Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic.

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.

Pregnancies in women receiving renal transplant for lupus nephritis: description of nine pregnancies and review of the literature.

BACKGROUND: Few data are available on pregnancy in renal transplanted women for lupus nephritis (LN). METHODS: Among 38 women with LN who received a renal transplant in our Unit, three had nine pregnancies. During the pregnancies, patients were followed by a multidisciplinary team including gynecologists and nephrologists. RESULTS: Two patients received a living related and one a deceased kidney transplant. The immunosuppressive therapy consisted of steroids calcinurin inhibithors and mycophenolate mofetil. The last drug was substituted with azathioprine in prevision of pregnancy. All patients had normal renal function and urinalysis. In two patients some signs of immunological activity persisted after transplantation. Five pregnancies ended in miscarriage and four in live births. Two pregnancies were uneventful. Pre-eclampsia occurred in a hypertensive patient in two pregnancies that ended in preterm delivery in one case and in a small for gestation age in both cases. And finally, follow-up graft function and urinalysis continued to be normal in all patients. CONCLUSIONS: After renal transplantation our LN women continue to have frequent miscarriages. The other pregnancies ended in live births and, with the exception of pre-eclampsia in a hypertensive patient, no renal or extra-renal complications occurred during or after pregnancy, even in cases with active immunological tests.

Obstetric and vascular APS: same autoantibodies but different diseases?

Beta2 glycoprotein I (ß2GPI)-dependent antiphospholipid antibodies (aPLs) are the main pathogenic autoantibody population and at the same time the laboratory diagnostic tool for the antiphospholipid syndrome (APS). These antibodies are responsible for both the vascular and the obstetric manifestations of the syndrome but the pathogenic mechanisms behind these manifestations are not the same. For example, thrombotic events do not appear to play a major role in APS miscarriages and a direct reactivity of ß2GPI-dependent aPLs on decidual and trophoblast cells was reported. A local expression of ß2GPI on these tissues was reported both in physiological conditions and in APS women, thus explaining the local tropism of the autoantibodies. The two hit hypothesis was suggested to explain why the vascular manifestations of APS may occur only occasionally in spite of the persistent presence of aPLs. This is not apparently the case for the obstetric variant of the syndrome, making the difference even more striking. A different pathogenesis may also provide the rationale for the well-known fact that the vascular and the obstetric manifestations may occur independently although in a minority of cases.

Monitoring and treatment of anti-D in pregnancy.

Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.

Immune function in children born to mothers with autoimmune diseases and exposed in utero to immunosuppressants.

The administration of immunosuppressive drugs during pregnancy is often necessary in women with autoimmune diseases. Teratogenicity of immunosuppressives during pregnancy has been evaluated, only few data exist about the effects on immune systems. We therefore performed a pilot study on the influence of foetal exposure to immunosuppressives on immune function of babies born to mothers with autoimmune disorders. We investigated serological and cellular parameters as indicators of immune system status. We included in the study 14 babies (mean age 11 months, range 1-24) born to mothers with autoimmune diseases and exposed in utero to different immunosuppressants and, as controls, 14 babies whose mothers had autoimmune manifestations but did not receive immunosuppressive therapy. We evaluated: (i) complete blood count, (ii) immunoglobulin levels and IgG subclasses, (iii) antibody response to hepatitis B vaccine, (iv) leukocyte subpopulations and (v) interleukin-2 and interferon gamma in vitro production by resting or activated peripheral blood mononuclear cells. We did not find statistically significant differences between exposed and not exposed babies or among treatments for the tested parameters. Immunosuppressive regimens currently in use for controlling maternal autoimmune disorders do not significantly affect the immune status of the offspring.

Electrocardiographic abnormalities in infants born from mothers with autoimmune diseases--a multicentre prospective study.

