Homepage of the Month

Homepages are redesigned or modified very frequently; therefore,please note that comments in this section are based on the contentsof the homepage at the time of writing. View larger version (55K): [in this window] [in a new window]     View larger version (38K): [in this window] [in a new window]     View larger version (81K): [in this window] [in a new window]     The UK National Cancer Research Institute (http://www.ncri.org.uk) National Cancer Research Network (http://www.ncri.org.uk/includes/ncrn.htm) National Translational Cancer Research Network (http://www.ntrac.org.uk/) The National Cancer Research     

Three approaches to surgical treatment of traumatic disruption of the thoracic aorta

Traumatic disruption of the thoracic aorta is said to occur most often near the aortic isthmus because of the mechanisms of aortic injury. Between November 1990 and August 1999, we encountered eight cases of surgical treatment for traumatic injury of the thoracic aorta combined with multi-system injury. In some cases, the injury was located near the aortic isthmus; in such cases, we selected surgical options that made use of three different approaches, namely, media sternotomy, posterolateral left thoracotomy, and anteroaxillal thoracotomy. Each approach has advantages and disadvantages. In selecting an appropriate approach, it is not only necessary to consider the various features of the approach itself, but it is also necessary to consider other factors, such as the assisting apparatus in use, the effects of other injuries sustained by perioperative positioning, safety measures against accidental bleeding during surgery, deployment of the operative field, and potential complications after surgery.     

Validation of the Proximal Isovelocity Surface Area Method for Assessing Mitral Regurgitation in Children

The proximal isovelocity surface area (PISA) method for calculating volume flow through the regurgitant orifice has attracted significant attention. A number of in vitro studies and clinical studies in adults suggest that the method is accurate. However, when applying the method to children it must be noted that the absolute regurgitation volume is small, and the range of body sizes is wide. This study investigated the accuracy of the PISA method for quantitative assessment of the severity of mitral regurgitation in children. Twenty children aged 7 months to 12 years (average 4.7 years) with mitral regurgitation but without interventricular shunt or aortic stenosis were selected for this study. Underlying cardiac diseases included atrioventricular septal defects in nine, isolated mitral regurgitation in five, and association with other heart defects in six. The PISA radius (r) and the duration of regurgitation (T) were measured on color M-mode recordings, with the M line passing through the center of the PISA. Assuming that the PISA is a hemisphere, maximal regurgitant flow rate (MFR: ml/s) was calculated as MFR = 2π×~ r ²×~ V (r= maximal radius, V= aliasing velocity), and regurgitant stroke volume (RSVpisa) as RSVpisa = 2π×~ MSR ×~ V×~ T (MSR = mean square of the PISA radius during regurgitation). As a validating standard, total stroke volume (TSV) using two-dimensional echocardiography determined by the area–length volumetry method and forward stroke volume (FSV) by the pulsed Doppler method were measured, and regurgitant stroke volume (RSV_D: RSV_D= TSV − FSV) and regurgitant fraction (RF: RF = RSV_D/TSV) were calculated. A linear correlation was found between MFR, RSVpisa, and RSV_D (X) (MFR = 4.2X + 54.0, r= 0.84. RSVpisa = 1.0X + 9.8, r= 0.90), and both RSVpisa and MFR divided by body surface area (BSA: m²) revealed a significant correlation with regurgitant fraction (X) by nonlinear regression analysis (RSVpisa/BSA = 26.2 ×~ X/(1 − X) + 16.8, r= 0.85. MFR/BSA = 121.8 ×~ X/(1 − X) + 92.2, r= 0.79). It is concluded that maximal regurgitant flow rate, regurgitant stroke volume, and regurgitant fraction can be accurately predicted in children using the PISA method by Doppler echocardiography.     

