Differentiation of multiple visceral artery aneurysm rupture from major bleeding after coronary artery bypass grafting.

BACKGROUND: Visceral artery aneurysm is a very rare disease, but it is clinically important because of the high risk of rupture involved. These ruptures must be differentiated from those that occur during hospitalization after extra-abdominal surgery. METHODS: During hospitalization after off-pump coronary artery bypass grafting, a 77-year-old woman developed hypovolemic symptoms and had decreased hemoglobin. There was no obvious bleeding, but while screening for possible complications after cardiac surgery, abdominal computed tomographic angiography showed multiple visceral artery aneurysms of the gastroduodenal and pancreaticoduodenal arteries along with hemoperitoneum. RESULTS: The patient underwent coil embolization of the visceral artery aneurysm and was discharged without any complications. CONCLUSIONS: In patients with coronary artery disease with risk factors for atherosclerosis, if anemia occurs without apparent bleeding after surgery, visceral artery aneurysm should be considered as a differential diagnosis.

Acute biological mitral valve thrombosis after the left atrial venting in a patient with a venoarterial extracorporeal membrane oxygenator.

BACKGROUND: Left atrial venting through atrial septotomy in patients with decreased left ventricular (LV) contractility after venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a simple and effective method for treating LV decompression. MATERIALS & METHODS: We report a case of prosthetic mitral valve thrombosis after left atrial venting in a patient with VA-ECMO. RESULTS: In patients undergoing mitral valve replacement, left atrial venting reduces the flow through the mitral valve and forms a prosthetic thrombosis. DISCUSSION: Therefore, excessive left atrial venting should be avoided. Other venting methods that can maintain the flow through the mitral valve should be considered after mitral valve replacement.

Role of pituitary adenylate cyclase-activating polypeptide in modulating hypothalamus-pituitary neuroendocrine functions in mouse cell models.

Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally identified as a hypothalamic activator of cyclic adenosine monophosphate production in pituitary cells. PACAP and its receptor are expressed not only in the central nervous system, but also in peripheral organs, and function to stimulate pituitary hormone synthesis and secretion as both a hypothalamic-pituitary-releasing factor and an autocrine-paracrine factor within the pituitary. PACAP stimulates the expression of the gonadotrophin α, luteinising hormone (LH) ß and follicle-stimulating hormone (FSH) ß subunits, as well as the gonadotrophin-releasing hormone (GnRH) receptor and its own PACAP type I receptor (PAC1R) in gonadotrophin-secreting pituitary cells. In turn, GnRH, which is known to be a crucial component of gonadotrophin secretion, stimulates the expression of PACAP and PAC1R in gonadotrophs. In addition, PAC1R and PACAP modulate the functions of GnRH-producing neurones in the hypothalamus. This review summarises the current understanding of the possible roles of PACAP and PAC1R in modulating hypothalamus and pituitary neuroendocrine cells in the mouse models.

Comparison of four facial muscles, orbicularis oculi, corrugator supercilii, masseter or mylohyoid, as best predictor of good conditions for intubation: a randomised blinded trial.

CONTEXT: Monitoring of facial muscles after neuromuscular blockade can give an early indication of respiratory muscle readiness for tracheal intubation. OBJECTIVE: To assess which facial muscle, the orbicularis oculi, corrugator supercilii, masseter or the mylohyoid, is the best predictor of readiness for intubation after rocuronium. DESIGN: Prospective, randomised, blinded trial. SETTING: Single centre: Seoul, Korea, from August 2012 to November 2012. PATIENTS: Two hundred and eighty-eight patients aged 22 to 64 years were randomised to one of eight study groups: orbicularis oculi, corrugator supercilii, masseter and mylohyoid for rocuronium 0.6 or 1.2 mg kg. INTERVENTION: The maximum twitch depression at the eyelid (orbicularis oculi), the superciliary arch (corrugator supercilii), the cheek (masseter) and the submental triangle (mylohyoid) was assessed after rocuronium 0.6 and 1.2 mg kg. Endotracheal intubation was performed after maximal neuromuscular blockade, and intubating conditions were appraised. MAIN OUTCOME MEASURES: The onset time of rocuronium and the quality of the intubation conditions were assessed. RESULTS: The onset times in the orbicularis oculi, corrugator supercilii and masseter were significantly faster than that in the mylohyoid (P < 0.001). 'Clinically acceptable' intubation conditions were significantly enhanced in the mylohyoid (94%) compared with those in the orbicularis oculi (80%) and masseter (78%) after rocuronium 0.6 mg kg (P < 0.05), and no difference with corrugator supercilii (92%). Despite differences in onset time of orbicularis oculi and masseter compared to mylohyoid (P < 0.05), intubating conditions were similar among the four muscles after rocuronium 1.2 mg kg. CONCLUSION: Following rocuronium 0.6 mg kg at similar depths of anaesthesia, the monitoring of the corrugator supercilii provided the best balance of a shorter onset time while maintaining 'clinically acceptable' intubation conditions. TRIAL REGISTRATION: IRB File No.: HYUH 2012-07-009.

