Elevated peritoneal soluble endoglin and GDF-15 in infertile women with severe endometriosis and pelvic adhesion.

OBJECTIVES: Chronic inflammation and pelvic adhesion play a critical role in endometriosis-related infertility. Research studies suggest that TGF-ß superfamily members, such as soluble endoglin (sEng), growth differentiation factor 15 (GDF-15) and tumor growth factor-beta (TGF-ß1) contribute to the regulation of inflammation, angiogenesis and cell adhesion. The objective of this study is to investigate the association between the concentrations of these TGF-ß-related members and the clinical parameters of infertile women with endometriosis. MATERIALS AND METHODS: Sixty-five infertile women who underwent laparoscopy were divided into two groups in this study: those who had endometriosis (n = 33) and control subjects with benign gynecologic disorders (n = 32). The levels of TGF-ß- related members in peritoneal fluid and serum were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. RESULTS: Endometriosis cases had significantly higher levels of sEng, GDF-15 and TGF-ß1 in peritoneal fluid (p<0.0005) compared to control subjects, but not in serum. Moreover, serum GDF-15 level was significantly elevated in the late-stage endometriosis compared to the early-stage group. The levels of three TGF-ß related molecules in peritoneal fluid showed positive correlations with rASRM score. Blood neutrophil counts have correlation with the peritoneal sEng concentration. CONCLUSION: Our novel evidence on the elevated concentration of peritoneal sEng and GDF-15 in endometriosis, specifically in the late-stage, may indicate the essential role of TGF-ß-dependent signaling in endometriosis. Serum GDF-15 might serve as a candidate biomarker for endometriosis severity. Further studies are warranted to investigate the role and regulation of these molecules in endometriosis.

Impact of early surgical management on tubo-ovarian abscesses.

This 5-year retrospective study aimed to investigate whether early surgical management improves outcomes in patients presenting with a tubo-ovarian abscess (TOA). Patient characteristics, investigation results and treatment outcomes were compared. 50 women were diagnosed with a TOA during the study period. Nineteen (38.0%) were treated with antibiotics (medical group) and thirty one (62.0%) were treated surgically on admission (early surgical group). The early surgical group was associated with a high success rate of 96.8% and the lowest risk of readmission within 12 months (16.1%). There was no significant difference in the length of stay between the early surgical and the successful medical group.Impact StatementWhat is already known on this subject? Tubo-ovarian abscess (TOA) is an inflammatory mass that forms most commonly as a complication of untreated pelvic inflammatory disease (PID). Traditionally, TOAs are treated first with broad-spectrum intra-venous antibiotics, with surgical intervention considered after 72 h. It is not known whether early surgical intervention would be beneficial to patient outcomes compared to traditional management.What do the results of this study add? In this study, we have demonstrated a high success rate with early surgical management. Readmission rate was lowest in the early surgical group compared to the medical and late surgical group. This suggests that early surgical intervention may be beneficial, compared to the standard management of trialling antibiotics and then proceeding to surgery 72 h later.What are the implications of these findings for clinical practice and/or further research? Our study suggests that early surgery may be beneficial in the management of TOAs. Although we were unable to demonstrate statistical significance, our data suggest that it would be worthwhile to investigate white blood cell (WBC) and C-reactive protein (CRP) further as a potential predictor for failure of medical management. In the future, more studies comparing early surgical management with medical and late surgical management could inform clinicians of the best mode of treatment for these patients.

Value of serum procalcitonin as an early predictor of antibiotic treatment response in inpatients with pelvic inflammatory disease (VALID).

