Palonosetron in combination with 1-day versus 3-day dexamethasone to prevent nausea and vomiting in patients receiving paclitaxel and carboplatin.

PURPOSE: The aim of the present study was to evaluate the efficacy and toxicity of palonosetron (PAL) and dexamethasone (DEX) on day 1 only in patients with gynecologic cancer receiving paclitaxel combined with carboplatin (TC). The primary endpoint was to evaluate the complete response (CR) rate in the delayed phase. METHODS: This study was a randomized phase 2. Regardless of assignment to either study arm, all patients received an intravenous prophylactic regimen of DEX (20 mg) within 15 min and then an intravenous dose of PAL (0.75 mg) as a bolus given 30 min before initiation of TC on day 1. Patients in the DEX 1-day group received no additional DEX on days 2 and 3. Patients in the DEX 3-day group received DEX (8 mg) orally on days 2 and 3. RESULTS: Eighty-two patients had evaluable data on the primary outcome. The CR rates in the delayed phase between the two groups were not statistically significantly different (3-day group, 76.9 % [30/39]; 1-day group 69.8 % [30/43]; p = 0.4652). The frequency of constipation and insomnia which were antiemetic treatment-related adverse events was similar between two groups, and no serious adverse events occurred. CONCLUSIONS: Administration of a combination of PAL and DEX 1 day may prevent chemotherapy-induced nausea and vomiting (CINV) in the delayed phase for TC as well as administration of DEX 3 days. Further evaluation of the antiemetic regimen of combination of PAL and DEX 1 day for TC is warranted in future phase 3 trials.

Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1ß transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1.

OBJECTIVE: Appropriate cell cycle checkpoints are essential for the maintenance of normal cells and chemosensitivity of cancer cells. Clear cell adenocarcinoma (CCA) of the ovary is highly resistant to chemotherapy. Hepatocyte nuclear factor-1ß (HNF-1ß) is known to be overexpressed in CCA, but its role and clinical significance is unclear. We investigated the role of HNF-1ß in regulation of the cell cycle in CCA. METHODS: To clarify the effects of HNF-1ß on cell cycle checkpoints, we compared the cell cycle distribution and the expression of key proteins involved in CCA cells in which HNF-1ß had been stably knocked down and in vector-control cell lines after treatment with bleomycin. HNF-1ß (+) cells were arrested in G2 phase because of DNA damage. RESULTS: HNF-1ß (-) cells died because of a checkpoint mechanism. G2 arrest of HNF-1ß (+) cells resulted from sustained CHK1 activation, a protein that plays a major role in the checkpoint mechanism. HNF-1ß (+) cells were treated with a CHK1 inhibitor after bleomycin treatment. Flow cytometric analysis of the cell cycle demonstrated that DNA damage-induced G2-arrested cells were released from the checkpoint and killed by a CHK1 inhibitor. CONCLUSIONS: The chemoresistance of CCA may be due to aberrant retention of the G2 checkpoint through overexpression of HNF-1ß. This is the first study demonstrating cell cycle regulation and chemosensitization by a CHK1 inhibitor in CCA.

Risk factors for wound complications after surgery for gynecologic malignancies.

INTRODUCTION: Factors in wound complications such as surgical duration and suture methods are surgeon-side problems. The purpose of the present study was to retrospectively evaluate the incidence of wound complications in patients who underwent wound closure with stainless steel staples or subcuticular sutures in surgery for gynecologic malignancies and to retrospectively determine the risk factors for wound complications. PATIENTS AND METHODS: From April 2007 through March 2012, a cohort of 317 consecutive patients undergoing surgery for gynecologic malignancies was evaluated in the retrospective study. The skin was closed with stainless steel staples before March 2010 (staples group). From April 2010, the skin was closed by subcuticular suturing (subcuticular group). We compared the incidence of wound complications between 2 groups and evaluated independent multivariate associations with the effect of clinical parameters on occurrence of wound complications. RESULTS: The incidence of wound disruption was 7.3% (23/317): 12.1% (17/140) in the staples group and 3.4% (6/177) in the subcuticular group (P = 0.0029). The incidence of wound infection was 2.5% (8/317): 5.0% (7/140) in the staples group and 0.6% (1/177) in the subcuticular group (P = 0.0124). Multivariate analyses performed with wound disruption as the end point revealed long-term steroid treatment, subcutaneous thickness, and skin staples as independent predictors. Subcutaneous thickness and skin staples were independent factors significantly associated with the possibility of wound infection. CONCLUSION: The findings of the present study indicated that risk factors for wound complications after surgeries for gynecologic malignancies include, as a surgeon-side problem, the use of staples for skin closure, and as a patient-side problem, a subcutaneous thickness of more than 30 mm.