Improved survival in patients with continuous-flow ventricular assist device for bridge to heart transplantation.

BACKGROUND: Contemporary continuous-flow ventricular assist devices (CFVADs) have greatly improved patient survival for indications of bridge to transplantation (BTT) and destination therapy. In Japan, CFVAD is limited for BTT use. The waiting period for heart transplantation (HT) is long owing to donor shortage. We examined the results of CFVAD for BTT indication. METHODS: Eighty-nine VAD treatments were performed among subjects whose preimplantation condition was profile 1 (n = 49) or profile 2 or 3 (n = 40). The device was the paracorporeal pulsatile Nipro VAD (n = 67) or CFVAD (n = 22). All CFVAD patients were profile 2 or 3. RESULTS: The median assist period was 529 days (Nipro VAD, 530; CFVAD, 528). Twenty-six patients were on the device for >2 years. Actuarial survival was 81.6%, 69.5%, and 61.1% at 1, 3, and 5 years. Survival in profile 1 was significantly worse than in profile 2 or 3. Survival of CFVAD patients was superior to that of paracorporeal VAD. Six-month mortality rate of 20% in cases before 2009 (n = 60) was dramatically improved to 3% among those after 2010 (n = 29). All patients with CFVAD were alive and discharged home. 26 patients were transplanted, 7 had been weaned from VAD and 27 were on a device. The rate of events requiring hospital admission was 0.98 per patient-year in CFVAD patients. CONCLUSIONS: Contemporary CFVADs have enabled advanced heart failure patients to await HT safely with an improved quality of life. The advent of CFVAD has also shifted their preimplantation condition to a less sick status. CFVADs were the safest, most reliable circulatory support devices for long-term waiting periods for the BTT indications.

Circulating tumour cells detected by a novel adenovirus-mediated system may be a potent therapeutic marker in gynaecological cancers.

BACKGROUND: Recently developed detection system for circulating tumour cells (CTCs) using a telomerase-specific replicative adenovirus generated nonspecific green fluorescent protein (GFP) signals because of the co-presence of white blood cells (WBCs) nonspecifically infected by viruses. Here, we established a unique detection system for CTCs that completely excludes nonspecific signals. METHODS: Blood obtained from the patients was subjected to haemolytic processes to eliminate red blood cells. The cell pellets were then infected with OBP-401, fixed, incubated with fluorescence-labelled anti-CD45 antibody to mark white blood WBCs, and examined on slides under a microscope. RESULTS: Preparatory experiments with cancer cells artificially added to healthy donor samples confirmed that CD45 labelling could distinguish GFP-positive cancer cells from WBCs. In 53 patients with gynaecological cancers, CTCs were detected in 21 patients (39.6%) when CD45-positive cells were excluded as WBCs among GFP-positive cells. No CTCs were detected in samples from healthy volunteers. There was no significant correlation between CTC counts and known clinicopathological factors. The CTCs rapidly vanished after surgery or chemotherapy in most patients whose treatments were effective. In contrast, the persistence of CTCs even after treatments was tightly associated with poor response to the treatments (P<0.005). CONCLUSION: The presence of CTCs in our system may potentially be a novel therapeutic marker in gynaecological cancers.

Creation of immortalised epithelial cells from ovarian endometrioma.