OBJECTIVES: To assess the prevalence of congenital heart block (CHB) and electrocardiographic (ECG) abnormalities in infants of anti-Ro/SSA-positive women. METHODS: Sixty anti-Ro-positive and 36 anti-Ro-negative patients were prospectively followed before/during pregnancy and underwent weekly fetal echocardiography from 18th to 26th weeks of gestational age. Infants' ECG and/or ECG-Holter were performed at 1, 3, 6 and 12 months. ECG of 200 consecutive neonates were used as a healthy control group. RESULTS: One of 61 fetuses of anti-Ro-positive mothers developed CHB (20th week); another anti-Ro-positive baby developed second degree atrioventricular (AV) block (30th week). The prevalence of transient first degree AV block detected post-natally was significantly higher in the anti-Ro-positive group, in comparison with healthy controls (P = 0.002). No differences in corrected QT (QTc) interval prolongation prevalence (>/=440 ms) was observed between the anti-Ro-positive and -negative groups, but both were significantly higher than that of the control population (P < 0.001). ECG-Holter showed QTc prolongation in 59% of infants of anti-Ro-positive and in 60% of infants of anti-Ro-negative mothers. Holter QTc was >/=470 ms in four infants of anti-Ro-positive group and two of anti-Ro-negative group. Known acquired causes of QTc prolongation were excluded. CONCLUSIONS: This prospective study confirms the low occurrence of CHB in newborns from anti-Ro-positive mothers. ECG abnormalities (first degree AV block and QTc interval prolongation) are frequent in infants of mothers with autoimmune diseases, independently of maternal disease, autoantibody profile and treatment during pregnancy.

Neonatal lupus: fetal myocarditis progressing to atrioventricular block in triplets.

We report a case of neonatal lupus syndrome (NLS) in an in vitro fertilization induced triplet pregnancy. Echocardiographic signs of myocarditis were evident at the 21st week of gestation (w.g.) in twin I, with a subsequent development of a complete atrioventricular (AV) block at the 25th w.g.; twin III also displayed echocardiographic signs of myocarditis at the same time. Treatment with dexamethasone (4mg/day) was started at the 25th w.g. A complete echocardiographic regression of the myocarditis signs was achieved, while AV block was unaffected. Caesarian section was performed at the 31.5 w.g. after a premature rupture of the membranes. Complete AV block was confirmed in twin I with a heart rate of 51 beats/min that required a pacemaker implant 40 days after. Twin III developed a first-degree AV block that switched to a periodic second-degree block later, while twin II displayed only liver enzyme abnormalities.

Pregnancy complications of the antiphospholipid syndrome.

Starting from their first description, antiphospholipid antibodies (aPL) were associated with repeated miscarriages and fetal losses. Other complications of pregnancy like preterm birth,with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome (APS). The titre, the isotype of the antibodies or their antigen specificity may be important in the risk level determination. Some of the difference in the reported results can be explained by the poor standardization achieved in aPL testing or by the not univocal classification of pregnancy complications. The pathogenesis of pregnancy failures is linked to the thrombophilic effect of aPL but also to different mechanisms including a direct effect of antibodies on the throphoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of aPL both in lupus prone and naive mice. The definition of APS as a condition linked to high obstetric risk and the application of an effective therapy have completely changed the prognosis of pregnancy in these patients. In fact, despite the high number of complications and preterm delivery, today a successful outcome can be achieved in the large majority of the cases.

Formulation study and anti-inflammatory efficacy of topical semi-solids containing a nitro ester of flurbiprofen.

A new nitro-oxybutylester of flurbiprofen (NO-FP) is a promising anti-inflammatory drug in the treatment of dermatological disorders, and the feasibility of its cutaneous administration was evaluated. Four different semi-solid formulations were evaluated in order to assess the influence of the composition on the drug amount retained in the stratum corneum and epidermis (SCE). The lipophilic ointment induced the highest NO-FP amount retained in the SCE and, therefore, skin permeation enhancers (Transcutol), Lauroglycol), oleic acid and isopropyl myristate) were added to this formulation. The in vitro NO-FP amounts retained in the SCE were correlated with the solubility parameters, and a good linear correlation was found (r(2) = 0.925). The formulation of the lipophilic ointment was optimized, and the activity of this preparation was verified in methyl-nicotinate-induced contact urticaria and UV-induced erythema obtaining good results in terms of efficacy and safety.

Fetal and maternal white cells and B- and T-lymphocyte subpopulations in pregnant women with recent infection.