Type II versus type III fertility-sparing abdominal radical trachelectomy for early-stage cervical cancer: a comparison of feasibility of surgical outcomes.

OBJECTIVE: The purpose of this study was to compare surgical outcomes using modified (type II) and traditional (type III) abdominal radical trachelectomy (ART) for fertility-sparing surgery in early cervical cancer. METHODS: A prospectively maintained database of ART procedures was analyzed. Data were collected regarding age, stage, histology, operative outcome, surgical complication, and fertility outcome. RESULTS: We performed 23 fertility-sparing ARTs for patients with International Federation of Gynecology and Obstetrics stages IA to IB1 tumors of less than 2 cm between 2006 and 2010. Type III ART was attempted in 8 patients and modified ART in 15 patients. The median operating time was greater in the type III group compared with that in the type II group (305 vs 247 minutes; P < 0.02). The median surgical blood loss was greater in the type III ART group (580 mL; range, 250-988 mL) compared with that in the modified type II group (366 mL; range, 200-850 mL; P < 0.05). The median time to recovery of bladder dysfunction was less in the type II group (9 days; range, 3-10 days) than that in the type III group (13 days; range, 10-23 days; P < 0.01). There were no recurrences at the time of this report. CONCLUSIONS: Type II ART provides surgical and pathological outcomes with better recovery of bladder function similar to those in type III ART. For patients with early cervical cancer who wish to preserve reproductive function, type II ART is a feasible and safe operation.

Chemokine and free fatty acid levels in insulin-resistant state of successful pregnancy: a preliminary observation.

Increased insulin resistance and inflammatory action are observed in pregnancy-induced hypertension (PIH), but similar insulin resistance is observed also in successful pregnancy. To estimate insulin resistance and inflammatory activity in normal pregnancy and PIH, serum concentrations of free fatty acids (FFA; corrected with albumin to estimate unbound FFA), monocyte chemoattractant protein (MCP)-1, and high-molecular weight (HMW) adiponectin were measured in severe PIH patients with a BMI less than 25 kg/m(2) and were measured 3 times during the course of pregnancy in women with normal pregnancies. FFA/albumin, MCP-1, and HMW adiponectin concentrations were significantly higher in PIH patients than in women with normal pregnancies. The 3 measurements of FFA/albumin showed a significant increase through the course of uncomplicated pregnancies. In contrast, MCP-1 and HMW adiponectin were significantly decreased during the course of pregnancy. These results suggest that the reduced MCP-1 concentration in normal pregnancy may be a pathway to inhibit the induction of pathological features from physiological insulin resistance and homeostatic inflammation.

New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal.

BACKGROUND: Various theories try to explain the development and progression of endometriosis, however, no single theory can explain all aspects of this disorder. Gene expression profiling studies might reveal factors that explain variability in disease development and progression, which can serve as specific biomarkers for endometriosis and novel drug development. We have recently showed that the upregulated genes were predominantly clustered in stress and detoxification, providing a mechanistic explanation for the oxidative stress and chronic inflammatory response in endometriosis. OBJECTIVE: This review aims: (1) to analyse the published data, with the aim of identifying pathways consistently regulated by the endometriosis genotype and (2) to summarise the findings of specific genes, which are involved in the process of oxidative stress and inflammation. METHODS: We identified gene array and proteomics studies whose data were accessible in PubMed. RESULTS: A major finding is the increased expressions of several markers including heat shock protein, S100, fibronectin, and neutrophil elastase, which might be involved in the process of Toll-like receptor (TLR)-dependent sterile inflammation. The study reviews a convergence in the main pathogenic process, where the TLR-mediated inflammation occurs possibly through the endogenous ligands. CONCLUSIONS: In conclusion, a circulus vitiosus of both the oxidative stress pathway and the TLR pathways is generated when the process becomes chronic (danger signal spiral).

Anti-inflammatory actions of serine protease inhibitors containing the Kunitz domain.