BACKGROUND: Epithelial cells of endometriotic tissues are difficult to propagate in vitro as experimental material is scarce owing to their limited life span. However, there is an increasing concern regarding their malignant transformation in ovaries. The present study sought to generate their stable culture system. METHODS AND RESULTS: Purified epithelial cells isolated from ovarian endometriomas using microscopic manipulation were successfully immortalised by combinatorial transfection of human cyclinD1, cdk4 and human telomerase reverse transcriptase (hTERT) genes, whereas the introduction of hTERT alone, or together with cdk4, was insufficient for immortalisation, leading to cellular senescence. We confirmed stable cytokeratin expression in the immortalised cells, proving their epithelial origin. These cells expressed progesterone receptor B and showed significant growth inhibition by various progestins. Oestrogen receptor (ER) expression was detected in these cells, albeit at low levels. Additional overexpression of ERα generated stable cells with oestrogen-dependent growth activation. Soft-agar colony formation assay and nude mice xenograft experiments demonstrated that these cells, even those with additional inactivation of p53, did not have transformed phenotypes. CONCLUSION: We for the first time generated immortalised epithelial cells from ovarian endometrioma that retained sex steroid responsiveness. These cells are invaluable tools not only for the consistent in vitro work but also for the study of molecular pathogenesis or carcinogenesis of endometriosis.

Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia.

Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC) transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP)-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

The efficacy of several neuromuscular monitoring modes at the P6 acupuncture point in preventing postoperative nausea and vomiting.

BACKGROUND: In this study, we tested the efficacy of several neuromuscular monitoring modes at the P6 acupuncture point for preventing postoperative nausea and vomiting (PONV). METHODS: In this prospective, double-blind, randomized, placebo-controlled trial, 264 women undergoing laparoscopic hysterectomy were evaluated for PONV. Neuromuscular blockade was monitored by acceleromyography with 1-Hz single twitch (ST) over the ulnar nerve (n = 54, control), and ST (n = 52), train-of-four (n = 53), double-burst stimulation (n = 53), or tetanus (n = 52) over the median nerve stimulating at the P6 acupuncture point. RESULTS: The incidence of PONV (P = 0.022), the number of requests for patient-controlled analgesia (P = 0.009), and total patient-controlled analgesia volume (P = 0.042) 6 hours after tetanic stimulation were significantly reduced in the treatment group compared with the control group. Overall, patients in the tetanus group were more satisfied with the management of PONV compared with patients in the control group. CONCLUSION: Tetanic stimulation applied to the P6 acupuncture point can reduce PONV after laparoscopic hysterectomy compared with ST stimulation of the ulnar nerve, resulting in a greater degree of patient satisfaction. None of the stimulations, ST, train-of-four, or double-burst, applied to the P6 acupuncture point significantly affected PONV.

Expression of HER-2 affects patient survival and paclitaxel sensitivity in endometrial cancer.

BACKGROUND: Disabled phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase signalling is involved in endometrial carcinogenesis, and there is evidence that expression of epidermal growth factor receptor (EGFR) family members has a role in such intracellular signalling pathways. This study analysed the prognostic impact of EGFR family expression in endometrial cancer in relation to PI3K-AKT and MAPK-ERK signalling, as well as drug sensitivity. METHODS AND RESULTS: Immunohistochemical analysis using 63 surgical specimens of endometrioid-type endometrial cancers revealed that EGFR, human epidermal growth factor receptor (HER)-2 and HER-4 were expressed in 25 (39.7%) of 63, 26 (41.3%) of 63 and 31 (49.2%) of 63 tumours, respectively. Gene amplification of HER-2 was observed in 2 of 26 patients with high HER-2 expression. Kaplan-Meier analysis revealed that high HER-2 expression was a factor that negatively influenced the progression-free and overall survival rate (P<0.05), and multivariate analysis showed high HER-2 expression to be an independent prognostic factor. Subsequently, we performed in vitro knockdown analysis to investigate the linkage between HER-2 expression and PI3K-AKT pathways. Short interfering RNA (siRNA)-based knockdown of HER-2 in endometrial cancer cells led to a significant reduction in phosphorylated AKT (p-AKT) expression, indicating the existence of a HER-2/PI3K-AKT axis. As the PI3K-AKT pathway is known to have crucial roles in anticancer drug sensitivity, we examined the involvement of HER-2 in sensitivity to paclitaxel. Short interfering RNA-based knockdown of HER-2 conferred increased sensitivity to paclitaxel in endometrial cancer cells, attenuating the induction of p-AKT on paclitaxel stimulation, which was cancelled by inactivating AKT by the introduction of a dominant-negative form. CONCLUSION: HER-2 is a significant prognostic factor of endometrioid-type endometrial cancer, as well as a key molecule that affects paclitaxel sensitivity by HER-2 interaction with the PI3K-AKT pathway.