OBJECTIVE: This study aimed to investigate the value of serum procalcitonin as an early predictor of antibiotic treatment response in the inpatient management of pelvic inflammatory disease (PID). MATERIALS AND METHODS: A prospective observational study was carried out at a university hospital. Patients admitted for pelvic inflammatory disease were classified into 2 groups: responders and non-responders. The primary outcome measure was the serum level of procalcitonin at the time of admission. The secondary outcome measures were other serum inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. RESULTS: Baseline characteristics were similar between the groups. Serum level of procalcitonin at the time of admission did not differ between the groups (P = 0.564). However, the non-responders had more elevated CRP and ESR compared to the responders (P = 0.045 and P = 0.030, respectively). CRP showed the highest accuracy of 72.1% (95% confidence interval [CI], 59.2 to 82.9) in predicting antibiotics response, while procalcitonin showed the lowest accuracy of 49.1% (95% CI, 35.1 to 63.2). CONCLUSION: Compared with standard inflammatory markers such as CRP or ESR, procalcitonin had limited diagnostic value in predicting antibiotics response in patients admitted for PID. Therefore, procalcitonin measurement cannot be recommended as a laboratory test for patients with PID and the value of its routine use remains inconclusive.

Can the Need for Invasive Intervention in Tubo-ovarian Abscess Be Predicted? The Implication of C-reactive Protein Measurements.

STUDY OBJECTIVE: To evaluate the clinical parameters of hospitalized patients with pelvic inflammatory disease (PID) for the presence of tubo-ovarian abscess (TOA) and predict the need for intervention. DESIGN: A prospective cohort study. SETTING: A tertiary care university medical center. PATIENTS: Ninety-four patients were diagnosed with complicated PID and hospitalized between 2015 and 2017. INTERVENTIONS: Patients with PID were treated with parenteral antibiotics according to Centers for Disease Control guidelines. Demographic, clinical, sonographic, and laboratory data for patients with PID were analyzed. Inflammatory markers including C-reactive protein (CRP), white blood cells (WBCs), erythrocyte sedimentation rate (ESR), and clinical parameters were collected at admission and during hospitalization. MEASUREMENTS AND MAIN RESULTS: Forty-eight of 94 patients (51.1%) hospitalized with complicated PID were diagnosed with TOA sonographically. CRP levels were the strongest predictor of TOA, followed by WBC count, ESR, and fever on admission. The areas under the receiver operating characteristic (ROC) curve for CRP, WBC, ESR, and fever were .92, .75, .73 and .62, respectively. CRP specificity was 93.4% and sensitivity was 85.4% for predicting TOA, with cutoff value of 49.3 mg/L. Twelve patients (25%) failed conservative management and underwent surgical intervention including laparoscopy (n = 7), computed tomography (CT)-guided drainage (n = 4), and laparotomy (n = 1). In this group, CRP levels significantly increased from admission to day 1 and day 2 during hospitalization (128.26, 173.75, and 214.66 mg/L, respectively; p < .05 for both). In the conservative management group, CRP levels showed a plateau from admission to day 1 and then a decrease until day 3 (110, 120.49, 97.52, and 78.45 mg/L, respectively). CONCLUSION: CRP is a sensitive, specific inflammatory marker for predicting TOA in patients with complicated PID, and levels >49.3 mg/L suggest the presence of TOA. In the TOA group, CRP level trends correlated well with success or failure of conservative management. Increasing CRP levels during treatment may be used as an indicator of the need for invasive intervention, and daily CRP measurements can help predict the need for invasive intervention.

The predictive role of CA-125 in the management of tubo-ovarian abscess. A retrospective study.

OBJECTIVE: Tubo-ovarian abscess (TOA) is a well-established sequel of acute pelvic inflammatory disease (PID). While as up to 25% of women will experience conservative treatment failure, the factors associated with treatment failure are not clearly-established, and the role of Cancer antigen 125 (CA-125) is under-studied. We aim to evaluate the role of CA-125 in the conservative management of TOA. STUDY DESIGN: A retrospective cohort study conducted at tertiary university-affiliated hospital during 2007-2018. Ninety one patients were diagnosed with a TOA and underwent a trial of conservative management with intravenous antibiotics. Patients who eventually underwent surgical intervention were compared with patients managed conservatively. RESULTS: Overall, 39/91 (42.8%) underwent an invasive intervention subsequent to failed antibiotic treatment. Patients who experienced conservative treatment failure had higher medians of inflammatory markers as CRP (15.7 vs. 10.8 mg/L, p = 0.02), WBC count (14.2 vs. 12.4 1,000/mm3, p = 0.04) and platelet count (374 vs. 295 109/L, p = 0.04) at admission. Higher levels of CA-125 at admission were found in those who required an invasive intervention (57 vs. 30 U\ml, p = 0.02) as well. The largest diameter of TOA at admission was higher in those who required an invasive intervention as compared to those who were successfully treated conservatively (75 mm vs. 57 mm, p = 0.01). CA-125 level was found to be the only independent factor associated with conservative treatment failure (OR; 95% confidence interval [CI], 1.27, 1.08-1.48, p = 0.03). CONCLUSION: Elevated CA-125 serum levels were found to be associated with failure of conservative parenteral antibiotic therapy for TOA. This finding should be better evaluated in a prospective manner.

