A multi-centered epidemiological study evaluating the reliability of the treatment difficulty indices developed by the Japan Prosthodontic Society

BackgroundThe diagnostic assessment of the level of difficulty in treating patients who need prosthodontic care is useful to establish a medico-economically efficient system with primary care dentists and prosthodontic specialists.Materials and methodsA multi-axis assessment protocol was established using the newly established treatment difficulty indices. The protocol contains Axis I: oral physiological conditions (e.g., teeth damage and/or missing teeth); Axis II: general health and sociological conditions (e.g., medical disorders); Axis III: oral health-related quality of life (OHRQOL; e.g., oral health impact profile: OHIP); and Axis IV: psychological health (e.g., mood, anxiety, somatoform disorders). A preliminary study on the test–retest consistency of the protocol was conducted to check the levels of reliability of the indices prior to a large-scale, multi-center cohort study on the validity of the protocol.ResultsThe test–retest consistency in terms of the oral physiological condition (Axis I) after data reduction was 0.63 for patients with teeth problems, 0.95 for partially edentulous patients, and 0.62 for edentulous patients. The reliability for general health and sociological conditions (Axis II), OHRQOL (Axis III), and psychological health (Axis IV) were 0.88, 0.74, and 0.61, respectively. These values reflect either “sufficient agreement” or “excellent agreement” in accordance with the criteria established by Landis and Koch (1977) [1].ConclusionThis protocol is the first multi-axis assessment scheme introduced for prosthodontic treatment with sufficient reliability. This new system is therefore expected to have a significant impact on future dental diagnostic nomenclature systems.     

Synergistic anti-tumor effects of RAD001 with MEK inhibitors in neuroendocrine tumors: a potential mechanism of therapeutic limitation of mTOR inhibitor

Mammalian target of rapamycin (mTOR) inhibitors have been clinically used as anticancer agents in several types of human malignancies including neuroendocrine tumor (NET) but the development of clinical resistances or their therapeutic limitations have been also reported. This clinical resistance has been proposed to be partly due to a compensatory activation of an mTOR upstream factor Akt and MEK/ERK pathway in NET cells but its details have not necessarily been reported. Therefore, in this study, we examined the effects of mTOR inhibitors on these activations and of the concomitant treatment of mTOR and MEK inhibitors in two NET cell lines, NCI-H727 and COLO320. We evaluated the effects of RAD001, mTOR inhibitor, and U0126, MEK inhibitor, on cell proliferation and migration of these cells. In addition, an alteration of the factors involved in Akt/mTOR and MEK/ERK pathways was also examined under administration of these agents. RAD001 and U0126 treatment significantly inhibited cell proliferation and their combined treatment synergistically decreased it in both cell lines. Additionally, these treatments above decreased the expression of cell cycle-related factors, suggestive of an involvement of cell cycle arrest in therapeutic effects. The combined treatment also inhibited the cell migration in NCI-H727 via the decrement of MMP2 and 9 in an additive manner. We demonstrated the potential synergistic/combined effects of inhibitors of mTOR and MEK on cell proliferation and migration. These results suggest the potential therapeutic efficacy of the combined therapy of mTOR and MEK inhibitors or a dual inhibitor for the treatment of NET patients.     

Inhibition of common cold-induced aggravation of childhood asthma by leukotriene receptor antagonists

Background: Virus infection is an important risk factor for aggravation of childhood asthma. The objective of this study was to examine the effect of drugs on aggravation of asthma induced by a common cold. Methods: Asthma control was examined in a survey of 1,014 Japanese pediatric patients with bronchial asthma. The occurrence of common cold, asthma control, and drugs used for asthma control were investigated using a modified Childhood Asthma Control Test (C-ACT) for patients aged <4 years old and 4 to 11 years old, and an Asthma Control Test (ACT) for patients aged 12 to 15 years old. Results: The status of asthma control did not differ among the age groups. The prevalence of common cold and aggravation of asthma were significantly higher in patients aged <4 years old. Control of asthma following common cold-induced aggravation was significantly less effective in patients aged <4 years old compared to those aged ≥4 years old. In patients aged <4 years old with a common cold, asthma control was significantly more effective for those treated with leukotriene receptor antagonists (LTRAs) compared to treatment without LTRAs. Asthma control did not differ between patients who did or did not take inhaled corticosteroids or long-acting β2 stimulants. Conclusions: These findings showed a high prevalence of common cold in younger patients with childhood asthma and indicated that common cold can induce aggravation of asthma. LTRAs are useful for long-term asthma control in very young patients who develop an asthma attack due to a common cold.     