Krüppel-like factor 4 mediates anti-proliferative effects of progesterone with G0/G1 arrest in human endometrial epithelial cells.

Activation of the progesterone receptor (PR) inhibits cell proliferation in various reproductive tissues. However, the molecular mechanisms underlying the regulation of cell proliferation by PR remain poorly understood. It is well established that Krüppel-like factor 4 (KLF4), a family of zinc fingercontaining transcription factors, induces cell cycle arrest in epithelial cells. In this study, we investigated whether KLF4 served as a target of PR activation during cell proliferation using human endometrial epithelial cells. PR agonists, progesterone and dienogest, were found to produce a lasting increase in the expression of KLF4 mRNA, followed by a decrease in cyclin D1 mRNA, and inhibit cell proliferation with G0/G1 arrest. KLF4 knockdown using KLF4 small interferingRNA abrogated the inhibition of cell proliferation by PR agonists. In addition, forced expression of KLF4 inhibited cyclin D1 promoter transactivation. These results suggest that PR agonists induce KLF4 expression and then inhibit cyclin D1 expression, and consequently inhibit cell proliferation in human endometrial epithelial cells. In terms of human reproductive tissue, KLF4 may be a factor concerning cell cycle, directly responsive to PR activation.

A novel translational approach for human malignant pleural mesothelioma: heparanase-assisted dual virotherapy.

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that is related to asbestos exposure. MPM is characterized by rapid and diffuse local growth in the thoracic cavity, and it has a poor prognosis because it is often refractory to conventional therapy. Although MPM is an extraordinarily challenging disease to treat, locoregional virotherapy may be useful against this aggressive disease because of the accessibility by intrapleural virus delivery. In this study, we show that telomerase-specific, replication-selective adenovirus OBP-301 can efficiently infect and kill human mesothelioma cells by viral replication. Intrathoracic administration of virus significantly reduced the number and size of human mesothelioma tumors intrathoracically implanted into nu/nu mice. A high-definition, fluorescence optical imaging system with an ultra-thin, flexible fibered microprobe clearly detected intracellular replication of green fluorescent protein-expressing oncolytic virus in intrathoracically established mesothelioma tumors. As the extracellular matrix (ECM) may contribute to the physiological resistance of a solid tumor by preventing the penetration of therapeutic agents (including oncolytic viruses), we also examined whether the co-expression of heparanase, an endoglucuronidase capable of specifically degrading heparan sulfate, that influences the physiological barrier to macromolecule penetration, can modify the permeability of the ECM, resulting in profound therapeutic efficacy. Co-injection of OBP-301 and a replication-defective adenovirus (Ad-S/hep)-expressing heparanase resulted in more profound antitumor effects without apparent toxicity in an orthotopic pleural dissemination model. Our results suggest that intrathoracic dual virotherapy with telomerase-specific oncolytic adenovirus in combination with heparanase-expressing adenovirus may be efficacious in the prevention and treatment of pleural dissemination of human malignant mesothelioma.

Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination.