Serum procalcitonin levels together with clinical features and inflammatory markers in women with tubo-ovarian abscess for discriminating requirements for surgery for full recovery.

Tubo-ovarian abscess (TOA) coexists in 15% of cases with pelvic inflammatory disease. Medical treatment is the first line of approach in women with TOA, however, 25% of cases fail to respond to antibiotics, therefore, these cases need to undergo surgical intervention. We aimed to determine factors leading to failure of medical treatment in women diagnosed with TOA. According to our results among 144 women, 27 cases required surgical intervention for full recovery. None of the demographic, sonographic or laboratory findings, including procalcitonin level, had significant predictive value for the failure of medical treatment in women with TOA. Impact statement What is already known on this subject? Tubo-ovarian abscess (TOA) coexists in 15% of cases with pelvic inflammatory disease. Medical treatment is the first line approach in women with TOA, however, 25% of cases fail to respond to antibiotics, therefore, these cases need to undergo surgical intervention. Several risk factors have been evaluated in order to predict the failure of medical treatment. What do the results of this study add? None of the variables, including age, parity, mass diameter, serum CRP, procalcitonin levels and sedimentation rate had significant value for predicting TOA cases that required surgical intervention for full recovery. What are the implications of these findings for clinical practice and/or further research? In clinical practice, identification of risk factors leading to the failure of medical treatment helps clinicians to inform patients and help surgeons predict those who need surgical intervention.

Anti-inflammatory effect of Man-Pen-Fang, a Chinese herbal compound, on chronic pelvic inflammation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has become the focus of research for the treatment of chronic pelvic inflammatory disease (CPID) based on unique medical theory system. Man-Pen-Fang (MPF), a Chinese herbal compound, which is composed of Thlaspi arvense L. (Cruciferae), Gleditsia sinensis Lam. (Leguminosae), Smilax china L. (Liliaceae), Euonymus alatus (Thunb.) Sieb. (Celastraceae) and Vaccaria segetalis (Neck.) (Caryophyllaceae) MPF has been used for the treatment of CPID and exerted significant clinical curative effects. However, the corresponding active principles and anti-inflammatory mechanism of MPF are still unknown. AIM OF THE STUDY: The objective of present study is to evaluate the effect of MPF on CPID in the chronic pelvic inflammation (CPI) rat model and elucidate its possible anti-inflammatory mechanism. MATERIALS AND METHODS: The CPI in rats was induced by administration with E. coli, Staphylococcus aureus and Beta-hemolytic streptococcus. MPF (8.112g/(kg d) (20 times of adult dosage), 4.056g/(kg d) (10 times of adult dosage) and 2.028g/(kg d) (5 times of adult dosage)) and Jingangteng Capsule 2g/(kg d) (20 times of adult dosage) were administered orally for 20 days. The serum levels of five inflammation-associated cytokines (IL-2, IL-6, IL-10, TNF-α and TGF-ß1) were determined by enzyme-linked immunoassay, and the mRNA expression levels of TGF-ß1, P53, Fas, FasL and MMP-2 in the uterus tissue were measured by quantitative RT-PCR. Furthermore, the expression of NF-κB p65 in uterus and ovary tissues was detected by immunohistochemistry assay and the pathological changes induced in the uterus and ovary tissues were observed by histology. RESULTS: MPF caused a reduction in serum levels of IL-2, IL-6, IL-10, TNF-α and TGF-ß1. The expression of P53 mRNA, Fas/FasL mRNA and MMP-2 mRNA in the uterus tissue was significantly elevated after treating with MPF, in contrast the expression of TGF-ß1 mRNA was decreased. Furthermore, the expression of NF-κB p65 in uterus and ovary tissue was inhibited after treating with MPF. CONCLUSIONS: These results taken together suggest that MPF has a significant anti-CPID effect, probably due to inhibition of the inflammation reaction by the promotion, and the induction of the apoptosis of inflammatory cells and downregulation of the serum levels of inflammation cytokines.

