Fact-finding survey of doctors at the departments of pediatrics and pediatric surgery on the transition of patients with childhood-onset chronic disease from pediatric to adult healthcare.

BACKGROUND: The number of adult patients with childhood-onset chronic diseases is increasing. However, the process of transitioning these patients from child- to adult-centered medical services faces many difficulties. Despite the key role that doctors in the pediatric field are considered to play in transition, few fact-finding surveys about transition have been conducted among these doctors. OBJECTIVE: The aim of this study was to demonstrate the current status and challenges in the transition of patients with childhood-onset chronic diseases by a fact-finding survey of pediatricians and pediatric surgeons at a university hospital. METHODS: A cross-sectional survey was performed using an anonymous self-administered questionnaire. Seventy-six doctors of pediatrics and pediatric surgery (excluding junior residents) in a university hospital were asked to answer an anonymous self-report questionnaire. A multidisciplinary research team selected items related to the transitional process. RESULTS: Sixty (79%) doctors participated, of whom 52 (87%) showed awareness of transition. No doctor answered that "Transition is conducted smoothly." Doctors with shorter pediatric department experience had lower awareness and poorer experience with transition. In contrast to pediatric surgeons, pediatricians explained "job-seeking activities" and "contraceptive methods" to the patient, and reported a higher patient age at which to initiate explanation of transition to the patient and his/her family. Among factors inhibiting transition, 39 (65%) respondents selected "The patient's family members do not desire transition" and 34 (57%) selected "Although a relevant adult healthcare department is available, it will not accept the patient." The medical providers most frequently considered to have responsibility for playing a central role in the transition process were "pediatrician/pediatric surgeon," "medical social worker," and "regional medical liaison office." DISCUSSION: To promote transition, pediatric and adult healthcare departments should share concerns about and cooperate in the establishment of more effective methods of transition, and provide multidisciplinary collaboration to support patients and their families.

Identification of Water-Soluble Polymers through Discrimination of Multiple Optical Signals from a Single Peptide Sensor.

The pollution of water environments is a worldwide concern. Not only marine pollution by plastic litter, including microplastics, but also the spillage of water-soluble synthetic polymers in wastewater have recently gained increasing attention due to their potential risks to soil and water environments. However, conventional methods to identify polymers dissolved in water are laborious and time-consuming. Here, we propose a simple approach to identify synthetic polymers dissolved in water using a peptide-based molecular sensor with a fluorophore unit. Supervised machine learning of multiple fluorescence signals from the sensor, which specifically or nonspecifically interacted with the polymers, was applied for polymer classification as a proof of principle demonstration. Aqueous solutions containing different polymers or multiple polymer species with different mixture ratios were identified successfully. We found that fluorophore-introduced biomolecular sensors have great potential to provide discriminative information regarding water-soluble polymers. Our approach based on the discrimination of multiple optical signals of water-soluble polymers from peptide-based molecular sensors through machine learning will be applicable to next-generation sensing systems for polymers in wastewater or natural environments.

Affinity-based thermoresponsive fluorescence switching of proteins conjugated with a polymer-binding peptide.

The affinity-based thermoresponsive fluorescence switching of proteins conjugated with a polymer-binding peptide is demonstrated. The specific affinity of the peptide and thermoresponsive structural transitions of the polymer are essential for reliable fluorescence switching behavior.

Bioinspired structural transition of synthetic polymers through biomolecular ligand binding.

Inspired by ligand binding-triggered structural transition of biopolymers in living systems, we demonstrated the structural transition of thermoresponsive poly(N-isopropylacrylamide) through specific ligand binding of artificially evolved peptides to the polymer.

Prognostic value of cyclin D1 expression in tumor-free surgical margins in head and neck squamous cell carcinomas.

CONCLUSION: It was proved that cyclin D1-positive status in surgical margins was an independent prognostic indicator of local recurrence. The expression of cyclin D1 in tumor-free surgical margins may better predict local recurrence in patients with head and neck squamous cell carcinoma (HNSCC) after surgical treatment with curative intent. OBJECTIVE: This retrospective study aimed to determine the prognostic indicators for local recurrence in HNSCC. METHODS: A total of 116 HNSCC patients who underwent surgical treatment with curative intent and had histopathologically tumor-free margins were eligible for this study. The expression of p53 and cyclin D1 was assessed by immunohistochemical staining in surgical margins as well as in tumor specimens. RESULTS: In all, 63 patients (54.3%) had p53-positive tumor specimens and 34 patients (29.3%) had p53-positive margins. Seventy-six patients (65.6%) had cyclin D1-positive tumor specimens and 54 patients (46.6%) had cyclin D1-positive margins. A significant difference in local control rates was observed between patients with cyclin D1-positive and -negative margins (77.2% vs 91.5%, log rank test, p = 0.0139). Multivariate Cox proportional hazards testing indicated that the hazard ratio of cyclin D1-positive margins for local recurrence was 4.58 (95% confidence interval 1.14-21.69, p = 0.0304).