Despite tremendous development in chemotherapy for ovarian cancer over the past few decades, the prognosis of advanced cases with massive peritoneal dissemination is still unsatisfactory, and novel treatment modalities that can combine with chemotherapy are urgently needed. We recently developed virotherapy for solid tumors using telomerase-specific replication-selective adenoviruses (Telomelysin: OBP-301), in which the human telomerase reverse transcriptase (hTERT) gene promoter has been inserted to direct tumor-specific E1 gene expression. In this study, we investigated the anti-tumor effects of OBP-301, combined with cisplatin (CDDP), on ovarian cancer cells. In vitro treatment of SKOV3 cells with OBP-301 at a multiplicity of infection (MOI) of 0.01-100 induced significant cell death in a dose-dependent manner, with moderate cytotoxicity at an MOI of 1-10 and maximal cytotoxicity at an MOI of 100. In contrast, OBP-301 treatment of normal human cells showed no significant cell death at an MOI of 1-10 and exhibited modest cytotoxicity at an MOI of 100. The effects of low-dose CDDP at 0.5-1 microM, which induced only 20% cell death, were significantly augmented by combination with OBP-301 at an MOI of 1-10, finally achieving 40% cell death. Such enhancement of CDDP sensitivity was also observed in CDDP-resistant ovarian cancer cells. The combinatorial effects were further tested using a xenograft mouse model of SKOV3 with peritoneal dissemination. After intraperitoneal administration of OBP-301, we confirmed that injected OBP-301 fused with the green fluorescent protein (GFP) gene (OBP-401) was preferentially localized to peritoneal disseminations, as determined by fluorescence imaging. Treatment of mice with CDDP at low dose (0.5 mg kg(-1)) had modest effects, showing a 10% decrease in disseminations, whereas combination with intraperitoneal administration of OBP-301 at an MOI of 10 led to enhanced effects, achieving an approximately 80% decrease in disseminations. Kaplan-Meier analysis showed improved overall survival of mice treated with CDDP plus OBP-301 compared with CDDP alone. These findings support the therapeutic potential of intraperitoneal administration of OBP-301 to sensitize ovarian cancer cells to CDDP.

Capsicum plaster at the Hegu point reduces postoperative analgesic requirement after orthognathic surgery.

BACKGROUND: Capsicum plaster at classical Chinese acupoints is an alternative to acupuncture, which has been used as an effective method for preventing postoperative nausea and vomiting, sore throat, and pain. In this study, we investigated the postoperative analgesic efficacy of capsicum plaster at Hegu (LI 4) acupoints in patients after bilateral sagittal split ramus osteotomy. METHODS: A double-blind, sham-controlled study was conducted with 84 patients undergoing orthognathic surgery, and who were randomly assigned to three treatment regimens (n = 28 each): Hegu group = capsicum plaster at Hegu acupoints and placebo tape on the shoulders as a nonacupoint; sham group = capsicum plaster on the shoulders and placebo tape at Hegu acupoints; and control group = placebo tape at Hegu acupoints and on the shoulders. The capsicum plaster was applied before induction of anesthesia and maintained for 8 h per day for 3 postoperative days. RESULTS: The total amount of patient-controlled analgesia, containing 6.5 microg/mL fentanyl and 1.2 mg/mL ketorolac, administered in the first 24 h after the operation was decreased in the Hegu group (26.8 +/- 3.4 mL) compared with the control (44.2 +/- 7.3 mL) and sham (42.1 +/- 6.9 mL) groups (P < 0.01). The incidence of postoperative nausea and vomiting and the need for rescue medication were reduced, and the overall satisfaction score was greater in the Hegu group compared with other groups (P < 0.01). CONCLUSION: The capsicum plaster at the Hegu acupoints decreased the postoperative opioid requirements and opioid-related side effects in patients after orthognathic surgery.

Efficacy and safety of torasemide in children with heart failure.

OBJECTIVE: To examine the efficacy and safety of torasemide in children with chronic heart failure (HF). METHODS: 102 children with chronic HF who had received oral torasemide were analysed. Of these, 62 (de novo group) were newly diagnosed as having HF and were given torasemide as a diuretic. The remaining 40 (replacement group) had been given furosemide for >3 months before the study, and furosemide was then replaced with torasemide. Clinical signs and symptoms of HF (assessed as the HF index), humoral factors and serum potassium concentrations before torasemide treatment were compared with those obtained 3-4 weeks after torasemide treatment. Patients were also monitored for adverse effects. RESULTS: In the de novo group, torasemide significantly improved the HF index with concomitant improvement in plasma brain natriuretic peptide concentration (median (interquartile range) 52 (51) vs 43 (49) pg/ml). In a randomly selected group of 25 de novo patients with ventricular septal defect, echocardiography showed that torasemide significantly improved left ventricular geometry and function. In the replacement group, brain natriuretic peptide concentrations were also significantly decreased from 50 (104) to 45 (71) pg/ml after substitution of torasemide, but the HF index showed only a tendency for improvement (p = 0.07). Torasemide also had a potassium-sparing effect (de novo group, no change in potassium concentration; replacement group, significant increase from 4.2 (0.5) to 4.3 (0.5) mEq/l), and caused a significant rise in serum aldosterone concentration, consistent with the anti-aldosterone effect of this drug. Serum concentrations of sodium and uric acid had not changed after torasemide treatment, and there were no serious adverse events that necessitated drug withdrawal. CONCLUSION: Torasemide can be safely used, and appears to be effective for treatment of HF in children. Future clinical trials are warranted to verify the present results.