INTRODUCTION: Protease inhibitors, including the Kunitz, Kazal, serpin and mucus families, play important roles in inhibiting protease activities during homeostasis, inflammation, tissue injury, and cancer progression. Interestingly, in addition to their anti-protease activity, protease inhibitors also often possess other intrinsic properties that contribute to termination of the inflammatory process, including modulation of cytokine expression, signal transduction and tissue remodeling. In this review we have tried to summarize recent findings on the Kunitz family of serine proteinase inhibitors and their implications in health and disease. MATERIALS AND METHODS: A systematic search was performed in the electronic databases PubMed and ScienceDirect up to October 2009. We tried to limit the review to anti-inflammatory actions and actions not related to protease inhibition. RESULTS AND CONCLUSION: Recent studies have demonstrated that the Kunitz inhibitors are not only protease inhibitors, but can also prevent inflammation and tissue injury and subsequently promote tissue remodeling.

The usefulness of photodynamic eye for sentinel lymph node identification in patients with cervical cancer.

AIMS AND BACKGROUND: We studied the potential use of sentinel lymph node identification using a near-infrared fluorescence imaging technique in the treatment of cervical cancer. METHODS AND STUDY DESIGN: Directly before the start of the operation, 0.2 ml of 5 mg/ml indocyanine green was prepared and injected into 4 sites in the cervix using a 26-gauge standard needle, at 3, 6, 9 and 12 o'clock positions. When the operation was advanced to the pelvis, near-infrared fluorescence imaging was performed using photodynamic eye (Hamamatsu Photonics Co., Japan). The sentinel lymph nodes and other dissected lymph nodes were histologically examined to find any metastases. RESULTS: Twelve patients were examined. Their ages ranged from 36 to 68 years (median, 58). Sentinel lymph nodes were identified in 10 patients (83%), and all were bilaterally identified. The median maximum tumor diameter of dissected cervical tumors was 35 mm (22-65); histology was squamous cell carcinoma in 8 patients and adenocarcinoma in 2 patients. Capillary lymphatic space involvement was found in 8 of the 10 patients. The site of the sentinel lymph node was the right external iliac node in 8 patients, the right obturator node in 8, the left external iliac node in 9, and the left obturator node in 8. Lymph node metastasis was found in 2 of the 12 patients, and all were sentinel lymph nodes. No metastasis from lymph nodes other than sentinel lymph nodes was observed. CONCLUSIONS: Photodynamic eye achieved a detection rate similar to that obtained with the blue dye and radioisotope method. It is also easier to use than the other two methods.

Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review).

Epithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) differ from the other histological types with respect to their clinical characteristics and carcinogenesis. Both tumor types are often associated with endometriosis. EAC is recently reported to be characterized by K-RAS activation and PTEN dysfunction. However, the molecular changes in CCC remain largely unknown. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis-associated CCC of the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss, comparative genomic hybridization, mutation, methylation status, microarray gene-expression profiling and proteomics are discussed in the context of CCC biology. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A histologically normal ectopic endometrium bears genetic damages caused by iron-dependent oxidative stress. DNA damage or LOH caused by oxidative stress is a critical factor in the carcinogenic process. LOH studies have implicated the involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q). Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K-RAS (late event) genes may be involved in CCC carcinogenesis. The molecular pathology of CCC is heterogeneous and involves various putative precursor lesions and multiple pathways of development, possibly via genetic alteration by oxidative stress.

The role of hepatocyte nuclear factor-1beta in the pathogenesis of clear cell carcinoma of the ovary.

PROBLEM: Clear cell carcinoma (CCC) of the ovary has a number of features distinguishing it from other epithelial ovarian carcinomas (EOC) because of its characteristic histology and biology, frequent concurrence with endometriotic lesion, and highly chemoresistant nature resulting in an extremely poor prognosis. The incidence of CCC has been steadily increasing in Japan. They comprise approximately 20% of all EOC. Understanding the mechanisms of CCC development and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for CCC. METHOD OF STUDY: This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Several data are discussed in the context of endometriosis and CCC biology. RESULTS: Recent studies based on genome-wide expression analysis technology have noted specific expression of hepatocyte nuclear factor-1beta (HNF-1beta) in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1beta-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of CCC to anticancer agents. CONCLUSIONS: This review summarizes recent advances in the HNF-1beta and its target genes; the potential challenges to the understanding of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel model is proposed.

Expression profiles of genes involved in poor prognosis of epithelial ovarian carcinoma: a review.

