The management of influenza has dramatically changed since the introduction of the rapid influenza diagnostic test, or RIDT, and neuraminidase inhibitors (NI). However, it is still far from optimal due to low RIDT sensitivity and problems involving NI such as side effects and the potential emergence of resistant virus.Therefore, we developed a decision-making model for the management of influenza, which includes Kampo medicines in its strategies. First, the severity of patients is evaluated. If a patient is judged at severe or high-risk, intravenous NI would be the main component of treatment. If a patient has neither a severe condition nor is at high-risk, the patient would be asked to choose either NI or Kampo medicine. In the former, RIDT would be used if pretest probability was less than 50%, but it would not be used if it was more than 50%, based on the lack of influence on the post-test probability. For the latter, RIDT would be not used in general as Kampo targets “phenomena”, not the virus per se. This model enables us to optimize the use of RIDT by appropriately selecting patients based on the characteristics of RIDT, and by avoiding unnecessary tests and their misinterpretation.

We performed the Senning operation and pulmonary valvotomy in an 11-month-old baby with transposition of the great arteries (TGA) with an intact ventricular septum (IVS), and bicuspid pulmonary valvular stenosis associated with pulmonary hypertension (PH). Preoperative catheterization showed a pressure gradient (PG) between the left ventricle (LV) and main pulmonary artery (MPA) of 35mmHg, mean pulmonary artery pressure (MPAP) of 56mmHg, and pulmonary vascular resistance (PVR) of 11.2unit·m². The pure oxygen inhalation test showed a decrease in MPAP from 56 to 38mmHg, and a decrease in PVR from 11.2 to 5.5 unit·m². We could not perform lung biopsy to determine the surgical indications in terms of PH due to preoperative progressive congestive heart failure in this patient. Postoperative catheterization (28 days after the Senning operation) showed a decrease in PG between the LV and MPA to 8mmHg, and MPAP also decreased to 17mmHg. Two radical operations were possible in this patient. One was the arterial switch operation (ASO), and the other was the atrial switch operation, i. e. the Senning or the Mustard operation. We selected the Senning operation because there was the possibility that the new aortic valve might develop persistent stenosis and regurgitation after ASO and pulmonary valvotomy. The Senning operation may be an alternative in selected patients with TGA with IVS and pulmonary valvular stenosis.

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigeniccapacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs.METHODS:Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44,EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJgenes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM).RESULTS:The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathwayPtch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal markerVimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited.CONCLUSION:EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.

Intestinal spirochetosis is a rare gastrointestinal infection caused by Brachyspira. Clinical manifestations vary, ranging from asymptomatic infection to gastrointestinal bleeding, diarrhea, or abdominal pain. Antimicrobial medications such as metronidazole are routinely given, but their clinical efficacy has not determined with any precision. We report a case of intestinal spirochetosis treated with daikenchuto extract with literature reviews. Treatment of intestinal spirochetosis can be difficult, and use of daikenchuto extract may be an option especially for patients with symptoms such as chronic diarrhea, abdominal distention, or change in flatus.

We performed exercise intervention for 12 weeks in young females (22.3±2.5 yrs ; mean±SD) with a %fat value of 30% or more (dual energy X-ray absorptiometry : DXA) despite a body mass index (BMI) of less than 25 kg/m², which indicates hidden obesity, and the following results were obtained.The intensity of exercise was established as the double product break point calculated from heart rate and systolic blood pressure, and the subjects were instructed to exercise for 30 minutes or more for 3 or more times a week. Six weeks after exercise intervention, the BMI, body fat level, and plasma glucose level were lower than those before exercise intervention, and the %fat value was lower 12 weeks after intervention. Furthermore, cardiac autonomic function (CAF) was negatively correlated with changes in Total power and changes in fat (kg), suggesting that exercise-related improvement in CAF is involved in a decrease in %fat.

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigenic capacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs. METHODS: Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for 14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44, EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJ genes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM). RESULTS: The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathway Ptch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal marker Vimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited. CONCLUSION: EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.

