The ability of a triplex-forming oligonucleotide to recognize T-A and C-G base pairs in a DNA duplex is enhanced by incorporating N-acetyl-2,7-diaminoquinoline.

A triplex-forming oligonucleotide (TFO) can recognize the homopurine-homopyrimidine sequence in DNA duplexes and inhibit the transcription of targeted mRNAs. Recently, we reported that N-acetyl-2,7-diamino-1,8-naphthyridine (DANac), incorporated into a TFO, has high binding ability and base recognition selectivity for the pyrimidine bases in the purine-rich chain of the DNA duplex at pH 7.4. However, it was found in this study that the difference in the Tm values between the pyrimidine bases and purine bases decreased by more than 4 °C at pH 6.0-7.0. To improve the low base recognition selectivity of the TFO, we designed a new artificial base, DAQac, with a quinoline skeleton. The Tm values of the triplexes containing DAQac:T-A or DAQac:C-G were more than 13 °C higher than those of the triplexes containing DAQac:A-T or DAQac:G-C at pH 7.4. We also observed that under more acidic conditions (pH 6.0-7.0), the base recognition selectivity of DAQac in a triplex was higher than that of DANac, although the binding ability of DAQac in a triplex was similar to that of DANac. Additionally, we found that DAQac, incorporated into the TFO, could accurately recognize the MeC-G base pair in the hairpin DNA, similar to the C-G base pair.

Taxane-based combinations as adjuvant chemotherapy for node-positive ER-positive breast cancer based on 2004-2009 data from the Breast Cancer Registry of the Japanese Breast Cancer Society.

BACKGROUND: Adding taxane to an anthracycline-based regimen improves survival in node-positive breast cancer patients, as shown by clinical trials and meta-analyses. However, no studies have analyzed the number of metastatic lymph nodes in patients with estrogen receptor (ER)-positive cancer. This study investigated whether adding a taxane to an anthracycline-based regimen improved prognosis in node-positive, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients in a real-world setting. METHODS: Using Japanese Breast Cancer Society registry data, we compared disease-free survival (DFS) of patients with ER-positive, HER2-negative breast cancer, excluding those receiving neoadjuvant chemotherapy, between those who received an anthracycline-based regimen followed by a taxane-based regimen (A + T) and those who received only an anthracycline-based regimen (A w/o T), stratified by lymph node status. A Cox proportional hazards model was used to evaluate DFS in both groups. RESULTS: There were 4566 eligible patients with ER-positive, HER2-negative breast cancer. During the median follow-up period of 60 months, there were 481 recurrences and 149 deaths. There was no significant difference in DFS between the A + T and A w/o T groups among patients with 1-3 positive nodes, while there was a significant difference among patients with ≥ 4 positive nodes. CONCLUSIONS: In patients with ER-positive, HER2-negative breast cancer, adding taxane to an anthracycline regimen did not improve DFS in patients with metastasis in 1-3 lymph nodes. We considered that the group without the addition of taxane might be present in patients with ER-positive, HER2-negative lymph node metastases.

Application of artificial intelligence using a convolutional neural network for detecting gastric cancer in endoscopic images.

BACKGROUND: Image recognition using artificial intelligence with deep learning through convolutional neural networks (CNNs) has dramatically improved and been increasingly applied to medical fields for diagnostic imaging. We developed a CNN that can automatically detect gastric cancer in endoscopic images. METHODS: A CNN-based diagnostic system was constructed based on Single Shot MultiBox Detector architecture and trained using 13,584 endoscopic images of gastric cancer. To evaluate the diagnostic accuracy, an independent test set of 2296 stomach images collected from 69 consecutive patients with 77 gastric cancer lesions was applied to the constructed CNN. RESULTS: The CNN required 47 s to analyze 2296 test images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the 71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive cancers were correctly detected. All missed lesions were superficially depressed and differentiated-type intramucosal cancers that were difficult to distinguish from gastritis even for experienced endoscopists. Nearly half of the false-positive lesions were gastritis with changes in color tone or an irregular mucosal surface. CONCLUSION: The constructed CNN system for detecting gastric cancer could process numerous stored endoscopic images in a very short time with a clinically relevant diagnostic ability. It may be well applicable to daily clinical practice to reduce the burden of endoscopists.

