Clinical significance of angiogenesis in rectal carcinoid tumors

This study was designed to examine angiogenesis in rectal carcinoid tumors in relation to the clinicopathologic features. Seventy-seven rectal carcinoid tumors were studied clinicopathologically and experimentally. Cellular proliferation and microvessel density (MVD) were examined immunohistochemically. We used the antibodies MIB-1 for Ki-67, DO7 for p53, and NU-4A1 for CD34 expression in this study. Ki-67 labeling index (LI) of all lesions was below 3%, and the median Ki-67 LI of all lesions was 0.68+/-0.70% (mean +/- SD). A correlation was recognized between tumor size, metastasis and Ki-67 LI (p<0.05). Median MVD of all lesions was 25.9+/-13.1 (mean +/- SD). MVD was correlated with the tumor size (p<0.01), presence of depression (p<0.01), lymphatic (p<0.01) or venous (p<0.05) invasion, and existence of metastasis (p<0.01). But there was no significant relationship between MVD and Ki-67 LI. p53 protein was detected sporadically in only 1 case (1.3%) demonstrating both liver and lymph node metastases. Rectal carcinoid tumors are slow-growing tumors with a lower proliferative activity. Angiogenesis plays an important role in progression of rectal carcinoid tumors independent of the cellular proliferative activity.     

Prognostic factors in elderly patients with acute myelogenous leukemia: a single center study in Japan

We retrospectively analyzed data of 47 patients aged 60 years or older, hospitalized in our institution with the diagnosis of acute myelogenous leukemia (AML), and searched for prognostic factors. Induction with anthracyclines significantly correlated with better complete remission (CR) rate (P = 0.0016) and overall survival (OS) (P < 0.001). Another factor significantly affecting CR rate was higher age (> 70 years) (P = 0.042). Therapy-non-related factors predictive for shorter OS in univariate analyses were age older than 70 years (P = 0.003), percentage of blasts in bone marrow more than 80% (P = 0.048), serum lactate dehydrogenase level higher than 250 U l(-1) (P = 0.032). In stepwise cox proportional hazard regression model, all the four factors predictive for poor OS remained to be independently and significantly prognostic for shorter OS. Only two patients receiving anthracyclines died within 30 days and the frequency was not different from that in patients not receiving anthracyclines. The use of anthracyclines as induction therapy is recommended even in the elderly patients.     

Pharmacokinetic study of CPT-11, SN-38 and SN-38 glucuronide in the ascites,plasma and bile after intraperitoneal administration of CPT-11

We studied the pharmacokinetics of CPT-11 with intraperitoneal administration in a patient with a PTCD tube. The patient had advanced gastric cancer with peritoneal metastasis. CPT-11 was administrated in a dose of 40 mg and the intraperitoneal, plasma and bile levels of CPT-11, SN-38 and SN-38 glucuronide (SN-38 GLU) were measured periodically. The results showed that the periodical concentration pattern of CPT-11, SN-38 and SN-38 GLU in the bile was closely related to that of CPT-11 in the abdominal cavity.     

Airway stent for airway obstruction caused by esophageal carcinoma

The result of airway stent and adjuvant therapy for airway obstruction caused by advanced esophageal carcinoma was evaluated. In Tokyo Metropolitan Ohkubo Hospital, four cases of esophageal carcinoma with airway obstruction were treated by tracheo-bronchial stent. Two were primary cases and the others were recurrent cases. Three of the patients demonstrated progressive dyspnea due to airway obstruction, and the other complained of bloody discharge. An ultraflex non-covered stent was used cases. After insertion of the airway stent. The patients' dyspnea improved immediately. One patient was discharged without adjuvant treatment, and died of the cancer one month later. Adjuvant treatment was adopted in the other three cases. The size of the tumor decreased, but fistula formation was observed in two cases. An airway stent is an effective treatment with immediate results for dyspnea caused by airway obstruction. Adjuvant treatment after stent placement is often associated with fistula formation. It should be considered carefully.     