Chronic Pelvic Inflammation Diminished Ovarian Reserve as Indicated by Serum Anti Mülerrian Hormone.

OBJECTIVE: To explore the potential damaging effect of chronic pelvic inflammation on ovarian reserve. DESIGN: Case-control study. PATIENTS: A total of 122 women with bilateral tubal occlusion, diagnosed by hysterosalipingography (HSG) and 217 women with normal fallopians were recruited. MEASUREMENTS: Serum anti-Mullerian hormone (AMH), basic follicle-stimulating hormone (FSH), luteining hormone (LH), estradiol (E2), and testosterone (T) were measured; and antral follicle counts (AFCs) were recorded. RESULTS: Significantly lower level of AMH was observed in women with bilateral tubal occlusion compared to control group [2.62 (2.95) ng/ml vs. 3.37 (3.11) ng/ml, P = 0.03], and the difference remained after adjustment of BMI (Padjust = 0.04). However, no statistical difference was found in the levels of FSH [7.00 (2.16) IU/L vs. 6.74 (2.30) IU/L], LH [4.18 (1.52) IU/L vs. 4.63 (2.52) IU/L], E2 [35.95 (20.40) pg/ml vs. 34.90 (17.85) pg/ml], T [25.07±11.46 ng/dl vs. 24.84±12.75 ng/dl], and AFC [6.00 (4.00) vs. 7.00 (4.00)] between two groups (p>0.05). CONCLUSIONS: Women with bilateral tubal occlusion showed decreased AMH level, suggesting that chronic pelvic inflammation may diminish ovarian reserve. More caution should be paid when evaluating the detriment of PID on female fertility.

Diagnosis and Management of Adnexal Masses.

Adnexal masses can have gynecologic or nongynecologic etiologies, ranging from normal luteal cysts to ovarian cancer to bowel abscesses. Women who report abdominal or pelvic pain, increased abdominal size or bloating, difficulty eating, or rapid satiety that occurs more than 12 times per month in less than a year should be evaluated for ovarian cancer. Pelvic examination has low sensitivity for detecting an adnexal mass; negative pelvic examination findings in a symptomatic woman should not deter further workup. Ectopic pregnancy must be ruled out in women of reproductive age. A cancer antigen 125 (CA 125) test may assist in the evaluation of an adnexal mass in appropriate patients. CA 125 levels are elevated in conditions other than ovarian cancer. Because substantial overlap in CA 125 levels between pre- and postmenopausal women may occur, this level alone is not recommended for differentiating between a benign and a malignant adnexal mass. Transvaginal ultrasonography is the first choice for imaging of an adnexal mass. Large mass size, complexity, projections, septation, irregularity, or bilaterality may indicate cancer. If disease is suspected outside of the ovary, computed tomography may be indicated; magnetic resonance imaging may better show malignant characteristics in the ovary. Serial ultrasonography and periodic measurement of CA 125 levels may help in differentiating between benign or potentially malignant adnexal masses. If an adnexal mass larger than 6 cm is found on ultrasonography, or if findings persist longer than 12 weeks, referral to a gynecologist or gynecologic oncologist is indicated.

Increased plasma soluble CD40 ligand concentration in pelvic inflammatory disease.