[Pulmonary artery sling and single ventricle treated with a simultaneous operation of slide tracheoplasty, left pulmonary artery reimplantation, and bidirectional cavo-pulmonary shunt].

Pulmonary artery sling is frequently combined with tracheal stenosis, and occasionally combined with congenital heart defects. However, there are few reports of successfully treated cases that were combined with single ventricle. In this article, we report a successfully treated case of pulmonary artery sling combined with tracheal stenosis, single ventricle, pulmonary atresia, vascular ring, and bilateral superior vena cava. A male infant was referred to our hospital for central cyanosis, and was diagnosed with single ventricle (tricuspid stenosis, multiple ventricular septal defect, and hypoplastic right ventricle)with pulmonary atresia by echocardiogram. Tracheal stenosis was shown at cardiac catheterization. Pulmonary artery sling and tracheal diverticulum were diagnosed by computed tomography (CT) and magnetic resonance imaging(MRI)examination. Furthermore, the patient was complicated by vascular ring, which consisted of right aortic arch, an aberrant left subclavian artery, and patent ductus arteriosus, and this ductus arteriosus was connected to the left subclavian artery and pulmonary arterial trunk. After 6 months of medical treatment, including continuous infusion of prostaglandin, re-evaluation was performed by cardiac catheterization. We considered that bidirectional cavo-pulmonary shunt was appropriate for the patient since his pulmonary vasculature had matured well. An operation was performed under the use of cardio-pulmonary bypass. Release of vascular ring by division of the ductus, bilateral bidirectional cavo-pulmonary shunt, and a slide tracheoplasty for tracheal stenosis were performed simultaneously. His recovery was uneventful, and he is currently waiting to receive a Fontan-type operation.

Subclavian and pulmonary artery steal phenomenon in a patient with isolated left subclavian artery and right aortic arch.

We describe a patient with an isolated left subclavian artery associated with right aortic arch, patent ductus arteriosus, and ventricular septal defect. As the isolated left subclavian artery is supplied by the left vertebral artery in which blood flows in the retrograde direction, this anomaly is usually responsible for a congenital subclavian steal phenomenon. Atrophy of the left cerebral hemisphere and inverted left vertebral arterial flow were clearly depicted by echoencephalography in this patient, whose subclavian artery was connected to the main pulmonary artery by a patent ductus arteriosus.

Ratio of early diastolic tricuspid inflow to tricuspid lateral annulus velocity reflects pulmonary regurgitation severity but not right ventricular diastolic function in children with repaired Tetralogy of Fallot.

The current study assessed relationships between the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity (tricuspid E/e') and right ventricular (RV) function in children after tetralogy of Fallot (TOF) repair. The RV function of 25 asymptomatic children with surgically repaired TOF (age 3.3 ± 2.0 years) was assessed by echocardiography and cardiac catheterization. Right ventricular end-diastolic pressure and volume (RVEDP and RVEDV), systolic pressure, and ejection fraction, as well as mean pulmonary arterial pressure, mean right atrial pressure (RAP), and the severity of both pulmonary regurgitation (PR) and tricuspid regurgitation (TR) were assessed in terms of the contribution to tricuspid E/e'. Univariate analysis discovered a relationship between tricuspid E/e' and RVEDV (R(2) = 0172), pressure half-time of PR (PR-PHT) (R(2) = 0.173), and TR grade (R(2) = 0.145) (p < 0.01 for each). After multivariate adjustment, PR-PHT was significantly associated with tricuspid E/e' (ß = 0.210; p < 0.001). Tricuspid E/e' was not significantly associated with RVEDP or RAP. In conclusion, tricuspid E/e' does not indicate RV diastolic function but reflects the severity of PR in asymptomatic children after TOF repair.