A GDP/GTP exchange protein for the Rab3 small G protein family up-regulates a postdocking step of synaptic exocytosis in central synapses

The Rab3 GDP/GTP exchange protein (Rab3 GEP) activates the Rab3 small GTP-binding protein (G protein) family, including Rab3A that is an important member controlling synaptic vesicle trafficking. Here, we examined the role of Rab3 GEP in regulating neurotransmitter release in autapses of mouse hippocampal neurons in culture. The release probability was markedly reduced in Rab3 GEP-/- neurons, whereas the readily releasable pool size was not different between WT and Rab3 GEP-/- neurons, indicating that Rab3 GEP up-regulates a postdocking step of synaptic exocytosis. Because Rab3A reportedly down-regulates Ca(2+)-triggered fusion of synaptic vesicles, these results provide evidence for a role of Rab3 GEP in the postdocking process distinct from Rab3A activation.     

Validation of quantitative gated single photon emission computed tomography and an automated scoring system for the assessment of regional left ventricular systolic function

Despite its ability to quantify regional perfusion and function, there is no established method for quantification of regional perfusion and function by myocardial gated single photon emission computed tomography (SPECT). The aim of this study was to establish a quantitative index for regional perfusion and systolic function assessment using gated SPECT. Myocardial SPECT was performed at rest using (99m)Tc sestamibi with 8-frame gating in 62 consecutive patients. In addition to computation of left ventricular ejection fraction (LVEF), a new computerized method for quantifying, displaying and automatically grading regional data was developed. Regional function was quantified as wall motion, regional EF, and imaged based, count based, and normalized per cent wall thickenings (%WTs). Regional perfusion was assessed as a relative per cent peak count. Data were displayed on a 25-segmented polar map and automatically graded with a 5-point scale, and then summed scores were calculated. These quantitative parameters were compared to data from radionuclide ventriculography (RNV) and contrast left ventriculography. Gated SPECT had high reproducibilities for calculating global and regional ejection fractions and %WT indices (r=0.811-0.984, P<0.0001), but measurement of wall motion was less reproducible (r=0.555, SEE=7.9, P<0.011). LVEF estimated by gated SPECT and summed perfusion scores correlated closely (P<0.0001) with angiographic LVEF. Among the summed function indices that correlated closely with LVEF, normalized %WT had the closest correlations with LVEF estimated by RNV (r=0.657, P<0.0001) and by gated SPECT (r=0.778, P<0.0001). Assessment by visual reviewing of cine-mode playback or by normalized %WT had greater overall sensitivity, specificity, and positive and negative predictive values for detecting impaired regional function among the functional parameters: 71%, 79%, 63% and 84% for cine format analysis, and 78%, 73%, 59% and 87% for normalized %WT, respectively. Thus, besides LVEF, quantitative gated SPECT can provide reproducible and reliable quantitative data on regional perfusion and function. Automated summed scores obtained by gated SPECT can reflect integrated abnormalities of regional perfusion and function of the left ventricle. Both visual analyses by cine-mode display and a functional map of normalized wall thickening have greater diagnostic values for detecting regional function deficit related to coronary artery disease.     

Quantitative assessment of right ventricular structural abnormalities by right ventricular polar mapping of single photon emission computed tomogram

The identification of right ventricular (RV) abnormalities is clinically important in the evaluation of arrhythmogenic substrates in right ventricular-originated ventricular tachycardia (RVT). The purpose of this study was to determine the diagnostic benefit of quantitative analysis in RV single photon emission computed tomography (SPECT) imaging with (99m)Tc-tetrofosmin/sestamibi in patients with RVT. Thirty patients with RVT (15 with idiopathic RVT and 15 with arrhythmogenic right ventricular cardiomyopathy (ARVC)) were compared with 27 control subjects (including 11 with right bundle branch block) with regard to the semiquantitative RV uptake score in each of six segments and the quantitative RV extent score in polar coordinate map displays by SPECT imaging. The RV total score and RV extent score were compared with the RV global function. Perfusion abnormalities were more frequently detected (P = 0.0001) in the ARVC group (59/90, 65.6%) than in the idiopathic RVT group (4/90, 4.4%) or controls (1/162, 0.6%). The RV extent score in the ARVC group (53.0 +/- 24.8) was significantly higher than that in the idiopathic RVT group (8.4 +/- 10.1) or controls (1.2 +/- 4.9). The RV extent score correlated well with the regional RV perfusion score (P < 0.0001) and with the RV ejection fraction (P < 0.0001). Non-invasive RV perfusion mapping using a (99m)Tc-labelled tracer is useful for the quantitative evaluation of RV substrates in patients with ARVC.