The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. PATIENTS AND METHODS: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks. RESULTS: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76). CONCLUSIONS: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.

Effect of proton pump inhibitors on the development of hypomagnesemia induced by panitumumab.

Panitumumab, a therapeutic agent for unresectable advanced/recurrent colorectal cancer, is a human IgG2 monoclonal antibody that binds to and inhibits the activity of the epidermal growth factor receptor (EGFR). The onset of hypomagnesemia is a known side effect of anti-EGFR inhibitors, including panitumumab, and it is thought that inhibition of reabsorption of Mg in renal tubules is one of the causes. In addition, recent reports have shown that long-term administration of proton pump inhibitors (PPIs) reduces serum magnesium levels. Therefore, in this study, 102 patients who received oral PPIs treated with panitumumab were classified into a PPI combination group and a PPI non-combination group, and the effect of PPIs on the development of grade 2 or higher hypomagnesemia was investigated. The incidence of hypomagnesemia in the PPI combination group (46.9%, 15/32) was higher than that in the PPI non-combination group (25.7%, 18/70). A comparison of the backgrounds of the two groups of patients showed a significant difference in serum albumin levels. PPI administration was significantly associated with panitumumab-induced hypomagnesemia development when adjusted for known risk factors, serum albumin level, renal function, and oral magnesium oxide tablets in Cox proportional hazards regression analysis (hazard ratio 2.09; 95% confidence interval 1.03-4.22; P =0.040). These results indicate that detailed monitoring of serum magnesium levels is recommended for patients treated with panitumumab and co-administration of PPIs.

CD9-positive cells in the intermediate lobe migrate into the anterior lobe to supply endocrine cells.

The adenohypophysis is composed of the anterior and intermediate lobes (AL and IL), and secretes important hormones for growth, sexual development, metabolism, and reproduction. In the marginal cell layer (MCL) facing Rathke's cleft between the IL and AL, cluster of differentiation (CD) 9-, CD81-, S100ß-, and SOX2-quadruple positive (CD9/CD81/S100ß/SOX2-positive) cells in the adult IL are settled as tissue-resident stem/progenitor cells supplying hormone-producing cells to the AL. However, it is unclear how CD9/CD81/S100ß/SOX2-positive cells in the IL-side MCL migrate into the AL across Rathke's cleft. In the present study, we performed chimeric pituitary tissue culture using S100ß/GFP-transgenic rats and Wistar rats, and traced the footprint of S100ß/GFP-expressing cells. We detected IL-side S100ß/GFP-expressing cells in the AL tissue, demonstrating that these cells migrate from the IL to the AL. However, the cells failed to migrate in the opposite direction. Consistently, scanning electron microscopic analysis revealed well-developed cytoplasmic protrusions in the IL-side MCL, but not in the AL-side MCL, suggesting that IL-side CD9/CD81/S100ß/SOX2-positive cells had higher migratory activity. We also searched for a specific marker for IL-side CD9/CD81/S100ß/SOX2-positive cells and identified tetraspanin 1 (TSPAN1) from microarray analysis. Downregulation of Tspan1 by specific siRNA impaired cell migration and significantly reduced expression of snail family transcriptional repressor 2 (Slug), a marker of epithelial-mesenchymal transition (EMT). Therefore, CD9/CD81/S100ß/SOX2-positive cells in the IL-side MCL can be stem/progenitor cells that provide stem/progenitor cells to the AL-side MCL via SLUG-mediated EMT and cell migration.

Video-based tracking approach for nonverbal synchrony: A comparison of Motion Energy Analysis and OpenPose.

The present study investigated the comparability of two video-based tracking techniques, namely, Motion Energy Analysis and OpenPose, in the context of nonverbal synchrony research. Participants aged 23-69 years held a 15-min unstructured conversation with a same-gender partner of the same generation. Each participant's movements were quantified with two algorithms, which were separately submitted to a wavelet transform to assess synchrony between the partners. Wavelet coherence and information in the relative phase were used to measure the intensities and patterns of synchrony, respectively. As a benchmark of the test results, gender effects and correlation with the Big Five personality traits were examined. Irrespective of the tracking technique used, the results consistently illustrated gender effects: female dyads showed more synchrony than male dyads. Among the Big Five personality traits, only Extraversion was significantly associated with synchrony in either tracking technique. The gender effect remained significant in both the tracking techniques even when controlling for personality traits, indicating that both individual (i.e., personality) and social (i.e., gender) factors contribute to synchrony. The use of video-tracking techniques in the research on synchrony for future studies was also discussed.

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer.

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.

Enhancing effects of Te substitution on the thermoelectric power factor of nanostructured SnSe1-xTex.