The involvement of neuropeptide Y in the antimuricide action of noradrenaline injected into the medial amygdala of olfactory bulbectomized rats

The present study was designed to clarify the functional role of neuropeptide Y (NPY) in the regulation of muricide induced by olfactory bulbectomy (OB) in relation to that of noradrenaline (NA) in the medial amygdala (AME). NA injected into AME inhibited muricide dose-dependently in OB rats. NPY at doses of 5 and 10 micrograms/microliter injected alone into AME failed to suppress muricide. When NPY 10 micrograms was injected into AME in combination with the maximal non-effective dose of NA, which was determined in each rat, muricide was suppressed in 80% of OB rats. The present study has provided the first evidence suggesting that NPY may be involved in the regulation of OB-induced muricide.     

Disturbance of SHH signalling pathway during early embryogenesis in the cadmium-induced omphalocele chick model

Introduction

Administration of cadmium (Cd) after 60 h (H) incubation induces ventral body wall defect (VBWD) similar to the omphalocele phenotype in the chick embryo. In this model, the earliest histological changes have been observed in somites commencing at 4-h post-treatment (4H). The molecular mechanism by which Cd acts in this critical period of embryogenesis still remains unclear. Sonic hedgehog (SHH) signalling plays an important role in vertebrate development, including somitogenesis and thus ventral body wall formation. Patched (PTCH), a cell membrane receptor for SHH, is expressed in somites and Patched knockout mice display somite dysfunction. Another transmembrane receptor, Smoothened (SMO), is also expressed in somites and transduces the SHH signal regulated by PTCH. We designed this study to test the hypothesis that SHH signalling is downregulated during the critical period of early embryogenesis in the Cd-induced omphalocele chick model.

Methods

After 60 h of incubation, chicks were exposed to either chick saline or 50 μL of 50 μM cadmium acetate and divided into two groups: control and Cd (n = 24 for each group). Chicks were harvested 1, 4, and 8 h post-treatment. Real-time RT-PCR was performed to evaluate the relative mRNA expression level of SHH, PTCH and SMO. Immunofluorescence confocal microscopy was then performed to evaluate protein expression/distribution of SHH, PTCH and SMO.

Results

The relative mRNA expression levels of SHH, PTCH and SMO were significantly downregulated in the Cd group compared to controls at 4H post treatment, whereas, there were no significant differences at the other time points. Immunohistochemistry revealed that the intensity of SHH, PTCH and SMO was markedly diminished at 4 h in Cd-treated embryos compared to controls.

Conclusion

Disturbance of the SHH signalling pathway as evidenced by SHH, PTCH and SMO downregulation during the narrow window of early embryogenesis may result in somite maldevelopment, contributing to the omphalocele phenotype in the Cd chick model.     

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study

New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients.     

Safety and usefulness of emergency maternal transport using helicopter

AIM: Japan has a shortage of tertiary medical care facilities for maternal and fetal medicine. Establishment of efficient medical transport systems is needed for pregnant women and fetuses with severe complications. Maternal transport by helicopters is expected to shorten transportation time to advanced facilities, although its feasibility has not yet been evaluated. The aim of the present study was to investigate the status of maternal helicopter transport, and conditions of the pregnant patients and children transferred by helicopter to Kameda Medical Center (KMC). METHODS: Between August 2005 and July 2006, 26 pregnant women were transported by helicopters to KMC. RESULTS: The median net flight time was 24 min (range 15-29 min), and the median of estimation of ground transportation time was 125 min (range 90-180 min). The causes for transfers were preterm labor in eight, preterm premature rupture of the membrane in five, cervical incompetence in five, pre-eclampsia in three and other medical reasons in five. Five of the 26 patients were discharged with restored stability of pregnancy. The remaining 21 patients underwent delivery at KMC. The median gestational age was 26 weeks (range 22-33 weeks) at the time of transfer and 31 weeks (range 22-37 weeks) at delivery. Four of 26 neonates who were born at KMC died after birth due to severe premature or congenital anomaly. Seventeen of the remaining 22 neonates, including 10 twins, received treatment in the neonatal intensive care unit. All of the 22 neonates and all the mothers were discharged in good condition. No patients developed any complications requiring treatment during flights. CONCLUSION: Helicopter transfer is feasible for pregnant patients with severe complications.     

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.