BACKGROUND: The role of soluble CD40 ligand (sCD40L) in pelvic inflammatory disease (PID) remains unclear. We sought to determine whether sCD40L was an efficient serum marker as with WBC and CRP in PID patients. METHODS: Enzyme-linked immunosorbent assay was used to measure the plasma levels of sCD40L before and after routine protocol treatments in sixty-four PID patients and seventy healthy controls. RESULTS: The level of plasma sCD40L (pg/ml) was significantly elevated in PID patients (1632.83±270.91) compared to that in normal controls (700.33±58.77; p=0.001) and decreased significantly as compared to that in the same patients (928.77±177.25; p=0.0001) after they received treatment. The concentration of sCD40L was significantly correlated with the level of plasma C-reactive protein (CRP) in the blood (r=0.202, p=0.01, n=134). When the cutoff level of plasma sCD40L levels was determined to be 1612.26pg/ml based on ROC, the sensitivity, specificity, and the area under the curve of plasma sCD40L level for predicting PID were 0.26, 0.97, and 0.58 (95% confidence interval: 0.48-0.68), respectively, while the adjusted odds ratio (AOR) with their 95% CI of plasma sCD40L for PID risk was 7.09 (95% CI=1.14-43.87, p=0.03). CONCLUSIONS: The expression of plasma sCD40L was increased in patients with PID and detection of plasma sCD40L could be useful for the diagnosis of PID.

Correlation of plasma osteopontin and neutrophil gelatinase-associated lipocalin levels with the severity and clinical outcome of pelvic inflammatory disease.

OBJECTIVE: To investigate the correlation of two important inflammatory biomarkers, plasma osteopontin and neutrophil gelatinase-associated lipocalin (NGAL), with the severity and outcome of pelvic inflammatory disease (PID). MATERIALS AND METHODS: Sixty-one patients with PID, including 25 patients with tubo-ovarian abscess (TOA), were consecutively recruited. Their blood samples were tested for the concentrations of plasma osteopontin and NGAL using enzyme-linked immunosorbent assay. The associations of these biomarkers with TOA, length of hospitalization, and incidence of surgery were also analyzed. RESULTS: Plasma osteopontin level was significantly increased in PID patients with TOA compared to PID patients without TOA (median 107.77 ng/mL vs. 72.39 ng/mL, p = 0.004). However, there was no significant difference for plasma NGAL. If the cutoff level of plasma osteopontin was set at 81.1 ng/mL, there was a 76.0% sensitivity and a 24.0% false negative rate in predicting TOA in PID patients. Plasma osteopontin significantly correlated with length of hospital stay (r = 0.467, p < 0.001), and this correlation was better than that of NGAL. However, neither biomarker was associated with incidence of surgery. CONCLUSION: Plasma osteopontin has a better correlation with TOA and length of hospitalization compared to NGAL. If plasma osteopontin level falls below 81.1 ng/mL, PID patients will have about a 20% chance of developing TOA. Incorporating plasma osteopontin, but not NGAL, will allow for an adjuvant diagnostic biomarker for TOA and predictor of length of hospital stay.

Factors that predict poor clinical course among patients hospitalized with pelvic inflammatory disease.

AIM: The aim of this study was to identify factors that can predict clinical course among patients hospitalized with pelvic inflammatory disease (PID). METHODS: Ninety-three patients who needed hospitalization with a diagnosis of PID were retrospectively studied. Patients who were discharged within 7 days by conservative treatment were defined as favorable course cases (n = 44). Patients who needed more than 7 days of hospitalization and/or surgery were defined as poor course cases (n = 49). Twenty variables were evaluated by univariate and logistic regression analysis: age, history of pregnancy/delivery, gynecological open/laparoscopic surgery, PID, oral contraceptives/intrauterine device use and intrauterine operation before onset, body temperature, signs of peritoneal irritation, vomiting/diarrhea, abnormal vaginal discharge, endometriosis/fibroid/adenomyosis/any cystic lesion detected by ultrasonography, white blood cell counts/C-reactive protein (CRP) levels . The cut-off value was calculated by receiver-operator curve (ROC) analysis. RESULTS: Factors associated with poor clinical course were advanced age (P < 0.01), history of gynecological open surgery (P < 0.05), any cystic lesion detected by ultrasonography (P < 0.05) and high CRP levels (P < 0.05). High CRP levels and intrauterine operation before onset were independently associated with poor clinical course. The cut-off value for CRP was 4.4 mg/dL. CONCLUSION: This study identified variables that can predict poor clinical course of PID. These results can assist gynecologists with identifying patients at risk and optimizing the choice of management.

