Placenta previa increta/percreta in Japan: a retrospective study of ultrasound findings, management and clinical course

AIM: Placenta accreta is an abnormally firm attachment of placental villi to the uterine wall, which may cause postpartum hemorrhage resulting in maternal morbidity and mortality. The purpose of the present study was to clarify the incidence, clinical background and prognosis of placenta previa increta/percreta treated with different modalities in Japan. METHODS: Medical records of cases with placenta previa increta/percreta in eight tertiary centers between January 1994 and December 2004 were reviewed. Placenta accreta without actual invasion into the myometrium confirmed by pathology was not included in placenta increta/percreta. Details of obstetric history, maternal background, ultrasonographical findings, the course of delivery, subsequent complications and management were noted. RESULTS: Among the total of 59,008 deliveries, 45,261 were by the vaginal route (76.7%) and 13 747 by cesarean section (23.3%). In this study, 408 cases were diagnosed as placenta previa (0.69%), 18 of these being placenta increta and 5 placenta percreta. Only 1.1% of cases of placenta previa without prior cesarean section were increta/percreta, in contrast to 37% of placenta previa after prior cesarean sections. Mean intraoperation blood loss was 3630 +/- 2216 g (increta) and 12,140 +/- 8343 g (percreta). One patient with placenta previa percreta died of hemorrhage. Stepwise treatment (cesarean section without separation of the placenta, arterial embolization and hysterectomy) was applied for 4 cases, which had the least blood loss. CONCLUSIONS: Placenta previa increta/percreta is a life-threatening disease. Patients who undergo hysterectomy after uterine arterial embolization demonstrate reduced intraoperation blood loss, and this treatment should be incorporated to reduce maternal morbidity.     

Polypoid endocervical adenomyoma: a case report with clinicopathologic analyses

A case of polypoid endocervical adenomyoma (PEA) in the uterine cervix was encountered in the uterine cervix of a 56-year-old woman. Grossly, a well-circumscribed polypoid tumor was observed protruding from the uterine cervix. Based on the findings of imaging studies, it was assumed to be an adenoma malignum in the uterine cervix. The tumor was composed of a mixture of proliferating glands of endocervical type and fascicles of smooth muscle. No distinct nuclear anaplasia, architectural abnormality or any evidence of destructive stromal invasion was observed. Adenoma malignum, which shows a gastric phenotype with immunoreactivity for HIK-1083, was a serious diagnostic possibility. In the present case, the tumor was a well-circumscribed polypoid lesion, with no cytologic or architectural abnormality; however, focal immunoreactivity was shown for HIK-1083, which thus suggested it to be PEA. Therefore, the results of these ancillary diagnostic modalities should be interpreted with caution and combined with the gross and light microscopy findings.     

Molecular and epidemiological trend of rotavirus infection among infants and children in Japan

This study investigated the prevalence of group A, B, and C rotavirus (RAV, RBV, RCV) and adenovirus (AdV) infections in infants and children with acute gastroenteritis in Japan from July 2006 to June 2007. A total of 628 fecal specimens collected from infants and children with acute gastroenteritis in five different places (Maizuru, Tokyo, Sapporo, Saga and Osaka) in Japan during the period of July 2006–June 2007 were examined for RAV, RBV, RCV and AdV by RT-multiplex PCR. RAV was further characterized to G-typing and P-typing by RT-multiplex PCR and sequencing method. It was found that 123 (19.6%) fecal specimens were positive for RAV followed by AdV of 4.5%. RBV and RCV could not be detected in this study. Serotype G1 (58.5%) was identified at high levels followed by G9 (20.3%), G2 (11.4%), and G3 (7.3%). P genotyping revealed P[8] as predominant (84.6%) followed by P[4] (13.8%) and P[6] (1.6%). During the 2006/2007 rotavirus season, G1P[8] strains were most common with G9P[8], G2P[4], G3P[8], G1P[4] and G9P[6] also detected. It is clear from this study that RAV is still the cause of diseases in Japan. To our knowledge, this is the first report of RV P[6] strain in humans in Japan.     