Synchronous double cancers of primary hepatic adenosquamous carcinoma and hepatocellular carcinoma: report of a case

A 76-year-old male was referred for the treatment of liver tumors detected by abdominal computed tomography (CT). Dynamic CT revealed a low-density tumor with an irregularly enhanced rim in the left lateral sector, and a highly enhanced, well-circumscribed tumor in the caudate lobe, accompanied by dilation of the intrahepatic biliary ducts in the left lobe. Preoperative imaging studies led to the diagnosis of double cancers consisting of intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC). Left hemihepatectomy with caudate lobectomy was performed. The postoperative course was uneventful. Microscopic evaluation revealed that the tumor in the left lateral sector was adenosquamous carcinoma (ASC), whereas that in the caudate lobe was HCC. This report presents the first case describing the resection of synchronous double cancers of primary hepatic ASC and HCC.     

Spontaneous remission in children with IgA nephropathy

Background

Some patients with IgA nephropathy (IgAN) achieve spontaneous remission even when not receiving medication. However, details on such remissions remain unknown. The aim of our study was to clarify this information in the clinical setting of childhood IgAN with minor glomerular abnormalities or focal mesangial proliferation (MGA/FMP).

Methods

This study was a retrospective analysis of 96 children with MGA/FMP who did not receive medication from among the 555 patients with newly diagnosed childhood IgAN treated between January 1972 and December 2000. The Kaplan?CMeier method and Cox proportional hazard model were used for the analysis.

Results

Of the 96 pediatric patients who did not receive medication, 57 (59.4?%) achieved spontaneous remission. The cumulative spontaneous remission rates among these patients were 57.5? and 77.4 % at 5?and 10 years, respectively, from onset. The mean time from onset to remission was 5.9?±?0.4?years. Clinical and histological findings were similar between the remission and non-remission groups. Of the 57 patients with spontaneous remissions, ten (17.5?%) also developed a recurrence of urinary abnormalities. The cumulative recurrence-free rates were 79.9?and 67.9 % at 5 and 10?years, respectively, after remission.

Conclusions

The spontaneous remission rate in childhood IgAN with MGA/FMP was higher than expected. Our results suggest that physicians should consider the potential for spontaneous remission and refrain from very aggressive treatment in IgAN patients with MGA/FMP.     

<Emphasis Type="Italic">KRAS</Emphasis> and <Emphasis Type="Italic">BRAF</Emphasis> Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review

Background

Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing.

Methods

The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay.

Results

The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs.

Conclusions

These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.

     

Submental perforator flap: Location and number of submental perforating vessels

The sites and numbers of submental perforator vessels were examined using a Doppler probe in 21 volunteers. The subcutaneous vascular network from each perforator was studied in three cases of dissection of upper-neck lymph nodes among the volunteers. A perforator from the submental vessels was noted in all 21 volunteers: a single perforator in 13 cases, and double perforators in eight. The main perforator, which had some subdermal branches, was located 31.8 (8.3) mm in front of the facial artery that was palpated at the mandible. Five patients who presented with skin defects on the cheek and the chin had the submental perforator flap reconstructed, excluding the platysma muscle. All flaps covered the wounds. The submental perforator flap was useful for reconstructing skin defects on the cheek and the chin, because the site of the submental perforator was stable and raising the flap was easy, and the colour and texture matches were acceptable.