Measurement of serum and peritoneal levels of amyloid protein A and their importance in the diagnosis of pelvic endometriosis.

OBJECTIVE: To evaluate serum and peritoneal concentrations of amyloid protein A in women with endometriosis and to compare them with those of women without endometriosis. STUDY DESIGN: A prospective study evaluated 76 women suspected of having pelvic endometriosis. Fifty-seven women (group A) were confirmed by videolaparoscopy and had their serum and peritoneal amyloid A concentrations measured by ELISA. The average levels from group A were compared to those obtained in group B. Group B was composed of 13 women without endometriosis, submitted to elective laparoscopy for tubal ligation. RESULTS: Peritoneal amyloid A concentrations in group A (310.3 +/- 97.8 ng/mL) were higher than those of group B (53.4 +/- 58.2 ng/mL); p = 0.0. However, serum concentrations in groups A (14.01 +/- 32.3 ng/mL) and B (9.5 +/- 15.9 ng/mL) did not differ significantly; p = 0.35. CONCLUSION: The peritoneal amyloid A protein concentration in pelvic endometriosis was higher when compared to normal controls, corroborating the inflammatory nature of the disease. This finding suggests that the procedure of evaluating the peritoneal amyloid A concentration in endometriosis merits further investigation.

[Expression of TLR2 and TLR9 genes by epithelial cells of cervical canal mucous membrane in women with inflammatory diseases of small pelvis organs].

AIM: Determine subpopulation composition of blood lymphocytes and the level of expression of TLR2 and TLR9 by epithelial cells of cervical canal mucous membrane in women of reproductive age with inflammatory disease of small pelvis organs (IDSPO) at exacerbation stage and remission period. MATERIALS AND METHODS: Clinical-laboratory and gynecological examination of 105 women was carried out and 3 groups were formed based on the results: patients at IDSPO exacerbation stage; patients at remission stage; clinically healthy women. By using real time PCR, TLR2, TLR9 gene expression levels were determined in epithelial cells of cervical canal mucous membrane in women of all the 3 groups. Subpopulation composition of blood lymphocytes was determined by flow cytofluorimetry by using monoclonal antibodies with CD45+ CD3+ -T-cell, CD45+ CD3+ CD4+ -T-helper, CD45+, CD3+, CD8+ -T-suppressors-cytotoxic killers, CD45+, CD3-, CD16+, CD56+ natural killers, CD45+, CD3-, CD19+ -B-lymphocytes. Immune fluorescence reaction evaluation was carried out in flow cytofluorimeter Cytomics FC 500 (Becton Coulter, USA). RESULTS: The level of expression of TLR2 gene in the studied groups of patients was established not to differ significantly from parameters in the comparison groups, however it should be noted that this parameter in women with IDSPO at exacerbation stage (causative agents of the infectious process--ureaplasma, staphylococcus, candida) was somewhat higher than in the comparison group. Significantly high level of TLR9 gene expression in cervical canal epithelial cells was detected to correlate with the presence of infectious causative agents. In the group of women with exacerbation of the infectious process the expression of TLR9 was 14.5 times higher compared with the group of women without IDSPO. Among groups of women with IDSPO significant differences in relation to control group in relative and absolute levels of CD3+ T-lymphocytes; CD4+ T-helpers; CD8+ cytotoxic killer T-suppressors, B-lymphocytes compared with the same parameters in clinically healthy women were not detected. CONCLUSION: The increase of TLR9 gene expression level in cervical canal cells of women with IDSPO may serve as an additional diagnostic feature of the presence and degree of severity of the disease.