BACKGROUND: Epithelial ovarian cancer (EOC) is the commonest cause of gynecological cancer-related mortality. Although the prognosis for patients with advanced cancer is poor, there is a wide range of outcomes for individual patients. OBJECTIVE: The aim of this study was to review molecular factors predictive of poor prognosis of women with EOC by reviewing microarray research identifying gene expression profiles. METHODS: A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2008, combining the keywords "genome-wide," "microarray," "epithelial ovarian cancer" "prognosis," and "epithelial-mesenchymal transition" with specific expression profiles of genes. RESULTS: Many genes that participated in cell signaling, growth factors, transcription factors, proteinases, metabolism, cell adhesion, extracellular matrix component, cell proliferation, and anti-apoptosis were overexpressed in patients with poor prognosis. Several important prognosis-related genes overlap with those known to be regulated by epithelial-mesenchymal transition (EMT). This signaling pathway of EMT (E-cadherin, beta-catenin, receptor tyrosine kinases, NF-kappaB, TGF-beta, or Wnt signalings) will be discussed, as it provides new insights into a new treatment strategy. CONCLUSIONS: This review summarizes recent advances in prognosis-related molecular biology. Collectively, molecular changes possibly through EMT are considered to be a major contributor to the poor prognosis of EOC.

The role of iron in the pathogenesis of endometriosis.

BACKGROUND: Endometriosis may cause symptoms including chronic pelvic pain and infertility, and increases susceptibility to the development of ovarian cancer. Genomic studies have started to delineate the wide array of mediators involved in the development of endometriosis. Understanding the mechanisms of endometriosis development and elucidating its pathogenesis and pathophysiology are intrinsic to prevention and the search for effective therapies. METHOD OF STUDY: The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis. Several recent genomic studies are discussed in the context of endometriosis biology. RESULTS: Severe hemolysis occurring during the development of endometriosis results in high levels of free heme and iron. These compounds oxidatively modify lipids and proteins, leading to cell and DNA damage, and subsequently fibrosis development. Recent studies based on genome-wide expression analysis technology have noted specific expression of heme/iron-dependent mediators in endometriosis. The heme/iron-dependent signaling pathway of endometriosis, which is providing new insights into the regulation of inflammation, detoxification and survival, is discussed. CONCLUSION: Several important endometriosis-specific genes overlap with those known to be regulated by iron. Other genes are involved in oxidative stress. Iron has a significant impact on endometriotic-cell gene expression. This review summarizes recent advances in the heme/iron-mediated signaling and its target genes, outlines the potential challenges to understanding of the pathogenesis and pathophysiology of endometriosis, and proposes a possible novel model.

Laparoscopic detorsion of the ovary in ovarian hyperstimulation syndrome during the sixth week of gestation: A case report and review.

INTRODUCTION: Ovarian torsion in ovarian hyperstimulation syndrome (OHSS) is a relatively rare but serious complication in pregnant women. A delay in treatment increases the risk for functional loss of the ovary and early termination of pregnancy. In this report, we present the case of a 40-year-old female with OHSS who experienced ovarian torsion that was successfully treated with laparoscopic detorsion. PRESENTATION OF CASE: A 40-year-old pregnant woman in the 6th week of gestation who had conceived following in vitro fertilization presented to us with severe and persistent lower abdominal pain. Ultrasound examination revealed a viable singleton intrauterine pregnancy and bilateral enlarged ovaries with scanty ascites. Approximately 14 h after symptom onset, exploratory laparoscopy was performed. The right ovary was found to be twisted once around over the pedicle, and laparoscopic detorsion was completed. Postoperative follow-up was uneventful, and she successfully delivered a healthy infant at 38 weeks of gestation. DISCUSSION: Although the reports on successful laparoscopic surgery for pregnant women with ovarian torsion are becoming more frequent, there are few reports on laparoscopic surgery for ovarian torsion in OHSS during the early first trimester. Optimal management of ovarian torsion during pregnancy needs to be explored for these patients. CONCLUSION: Immediate explorative laparoscopic surgery is a potentially safe and useful strategy for treating ovarian torsion during the early first trimester of pregnancy.

Molecular structure and function analysis of bikunin on down-regulation of tumor necrosis factor-alpha expression in activated neutrophils.