OBJECTIVE: The aim of this study was to investigate the risk and recurrence of early invasive adenocarcinoma of the cervix, and to determine whether non-radical methods of management could be performed. METHODS: The medical and histopathological records of 50 patients with early invasive adenocarcinoma of the cervix treated at Keio University Hospital between 1993 and 2005 were reviewed, and compared with the literature. RESULTS: The median follow-up period was 64.3 months. The depth of stromal invasion was < or =3 mm in 33 cases and >3 mm, but < or =5 mm in 17 cases. The horizontal spread was < or =7 mm in 25 cases and >7 mm in 25 cases. One of the 33 cases that had tumor volumes of < or =500 mm3, and three of the 17 cases with tumor volumes of >500 mm3 were positive for lymph node metastasis. When our data were combined with previously reported results, statistically significant differences were observed between the tumor volume and the frequency of pelvic lymph node metastasis/the rate of recurrence (p<0.0001). The frequency of pelvic lymph node metastases was significantly higher in the lymphovascular space invasion (LVSI)-positive group than in the LVSI-negative group (p=0.02). No adnexal metastasis or parametrial involvement was noted. CONCLUSION: Assessment of the depth of stromal invasion, tumor volume, and LVSI is critical for selecting an appropriate therapeutic modality. Non-radical methods of management are considered suitable for patients with LVSI-negative adenocarcinoma of the cervix exhibiting a stromal invasion depth of < or =5 mm and a tumor volume of < or =500 mm3.
Adenocarcinoma ; Cervix Uteri ; Conization ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Recurrence ; Tumor Burden ; Uterine Cervical Neoplasms

Objective: To identify candidate predictors for the prognosis of cervical intraepithelial neoplasia 2 (CIN2) lesions and evaluate the prognostic value of the local immune response. Methods: One hundred fifteen CIN2 patients were enrolled. The percentage of p16-, minichromosome maintenance complex component 2- or apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G)-positive cells was determined immunohistochemically. Tumor-infiltrating lymphocytes (TILs) in intertumoral lesions were scored using an automated system. CIN3 disease progression and regression rates were estimated by the Kaplan–Meier method. A case-control study was conducted to screen CIN2 prognostic factors in 10 regression and 10 progression patients. Selected factors were examined in a cohort study to determine their prognostic value for CIN2. Results: Among all participants, the cumulative progression and regression rates at 60 months were 0.477 and 0.510, respectively. In the case-control study, p16- and APOBEC3G-positive cells were higher in the progression group (p=0.043, p=0.023). Additionally, CD4+ cell infiltration was enhanced in the regression group (p=0.023). The cohort study revealed a significantly increased progression rate in patients with elevated p16-positive cells (p<0.001), and increased CD4+ TIL infiltration was associated with better regression (p=0.011). Kaplan–Meier analysis according to human papillomavirus (HPV) positivity revealed a greater CIN3 development risk in HPV16-positive patients than in HPV16-negative cases. Finally, multivariate analysis identified HPV16 infection and CD4+ TIL infiltration as independent prognostic factors in CIN2 regression. Conclusion CD4+ TIL infiltration in intertumoral lesions was related with CIN2 regression. Our findings suggest CD4+ TIL infiltration may be useful for the triage of CIN2 patients.

OBJECTIVE: In cervical intraepithelial neoplasia (CIN), p16INK4a immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16INK4a immunohistochemistry and the outcomes of CIN. Here, we report p16INK4a immunohistochemistry as an effective biomarker to predict the outcomes of CIN. METHODS: p16INK4a immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16INK4a expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes. RESULTS: A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16INK4a overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16INK4a overexpression than for those not showing p16INK4a overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16INK4a overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively). CONCLUSION: p16INK4a overexpression was correlated with the outcome of CIN 1-2, and p16INK4a is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.
Cervical Intraepithelial Neoplasia ; Genotype ; Humans ; Immunohistochemistry ; Medical Records ; Retrospective Studies

Objective: Human papillomavirus subtypes are predictive indicators of cervical intraepithelial neoplasia (CIN) progression. While colposcopy is also an essential part of cervical cancer prevention, its accuracy and reproducibility are limited because of subjective evaluation. This study aimed to develop an artificial intelligence (AI) algorithm that can accurately detect the optimal lesion associated with prognosis using colposcopic images of CIN2 patients by utilizing objective AI diagnosis. Methods: We identified colposcopic findings associated with the prognosis of patients with CIN2. We developed a convolutional neural network that can automatically detect the rate of high-grade lesions in the uterovaginal area in 12 segments. We finally evaluated the detection accuracy of our AI algorithm compared with the scores by multiple gynecologic oncologists. Results: High-grade lesion occupancy in the uterovaginal area detected by senior colposcopists was significantly correlated with the prognosis of patients with CIN2. The detection rate for high-grade lesions in 12 segments of the uterovaginal area by the AI system was 62.1% for recall, and the overall correct response rate was 89.7%. Moreover, the percentage of high-grade lesions detected by the AI system was significantly correlated with the rate detected by multiple gynecologic senior oncologists (r=0.61). Conclusion Our novel AI algorithm can accurately determine high-grade lesions associated with prognosis on colposcopic images, and these results provide an insight into the additional utility of colposcopy for the management of patients with CIN2.