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PubMed2001

Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors often affect women of childbearing age and the prognosis is outstanding. Given the young age of several patients and the good prognosis, fertility-sparing surgery is considered adequate for stage I tumors. However, women treated conservatively have a relatively small but well-defined risk of recurrence and no study has specifically addressed the optimal follow-up technique. METHODS: From 1981 to 1997, 164 women underwent fertility-sparing surgery for stage I borderline ovarian tumor and were followed prospectively. After surgery all women underwent physical examination and ultrasound examination every 3 months for 2 years after first diagnosis and every 6 months thereafter. Measurement of serum CA 125 levels was planned every 6 months in patients with a serous tumor. RESULTS: With a median follow-up of 71, months 28 women treated with fertility-sparing surgery (28/164 = 17%) had either recurrence of borderline tumor (23) or recurrence with carcinoma. Complete details of follow-up procedures are available for 24 women and they represent the study population. An abnormal adnexal mass was detected in 18 of 19 women with recurrent borderline tumor. One patient had diagnosis due to persistent free fluid. All five women with invasive carcinoma had diagnosis of a complex adnexal mass. Gynecologic examination was suspicious (palpable mass) in 7 cases and obviously abnormal (large mass or nodules) in another 7. CA 125 serum levels were elevated in 8 cases. CONCLUSION: Transvaginal ultrasound is currently the most effective diagnostic technique for the follow-up of young patients treated conservatively for early borderline ovarian tumor.

Adenocarcinoma, Mucinous↗
PubMed2001

Risk factors for epithelial borderline ovarian tumors: results of a Swedish case-control study.

OBJECTIVE: Borderline ovarian tumors have a favorable prognosis. Previous epidemiological studies indicate common risk factors for invasive epithelial ovarian cancers and borderline tumors, but it remains unresolved whether these tumors are precursors of invasive cancers or a separate disease entity. The objective of this population-based case-control study conducted in 1993-1995 was to examine reproductive and other factors in relation to the risk of borderline ovarian tumors. METHODS: Subjects were 193 histologically verified incident epithelial borderline tumor cases and 3899 randomly selected controls aged 50-74 years, whose data were collected through mailed questionnaires. Risk estimates were calculated by unconditional logistic regression. RESULTS: Ever parous women were at reduced risk, with odds ratios of 0.44 (95% confidence interval (CI) 0.26-0.75) for serous and 0.63 (95% CI 0.34-1.19) for mucinous tumors. No clear trends emerged for age at first birth, at menarche, and at menopause. Lactation reduced tumor risk. Oral contraceptive ever use conferred no protection, with odds ratios of 1.40 (95% CI 0.87-2.26) for serous and 1.04 (95% CI 0.61-1.79) for mucinous tumors. The odds ratio for serous tumors following unopposed estrogen ever use was 2.07 (95% CI 1.08-3.95), whereas no risk increase appeared with estrogens supplemented by cyclic or continuous progestins. Mucinous tumors were not associated with hormone replacement therapy. The odds ratio for serous tumors in the highest category of body mass index was 6.47 (95% CI 3.09-13.5). CONCLUSIONS: Increasing parity and lactation reduce the risk of borderline ovarian tumors in women aged 50-74, while no protection follows oral contraceptive use. Hormonal situations such as unopposed estrogen use and obesity, where estrogens are not counteracted by progestins, may increase the risk of serous tumors.

Aged↗
PubMed1985

Borderline-tissues as sites of antigen deposition and persistence--a unifying concept of rheumatoid inflammation?

In organs of rheumatoid inflammation avascular tissue is nourished by perfusion either directly from the blood stream or by neighbouring blood vessels (borderline-tissue). An open question remains whether this borderline-tissue promotes only the known antigen persistence, or also the first deposition of the pathogenetically important microbial antigen, and subsequently a deposition of immune complexes. The three markers (carbon, latex, and living bacteria) used in this study led to nearly the same pattern of deposition in two groups of organ systems: Organs with clearance function belonging to the mononuclear phagocyte system (MPS); organs with borderline-tissues: joint, kidney, artery, heart valve, and eye. This deposition at the borderline can be observed best in areas of the joint where highly vascularized tissues are adjacent to avascular tissues nourished via perfusion: perichondrium, peritendineum, periosteum, and endo- and perimysium. These localisations of particle deposition correspond exactly with the intraarticular predilection sites of chronic rheumatoid inflammation in man and animals. Our results indicate an easier settlement of corpuscular material in these localisations, which at the same time are unable to eliminate such substances, unlike the organs of the MPS. Our studies seem to support the theory of pathogenetic importance of the borderline-tissues as a localizing factor in the perpetuating rheumatoid inflammation.