Arterial haemodynamics in patients after repair of tetralogy of Fallot: influence on left ventricular after load and aortic dilatation.

BACKGROUND: Recent histological studies of the aortic wall of patients with tetralogy of Fallot (TOF) have shown massive degeneration of the tunica media of the aorta. Such changes in arterial wall structure may significantly alter arterial wall mechanical properties, and thus cause abnormal arterial haemodynamics. OBJECTIVE: To test the hypothesis that after repair of TOF, there are abnormal arterial haemodynamics which are associated with aortic dilatation and which increased after load on the left ventricle. METHODS AND RESULTS: The subjects comprised 38 patients who had undergone complete repair of TOF, and 55 control subjects. Systemic arterial haemodynamics were investigated by measuring aortic input impedance during cardiac catheterisation. The patients with TOF had significantly higher characteristic impedance (158 (43) dyne x s x cm(-5) x m(2) vs 105 (49) dyne x s x cm(-5) x m(2)) and pulse wave velocity (561 (139) cm/s vs 417 (91) cm/s) and significantly lower total peripheral arterial compliance (0.93 (0.39) ml/mm Hg/m(2) vs 1.24 (0.58) ml/mm Hg/m(2)) than the controls (for all three variables, p<0.01 vs controls), suggesting that central and peripheral arterial wall stiffness are increased after TOF repair. Additionally, patients with TOF had significantly higher arterial wave reflection than the controls (reflection coefficient: 0.21 (0.12) vs 0.16 (0.06)). These abnormalities in patients with TOF increased the pulsatile load on the left ventricle and significantly contributed to decreased cardiac output, even when right ventricular function was taken into account by multivariate regression analysis. The increase in aortic wall stiffness was closely associated with the increase in aortic root diameter. CONCLUSION: These results indicating abnormal arterial haemodynamics after TOF repair highlight the importance of regular monitoring of the systemic arterial bed and potentially relevant cardiovascular events in long-term follow-up of TOF.

Analysis of outcome of Stage I-III endometrial cancer treated with systematic operation omitting paraaortic lymphadenectomy.

PURPOSE: The aim of this study was to assess the outcomes of endometrial cancer patients treated with systematic surgery omitting paraarotic lymphadenectomy. PATIENTS AND METHODS: We retrospectively analyzed a consecutive series of 84 endometrioid-type endometrial cancer patients at FIGO Stage I, II or III without grossly metastatic paraaortic lymphadenodes, who underwent surgery at our institute. RESULTS: Sixty-five patients (77%) underwent primary surgery with pelvic lymphadenectomy while the remaining 19 patients underwent surgery without lymphadenectomy due to severe medical complications or age greater than 70 years. The patients with high risk for recurrence were treated mainly by adjuvant irradiation therapy of the whole pelvis. The median follow-up period was 44 months. The 5-year overall survival (OS) rate was 92%, 92% and 65% for FIGO Stage I, II and III, respectively. Recurrence was detected in eight of the 82 optimally operated patients (9.8%). Out of the eight recurrent patients, five patients had a recurrent tumor at extra-pelvic sites (chest or abdomen), two patients had a recurrent tumor only in a paraaortic lymph node, and one patient had a recurrent tumor only in the vagina. Thus, the recurrence rate was relatively low, with 2.4% relapse at the paraarotic lymph nodes, and 5-year OS rate appeared to be favorable. However, all the six recurrent patients who underwent adjuvant radiation therapy had distant recurrence. CONCLUSIONS: These findings indicate that omission of paraarotic lymphadenectomy may be acceptable for endometrial cancer patients without gross metastasis at this site. However, the high rate of distant recurrence after whole pelvic irradiation strongly indicates an urgent need to develop potent systemic adjuvant therapy, potentially by chemotherapy or chemoradiation therapy.

Early growth response-1 mediates up-regulation of telomerase in placenta.