Nanostructured SnSe1-xTex (0 < x < 0.2) was prepared by the planetary ball milling method. The prepared materials were studied by various analytical techniques. XRD analysis shows the pure phase of SnSe when x ≤ 0.1 and the secondary phase of SnTe was observed when x ≥ 0.1, possibly due to the low solid solubility limit of Te in SnSe. FESEM images revealed that the grain sizes of all the samples were in the range of 100 to 500 nm. TEM images showed the grain structures, sizes and grain boundaries of the samples. XPS analysis confirmed the incorporation of Te in SnSe1-xTex and the binding states of the elements in the samples. The samples were made into pellets and sintered at high temperature. The electrical resistivity of the SnSe1-xTex pellets decreased by up to two orders of magnitude as the x value increased in the samples. Concomitantly, the Seebeck coefficient of the SnSe1-xTex samples decreased drastically as the x value increased in the samples. A power factor (PF) of 102.8 µW K-2 m-1 was obtained for the SnSe0.9Te0.1 sample at 550 K, which is higher than the reported values for SnSe and SnSe1-xTex. When substituting Se with Te, the band structure of SnSe changes, which significantly enhances the thermoelectric PF of SnSe1-xTex for x ∼ 0.1. The PF decreased when the x value was increased further (x ≥ 0.1), possibly due to the precipitation of the SnTe phase. These experimental results demonstrate that the addition of a reasonable amount of Te is a promising approach for improving the thermoelectric properties of SnSe.

Oligonucleotide-targeting periostin ameliorates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3-4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-ß1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.

Harmonising clinical trials within the Gynecologic Cancer InterGroup: consensus and unmet needs from the Fifth Ovarian Cancer Consensus Conference.

The Gynecologic Cancer InterGroup (GCIG) Fifth Ovarian Cancer Consensus Conference (OCCC) was held in Tokyo, Japan from 7 to 9 November 2015. It provided international consensus on 15 important questions in 4 topic areas, which were generated in accordance with the mission statement to establish 'International Consensus for Designing Better Clinical Trials'. The methodology for obtaining consensus was previously established and followed during the Fifth OCCC. All 29 clinical trial groups of GCIG participated in program development and deliberations. Draft consensus statements were discussed in topic groups as well as in a plenary forum. The final statements were then presented to all 29 member groups for voting and documentation of the level of consensus. Full consensus was obtained for 11 of the 15 statements with 28/29 groups agreeing to 3 statements, and 27/29 groups agreeing to 1 statement. The high acceptance rate of the statements among trial groups reflects the fact that we share common questions, and recognise important unmet needs that will guide future research in ovarian cancer.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours.

This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (i) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review and translational research are crucial. (ii) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (iii) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be carried out as a subset of male and/or paediatric germ cell studies.

Nanoscopic analysis of oxygen segregation at tilt boundaries in silicon ingots using atom probe tomography combined with TEM and ab initio calculations.

We have developed an analytical method to determine the segregation levels on the same tilt boundaries (TBs) at the same nanoscopic location by a joint use of atom probe tomography and scanning transmission electron microscopy, and discussed the mechanism of oxygen segregation at TBs in silicon ingots in terms of bond distortions around the TBs. The three-dimensional distribution of oxygen atoms was determined at the typical small- and large-angle TBs by atom probe tomography with a low impurity detection limit (0.01 at.% on a TB plane) simultaneously with high spatial resolution (about 0.4 nm). The three-dimensional distribution was correlated with the atomic stress around the TBs; the stress at large-angle TBs was estimated by ab initio calculations based on atomic resolution scanning transmission electron microscopy data and that at small-angle TBs were calculated with the elastic theory based on dark-field transmission electron microscopy data. Oxygen atoms would segregate at bond-centred sites under tensile stress above about 2 GPa, so as to attain a more stable bonding network by reducing the local stress. The number of oxygen atoms segregating in a unit TB area NGB (in atoms nm-2 ) was determined to be proportional to both the number of the atomic sites under tensile stress in a unit TB area nbc and the average concentration of oxygen atoms around the TB [Oi ] (in at.%) with NGB ∼ 50 nbc [Oi ].

Associations of pre-pregnancy obesity with adverse pregnancy outcomes and the optimal gestational weight gain in Japanese women.