Regional control after concomitant chemoradiotherapy without planned neck dissection in node-positive head and neck squamous cell carcinomas.

OBJECTIVES: Although three-weekly high-dose (100mg/m(2)) cisplatin (three cycles) chemoradiotherapy has been considered a standard regimen for patients with advanced head and neck squamous cell carcinomas (HNSCC), this protocol is associated with significant acute and late toxicities. Therefore, weekly cisplatin at a dose of 40mg/m(2) has been used at our institution since 2006. This retrospective study was aimed at assessing the oncologic efficacy of weekly cisplatin chemoradiotherapy for the control of nodal metastasis. METHODS: We analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and concurrent radiotherapy. Computed tomography was performed 4-8 weeks after the completion of chemoradiotherapy to evaluate nodal response. If residual neck disease was apparent or suspected, we performed early salvage neck dissection (ND). In cases with a complete response (CR), we took a "wait and see" approach. When no viable tumor cells were observed in the surgical specimens obtained by ND, nodal metastasis was defined as controlled by weekly cisplatin chemoradiotherapy alone. RESULTS: Nodal metastasis was evaluated as having a CR in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent primary tumors were observed in the other four patients (14%). Salvage primary resection and associated ND were performed for these four patients. In 7 of 12 patients undergoing ND, no viable tumor cells were observed. In 23of 28 patients, neck diseases were controlled by chemoradiotherapy alone (not including salvage by ND). In 27 of 28 patients, neck diseases were controlled by the overall treatment (including salvage by ND). The rate of nodal control by chemoradiotherapy alone and by the overall treatment was found to be 82.0% and 96.3%, respectively, using the Kaplan-Meier method. The three-year overall and disease free survival rates were 86.8% and 80.8%, respectively. CONCLUSION: Concomitant weekly cisplatin at a dose of 40mg/m(2) chemoradiotherapy showed a good control rate of not only primary lesions but also neck diseases.

Improved survival of Japanese patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: The prevalence of oropharyngeal carcinoma is rising in western Europe and the United States, where there appears to be a strong association between human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC). However, such a correlation has not yet been fully evaluated in Japan. METHODS: We performed a retrospective analysis of the association between tumour HPV status and the demographic and clinicopathological parameters of 71 patients with OPSCC at Hokkaido University Hospital, Japan, between 1998 and 2009. The parameters included age, gender, survival, tumour subsite, tumour-node-metastasis (TNM) stage, smoking history, second primary tumour status, recurrence/residual disease at the primary site, and overall survival. HPV status was established by multiplex polymerase chain reaction (PCR) analysis. RESULTS: Of the 71 oropharyngeal cancers, 20 were positive for HPV-16, two for HPV-18, and one for HPV-58. Kaplan-Meier survival analysis showed improved overall survival rates in patients with HPV-positive tumours (p = 0.0038) compared with HPV-negative tumours. Of the 45 patients who received chemoradiotherapy, HPV-positive patients experienced better overall survival than HPV-negative patients (p = 0.0032). In a multivariate analysis, the survival benefit of HPV-positive patients was independent of age and T and N classification. CONCLUSIONS: HPV status is a significantly favourable prognostic factor in oropharyngeal cancer and could be used as a marker to optimize the treatment of patients with this type of cancer in Japan.

Platinum concentration in sentinel lymph nodes after preoperative intra-arterial cisplatin chemotherapy targeting primary tongue cancer.

CONCLUSION: We conclude that intra-arterially injected cisplatin passed via lymph flow into sentinel nodes (SNs) as the platinum concentration in the SNs was higher than that in the non-sentinel nodes (NSNs). It is possible that preoperative intra-arterial chemotherapy targeting primary cancer also has a therapeutic effect on subclinical metastatic SNs. OBJECTIVES: Intra-arterial chemoradiotherapy has been reported to be effective against not only primary tumors but also nodal metastases. We considered the hypothesis that intra-arterially injected cisplatin passed via lymph flow into regional nodes. This study aimed to investigate intra-arterially injected cisplatin distribution to regional nodes by comparing platinum concentrations in SNs and NSNs. METHODS: Five patients with T1-2 N0 tongue cancer were treated with preoperative intra-arterial chemotherapy (cisplatin, 100 mg/m(2)) targeting primary cancer. Partial glossectomy together with SN biopsy and elective neck dissection were performed 2 weeks after intra-arterial chemotherapy. Platinum concentrations in the lymph nodes were measured using a Zeeman atomic absorption spectrometer. RESULTS: Thirteen SNs were harvested together with eight NSNs from the areas adjacent to the SNs. Platinum concentrations were then measured, revealing a significant difference in platinum concentration between the SNs and the NSNs (mean ± SD, 0.682 ± 0.246 µg/g vs 0.506 ± 0.274 µg/g; p = 0.049).