OBJECTIVE: We performed a detailed molecular analysis of bikunin-mediated anti-inflammation (suppressive effect of cytokine release, MAP kinase activation, and nuclear translocation of NF-kB) using a truncated form of bikunin. MATERIALS AND METHODS: We obtained bikunin derivatives that contained O-glycoside-linked N-terminal glycopeptide (Bik-m1), N-glycoside-linked C-terminal tandem Kunitz domains (Bik-m2), bikunin lacking O-glycoside (Bik-c), asialo bikunin (Bik-a), bikunin lacking N-glycoside (Bik-n), and purified C-terminal Kunitz domain II (kII) of bikunin (HI-8). Enzyme-linked immunosorbent assay and Western blot were carried out to measure secreted TNF-alpha and MAP kinase activation. RESULTS: We examined the TNF-alpha secretion in control and lipopolysaccharide (LPS)-treated neutrophils and did not see any changes of its protein levels in the cells pretreated with Bik-m1, Bik-m2, Bik-c, or HI-8. In all of the derivatives tested, only the derivatives that lacked N-glycoside side chain showed a significant suppression of TNF-alpha secretion by LPS. Only a small (21 amino acids) deletion of the N-terminal portion of bikunin (which corresponds to Bik-m2) abolished its suppressing activity of TNF-alpha secretion, thus suggesting that the N-terminal 21 amino acids play a critical role in anti-inflammation. Bik-m1 alone failed to show anti-inflammatory response. Bikunin failed to inhibit ionomycin-induced phosphorylation of MAP kinases. CONCLUSION: These data allow us to conclude that the cytokine expression was inhibited only by the O-glycoside-linked core protein without the N-glycoside side chain. Our results also suggest a possible role of bikunin for receptor-dependent MAP kinase activation.

Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells.

Cyclooxygenase-2 (COX-2) has been implicated in the promotion of carcinogenesis. Although the role of COX-2 in endometrial cancer remains unclear, recent experiments suggest that COX-2 antagonizes cell apoptosis, increases the invasiveness of malignant cells, and promotes angiogenesis. Hepatocyte growth factor (HGF) is a mesenchymal-derived cytokine and the interaction between HGF and its tyrosine kinase receptor, c-Met proto-oncogene, is associated with tumor progression and metastasis. To investigate the molecular mechanism of HGF-induced anoikis resistance, we analyzed the signal transduction and COX-2 expression in endometrial cancer cells. Here, we show i) the expression of COX-2 protein significantly increased in a dose-dependent manner after HGF stimulation in endometrial cancer cell lines (HEC-IB and RL95-2), reaching 200-270% stimulation at the highest doses of HGF tested (40 ng/ml); ii) flow cytometry and TUNEL analyses revealed that HGF significantly inhibited anoikis of RL95-2 cells; iii) phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), but not mitogen-activated protein kinase/ERK kinase (MEK) inhibitor (PD98059), specifically blocked HGF-mediated anoikis resistance in RL95-2 cells; and iv) COX-2 inhibitor, Meloxicam, abrogated HGF-mediated anoikis resistance. Our data suggest that HGF induces anoikis resistance in endometrial cancer cells possibly through PI3K/Akt pathway-dependent up-regulation of COX-2 expression.

Ovarian endometrioma--risks factors of ovarian cancer development.

OBJECTIVE: Our prospective studies in Japan have found an increased ovarian cancer incidence in women with ovarian endometrioma (standardized incidence ratio, 8.95; 95% confidence intervals, 4.12-5.3). The risk increased with increasing age at ovarian endometrioma diagnosis. The goal of this study was to define the risk factor(s) of ovarian cancer development in a Japanese population with ovarian endometrioma. We also analyzed whether the predisposition toward ovarian cancer is limited to endometrioid and clear cell carcinoma. STUDY DESIGN: A total of 6398 participants at 212 participating hospitals in Shizuoka, Japan, were enrolled in the Shizuoka Cohort Study on Endometriosis and Ovarian Cancer (SCSEOC) Trial, which had prospective and retrospective components. The follow-up period was up to 17 years (median, 12.8 years). The risks of development of ovarian cancer were assessed in 6398 women with ultrasonographically diagnosed ovarian endometriomas. Cox proportional-hazards regression function was used to estimate impact in terms of risk factors and possible development of ovarian cancer. RESULTS: The prospective study demonstrated that 46 (0.72%) of 6398 women developed histologically proven ovarian cancer and were operated upon during follow-up. Clear cell carcinoma (39%) and endometrioid adenocarcinoma (35%) were commonly observed among women with ovarian cancer. By multivariate analysis, tumor size > or =9 cm in diameter and postmenopausal women were independent predictive factors of patients with development of ovarian cancer. CONCLUSIONS: Some endometriosis lesions may predispose to clear cell and endometrioid ovarian cancers. Advancing age and the size of endometriomas were independent predictors of development of ovarian cancer among women with ovarian endometrioma.