OBJECTIVE: To study maternal and fetal white cell counts, B- and T-lymphocyte subpopulations in pregnant women with evidence of recent infection. METHODS: Thirty-seven pregnant women with recent infection and 38 controls were studied. All were referred for fetal blood sampling to exclude congenital infection, or to perform fetal chromosome analysis. There were 16 infected fetuses: 9 cytomegalovirus (CMV), 4 rubella, and 3 toxoplasmosis. Maternal and fetal blood was taken and white cell counts, the percentage of CD3+, CD4+, CD8+, CD56+, HLADR+CD3+ T-lymphocyte subpopulations and CD19+ B lymphocytes were measured. RESULTS: The percentage of CD3+, CD8+, and HLADR+CD3+ lymphocytes were significantly higher in infected mothers compared to controls, while CD19+ and the CD4+/CD8+ ratio were lower. Infected mothers carrying infected fetuses had significantly lower white blood cell counts compared to those infected mothers without fetal infection. The percentage of HLADR+CD3+ T lymphocytes was significantly higher and the CD4+/CD8+ ratio lower in infected fetuses compared to controls and noninfected fetuses of infected mothers. Abnormal CD4+/CD8+ ratios and/or increased HLADR+CT3+ T lymphocytes were found in 8 of 10 fetuses with structural abnormalities and/or hematological/biochemical signs of systemic damage, and in 7 of 27 without (RR = 3.1, 95% CI = 1.5-6.3). CONCLUSION: Both infected fetuses and their mothers have significant identifiable changes in white cell counts and T-lymphocyte subpopulations compared to controls. These tests may help in diagnosing maternal and fetal infection.

Serial amniocenteses in the management of twin-twin transfusion syndrome: when is it valuable?

Serial decompressive amniocenteses were performed at 18-23 weeks of gestation in 23 pregnancies referred due to echographic signs typical of twin-twin transfusion syndrome. The procedures were repeated until delivery or permanent normalization of the amniotic fluid volume both in the donor and the recipient twin sac. The overall survival rate was 57%, but in only 39% of the pregnancies did both twins survive without handicaps. The absence of end diastolic flow in the umbilical artery of the donor twin was associated with poor chances of survival for both fetuses; in contrast, the presence of hydrops or ascites in the recipient twin did not worsen the prognosis. A policy of aggressive amniotic fluid decompression may achieve permanent resolution of the fluid in over 50% of the pregnancies complicated by twin-twin transfusion syndrome.

Serum beta 2-microglobulin in fetuses with urinary tract anomalies.

OBJECTIVE: Our purpose was to establish a reference range of fetal serum beta 2-microglobulin, an index of glomerular filtration rate, and to compare the values obtained in fetuses with urinary tract anomalies with this range. STUDY DESIGN: Serum beta 2-microglobulin was measured in 53 control fetuses at 18 to 39 weeks' gestation and in 14 fetuses with urinary tract anomalies, 9 of which had simultaneous urine sampling. RESULTS: In controls fetal serum beta 2-microglobulin had a mean value of 3.4 mg/L (95% data intervals 2.0 to 4.9) and did not correlate with gestational age. In the 14 fetuses with urinary tract anomalies beta 2-microglobulin levels were increased overall compared with controls (median Z score 1.7, range -0.1 to 9.2), and this was also the case in the five fetuses with unilateral renal disorders (median Z score 1.7, range -0.1 to 3.8) and in a fetus who underwent vesicoamniotic shunting and had normal renal function at birth. Serum beta 2-microglobulin was normal in 4 fetuses with bilateral urinary tract obstruction and normal function at postnatal follow-up and also in 1 of 5 fetuses with renal failure. In fetuses with bilateral uropathy urinary sodium correlated with serum beta 2-microglobulin levels. CONCLUSIONS: Increased values of serum beta 2-microglobulin in fetuses with urinary tract anomalies indicate an impaired glomerular filtration rate. The finding of raised concentrations in fetuses with unilateral damage suggests that the compensatory role of the normal kidney is not complete during intrauterine life. Larger series are required to ascertain whether fetal blood sampling is warranted in the antenatal investigation of renal function, especially in view of the close correlation between urinary sodium and serum beta 2-microglobulin levels in fetuses with bilateral obstruction.