Increased concentrations of plasma growth arrest-specific 6 and its soluble tyrosine kinase receptor sAxl in Taiwanese women with pelvic inflammatory disease.

BACKGROUNDS: To investigate the concentrations of plasma growth arrest-specific protein 6 (Gas6) and its soluble tyrosine kinase receptor sAxl in women with pelvic inflammatory disease (PID) and their association with clinical outcomes of PID. METHODS: Blood specimens were consecutively collected from the 64 patients with PID before and after treatment and 70 healthy women in university hospital. Concentrations of plasma Gas6 and sAxl were detected using enzyme-linked immunosorbent assay. RESULTS: The concentration of plasma Gas6 and sAxl was significantly increased in the patients with PID compared to the healthy controls, and then reduced significantly after treatment. Gas6 was significantly correlated with sAxl. When we selected 7.5 and 15.2 ng/ml as the cutoff concentration of plasma Gas6 and sAxl to detect PID respectively, the sensitivities of Gas6 and sAxl were 76.6% and 75.0%. When Gas6 and sAxl were combined, the sensitivity rose to 92.2%. They were not related to the incidences of tuboovarian abscesses and surgery, which were, however, significantly associated with length of hospital stay. CONCLUSIONS: Novel application of Gas6 or sAxl in combination had a high sensitivity to detect PID and is important in order to prevent severe sequelae.

Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response.

BACKGROUND: Human epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases. METHODS: CA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively. RESULTS: Serum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p = 0.001 and p < 0.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4 + CA125 the sensitivity and PPV reached 96.7% and 97% respectively. CONCLUSION: Measuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759.

Significant association of elevated concentration of plasma YKL-40 with disease severity in patients with pelvic inflammatory disease.

INTRODUCTION: To date, no study reports the implication of YKL-40 in pelvic inflammatory disease (PID). Therefore, we investigate the levels of plasma YKL-40 in patients with PID and further associate its expression with the severity of disease. METHODS: We designed a hospital-based case-control study with approximate 1:1 ratio and consecutively recruited 64 patients with PID and 70 control women. We collected blood samples from 64 women with PID before and after they received treatment and 70 control women to detect levels of plasma YKL-40 and C-reactive protein (CRP) as well as white blood cell and neutrophil counts. RESULTS: The results revealed that levels of plasma YKL-40 were significantly elevated in patients with PID as compared to those in controls (38.36 vs. 21.69 ng/ml, P = 0.001) but the significant difference was restricted to women aged 30 years or old after age stratification (56.75 vs. 23.61 ng/ml, P ≤ 0.001). It declined significantly after they received treatment (median: 38.36 vs. 27.54 ng/ml; P ≤ 0.001). Although both plasma YKL-40 and CRP were elevated in patients with tubo-ovarian abscess, PID patients with surgery exhibited higher YKL-40 concentration than those without surgery (median: 82.05 vs. 30.19 ng/ml, P = 0.005) and only plasma YKL-40 was significantly associated with the length of the hospital stay (P ≤ 0.001, R = 0.604). CONCLUSION: We conclude that once individuals are diagnosed to have PID, YKL-40 may act as a biomarker to predict the severity and clinical outcome of the disease.

Serum HE4 as a useful biomarker in discriminating ovarian cancer from benign pelvic disease.