Orexin 2 receptor is involved in orexin A-induced hyperlocomotion in rats

BackgroundThe orexin system regulates various functions, including sleep/wake cycles, feeding, and cognition. Orexin A and orexin B are endogenous neuropeptides for both orexin 1 (OX₁) and orexin 2 (OX₂) receptors. Orexin A has a potent agonistic activity for both the receptors and is known to increase locomotor activity in rats. However, it has not been elucidated how each receptor contributes to orexin A-induced hyperlocomotion.MethodsWe examined the effects of an OX₁ receptor antagonist, SB 334867, and an OX₂ receptor antagonist, EMPA, as well as an OX₁ and OX₂ receptor antagonist on hyperlocomotion caused by intracerebroventricular administration of orexin A or an OX₂ receptor agonist, ADL-OXB ([Ala¹¹,d-Leu¹⁵]-orexin B), in rats.ResultsEMPA (100 mg/kg, ip) but not SB 334867 (3–10 mg/kg, ip) showed antagonistic effects on ADL-OXB-induced hyperlocomotion without affecting the spontaneous locomotor activity. Both EMPA (100 mg/kg, ip) and the OX₁ and OX₂ receptor antagonist (3–30 mg/kg, po) antagonized orexin A-induced hyperlocomotion, while SB 334867 (3?–10 mg/kg, ip) showed no effects.ConclusionsOur results suggest that orexin A-induced hyperlocomotion is mainly mediated by the activation of the OX₂ receptor.     

Adult and infant pharmacokinetic profiling of dihydrocodeine using physiologically based pharmacokinetic modeling

We previously analysed the serum concentrations of dihydrocodeine in a 1‐month‐old infant with respiratory depression after being prescribed dihydrocodeine phosphate 2.0 mg/day divided t.i.d. for 2 days. The purpose was to develop a full physiologically based pharmacokinetic (PBPK) model that could account for these and other drug monitoring results. Based on experiments in Caco‐2 cell monolayers, the effective permeability of dihydrocodeine in human jejunum was established as 1.28 × 10^?4 cm/s. The in vitro V_max/K_m values for dihydrocodeine demethylation mediated by recombinant cytochrome P450 2D6 and 3A4 were 0.19 and 0.066 μl/min/pmol, respectively, and for dihydrocodeine 6‐O‐glucuronidation mediated by recombinant UGT2B4 and 2B7, the V_max/K_m values were 0.14 and 0.22 μl/min/mg protein, respectively. Renal clearance was calculated as 5.37 L/h on the total clearance value multiplied by the fraction recovered in urine. The reported plasma concentration–time profiles of dihydrocodeine after intravenous administration in healthy volunteers were used to adjust the tissue partitioning ratios. The developed model simulated the pharmacokinetic profiles of dihydrocodeine after single and multiple oral administrations reasonably well in the same population. Subsequently, the validated model was used to simulate pharmacokinetic profiles for five pediatric cases, including the 1‐month‐old Japanese boy and a 14‐year‐old Japanese girl who took an overdose of dihydrocodeine phosphate (37 mg). The simulated pharmacokinetic profiles for five virtual pediatric subjects matching the age, gender, and P450 2D6 phenotype of each case approximately reflected the observed values. These results suggested that our dihydrocodeine PBPK model reproduced the results of clinical cases reasonably well for subjects.     

Effect of prostaglandin E1 on vascular endothelial growth factor production by human macrophages and colon cancer cells

We previously demonstrated that cyclooxygenase-2 (COX-2) was predominantly expressed in macrophages of sporadic human colonic adenomas; however, the role of COX-2-expressing cells during colon carcinogenesis has not yet been elucidated. In the present study, we showed the effect of PGE, on vascular endothelial growth factor (VEGF) production by PMA-differentiated U937 cells, a human macrophage model (H-Mac), and by human colon cancer cells T84. PGE1 dramatically induced VEGF production by H-Mac, but not that by T84. PGE1 significantly increased intracellular cAMP formation by H-Mac, but only modestly increased that by T84. 8-bromo-cAMP and cholera toxin also increased VEGF production by H-Mac. In contrast, neither of these agents modulated VEGF production by T84. EP2 and EP4 (PGE specific receptors) mRNA was expressed in both cells. PG dramatically increased VEGF production by activated macrophages, but not by cancer cells, through a specific PGE receptor-mediated process. These findings suggest that PGs produced by COX-2-expressing macrophages induce VEGF production by macrophages, but not by cancer cells, in an autocrine fashion.     