A novel bilayer approach to ventricular septal deformation analysis by speckle tracking imaging in children with right ventricular overload.

BACKGROUND: The aim of this study was to evaluate functional differences between the left and right sides of the ventricular septum in children with right ventricular overload. METHODS: Radial, longitudinal, and circumferential strain on both sides of the ventricular septum were compared using speckle-tracking echocardiography in patients with preoperative atrial septal defects (n = 22), postoperative tetralogy of Fallot (n = 23) and age-matched normal controls (n = 44). The duration between peak strain of the left and right ventricular septum (TLt-Rt) was also evaluated. RESULTS: Radial and circumferential strain in the control group were significantly higher on the left than the right ventricular septum (41.3 ± 12.8% vs 22.6 ± 6.8% and -28.0 ± 5.4% vs -22.5 ± 4.8%, respectively; P < .0001 for both), whereas longitudinal strain did not significantly differ (-22.0 ± 4.9% and -20.7 ± 5.2%, respectively). TLt-Rt was 52.9 ± 35.6, 33.4 ± 29.0, and 38.7 ± 31.0 msec for radial, longitudinal, and circumferential strain, respectively. Longitudinal and circumferential strain on both sides were significantly increased in patients with atrial septal defects compared with controls (P < .05), although radial strain was similar on both sides. Radial strain on the right side was significantly increased in patients with tetralogy of Fallot compared with controls (P < .05), whereas that on the left side was significantly reduced (P < .001). Longitudinal strain on both sides was significantly decreased (P < .01 and P < .001 for the left and right sides, respectively). In addition, TLt-Rt in patients with tetralogy of Fallot was significantly increased with radial and circumferential deformation (P < .05 for both). CONCLUSIONS: Deformation of both sides of the ventricular septum functionally differed. Bilayer analysis of the ventricular septum can help in the evaluation of right ventricular performance under volume and pressure overload.

Pulmonary emphysematous changes in patients with congenital heart disease associated with increased pulmonary blood flow: evaluation using multidetector-row computed tomography.

BACKGROUND: The present study aimed to evaluate the prevalence and the location of segmental emphysematous change in congenital heart disease (CHD) patients with increased pulmonary blood flow using multidetector-row computed tomography (MDCT). METHODS: A total of 129 consecutive patients (mean age, 5.8±5.4 years; range, 1 month to 24 years) underwent MDCT angiography of the thorax. The frequency of emphysematous change was evaluated in patients with ventricular septal defect (VSD, n=61), atrial septal defect (ASD, n=27), patent ductus arteriosus (PDA, n=36) and complete atriventriclar septal defect (CAVSD, n=5). In 59 patients who underwent cardiac catheterisation, the relationships between the emphysematous change and both pulmonary to systemic blood flow ratio (Qp/Qs) and mean pulmonary arterial pressure (mPAP) were evaluated. RESULTS: The emphysematous change was detected in 57 patients (44.2%) out of 129 patients. The frequency of segmental emphysematous change in left side was higher than in right side (14.8% vs. 6.5%). Both Qp/Qs and mPAP affected the presence of emphysema. CONCLUSION: MDCT can provide accurate detection of segmental emphysema in patients with CHD. Emphysematous change is not uncommon pathological lesion in children and adolescents with CHD.

Serum concentration of heart-type fatty acid-binding protein in children and adolescents with congenital heart disease.