Animals↗
PubMed2007

Perinatal outcomes of pregnancies with borderline amniotic fluid index.

OBJECTIVE: Our aim was to determine whether a borderline amniotic fluid index observed during antepartum testing confers a significant risk of adverse perinatal outcome. METHODS: Between April 2001 and May 2005, uncomplicated gestations with a singleton non-anomalous fetus, who underwent weekly monitoring of amniotic fluid index (AFI) until delivery during the last trimester and who gave birth at our hospital, were identified for our study. Normal amniotic fluid volume and borderline amniotic fluid were defined as AFI of >10 and <24 cm and >5 and <10 cm, respectively. The groups were compared on maternal data, mode of delivery and perinatal outcomes such as fetal distress, intrauterine growth restriction and meconium fluid. RESULTS: A total of 90 cases were identified as borderline amniotic fluid and 277 cases as normal AFI. We observed significant increased incidences of admission to neonatal intensive care unit, intrauterine growth restriction, meconium-stained amniotic fluid, intrapartum fetal distress in the group with borderline amniotic index (P < 0.05). CONCLUSIONS: A borderline amniotic fluid index observed in antepartum testing during the last trimester carries an increased risk of adverse perinatal outcomes. These patients should be followed up carefully during the antepartum and intrapartum period.

Amniotic Fluid↗
PubMed2005

Aberrant hypermethylation of RASSF1A promoter in ovarian borderline tumors and carcinomas.

The newly identified 3p21.3 tumor suppressor gene RASSF1A is inactivated by hypermethylation in variable solid tumors, including those of the lung, breast, prostate, kidney, and ovary. The purpose of this study was to evaluate the methylation status of RASSF1A in various types and stages of ovarian epithelial tumors. We analyzed the DNA methylation status of ovarian tumors using methylation-specific polymerase chain reaction in 54 frozen ovarian tumor tissues and in 97 cases of archival ovarian serous epithelial tumors using a microdissection procedure. Hypermethylation statuses were examined vs clinicopathologic findings. RASSF1A promoter methylation rates in the various types of fresh ovarian tissues were as follows: serous cystadenoma (1/5), serous tumor of borderline malignancy (2/7), serous adenocarcinoma (4/10), mucinous cystadenoma (0/5), mucinous tumor of borderline malignancy (2/7), mucinous adenocarcinoma (3/6), transitional-cell carcinoma (1/3), clear-cell carcinoma (3/3), and malignant müllerian mixed tumor (3/3). In archived serous tumor tissues, RASSF1A promoter hypermethylation was detected in serous cystadenoma (1/6, 16.6%), serous tumor of borderline malignancy (20/41, 48.8%), and in serous adenocarcinoma (25/50, 50%). The status of RASSF1A hypermethylation in borderline tumors was found to correlate statistically with the presence of microinvasion (p=0.002), peritoneal implant (p<0.001), and bilaterality (p=0.019). The RASSF1A promoter hypermethylation was frequently found in borderline tumors and carcinomas, suggesting that RASSF1A promoter hypermethylation may be a useful molecular marker for the early detection of ovarian tumors.

Adenocarcinoma↗
PubMed1975

Autonomic nervous cardiovascular regulation in borderline hypertension.