Retrospective analysis of efficacy and safety of amrubicin in refractory and relapsed small-cell lung cancer

Background  Amrubicin, a totally synthetic 9-aminoanthracycline, was evaluated retrospectively for the treatment of refractory and relapsed small-cell lung cancer (SCLC). Methods  Retrospective analysis was performed in 32 patients. Amrubicin was infused over 5 min on days 1–3, with courses repeated at 3- or 4-week intervals. Amrubicin was given at a dose of 45 mg/m² per day, 40 mg/m² per day, 35 mg/m² per day, 30 mg/m² per day, or 25 mg/m² per day depending on medical conditions (patients’ age and performance status [PS]), and the dose was modulated according to myelosuppression. Results  The median number of treatment cycles was 3 (range, 1–6). Seventeen patients (53.1%) had a partial response. Median progression-free survival time for all patients was 96 days, and median survival time was 166 days. Grade 3 or 4 hematologic toxicities comprised neutropenia (78.1%), anemia (65.6%), and thrombocytopenia (50.0%). Febrile neutropenia was observed in 8 patients (25.0%). Nonhematologic toxicities were mild. Treatment-related death was observed in 1 patient. Conclusion  Treatment with amrubicin appeared effective in SCLC patients previously treated with chemotherapy, although it was not necessarily safe, because of myelosuppression. Further research is warranted to investigate amrubicin treatment for patients with SCLC.     

Intra arterial infusion chemotherapy combined with interferon-alpha following palliative hepatic resection against advanced hepatoma with portal venous tumor thrombus in the major trunk and multiple nodules--a preliminary study

Recently, we reported the beneficial effects of intra arterial 5-FU infusion chemotherapy combined with interferon-alpha (IFN-alpha/5-FU combined chemotherapy) for advanced hepatocellular carcinoma (HCC). This report describes the preliminary results of treatment of IFN-alpha/5-FU combined chemotherapy following palliative hepatic resection for advanced hepatocellular carcinoma with tumor thrombus in the main trunk of the portal vein with multiple nodules in the whole liver. The 15 patients of HCC with portal venous tumour thrombi (PVTT) and multiple intra-hepatic multiple nodules (IM3) were treated with IFN-alpha/5-FU combined chemotherapy following palliative surgery in this study. No leukopenia, thrombocytopenia, or myelosuppression was observed in any of the 15 patients. Other adverse effects were, in general, clinically manageable. Concerning the anti-tumor effect, 6 showed an objective response and 9 showed a progressive disease; the response rate was 40.0% (6/15). The 1-year and 3-year survival rates were 48% and 21% in all 15 cases, respectively. In conclusion, IFN-alpha/5-FU combined therapy may be a promising modality for advanced HCC with tumor thrombi in the major trunk with multiple nodules after following palliative surgery.     

Clinical evaluation of panipenem/betamipron in severe infections complicating hematological disorders]

Forty-three patients with severe infections which were complicating hematological disorders were treated with panipenem/betamipron, and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 40 patients in whom efficacies are evaluable, the clinical responses were excellent in 17 patients, good in 4, fair in 7 and poor in 12, and the total clinical efficacy rate was 52.5%. 2. The efficacy rate in 7 patients who had failed to respond to prior treatment with other antibiotics was 57.1%. Thus, no significant difference was observed in efficacy rates between the patients who had failed to respond to prior treatment with other antibiotics and the patients who received no preceding antibiotics therapy. 3. Out of the 43 patients in whom the safety was evaluable, no side effects nor abnormal laboratory findings were found.