Prevalence of ovarian cancer among women with a CA125 level of 35 U/ml or less.

BACKGROUND: The optimal upper limit of the normal range for CA125 in ovarian cancer screening is unknown. We investigated the prevalence of ovarian cancer among women in the Shizuoka Cohort Study on Ovarian Cancer Screening (SCSOCS) trial who had an abnormal ultrasound (US) and a CA125 level of 35 U/ml or less. METHODS: Of 48,027 women enrolled in the SCSOCS trial, 40,801 women never had a CA125 level of more than 35 U/ml, and underwent transvaginal US. RESULTS: Among the 40,801 women (age range 45-85 years), 4,859 women had an abnormal transvaginal US examination (category 1 [simple morphology], 4,741 women, and category 2 [complex morphology], 118 women). Of the 4,859 women, 981 (912 with the category 1 and 69 with the category 2) had a surgery. Of the 981 women, ovarian cancer was diagnosed in 8 (0.815%), and 5 of these 8 cancers (63%) were in stage I. The prevalence of ovarian cancer with abnormal US was 0.207% among women with a CA125 level of up to 15 U/ml, 0.488% among those with values of 15-20 U/ml, 0.685% among those with values of 20-25 U/ml, 2.04% among those with values of 25-30 U/ml, and 6.12% among those with values of 30-35 U/ml. CONCLUSIONS: Surgery-detected ovarian cancer is not rare among women with CA125 levels of 35 U/ml or less - levels generally thought to be in the normal range.

Peritoneal disseminated recurrence and lung metastasis after surgery for stage IA uterine papillary serous carcinoma of the endometrium: a case report.

CASE REPORT: We describe a case of synchronous peritoneal dissemination and multiple lung metastases after surgery for stage IA primary uterine papillary serous carcinoma (UPSC) of the endometrium, revealed by an uncontrollable retention of ascites. RESULTS AND DISCUSSION: She was initially treated with a hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy after initial presentation. Tumor recurrence, diagnosed 12 months later, has been treated with six cycles of Paclitaxel 175 mg/m(2) and Carboplatin [area under the curve 5 (Calvert Formula)] every 3 weeks and showed an advantage of this regimen. Early recurrences of the stage IA UPSC can occur and continued close surveillance is recommended. We report herein the case about this entity.

Two cases of pregnant women with ovarian endometrioma mimicking a malignant ovarian tumor.

The detection of an ovarian mass during pregnancy is often a diagnostic challenge. We describe 2 cases of ovarian endometrioma during pregnancy with marked mural nodules on the cyst wall. The sonographic and MR imaging findings mimicked ovarian cancer. Surgical intervention may still be inevitable to exclude the possibility of malignancy.

Bikunin suppresses expression of pro-inflammatory cytokines induced by lipopolysaccharide in neutrophils.

Activated neutrophils contribute to the development of preterm delivery. Because of its ability to suppress inflammation, bikunin, a Kunitz-type protease inhibitor, is currently in clinical trials. To investigate the molecular mechanism of this inhibition, we analyzed the effect of bikunin on pro-inflammatory cytokine production and nuclear factor-kappaB (NF-kappaB) activation in mouse neutrophils stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Here, we show that bikunin: (i) blocks LPS-induced secretion of pro-inflammatory cytokines, including TNF-alpha and IL-1beta, in a dose-dependent manner; (ii) has an inhibitory effect on cytokine production at a concentration of 0.2 microM, reaching 65% inhibition at the highest doses of bikunin tested (5 microM); (iii) has the suppressive capacity of ERK1/2 and p38 signaling pathways; and (iv) inhibited sequentially the LPS-induced phosphorylation of IkappaB-alpha, degradation of IkappaB-alpha, and nuclear translocation of NF-kappaB. When the MAPK data are analyzed, a significant decrease in phosphorylation is not seen at 0.2 microM bikunin but is at 1.0 microM dosing. Bikunin can inhibit LPS-induced neutrophil activation and cytokine release, although it is unlikely that it works primarily through the inhibition of MAPK phosphorylation. These data suggest that such effects are important in vivo and play a major contributory role in abrogation of neutrophil-mediated inflammatory responses, such as preterm delivery.