Borderline hypertension attracts investigative interest since it is an early predictor of established hypertension and its sequelae. This condition offers the opportunity of studying arterial hypertension at its inception, before the development of secondary pressure-related changes. A number of abnormalities of the circulation have been described in borderline hypertension. The peripheral resistance is either elevated or inappropriately adjusted to the prevailing increased cardiac output and blood flow. Cardiac output, heart rate and stroke volume are elevated in a proportion of patients. Decreased plasma volume, enhanced pressor responsiveness and elevated plasma renin activity have also been noted. All these changes could hypothetically be explained by a neurogenic mechanism. Although the experimental evidence supporting a neurogenic origin of borderline hypertension is incomplete and often indirect, most findings point toward an abnormal autonomic control of the circulation in this disorder. It is postulated that in a subgroup of patients with borderline hypertension a neurogenic mechanism is in fact operative. There is a need for further characterization of this category of borderline hypertension and for description of its natural history, particularly in relation to the possible subsequent development of essential hypertension.

Autonomic Nervous System↗
PubMed1993

Echocardiographic assessment of left ventricular structure and diastolic filling in elderly subjects with borderline isolated systolic hypertension (the Framingham Heart Study).

Abnormalities in left ventricular (LV) structure and function have been shown in patients with diastolic hypertension and recently in subjects with isolated systolic hypertension. The purpose of this study was to determine whether abnormalities of cardiac structure or function are present in elderly subjects with borderline isolated systolic hypertension (defined as systolic blood pressure [BP] between 140 and 159 mm Hg, and diastolic BP < 90 mm Hg). Ninety-one subjects (mean age 77 years) from the original Framingham Heart Study with untreated borderline isolated systolic hypertension, who were free of cardiovascular disease, were compared with 139 normotensive (BP < 140/90 mm Hg) subjects (mean age 76 years). Measurements included M-mode values for LV structure, and 6 Doppler indexes of LV diastolic filling. Subjects with borderline isolated systolic hypertension and the control group differed in mean systolic (147 vs 125 mm Hg) and diastolic (76 vs 70 mm Hg) BP. Borderline systolic hypertension was the most frequent form of untreated hypertension in this elderly group. The sum of LV wall thicknesses (septum+posterior wall) was significantly higher in borderline hypertensive subjects than in normotensive ones (20.5 vs 19.7 mm; p = 0.002). No difference was detected in LV internal dimension or systolic function. After adjustment for age and other clinical variables, comparisons between the groups revealed significant differences in indexes of Doppler diastolic filling. Peak velocity of early filling, and the ratio of early to late peak velocities were lower in the hypertensive group (40 vs 44 cm/s [p = 0.03] and 0.69 vs 0.76 [p = 0.01], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Cardiac adaptation to increased systemic blood pressure in borderline hypertensive men.

The present study examined cardiac characteristics of borderline hypertensive men with a positive parental history of hypertension. Hemodynamics in relation to left ventricular function and structure were evaluated in 15 borderline hypertensive men with a parental history of hypertension and in 20 normotensive control subjects with a negative parental history. Groups were matched in age, height, weight and percent body fat. Left ventricular mass and dimensions were measured by M-mode echocardiography, and left ventricular function was assessed by radionuclide ventriculography. Both groups had similar left ventricular mass, dimensions and wall thicknesses. In relation to control subjects, borderline hypertensive men had a significantly higher heart rate and blood pressure (BP) (p < 0.001), but a similar cardiac index. Borderline hypertensive men had a higher peripheral resistance index (p < 0.02), longer time to peak filling rate, and reduced cardiac efficiency, whereas they had higher contractility, minute and stroke work indexes than did control subjects (all p < 0.05); they also had higher diastolic BP (p < 0.03) during exercise, and sustained higher BP during recovery than did controls. Although this group of borderline hypertensive men did not have an altered cardiac anatomy, they had an increased vascular resistance, an altered diastolic function and a reduced cardiac efficiency while undergoing a greater work load. These cardiodynamic profiles are consistent with functional vascular changes and a parallel compensation by the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1987

Borderline fasting hypertriglyceridemia: absence of excess risk of all-cause and cardiovascular disease mortality in healthy men without hypercholesterolemia.