BACKGROUND: Serum heart-type fatty acid-binding protein (H-FABP) is widely applied as a marker of cardiac myocyte injury. Recently, it has been reported that levels of H-FABP are elevated in adult patients with chronic heart failure and thus provide useful prognostic information. The aim of the present study was to examine the relationships between serum H-FABP levels and pathophysiological characteristics in children and adolescents with congenital heart disease (CHD). METHODS AND RESULTS: Serum H-FABP levels were preoperatively and postoperatively measured in 238 consecutive patients with CHD aged 1-31 years. The relationships between H-FABP levels and severity of heart failure, circulatory status and laboratory data were cross-sectionally analyzed. Multivariate regression analysis indicated that serum H-FABP levels are independently affected by age, New York Heart Association functional class, creatine kinase MB, creatinine and arterial oxygen saturation (standard regression coefficients, -0.378, 0.237, 0.422, 0.615, and -0.210, respectively). Neither left ventricular ejection fraction nor B-type natriuretic peptide correlated with H-FABP levels. CONCLUSIONS: H-FABP could serve as a new monitoring tool to provide information that will guide the optimal therapy and management of CHD patients.

Consideration of the Pathological Features of Pediatric Congenital Heart Diseases Which Are Ideally Suitable for Diagnosing With Multidetector-row CT.

BACKGROUND: A lots of articles published regarding the usefulness of multidetector-row computed tomography (MDCT) in children with congenital heart disease (CHD) mostly describe that it can be an alternative to the invasive catheterization and angiography. The unique diagnostic features of this imaging modality have been largely ignored or disregarded. We described the pathological conditions that cannot be diagnosed by conventional angiography with cardiac catheterization but can be accurately diagnosed by MDCT. METHODS: We retrospectively reviewed non-ECG-gated MDCT images acquired from 452 children and young adults with CHD between 2005 and 2010 in our institute. In this article, we focused on the diagnostic advantages of MDCT, and indicated five pathological conditions. (1) When Blalock-Taussig shunt total occlusion prevents catheter insertion into the artificial vessel and angiography is ruled out, the peripheral pulmonary artery during the peripheral pulmonary artery can be imaged and diagnosed using MDCT based on blood flow supplied from many small collateral vessels originating from the aorta. (2) The location and protrusion of the device in the vessel after coil embolization to treat patent ductus arteriosus can be accurately visualized by virtual endoscopy using MDCT. (3) Calcification of patches, synthetic blood vessels, and other prostheses that is indistinct on conventional angiograms is clear on MDCT. (4) Simultaneous MDCT observations of the anatomical relationships between arterial and venous systems on the same image can clarify the detail diagnosis for surgical treatment. (5) Compression of the airways by the great vessels and pulmonary segmental emphysematous change can be diagnosed by MDCT. RESULTS AND CONCLUSIONS: Among patients with CHD, MDCT is useful not only as a non-invasive alternative to conventional angiography, but also as a tool for specific morphological diagnoses. In the future, it will be necessary to accumulate experience in the recognition of cardiovascular conditions under which MDCT is necessary and to perform as the appropriate examination.

Telomerase activity of blood samples and recurrence of colorectal cancer.

BACKGROUND/AIMS: Recurrence, which occurs in about 20-30% of colorectal cancer patients after curative surgical treatment, is an important factor in determining prognosis. Therefore, early detection and prediction of recurrence is an important issue in the treatment of the disease. Telomerase is a reverse transcriptase that synthesizes telomere DNA, thereby compensating for telomere loss that occurs with each replication cycle, and limits proliferation cells. Telomerase is expressed in the majority of primary human tumors and hTERT is considered one of the most important proteins affecting telomerase activity. We evaluated telomerase activity in mesenteric and peripheral blood samples in addition to hTERT expression in cancerous tissues by means of immunohistochemistry in 120 patients who underwent curative surgical treatment at our department. METHODOLOGY: We investigated the factors correlated with recurrence. RESULTS: In univariate analysis, we found recurrence was significantly correlated with positive telomerase activity in the mesenteric vein (p=0.0021), positive telomerase activity in the peripheral vein (p=0.0032), histological type except well differentiated adenocarcinoma (p=0.0013), lymphatic infiltration (p=0.044), lymph node metastasis at surgery (p<0.0001), positive CEA (p=0.0004) and negative TERT immunoreactivity (p=0.012). In multivariate analysis, we found lymph node involvement at surgery (p=0.0045, hazard ratio: 6.21) and positive telomerase activity in peripheral vein (p=0.037, hazard ratio: 3.13) were significantly associated with the existence of recurrence. CONCLUSIONS: Our results show that measuring telomerase activity in peripheral blood samples is effective in predicting future recurrence to a degree greater than macroscopically examined tumor depth or other clinicopathological parameters.