In fetuses with isolated hydronephrosis, urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) have a limited role in the prediction of postnatal renal function.

Seventy-one fetal urine samples were taken from the bladder or renal pelvis of 33 fetuses at 13-36 weeks' gestation with a diagnosis of urinary tract anomaly. Severe isolated hydronephrosis in the absence of an enlarged bladder was the indication for sampling in 12/33 fetuses (26 samples), who were retrospectively classified into three groups: normal, intermediate, and dysplastic, based on the evaluation of postnatal renal function or histology. For all samples, urinary sodium (Na+), calcium (Ca2+), creatinine, beta 2-microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG) were measured. Among the 71 fetal urine samples, both beta 2-microglobulin and NAG correlated inversely with gestational age, Na+, and Ca2+, but not with creatinine concentrations. However, the correlation of urinary beta 2-microglobulin with gestational age was dependent on the Na+ and Ca2+ concentrations, whereas urinary NAG correlated significantly with urinary Na+ and Ca2+, and also with gestational age. In fetuses with isolated hydronephrosis, only Na+, and not Ca2+, was significantly related to both beta 2-microglobulin and NAG. Only Na+ and beta 2-microglobulin were significantly, and similarly, higher in both dysplastic and intermediate kidneys when compared with fetuses with normal postnatal function. If only the last urine sampled was considered, there was overlapping of all parameters in the three groups. In isolated hydronephrosis, only the most extreme forms of renal failure might be suggested by elevated levels of Na+, Ca2+, beta 2-microglobulin, and NAG, without an obvious superiority of any of these parameters.

Treatment with a gonadotrophin releasing hormone agonist before endometrial resection: a multicentre, randomised controlled trial.

OBJECTIVES: To ascertain whether treatment with a gonadotrophin releasing hormone agonist before endometrial resection reduces absorption of distension fluid and operating time and facilitates the procedure. DESIGN: A multicentre, prospective, randomised controlled study. PARTICIPANTS: Seventy-one premenopausal women with established menorrhagia. INTERVENTIONS: Eight weeks of goserelin depot treatment before endometrial resection of immediate surgery in the early proliferative phase of the cycle. MAIN OUTCOME MEASURES: Irrigation fluid deficit, operating time and degree or difficulty of the procedure. RESULTS: After randomisation eight women withdrew from the study, leaving 33 women in the goserelin arm and 30 in the immediate surgery arm. Mean (SD) operating time was 15.1 (9.0) min in the goserelin group versus 16.9 (9.5) min in the controls; mean difference + 1.8 min, 95% CI, -2.9 to + 6.4. Mean (SD) distension medium deficit was, respectively, 422 (287) ml versus 564 (291 ml); mean difference + 142 ml, 95% CI -4 to + 288. The goserelin effect was restricted to the 29 women with adenomyosis as the mean (SD) fluid deficit was considerably less in the 19 treated women than in the 10 controls (299 (206) ml versus 597 (135) ml; mean difference + 298 ml, 95% CI + 149 to + 447). The surgeons classified the intraoperative difficulties as none in 6, minimal in 20, moderate in 7, and severe in no cases in the goserelin group; corresponding figures in the group without pretreatment were 2, 14, 13, and 1. CONCLUSIONS: Goserelin administration before endometrial resection may reduce absorption of fluid at surgery in women with adenomyosis and may facilitate intrauterine operating conditions.

Laparoscopic uterine biopsy for diagnosing diffuse adenomyosis.

OBJECTIVE: To investigate the possibility of diagnosing diffuse adenomyosis with the uterus in situ. STUDY DESIGN: Myometrial needle biopsy was performed on a prospectively evaluated series of 72 women undergoing laparoscopy for infertility and/or chronic pelvic pain. Before surgery the patients completed a questionnaire on the presence and severity of dysmenorrhea according to a linear analog and verbal rating scale. A single specimen was taken from along the median line in the upper third of the posterior uterine wall using a 14-gauge Tru-cut needle inserted through the anterior abdominal wall under laparoscopic guidance. RESULTS: No complications occurred. Adenomyosis was diagnosed in 8 of the 42 subjects with menstrual pain and 5 of the 30 asymptomatic ones (19% versus 17%) and pelvic endometriosis in 27 and 10, respectively (64% versus 33%, P = .02). The frequency of moderate or severe dysmenorrhea was greater in women with adenomyosis than in those without adenomyosis or endometriosis, but the difference was not statistically significant. Conversely, menstrual pain was significantly more frequent and severe in patients with endometriosis as compared with women who had neither endometriosis nor adenomyosis. CONCLUSION: Uterine needle biopsy is simple, rapid and safe, but its overall clinical importance, as well as the predictive value of a normal histologic result, requires further investigation.

