Electrophysiologic Studies and Radiofrequency Catheter Ablation of Ectopic Atrial Tachycardia in Children

Ectopic atrial tachycardia (EAT) often resists medical therapy, making radiofrequency catheter ablation (RFCA) the preferred treatment. This study reviewed the records of 35 patients who underwent electrophysiologic studies (EPS) and 39 RFCA procedures for EAT during a 10-year period. Of the 35 patients, 10 (28%) presented with decreased ventricular function and tachycardia-induced cardiomyopathy (TIC). The EAT originated on the right atrial side in 19 patients (54%) and on the left atrial side in the remaining 16 patients (46%). The right atrial sites included the right atrial appendage (RAA) (n = 9, 25%), the tricuspid annulus (n = 7, 20%), and the crista terminalis (n = 3). The left atrial sites included the left atrial appendage (LAA) (n = 6, 17%), the pulmonary veins (n = 5, 14%), the mitral annulus (n = 3), and the posterior wall of the left atrium (n = 2). The mechanism of all EAT probably is automaticity. All EATs could be abolished using RFCA. Follow-up data were available for all patients 2 to 8 years after RFCA. All 35 patients remained recurrence free, and ventricular function improved for all 10 patients with TIC. The origin of EAT in children differed from its origin in adults. The authors conclude that RFCA is a safe and effective treatment option for children with refractory EAT and should be considered early in the course of their illness.     

A case of congenital high airway obstruction syndrome managed by ex utero intrapartum treatment: case report and review of the literature

Congenital high airway obstruction syndrome (CHAOS) has been reported to be fatal. Ten cases of CHAOS that underwent ex utero intrapartum treatment (EXIT) procedure to secure the fetal airway have been reported. A 36-year-old woman (gravida 3, para 2) was referred to our hospital at 22 weeks of gestation. Sonography revealed large echogenic lungs, flattened diaphragm, and marked hydrops. Magnetic resonance imaging confirmed the diagnosis of CHAOS. Polyhydramnios and fetal skin edema were improved and the fetal ascitic fluid was regressed gradually. At 36 weeks of gestation, an EXIT procedure was undertaken. Fetal laryngoscopy and bronchoscopy showed complete laryngeal obstruction, and a tracheostomy was performed immediately. The infant was discharged from hospital at 6 weeks of age. Thereafter, he developed well both physically and mentally. A laryngoplasty was performed at 20 months of age using silicon sheet as a patent airway. The child has a tracheostomy, is able to phonate but does not speak, and is awaiting decannulation. Use of the EXIT procedure in CHAOS cases offers the potential for salvage and excellent long-term outcome of these fetuses that otherwise would not survive. However, management of the airway, particularly with regard to long-term reconstruction in children with CHAOS, remains challenging.     

Niemann-Pick C1-like 1 overexpression facilitates ezetimibe-sensitive cholesterol and beta-sitosterol uptake in CaCo-2 cells

Previous in vivo studies including those with knockout mice suggested that Niemann-Pick C1-like 1 (NPC1L1) plays an essential role in the intestinal absorption of cholesterol. To characterize the mechanism of cholesterol uptake mediated by NPC1L1, an in vitro system reflecting the function of this transporter needs to be established. In the present study, we constructed NPC1L1 overexpressing CaCo-2 cells as an in vitro model and characterized the transport properties of NPC1L1. Immunohistochemical staining revealed that CaCo-2 cells express NPC1L1 on the apical membrane. It was also demonstrated that the uptakes of both cholesterol and beta-sitosterol are increased by NPC1L1 overexpression. In addition, the uptake of cholesterol was increased in a dose-dependent manner by an increase in the content of taurocholate in micelles, whereas micellar phosphatidylcholine showed a negative correlation with cholesterol uptake. Furthermore, it was confirmed that sterol uptake increased by NPC1L1 overexpression was inhibited by ezetimibe. We could thus establish an in vitro intestinal model to study the mechanism of NPC1L1-dependent sterol uptake and to screen drug candidates whose target is NPC1L1.     

Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases

BACKGROUND: Removal of the primary lesion with a clear operative margin is the standard treatment for gastrointestinal stromal tumor (GIST) of the stomach. However, there are few reports on the operative indications for relatively small GIST. METHODS: Clinicopathologic features and survival data of all 60 patients with GIST of the stomach treated at Keio University Hospital from 1993 to 2004 were analyzed. Laparoscopic wedge resection was used as the primary procedure for tumors between 2 to 5 cm. Tumors larger than 5 cm were resected by laparotomy or laparoscopy-assisted operation. RESULTS: Thirty-five lesions (58.3%) were resected by laparoscopic wedge resection, 3 by laparoscopic operation with a small skin incision and 22 by conventional open procedures. The mean size of the tumors was 42.5 mm, with a range of 18 to 150 mm and a median value of 35.5 mm. All operative margins were clear, but 1 patient had liver metastases at the time of resection of the primary lesion. The median follow-up period was 53 months and the 5-year disease-free survival rate (DFS) was 96.1%. No local recurrence or distant metastasis was encountered in patients with tumors smaller than 4 cm. A statistically significant correlation was observed between tumor size and mitotic count in this cohort (P = .010). Tumors from the intermediate- (n = 14) and high-risk (n = 10) groups as classified by the Risk Assessment Classification showed significantly worse DFS than the low-risk and very low risk group (n = 35) (89.9% vs 100% in 5-year DFS, P = .045). Even among tumors smaller than 3 cm, 2 of 14 cases (14.3%) were classified into the intermediate-risk group. CONCLUSIONS: Although a prospective randomized trial remains to be performed, this study provides additional evidence suggesting that the early removal of GIST, at 5 cm or less in size, provides better DFS than later removal of the tumor at a larger size.     

Calcium oxalate saturation in dialysis patients with and without primary hyperoxaluria

Calcium oxalate supersaturation of the blood is associated with deposition of crystals in various tissues. We measured the serum levels of oxalate, citrate, calcium, and magnesium to estimate their saturation in 112 hemodialysis patients without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum levels of oxalate and citrate were determined by high-performance capillary electrophoresis, while calcium and magnesium were measured by ICP spectroscopy. The serum levels of oxalate, citrate, calcium, and magnesium were 44.9±16.5, 138.1±54.9 μmol/l, 2.30±0.28, and 1.07±0.18 mmol/l, respectively, while the levels in patients with primary hyperoxaluria were 83.9±34.3, 197.9±63.5 μmol/l, 2.53±0.15, and 1.14±0.34 mmol/l, respectively. Serum calcium oxalate saturation (SS), as calculated by the Equil program, was significantly correlated with the serum oxalate level. Most patients showed metastable supersaturation (1<SS<8.9), which was associated with a serum oxalate level of more than 30 μmol/l. Serum saturation exceeded the formation product (SS=8.9) in some specimens from patients with type 1 primary hyperoxaluria. The serum calcium oxalate saturation [SS(CaOx)] showed a significant positive correlation with the levels of oxalate [Ox], calcium [Ca], and citrate [Cit]: (all mmol/l, r=0.9848, P<0.01). This formula is useful for estimating the saturation. In conclusion, the serum oxalate level is a good indicator of calcium oxalate saturation and should be monitored accurately while keeping it lower in dialysis patients.     

The combination of cisplatin and vinorelbine with concurrent thoracic radiation therapy for locally advanced stage IIIA or IIIB non-small-cell lung cancer

Aims: The aims of this study were to assess the efficacy and toxicity of concurrent chemoradiotherapy with divided schedule of cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: Patients with previously untreated, unresectable, and stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Twenty-six patients (24 men and 2 women; median age, 66 years; age range, 42–75 years) were enrolled. Both cisplatin (40 mg/m²) and vinorelbine (20 mg/m²) were given on days 1 and 8 every 3 weeks. Beginning on day 2 of chemotherapy, thoracic radiotherapy was given for approximately 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results: Five of the 26 patients achieved a complete response, and 16 achieved a partial response for an overall response rate of 80.8% (95% confidence interval, 60.6–93.4%). The median survival time was 23 months (range, 4–43 months). Overall survival rates at 1 and 2 years were 80 and 56%, respectively. Hematologic toxicities included grade 3–4 neutropenia in 84.6% of patients, grade 3–4 thrombocytopenia in 3.8%, and grade 3–4 anemia in 61.5%. Two patients (7.7%) had grade 3 radiation esophagitis that resolved completely without dilation. Grade 3–4 radiation pneumonitis occurred in two patients (7.7%) and was treated with corticosteroids. Both patients had a good partial resolution of symptoms and radiographic abnormalities. There were no treatment-related deaths. The actual delivered dose intensities for both cisplatin and vinorelbine were 79.5%. Radiotherapy was completed in 96% of patients. Conclusion: Concurrent chemoradiotherapy with cisplatin and vinorelbine administered on a divided schedule is effective and well tolerated in patients with locally advanced NSCLC.     

Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer: comparison of two different definitions of PSA failure

Background We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Methods Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4–430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. Results The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the “nadir plus 2” definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Conclusion Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial.     

Cancer research with non-coding RNA

Cancer research is not limited to medical research; it expands over several disciplines, incorporating molecular bioscience at both the macro and micro levels. All stages and aspects of cells, from development and differentiation, apoptosis, cell adhesion and many more, are research fields with a connection to cancer. Cancer research in itself is the research of cancer cures. Recently, not only cancer but also bioscience research has surfed on the new wave of RNA knowledge. Most of those RNAs are non-protein-coding RNAs and are connected to cell development and differentiation, and thereby with cancer differentiation and treatment. Here we would like to introduce the latest in cancer research that has emerged from the field of molecular biology research.