Telomerase is thought to play a very important role in oncogenesis. It is also believed to wind back the "mitotic clock" which leads to ageing and enable permanent cell division. We evaluated telomerase activity in chorionic tissues, with particular attention to the early growth response-1 (EGR-1) gene, the importance of what was recently shown by Khachigian et al. We started our study by evaluating the relationship between activation of transcription of the human telomerase reverse transcriptase (hTERT) gene and EGR-1 gene. For this purpose, we first evaluated telomerase activity using the villous cancer cell lines JAR and JEG-3. We then demonstrated that EGR-1 plays an important role in activation of the transcription of hTERT by luciferase assay using hTERT promoter constructs. As a result of further computer analysis, we discovered a site postulated to be an EGR-1 consensus binding site at -273 to -281 in the hTERT promoter region. With forced expression of EGR-1, an increase in hTERT protein concentration was detected on Western blot analysis, while marked high expression of hTERT mRNA was observed by reverse transcriptase polymerase chain reaction. Furthermore, we evaluated the expression of EGR-1 and hTERT at the mRNA level in the placenta during the first, second and third trimesters of pregnancy and in patients with preeclampsia. Expression of EGR-1 and hTERT in the chorion increased in the first trimester of pregnancy and decreased later. Increased expression was noted in the placenta of patients with preeclampsia. The present findings suggest that EGR-1 plays an important role in activating the transcription of hTERT, showing that activation of the transcription of hTERT by EGR-1 is involved in the trophoblast growth mechanism.

[Coronary malperfusion due to acute type A aortic dissection; surgical strategy and results].

Coronary malperfusion due to acute type A aortic dissection (DAA) is a lethal complication. It is especially difficult to rescue the patients with left coronary malperfusion because of acute global myocardial infarction (AMI), even with successful surgical treatments, including the replacement of the ascending aorta and coronary artery bypass grafting (CABG). We review our experience and illustrate our approach to these critically ill patients. In addition, we classify the mechanism of malperfusion into 4 types based upon perioperative findings and discuss surgical management indivisually. From January 1990 to April 2005, a total of 260 patients were operated for DAA in our institution. Twenty (7.7%) patients, 11 men and 9 women were suffering from coronary malperfusion due to DAA. The mean age was 55 (range 28-72) years. The right coronary artery was involved in 9 patients, and the left in 11. All procedures such as graft replacement and CABG were done on an emergent or urgent basis. Hospital mortality rate of right coronary malperfusion was 22% (2/9 patients), and that related to left coronary malperfusion was 5/11 (45%). Assisting device was required in 9 cases, veno-arterial bypass (VAB) in 6 cases, left ventricular assist system (LVAS) in 1, left heart bypass (LHB) in 1, LHB+right heart bypass (RHB) in 1. We lost all patients using VAB. Only 3 patients supported with strong assist device survived. Aggressive myocardial resuscitation and early operation are the key factors in the management of these critically ill patients. But once severe myocardial infarction occurs, V-A bypass (percutaneous cardiopulmonary support) is useless in treating patients with DAA who develop severe heart failure. We recommend to implant stronger assist device including LVAS immediately before exacerbation of multiple organ failure. In conclusion, surgical management is not easy for emergency patients with DAA in association with myocardial ischemia. However, reasonable surgical results can be obtained with supplemental CABG and strong mechanical support of the left ventricle.

[Ventricular septal perforation due to weak blunt chest trauma; report of a case].

We report a 67-year-old female patient with ventricular septal perforation after weak blunt chest trauma. She tumbled down on a frozen street. Approximately 1 week later, the patient was aware of shortness of breath on exertion. On admission, holosystolic murmur was detected on chest wall and routine electrocardiogram examination showed ST-T change which suggested myocardial ischemia. Acute myocardial infarction and ventricular septal defect with left-to-right shunt was suspected. The echocardiography and cardiac catheterization revealed the muscular type ventricular septal perforation near the apex with large left-to-right shunt flow (82% shunt ratio). The congestive heart failure was controlled successfully by conservative medical treatment. Surgical repair was scheduled on the 28th day after initial chest trauma because of large left-to-right shunt. A hole of about a diameter of 2 cm with fibrous edge of the muscular septum was closed through a left ventriculotomy using a Dacron patch under cardiopulmonary bypass. Postoperative course was uneventful and the patient was discharged without symptoms of congestive heart failure.