Malignant melanoma of the head and neck: a multi-institutional retrospective analysis of cases in northern Japan.

BACKGROUND: Mucosal melanoma of the head and neck is rare and is associated with a poor prognoses because of locoregional failure and distant metastasis. The aim of our study was to review the characteristics of these patients in northern Japan and to analyze their outcomes. METHODS: The medical records of 94 patients who had been provided initial treatment in 12 institutes from 1998 to 2007 were reviewed. RESULTS: When the 5-year overall survival rates of patients were evaluated, we found that the survival rates of patients treated by chemotherapy were significantly lower than those of patients treated by surgery or radiation. The survival rates of the single-treatment modality, 2-modality, and ≥3-modality groups were 23.4%, 38.0%, and 33.6%, respectively. CONCLUSION: Our results suggest that patients who underwent combined treatment had better prognoses. However, we found that chemotherapy had no additional survival benefits.

Concomitant weekly cisplatin and radiotherapy for head and neck cancer.

OBJECTIVE: The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. METHODS: Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. RESULTS: Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). CONCLUSIONS: Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy.

FDG PET/CT in a patient with spontaneous remission of methotrexate-associated lymphoproliferative disorders after interruption of methotrexate.

We report a case that fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) depicted systemically multiple lesions of methotrexate (MTX)-associated lymphoproliferative disorders. A 70-year-old man receiving MTX for rheumatoid arthritis complained of neck swelling. FDG PET/CT revealed multiple FDG-avid lesions in lymph nodes, lungs, bones, and muscles. Lesions in bones and muscles were not detected on X-CT. Final diagnosis of cervical node was confirmed as MTX-associated lymphoproliferative disorders. FDG PET/CT performed 148 days after discontinuing MTX demonstrated complete remission.

[Clinical analysis of malignant submandibular tumor].

The 14 cases of malignant submandibular tumor whose treatment outcome we analyzed between 1989 and 2008 included 5 of adenoid cystic carcinoma, 3 of squamous cell carcinoma, 2 each of mucoepidermoid carcinoma, and carcinoma ex pleomorphic adenoma, and 1 each of carcinosarcoma and large-cell carcinoma. One subject was diagnosed with T1, 7 with T2, 4 with T3, and 2 with T4. Lymph node involvement occurred in 5, -1 with N1 and 4 with N2. None had distant metastasis on the first visit. Seven were treated by surgery alone, 3 by surgery followed by radiotherapy, 2 by surgery followed by radio-and chemotherapy, and 1 by optimized supportive care. The surgical resection area was decided by tumor extension. Neck dissection was done in 9. Overall 5-year survival for all cases based on the Kaplan-Meier method was 57%. All with carcinoma ex pleomorphic adenoma, carcinosarcoma, or large-cell carcinoma remain alive. For those with adenoid cystic carcinoma 5-year survival is 80%, with mucoepidermoid carcinoma 50%, with squamous cell carcinoma 0%, and with carcinosarcoma 0%, respectively. The 5-year survival for stage I subjects was 100%, for stage II 83%, for stage III 50%, and for stage IV 0%. Surgical resection and postoperative radiotherapy were done in cases of minimal extraglandular extension or microscopically positive margins, with satisfactory results. Treatment efficacy for high-grade and advanced stage, however, requires more improvement.

Salvage surgery for local recurrence after chemoradiotherapy or radiotherapy in hypopharyngeal cancer patients.

This retrospective study aimed to assess the role of salvage surgery for local recurrence in hypopharyngeal cancer (HPC) patients who had received radiotherapy (RT) or concomitant chemoradiotherapy (CRT) as an initial treatment. The local recurrence rate, salvage rate after local recurrence and overall survival rate were investigated in 104 HPC patients who received treatment between 1991 and 2005. Local recurrence in the primary site was observed in 41 patients (rate, 39.4%) of whom only 12 could undergo further salvage surgery. Disease control was achieved in seven of these patients (successful salvage rate, 17.1%). The 5-year overall survival rate was 40.6% in the RT/CRT patient group and successful salvage rates for T1, T2, T3 and T4 primary disease were 33.3% (1/3), 20.0% (4/20), 16.7% (2/12) and 0% (0/6), respectively. Severe postoperative complications such as pharyngo-cutaneous fistula were seen in six patients (50.0%). Prognosis of patients with locally recurring HPC after RT/CRT is poor at any primary T-stage and the incidence of postoperative complication is relatively high. This should be taken into consideration when the initial treatment plan is decided and the choice of salvage surgery for such recurrent cases should be carefully determined.