Endometriosis and pelvic pain: relation to disease stage and localization.

OBJECTIVES: To determine whether prevalence and severity of pain symptoms are related to endometriosis stage and site, with particular reference to deep infiltrating vaginal lesions. DESIGN: Systematic assessment of chronic pelvic pain symptoms. SETTING: University hospital endometriosis center. PATIENTS: A total of 244 consecutive symptomatic patients with endometriosis diagnosed at laparoscopy or laparotomy. INTERVENTIONS: Assessment of dysmenorrhea and nonmenstrual pain by means of a 10-point linear analog scale, a 7-point multidimensional rating scale, and a 3-point verbal scale; evaluation of deep dyspareunia with the first and third systems only. MAIN OUTCOME MEASURES: Prevalence and severity of pain symptoms in relation to endometriosis stage and site of lesions. Correlation between revised American Fertility Society score and symptoms severity, as well as between two pain scales to assess dysmenorrhea and nonmenstrual pain. RESULTS: Eighty-eight women had stage I and II disease and 156 had stage III and IV disease. Only ovarian endometriosis was present in 108 patients, only peritoneal implants were present in 37, combined ovarian and peritoneal lesions were present in 57, and histologically confirmed vaginal endometriosis was present in 42. The frequency and severity of deep dyspareunia and the frequency of dysmenorrhea were less in patients with only ovarian endometriosis than in those with lesions at other sites. Patients with vaginal endometriosis had a significantly increased risk of deep dyspareunia compared with those whose lesions were at other sites (odds ratio, 2.55; 95% confidence interval, 1.21 to 5.39). Stage per se, independent of lesion site, was not correlated with frequency and severity of dysmenorrhea and nonmenstrual pain. The severity of deep dyspareunia was related inversely to the endometriosis score (Spearman correlation coefficients for linear analog and verbal rating scales, respectively, -0.22 and -0.20). Kendall test by ranks revealed a correlation between linear analog and multidimensional pain scales in the rating of both dysmenorrhea and nonmenstrual pain (respectively, tau-b, 0.59 and tau-b, 0.68). CONCLUSIONS: Endometriosis stage in the current classification was not related consistently to pain symptoms. The presence of vaginal lesions was associated frequently with severe deep dyspareunia. Dysmenorrhea and nonmenstrual pelvic pain were assessed with equal accuracy by a linear analog and a multidimensional scale.

Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study.

OBJECTIVES: To evaluate the efficacy and safety of very low dose danazol in improving pelvic pain in women with endometriosis, the benefit of preceding the treatment by a short course of a GnRH agonist, symptoms recurrence after drug withdrawal, and variations in menstrual pattern. DESIGN: Open-label, randomized study. SETTING: University hospital endometriosis center. PATIENTS: Forty-two women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis. INTERVENTIONS: Treatment with oral danazol, 50 mg/d, for 9 months (group I, n = 21) or leuprolide depot for 3 months followed by oral danazol, 50 mg/d, for 6 months (group II, n = 21), and a 6-month follow-up. MAIN OUTCOME MEASURES: Variations in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale; menstrual blood loss as assessed by a pictorial chart. RESULTS: Four patients withdrew from the study, one in each group at the fifth month of treatment (for persistent pain) and one in each group during follow-up (they requested additional therapy); one woman in group I was lost to follow-up. Significant improvements were obtained in dysmenorrhea, deep dyspareunia, and nonmenstrual pain in both treatment schedules without differences between the groups. Also menstrual blood loss was significantly reduced in both groups. A temporary fall in high and rise in low density lipoprotein cholesterol was observed in the study population. At the end of follow-up symptoms recurred without significant differences in median pain scores with respect to baseline. CONCLUSION: Very low dose danazol may be an alternative for temporary relief of endometriosis-associated pain. Ovulation is not always inhibited and barrier contraception is needed. Side effects occur but are rarely severe. Further data are required to evaluate the influence of long-term administration on the lipid profile.