OBJECTIVES: The authors determined associations of maternal pre-pregnancy obesity with adverse pregnancy outcomes and evaluated how gestational weight gain affects risks for such outcomes in Japanese obese pregnant women. MATERIALS AND METHODS: Among women who delivered at the Perinatal Center for Maternity and Neonatal, Yokohama City University Medical Center, between January 2001 and December 2012, the authors ascertained adverse pregnancy outcome incidences in 207 pre-pregnancy obese (body mass index [BMI] = 30 kg/m², obese group), 661 pre-pregnancy overweight (BMI = 25-29.9 kg/m², overweight group), and 6,801 pre-pregnancy normal weight (BMI= 18.5-24.9 kg/m², normal group) women. Subjects were stratified by weekly weight gain during the second/third trimesters to investigate associations between gestational weight gain and adverse pregnancy outcomes. Optimal weight gain for obese pregnant women was also examined. RESULTS: In the obese and overweight groups, incidences of pregnancy induced hypertension (PIH), gestational diabetes mellitus (GDM), large for gestational age (LGA), preterm birth, preterm prelabor rupture of membranes (PPROM), and spontaneous preterm birth were significantly higher than in the normal group. Incidences of adverse pregnancy outcomes were ap- parently higher in the obese than in the overweight group. In the latter, the incidence of large for gestational age was significantly higher in women with weight gains of 0.5 kg/week, whereas no difference in pregnancy outcomes was observed in the obese group regardless of gestational weight gain. CONCLUSION: In obese women, incidences of adverse pregnancy outcomes were higher, and pregnancy out- comes were difficult to improve with gestational weight control. Thus, it.is important to reach an optimal weight before pregnancy.

Clear-cell carcinoma of the ovary.

Clear-cell carcinoma of the ovary (CCCO) is a distinct entity of epithelial ovarian cancer in terms of clinical, histopathological, or genetic features. The incidence of CCCO is different by ethnicity but the reason is not clear yet. Overall prognosis of CCCO is good because most CCCO is found in stage I. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. The same is true for recurrent disease. Therefore, genetic analysis of CCCO is important to find the right target(s) and better therapeutic approaches. Because of its rarity, international collaboration is necessary to conduct randomized clinical trials for CCCO.

Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study.

BACKGROUND: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). RESULTS: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). CONCLUSION: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. CLINICAL TRIAL REGISTRY IDENTIFIER: UMIN000004863.

Health-related quality of life in women with recurrent ovarian cancer receiving paclitaxel plus trebananib or placebo (TRINOVA-1).

BACKGROUND: To evaluate the influence of treatment on health-related quality of life (HRQoL) in 919 women with recurrent ovarian cancer enrolled in the TRINOVA-1 study, a randomized, placebo-controlled phase III study that demonstrated that trebananib 15 mg/kg QW plus weekly paclitaxel significantly improved progression-free survival (PFS) compared with placebo plus weekly paclitaxel (7.2 versus 5.4 months; hazard ratio, 0.66; 95% confidence interval 0.57-0.77; P < 0.001). PATIENTS AND METHODS: HRQoL was assessed with the Functional Assessment of Cancer Therapy-Ovary [FACT-O; comprising FACT-G and the ovarian cancer-specific subscale (OCS)] and EuroQOL EQ-5D instruments before treatment on day 1 of weeks 1, 5, 9, 13, 17, and every 8 weeks thereafter and at the safety follow-up visit. A pattern-mixture model was used to evaluate the influence of patient dropout on FACT-O and OCS scores over time. RESULTS: Of 919 randomized patients, 834 (91%) had a baseline and ≥1 post-baseline HRQoL assessment. At baseline, scores for all instruments were similar for both arms. At 25 weeks, mean ± SD changes from baseline were negligible, with mean ± SD changes typically <1 unit from baseline: -2.4 ± 16.6 in the trebananib arm and -1.6 ± 15.2 in the placebo arm for FACT-O, -0.71 ± 5.5 in the trebananib arm and -0.86 ± 4.9 in the placebo arm for OCS, and -0.02 ± 0.22 in the trebananib arm and 0.02 ± 0.19 in the placebo arm for EQ-5D. Distribution of scores was similar between treatment arms at baseline and over the course of the study. In pattern-mixture models, there was no evidence that patient dropout affected differences in mean FACT-O or OCS scores. Edema had limited effect on either FACT-O or OCS scores in patients with grade ≥2 edema or those with grade 1 or no edema. CONCLUSIONS: Our results demonstrate that the improvement in PFS among patients in the trebananib arm in the TRINOVA-1 study was achieved without compromising HRQoL. CLINICALTRIALSGOV IDENTIFIER: NCT01204749.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Circulating fibrocytes correlate with the asthma control test score.