OBJECTIVE: To evaluate the role of the novel tumor marker human epididymal secretory protein E4 (HE4) in discriminating ovarian cancer from benign pelvic disease in patients with a pelvic mass. METHODS: Serum samples from 131 patients with epithelial ovarian cancer (EOC) and 126 patients with various benign pelvic diseases were collected preoperatively and tested for cancer antigen (CA)125 and HE4 levels. Receiver operator characteristic curves were constructed, and the area under the curve (AUC) was compared between the markers. RESULTS: The median CA125 and HE4 levels were significantly higher in the patients with EOC than in those with benign disease (P < 0.001). Using benign controls as the comparison group for all cases, the AUC for combined HE4 and CA125 (0.955) was significantly higher than that for HE4 (0.941) or CA125 alone (0.924; P < 0.05). A comparison of premenopausal benign controls to EOC cases showed that the AUC for combined HE4 and CA125 (0.97) was significantly higher than that for CA125 (0.93; P < 0.004). The AUC for HE4 was significantly higher compared to that of CA125 in discriminating EOC from ovarian endometriosis (0.969 vs 0.904; P = 0.014) and pelvic inflammatory disease (0.909 vs 0.819; P = 0.034). CONCLUSION: Serum HE4 testing is a more powerful tool than CA125 assay to discriminate EOC from ovarian endometriosis and pelvic inflammatory disease. For patients with a pelvic mass, especially premenopausal patients, the serum concentration of HE4 adds valuable information to CA125 in identifying patients with EOC from those with benign pelvic disease.

The anti-inflammatory and anti-nociceptive activities of Patrinia villosa and its mechanism on the proinflammatory cytokines of rats with pelvic inflammation.

This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX group), and model-control group (CON group) to perform an ear edema test, a carrageenin-induced paw edema test, a cotton pellet-induced granuloma formation test, and an acetic acid-induced writhing test. The model rats with pelvic inflammation were established, and the serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) in each group was detected with the Enzyme-Linked ImmunoSorbent Assay (ELISA). The results of the ear edema test, carrageenin-induced paw edema test, cotton pellet-induced granuloma formation test, and acetic acid-induced writhing test all showed that Patrinia villosa had strong anti-inflammatory and anti-nociceptive effects. In the experiment using model rats with pelvic inflammation, we found that the serum levels of IL-6, IL-8 and TNF-α in PV and DEX group were all significantly lower than those of the CON group, and the serum levels of IL-6 and IL-8 in PV group were significantly lower than those of the DEX group. Patrinia villosa, with its strong anti-inflammatory and anti-nociceptive activities, can be used to treat pelvic inflammation and to relieve the associated pain.

Evaluation of proteomics-identified CCL18 and CXCL1 as circulating tumor markers for differential diagnosis between ovarian carcinomas and benign pelvic masses.

A lack of sensitive and specific tumor markers for early diagnosis and treatment is a major cause for the high mortality rate of ovarian cancer. The purpose of this study was to identify potential proteomics-based biomarkers useful for the differential diagnosis between ovarian cancer and benign pelvic masses. Serum samples from 41 patients with ovarian cancer, 32 patients with benign pelvic masses, and 41 healthy female blood donors were examined, and proteomic profiling of the samples was assessed by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy (MS). A confirmatory study was also conducted with serum specimens from 58 patients with ovarian carcinoma, 37 patients with benign pelvic masses, and 48 healthy women. A classification tree was established using Biomarker Pattern Software. Six differentially expressed proteins (APP, CA 125, CCL18, CXCL1, IL-8, and ITIH4) were separated by high-performance liquid chromatography and identified by matrix-assisted laser desorption/ionization (MALDI)-MS/MS and database searches. Two of the proteins overexpressed in ovarian cancer patients, chemokine CC2 motif ligand 18 (CCL18) and chemokine CXC motif ligand 1 (CXCL1), were automatically selected in a multivariate predictive model. These two protein biomarkers were then validated and evaluated by enzyme-linked immunosorbent assay (ELISA) in 535 serum specimens (130 ovarian cancer, 64 benign ovarian masses, 36 lung cancer, 60 gastric cancer, 55 nasopharyngeal carcinoma, 48 hepatocellular carcinoma, and 142 healthy women). The combined use of CCL18 and CXCL1 as biomarkers for ovarian cancer had a sensitivity of 92% and a specificity of 97%. The multivariate ELISA analysis of the two putative markers in combination with CA 125 resulted in a sensitivity of 99% for healthy women and 94% for benign pelvic masses, and a specificity of 92% for both groups; these values were significantly higher than those obtained with CA 125 alone (p and lt;0.05). We conclude that serum CCL18 and CXCL1 are potentially useful as novel circulating tumor markers for the differential diagnosis between ovarian cancer and benign ovarian masses.