The majority of prospective studies have shown no independent effect of triglyceride on the prediction of cardiovascular disease after the effects of cholesterol and other heart disease risk factors have been accounted for statistically. Because the association of borderline elevation of triglyceride levels (250-499 mg/dl) with cardiovascular risk might be obscured by its strong correlation with hypercholesterolemia, we examined the relationship in healthy men without hypercholesterolemia. In a population sample of 1,589 healthy fasting men ages 30-79 without known cardiovascular disease or categorical hypercholesterolemia, the prevalence of borderline hypertriglyceridemia was 4.2%, and was unrelated to age. There was no significant excess of borderline hypertriglyceridemia in men with systolic hypertension, or in men who reported use of antihypertensive drugs, current cigarette smoking, or a family history of heart attack before or after age 50. Only obesity, a personal history of diabetes, and fasting hyperglycemia were significantly more common in men with borderline hypertriglyceridemia. Moreover, hypertriglyceridemia was a relatively weak marker for those with diabetes or obesity, being present in only 9% of the former and 6% of the latter. A 12-year follow-up of these men showed no significant association of hypertriglyceridemia with all-cause or cardiovascular death either by univariate analysis or after adjusting for risk factors. These data support the conclusion that borderline hypertriglyceridemia is a poor marker for cardiovascular risk in healthy older men without hypercholesterolemia.

Adult↗
PubMed1982

A simple exercise test in borderline and sustained essential hypertension.

We measured blood pressure and heart rate at rest and during exercise on a bicycle ergometer in 19 patients with borderline hypertension, in 58 with sustained essential hypertension and in a group of 30 healthy subjects of the same age. On each subject, we determined the systolic blood pressure/heart rate curve during exercise and calculated the slope and intercept. In patients with borderline hypertension, blood pressure was elevated in basal conditions but was within the normal range at the end of exercise. This caused an increased intercept (P less than 0.001) and a reduced slope (P less than 0.05) of the curve. In patients with sustained hypertension, blood pressure was elevated throughout the exercise test. This caused an increased slope (P less than 0.001) of the blood pressure/heart rate curve. The slope of the curve correlated negatively with basal heart rate in borderline hypertensive patients (P less than 0.01) and correlated positively with basal total peripheral resistance in sustained hypertensive patients (P less than 0.01). Exercise testing can help one diagnose borderline and sustained hypertension and predict the evolution of borderline hypertension toward fixed hypertension.

Adult↗
PubMed1993

Precursors of established hypertension in borderline hypertensives. A two-year follow-up.

We performed exercise testing, 24-h ambulatory blood pressure monitoring and echocardiography in 37 selected patients with borderline hypertension (24 men and 13 women, mean age 39.8 years, range 23-50) in an attempt to detect early cardiovascular changes that could predict future established hypertension. All subjects were clinically reinvestigated after a mean period of 28 +/- 4 months. At entry 24/37 (65%) showed an exaggerated blood pressure response to exercise (systolic pressure > or = 220 mmHg and/or diastolic pressure > or = 105 mmHg) while 13 (35%) had a normal pressure response. Patients with exaggerated pressure response showed significantly higher left ventricular mass index in comparison to those with normal pressure response (98.1 +/- 10.7 vs. 84 +/- 13, respectively; P < 0.05). They also had higher, although not significantly different, average 24-h systolic and diastolic blood pressure levels. At follow up seven subjects (16%) were diagnosed as having established hypertension, while 30 (84%) remained borderline hypertensives. No subject was judged normotensive. All of the seven hypertensive subjects were a proportion (7/24 = 29%) of the group with exaggerated blood pressure response to exercise. Also, they were the eldest of the total group of borderlines (mean age 44 years) and had the highest left ventricular mass index (100.6 +/- 13 g/m2). Borderline hypertensives show a spectrum of cardiovascular changes that could be considered as a part of the hypertensive risk profile. However, there are no specific characteristics that reliably distinguish subjects prone to develop hypertension. Repeated clinical observations and correct measurements of resting blood pressure may have greater relevance in the management of patients with borderline hypertension.

Adult↗
PubMed2005

Cytoplasmic CD24 expression in advanced ovarian serous borderline tumors.