BACKGROUND: Bronchial asthma is characterised by airway inflammation and remodelling with a decline of lung function. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that play important roles in the pathogenesis of airway remodelling. Several clinical parameters are currently being used in routine clinical practice to assess outcome of therapy in asthma including frequency of rescue with short-acting ß2-agonist and the asthma control test. In this study, we hypothesised that asthma control test is associated with circulating levels of fibrocytes in bronchial asthma. METHODS: There were 20 patients with asthma and seven healthy controls. The number of CD45(+)Collagen I(+) circulating fibrocytes was assessed in the peripheral blood by flow cytometry. RESULTS: The number of circulating fibrocytes was significantly increased in asthma patients with moderate and severe disease compared to controls, and it was inversely correlated with % forced expiratory volume in one second and % forced vital capacity (%FVC). The frequency of inhalation of short-acting ß2 agonist and the asthma control test score was significantly and inversely correlated with the number of circulating fibrocytes. CONCLUSION: The results of this study showed that the number of circulating fibrocytes is inversely correlated with clinical asthma control parameters, further supporting the relevance of measuring circulating fibrocytes as a marker of clinical control in bronchial asthma.

Serous tubal intraepithelial carcinoma arising from the intrauterine portion of the fallopian tube after bilateral salpingo-oophorectomy.

Serous tubal intraepithelial carcinoma (STIC) is considered the precursor of pelvic serous carcinomas and the earliest malignant alteration in BRCA mutation-positive women. Recently, risk-reducing salpingo-oophorectomy (RRSO) is being performed in BRCA mutation-positive women and STIC is often discovered incidentally in the fallopian tubes. A 62-year-old woman underwent bilateral salpingo-oophorectomy (BSO) for ovarian cysts. Ten months later, cytological screening for the endometrium revealed adenocarcinoma. No atypical tissue was detected by the endometrial curettage. Imaging tests and hysteroscopy found no abnormal findings. She underwent hysterectomy and was diagnosed with STIC originating from the intrauterine portion of the residual fallopian tube. Here, the authors report the first case of STIC being detected during an endometrial cytological examination after BSO. Although STIC associated with the BRCA mutation usually involves the distal fallopian tube, the present case suggests that the intrauterine portion of the fallopian tube should be removed or cauterized during RRSO.

Acute pancreatitis induced by paclitaxel and carboplatin therapy in an ovarian cancer patient.

A 46-year-old female was treated with a regimen of paclitaxel and carboplatin (TC therapy) as adjuvant chemotherapy for Stage IC ovarian adenocarcinoma. There was no severe toxicity except for grade 3 neutropenia during the first four cycles of TC therapy. However, she developed acute pancreatitis at 14 days after fifth cycle. TC therapy is commonly associated with adverse effects such as myelosuppression, hypersensitivity, alopecia, and peripheral neuropathy, but acute pancreatitis has rarely been reported. Ovarian cancer patients often present with nausea and abdominal pain, which are the same symptoms of pancreatitis. It is very important to keep in mind that acute pancreatitis may be concealed in these common symptoms of ovarian cancer during and after TC therapy. Because acute pancreatitis is fatal complication and quitting the drug usually leads to complete cure. The authors report an uncommon case in which TC therapy may have caused acute pancreatitis.

Virological efficacy of combination therapy with corticosteroid and nucleoside analogue for severe acute exacerbation of chronic hepatitis B.

The short-term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.

Local pressure components and interfacial tensions of a liquid film in the vicinity of a solid surface with a nanometer-scale slit pore obtained by the perturbative method.

A classical molecular dynamics simulation was conducted for a liquid-solid interfacial system with a nanometer-scale slit pore in order to reveal local thermodynamic states: local pressure components and interfacial tensions of a liquid film in the vicinity of the slit. The simulation also examined the transition mechanism between the two states of the liquid film: (a) liquid film on the slit and (b) liquid film in the slit, based on the local thermodynamic quantities from a molecular point of view. An instantaneous expression of the local pressure components and interfacial tensions, which is based on a volume perturbation, was presented to investigate time-dependent phenomena in molecular dynamics simulations. The interactions between the particles were described by the 12-6 Lennard-Jones potential, and effects of the fluid-solid interaction intensity on the local pressure components and interfacial tensions of the fluid in the vicinity of the slit were examined in detail by the presented perturbative method. The results revealed that the local pressure components tangential to the solid surface in the vicinity of the 1st fluid layer from the solid surface are different in a two dimensional plane, and the difference became pronounced in the vicinity of the corner of the slit, for cases where the fluid-solid interaction intensities are relatively strong. The results for the local interfacial tensions of the fluid inside the slit suggested that the local interfacial tensions in the vicinity of the 2nd and 3rd layers of the solid atoms from the entrance of the slit act as a trigger for the transition between the two states under the influence of a varying fluid-solid interaction.