Veralipride for hot flushes induced by a gonadotropin-releasing hormone agonist: a controlled study.

OBJECTIVES: To evaluate the efficacy of veralipride, a benzamide derivative, in the treatment of hot flushes induced by GnRH agonists (GnRH-a) and to study peripheral blood mononuclear cell beta-endorphin concentrations during drug administration. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Academic department of obstetrics and gynecology. PATIENTS: Forty women of mean age 43 +/- 5 years who experienced disturbing hot flushes during a 4-month course of tryptorelin depot for myoma-associated menorrhagia. INTERVENTIONS: Treatment with oral veralipride 100 mg/d (20 subjects) or matching placebo (20 subjects) during the third month of GnRH-a administration. MAIN OUTCOME MEASURES: Modifications of frequency and severity of hot flushes as shown by a 0 to 6-point vasomotor scoring system and variations of beta-endorphin levels in peripheral blood mononuclear cells. RESULTS: Two subjects in each group dropped out of the study. The median (range) vasomotor score at the end of the second month of treatment was 4 (3 to 6) in both the veralipride and placebo group. At the end of the third and fourth months the median (range) scores were, respectively, 2 (0 to 6) versus 4 (1 to 6) and 2 (0 to 5) versus 4 (1 to 6). No significant variations in mononuclear cell beta-endorphin concentrations were recorded. Serum PRL levels rose from 11.7 +/- 5.7 to 132.3 +/- 65.0 ng/mL (conversion factor to SI unit, 1.0) during veralipride administration and returned to 10.6 +/- 3.7 ng/mL after drug withdrawal. CONCLUSION: Veralipride reduced vasomotor symptoms induced by a GnRH-a. Transient hyperprolactinemia was the main side effect observed. The mode of action of the drug in GnRH-a-treated patients and possible interactions with endogenous opioid peptides need further elucidation.

Serum and Cyst Fluid Tumor Marker Levels in the Differential Diagnosis of Benign Ovarian Cysts

Serum and cystic fluid levels of CA 125, CA 19.9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) were assayed in 74 consecutive women of median age 30 years (range 15 to 74 years) undergoing surgery for adnexal cysts of presumed benign nature. Median (range) serum levels of CA 125, CA 19.9, CEA and AFP were 46.5 IU/ml (4.3-406), 28.5 IU/ml (1-96.3), 1.4 ng/ml (0.5-3.5) and 2.4 ng/ml (1-9.9) in 44 endometriotic cysts; 22.5 (4.7-82), 4.9 (1-226),1.3 (0.7-4.8) and 4 (0.5-10.5) in 11 dermoid cysts, 14 (8.6-25.1), 3.2 (1-6), 1 (0.3-2.8) and 3.7 (1.9-6) in 9 mucinous cysts, and 6.9 (0.5-104), 18 (1-132), 0.8 (0.1-1.9) and 2.1(1-5.4) in 10 cases with mixed histotypes. Corresponding cystic fluid levels were 342,864 (1,418-3,404,682), 228,000 (117-2,500,000), 106 (0.5-2,908) and 1.3 (0.4-51) in endometriomas; 843,895 (10,842-1,676,948), 740,039 (77-1,280,000), 470 (61-880) and 2.5 (1-4) in dermoids; 3,485 (27.2-149,804), 9,007 (36.4-153,475), 1,631 (402-11,096) and 1 (0.5-2.5) in mucinous cysts, and 13,068 (5,300-43,767), 412 (1-142,700), 0.8 (0.4-5.3) and 2.3 (1-4) in the mixed histotype group. No significant between group differences were detected in serum marker levels. Patients in the mucinous cyst group had significantly lower CA 125 cystic fluid levels compared with women with endometriomas and dermoids (P<0.05). Fluid aspirate tumor marker measurements did not aid in the differential diagnosis of benign ovarian cysts, mainly due to the extremely wide scattering of values.