OBJECTIVES: CD24, originally described as a B-cell marker, has been revealed as one of the candidate molecular markers of epithelial ovarian cancer. We aimed to determine the pattern and extent of CD24 expression in ovarian serous tumors and to clarify its relationship with pathological parameters, especially those associated with the early events of tumor progression in serous tumors of borderline malignancy. METHODS: A total of 114 ovarian serous tumors, including 9 adenomas, 34 borderline, and 71 carcinomas, were analyzed immunohistochemically using a CD24 monoclonal antibody on paraffin blocks. RESULTS: In normal epithelium and serous cystadenomas, the CD24 expression was localized to the apical membranous portion. In some of borderline tumors (26.4%), additional cytoplasmic expression was observed. The cytoplasmic expression of CD24 in borderline tumors was associated with microinvasion (P = 0.001) and omental implants (P = 0.033) with statistical significance. Serous adenocarcinomas showed strong diffuse cytoplasmic expression of CD24, which was significantly associated with shortened survival rate both in univariate (P = 0.011) and multivariate (P = 0.009) analysis. CONCLUSION: The loss of apical localization with the acquisition of the cytoplasmic staining of CD24 protein is a surrogate marker of stromal invasion in ovarian serous tumors of borderline malignancy. Furthermore, the increase in the cytoplasmic expression of CD24 protein is a strong independent molecular marker for shortened survival rate of patients with ovarian serous adenocarcinomas.

Adult↗
PubMed1984

Abnormal relation of extracellular fluid volume and exchangeable sodium with systemic arterial pressure in early borderline essential hypertension.

Interrelations between systemic arterial pressure, extracellular fluid (ECF) volume, exchangeable sodium (Na) and the renin-angiotensin-aldosterone system were studied in 38 young patients with borderline hypertension and in 37 age- and sex-matched control subjects. ECF volume and exchangeable Na were subnormal (not significant) in borderline hypertension. In normal subjects, volume data did not relate to arterial pressure; in contrast, negative correlations were observed between arterial pressure and ECF volume or exchangeable Na in patients with borderline hypertension (in hypertensive women, r greater than or equal to 0.7, p less than 0.01). Plasma renin activity was consistently elevated in borderline hypertension, mainly in the upright posture, and these values were inversely correlated with ECF volume and exchangeable Na. No correlation was observed between arterial pressure and plasma renin activity. These results show that slight elevation of arterial pressure in the early stage of hypertension induces a proportional decrease in ECF volume, suggesting that the phenomenon of pressure-natriuresis is operative in young borderline hypertensive persons. The renin-angiotensin system is activated in these patients, in part to preserve sodium homeostasis.

Adult↗
PubMed2000

Borderline tumors of the ovary: correlation of frozen and permanent histopathologic diagnosis.

OBJECTIVE: To evaluate the correlation between the diagnosis of borderline tumor of the ovary by frozen and permanent pathology. METHODS: All pathology reports with diagnoses of borderline tumor of the ovary between 1980 and 1998 at Massachusetts General Hospital were reviewed. Univariate and multivariable logistic regression models were constructed for patient age, tumor size, histology, presence of bilateral or extraovarian disease, and concurrent diagnosis of endometriosis or endosalpingiosis. RESULTS: We reviewed 140 cases. The average age of patients was 52.3 years. Eighty tumors were serous, 47 mucinous, 11 mixed, and two endometrioid. The mean diameter overall was 13.7 cm (range 1-70 cm), 10.2 cm for serous, and 20.1 cm for mucinous. Diagnoses of borderline tumors by frozen and permanent pathology were consistent in 60% of cases. Frozen section interpreted a benign lesion as malignant (overdiagnosed) in 10.7% of cases, and interpreted a malignant lesion as benign (underdiagnosed) in 29.3%. No variable was a significant predicator of overdiagnosis. In univariate analysis, underdiagnosis was more likely for other types of tumors than serous (P <.001), tumors larger than 20 cm (P =.039), and tumors confined to the ovaries (P =. 009). When all variables were included in a multiple regression model, only histology was a significant predictor of underdiagnosis (P =.039). CONCLUSION: Frozen or permanent pathology reports of diagnoses of borderline tumor were consistent 60% of the time, whereas the positive predictive value of borderline by frozen section was 89.3%. Tumors other than serous are more likely to be misinterpreted.

Adenocarcinoma↗
PubMed1997

Expression of cadherins in benign, borderline, and malignant ovarian epithelial tumors: a clinicopathologic study of 60 cases.

