Medicine and Dentistry (Male = 22, Female = 14; age = 41.6 +/- 16.2 years old) were enrolled in this study. Moisture in the oral mucosa was measured by MCM in accordance with the manufacturer's instructions. The results were obtained as MCM values (%), which are the weight percentage of water content in the oral mucosal epithelium. As controls, moisture of the oral mucosa was also examined in healthy volunteers (Male = 27, Female = 35; age = 43.0 +/- 14.6 years old).
Throughout the examination period, MCM values were significantly lower in patients who underwent HCT than in controls. The degree of mucosal moisture in HCT patients showed wide interindividual differences.
The degree of mucosal moisture in HCT patients was low and showed wide interindividual differences. Evaluation of xerostomia using such a device may contribute to appropriate oral care with saliva substitute.
Supportive Care Cancer 07/2008; 16(10):1197-200. · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The commercially available saliva substitute Oralbalance has been reported to alleviate symptoms of post-radiotherapy xerostomia in head and neck cancer patients. Oralbalance may also be effective for xerostomia in patients undergoing hematopoietic cell transplantation (HCT) with high-dose chemotherapy and total-body irradiation. However, HCT patients are severely compromised, and saliva substitute must therefore not promote infection. This study was performed to determine the effects of Oralbalance on microbial species identified during HCT.
Microbial identification of oral mucosa was performed in 28 patients undergoing HCT. The antimicrobial effects of Oralbalance against bacteria and fungi detected in the HCT period were examined in vitro. Briefly, bacteria and fungi were spread on agar plates, and 0.1g of Oralbalance gel was applied (about phi1cm). After incubation at 37 degrees C for 24h, the presence of a transparent zone of inhibition around Oralbalance was observed.
Not only bacterial species constituting normal flora of the oral mucosa but also those not usually constituting normal flora, e.g., coagulase-negative Staphylococcus, were detected. A transparent zone was observed around Oralbalance in all bacterial species examined. No transparent zone was observed for Candida albicans, but growth was inhibited in the area where Oralbalance was applied.
Oralbalance does not facilitate increases in microorganisms in the HCT period. Oral care with Oralbalance does not promote infection in patients undergoing HCT.
Supportive Care Cancer 05/2008; 16(4):421-4. · 2.65 Impact Factor