An uncommon case of diabetic mastopathy in type II non-insulin dependent diabetes mellitus.

Diabetic mastopathy is an uncommon tumor-like proliferation of fibrous tissue of the breast that usually occurs in a patient who has suffered from type I diabetes mellitus of long duration. Here we report a rare case of diabetic mastopathy that occurred in type II non-insulin dependent diabetes mellitus. This patient was a 63-year-old postmenopausal woman. Mammography, ultrasonography and MR imaging could not distinguish it from breast cancer. Although the core needle biopsy specimen showed fibrosis without evidence of malignancy, excisional biopsy was performed. Histological findings demonstrated typical diabetic mastopathy with keloid-like fibrosis, perivascular lymphocytic infiltration, and lymphocytic lobulitis without evidence of malignancy. These lymphocytes were composed predominantly of B-cells. Five months after surgical biopsy, a nodular formation approximately 4 cm in diameter recurred adjacent to the resected end of the biopsy.

Telomerase subunit immunoreactivity and recurrence in colorectal cancer.

BACKGROUND/AIMS: Telomerase is expressed in human germ tissues and in the majority of primary human tumors. The catalytic subunit of telomerase, hTERT is one of the most important components of telomerase. In this study we attempted to show by means of immunohistochemistry the association between hTERT expression and recurrence in 128 colorectal cancer patients surgically treated in the University of Tokyo Hospital. METHODOLOGY: Immunostaining was performed in a conventional manner using a commercial monoclonal antibody. RESULTS: In our results, negative TERT immunoreactivity in the primary lesion was significantly associated with advanced tumor stage (p=0.0007), the presence of lymph node metastasis (p=0.00018) and recurrence (p<0.0001). Recurrence-free survival rate was significantly lower in patients with negative TERT immunoreactivity (p=0.0002). In the same way, if limited in patients without metastatic lymph nodes at surgery or in patients with T3 or T4 tumor, the recurrence-free survival rate was significantly lower in those with negative TERT immunoreactivity (p=0.019, p=0.016). CONCLUSIONS: Negative TERT immunoreactivity may be a novel indicator for poor prognosis of colorectal cancer patients and additional studies with a larger number of patients may lead to identifying patients at high risk for recurrence more accurately.

Detection of cancer cells in mesenteric vein and peripheral vessels by measuring telomerase activity in patients with colorectal cancer.

BACKGROUND: Liver metastasis is an important factor determining prognosis in colorectal cancer. The objective of this study was to assess whether colorectal cancer cells in the drainage veins can be detected by measuring telomerase activity and its detection is correlated with liver metastasis. METHODS: Telomeric repeat amplification protocol assay in combination with an immunomagnetic sorting was used for measuring telomerase activity of epithelial cells in blood samples collected from mesenteric (tumor-drainage) vein and peripheral vessels of 41 colorectal cancer patients. Telomerase activity was calculated as relative telomerase activity (RTA) against a control template and analyzed in terms of liver metastasis. RESULTS: RTA of mesenteric blood samples was significantly higher in patients with liver metastasis (60.8%; n=7) than in those without metastasis (19.7%; n=34; P=.019). The RTA of peripheral blood sample was also higher in patients with liver metastasis (26.8%) than in those without metastasis (11.1%; p=.17). Moreover, 57% of cases with liver metastasis exhibited a positive telomerase activity in mesenteric blood sample, whereas it was 18% in cases without metastasis. CONCLUSIONS: Our assay was proven to be a feasible method for detecting cancer cells in tumor-drainage veins. High telomerase activity of mesenteric blood samples reflected the existence of liver metastasis of colorectal cancer.