Importance of comorbidity in hypopharyngeal cancer.

BACKGROUND: Comorbidity has an impact on survival in laryngeal cancer in several reports. However, the importance of comorbidity in hypopharyngeal cancer (HPC) has not been reported. METHODS: A retrospective medical record review of 156 patients with HPC treated between 1995 and 2005 was performed. Comorbid illness was measured by the Adult Comorbidity Evaluation-27. A Cox proportional hazards model was used to determine the factors related to overall survival. RESULTS: Comorbidity was absent in 55 (35.2%) of the patients, mild in 39 (25%), moderate in 28 (17.9%), and severe in 34 (21.8%). There were statistically significant differences between the survival rates in accord with age, stage, subsite, and comorbidity (45.1% for none or mild vs 27.7% for moderate or severe; p = .0073). Age, stage, and comorbidity were identified as independent prognostic factors in the multivariate analysis. CONCLUSION: Comorbidity, along with the clinical stage, should be considered in treatment planning for patients with HPC.

Voice-related quality of life after treatment of laryngeal cancer.

OBJECTIVE: To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires. DESIGN: The VRQOL and VHI-10 questionnaires. SETTING: University hospital. PATIENTS: One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey. MAIN OUTCOME MEASURE: Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires. RESULTS: The mean VRQOL scores for patients who had undergone radiotherapy (n = 63), chemoradiotherapy (n = 29), laser surgery (n = 14), or total laryngectomy (n = 27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively. CONCLUSION: The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

Constitutive activation of AKT pathway inhibits TNF-induced apoptosis in mitochondrial DNA-deficient human myelogenous leukemia ML-1a.

TNF plus protein synthesis inhibitor cycloheximide-induced apoptosis in human myelogenous leukemia ML-1a but not in C19, respiration minus mitochondrial DNA-deficient C19 cells, derived from ML-1a. To investigate how mitochondrial DNA depletion inhibits apoptosis, we investigated AKT. Both AKT and its phosphorylated form were observed only in C19, indicating that depletion of mtDNA increased protein and the active form of AKT. Treatment of C19 with LY294002, which inhibits PI-3 kinase and inhibits AKT, significantly increased apoptosis induction by TNF plus cycloheximide and eliminated phosphorylation of AKT. These results indicate that AKT activation was induced by the depletion of mtDNA and inhibited TNF-induced apoptosis.

Differentially expressed genes associated with CIS-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and CDNA microarray.

BACKGROUND: The mechanism by which cancer cells become resistant to cis-Diamminedichloroplatinum (II) (cDDP) is not completely understood. To investigate the molecular markers involved in the cDDP resistance, we compared the gene expression profiles between a head and neck squamous cell carcinoma (HNSCC) line sensitive to cDDP and its cDDP-resistant variant. METHODS: Both a fluorescent differential display and a cDNA microarray analysis were applied to distinguish the gene profiles between KB, a human HNSCC line, and its cDDP-resistant variant (KB/cDDP). These results were confirmed by Northern blot analysis. RESULTS: One up-regulated gene, glycoprotein hormone alpha-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells. CONCLUSIONS: Our findings suggest that development of the cDDP-resistant phenotype is accompanied by alternations of gene expression including a glycoprotein hormone and membrane proteins. These gene products could be new molecular markers for resistance to cDDP.

Expression of tenascin-C long isoforms is induced in the hypothalamus by FGF-1.

Fibroblast growth factor (FGF)-1 modulates various brain functions, such as the hypothalamic control of feeding. In the rat, we examined the effect of intracerebroventricularly infused FGF-1 on the hypothalamic expression of tenascin-C, a selective mediator of neuron-glial interaction. In situ hybridization revealed little tenascin-C mRNA expression in control brains, but greatly increased expression in ependymal cells around the third ventricle in the FGF-1-infused rats. Reverse transcription-linked PCR analysis of hypothalamic mRNA revealed an FGF-1-induced expression not of the shortest isoform of tenascin-C, but of the long isoforms (with additional fibronectin type III-domain insertions). Quantitative analysis by real time PCR revealed that this induction was transient and dose-dependent. Specific modulation of hypothalamic neuron-glial interactions by tenascin-C may mediate FGF-1-induced feeding suppression.