We have analyzed the expression of E- and N-cadherins in benign, borderline, and maligant ovarian tumors, and we have correlated the pattern of cadherin expression with the standard clinicopathological parameters. An immunohistochemical technique has been applied to formalin-fixed, paraffin-embedded samples of 20 benign cystic tumors, 20 borderline tumors, and 20 cancers. Expression of E- and N-cadherins immunostaining were compared with the histological type, degree of histological differentiation, International Federation of Gynecology and Obstetrics (FIGO) stage, presence of ascites, occurrence of recurrence, and survival. E-cadherin was homogeneosuly expressed in benign tumors but was heterogeneously expressed or undetectable in most borderline and malignant tumors. In contrast, N-cadherin was detected in most benign and borderline tumors but was absent or heterogeneous in most carcinomas. The difference of expression of E-cadherin and N-cadherin between the three groups of ovarian tumors was statistically significant (respectively, P = .03 and P < .001). In ovarian carcinoma, patients with negative E-cadherin staining present a significantly shorter survival. No correlation was found between cadherin expression and clinicopathological parameters in borderline tumors. Our results suggest that alterations in E-cadherin and N-cadherin expressions are differentially involved in ovarian carcinogenesis and may have diagnostic and prognostic values.

Adult↗
PubMed2003

Analysis of microsatellite instability and X-inactivation in ovarian borderline tumors lacking numerical abnormalities by comparative genomic hybridization.

The genetic events underlying development of ovarian borderline tumors (tumors of low malignant potential) are not well understood. In our previous studies of microdissected samples from serous borderline tumors, comparative genomic hybridization (CGH) and/or fluorescence in situ hybridization (FISH) analyses showed that 3 of 13 tumors had detectable numerical abnormalities; the remaining 10 had none. In the present study, we examined microsatellite instability (MSI) and clonality in this same set of tumors. Although absence of chromosomal imbalances has been associated with the presence of MSI in some types of solid tumors, the extent of MSI in borderline tumors, and its role in their pathogenesis, is unclear. In our set of 13 tumors, no MSI was detected despite analysis with microsatellite markers recommended by the National Cancer Institute for assessment of MSI. Quantitative X-inactivation studies were informative at the androgen receptor gene AR in 9 of the 13 tumors and revealed that each of the 9 tumors was clonal. In two patients, bilateral tumors showed identical patterns of skewed X-inactivation. These studies confirm the clonality of borderline tumors and suggest that some borderline tumors may develop through mechanisms other than chromosomal imbalances or microsatellite instability.

Adult↗
PubMed1999

Induction of ovulation and borderline ovarian cancer--the hormonal connection?

While the data regarding the possible association between fertility drugs and invasive ovarian cancer are inconclusive, there is evidence to suggest an association between induction of ovulation and borderline ovarian tumors. The plausibility of these results is heightened by the finding that estrogen receptor expression is a common feature of ovarian borderline tumors. On the other hand, recent data indicate that in contrast to the crucial role of germline mutations in the pathogenesis of invasive ovarian cancer, these mutations play a minor role, if any, in the pathogenesis of borderline ovarian tumors. This evidence suggests that the differences between invasive and borderline ovarian tumors are not based on minor morphological criteria, but that, most probably these represent two different entities, with different clinical behavior, and that borderline tumors might be associated with hormonal factors rather than genetic mutations.

Female↗
PubMed1998

Borderline ovarian malignancy: ultrasound and fast dynamic MR findings.

Ovarian tumors of borderline malignancy are low-grade malignant neoplasms, and have a rather good prognosis. They account for approximately 10-20% of all ovarian tumors. Very few reports available in literature that analyses ultrasound and MR findings in establishing the diagnosis. The purpose of this study is to describe eight cases of ovarian tumors of borderline malignancy with dynamic gadolinium-enhanced MR imaging. Comparison is made with CA 125 serum levels and ultrasound findings. Early enhancing endocystic vegetations, local cystic masses in, and (irregular) thickened walls of large multicystic tumors were important findings in borderline malignant tumors. The accuracy to detect a malignant tumor of borderline malignancy with CA 125, ultrasound and MRI in these eight cases was 50, 63 and 75%, respectively. MRI is a valuable imaging modality to characterize adnexal tumors and might play a role in preoperative evaluation of borderline malignancies.

Female↗