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Borderline microinvasive carcinoma of the cervix.

This study identifies borderline microinvasive carcinoma of the cervix as a subgroup of microinvasive carcinoma. We define borderline microinvasive carcinoma of the cervix as the infiltration of neoplastic squamous epithelial cells into the stroma where the depth of infiltration is 1 mm or less from the basement membrane of the epithelial surface immediately adjacent to the site of infiltration without capillary-like or lymphatic-like space involvement. In a 20-year review of cervical neoplasia in our institution, 29 cases of borderline microinvasion were identified. None of these 29 patients had recurrent carcinoma. Of our in situ carcinomas, 4.8% were found to be borderline lesions on review. Of our cases initially interpreted as microinvasion, 27.1% were, in fact, borderline lesions. There are better data to establish the criteria for borderline microinvasive carcinoma than there are to establish the absolute depths of invasion that would be unequivocally acceptable as "microinvasion." Borderline microinvasive carcinoma of the cervix is a lesion which is not metastatic and can be treated by nonradical methods.

Carcinoma in Situ↗

Subclinical rejection and borderline changes in early protocol biopsy specimens after renal transplantation.

BACKGROUND: To determine the significance of early subclinical rejection, we reviewed protocol biopsies performed on days 7 and 28 during a 4-year period. METHODS: The study was confined to patients (n=115) with stable graft function at the time of biopsy; 76 adequate biopsies at day 7 and 79 at day 28 were performed. RESULTS: At day 7, 10 biopsy specimens (13%) showed acute rejection (AR) and 9 (12%) showed borderline changes. Eight of 10 patients with AR received immediate pulsed methylprednisolone (MP) and one untreated patient developed clinical rejection (CR) within 3 days. Four of nine patients whose biopsy specimens showed borderline changes received MP and three untreated patients developed CR within 3 days. At day 28, six biopsy specimens (8%) showed AR and 13 (16%) showed borderline changes. Three of six patients with AR received immediate pulsed MP and one untreated patient developed CR within 6 days. Ten of 13 patients with borderline changes had been treated for AR in the previous 3 weeks. Twelve patients with subclinical rejection or borderline changes at day 28 were never subsequently treated for rejection, and outcome at 6 years did not differ from those patients whose biopsy specimens showed no rejection. CONCLUSIONS: Compared with some units, the incidence of subclinical rejection is low. The majority of untreated subclinical borderline changes and rejection at day 7 behaved as early clinical rejections and at day 28 as resolving clinical rejections. Untreated subclinical rejection or borderline change at day 28 was not an adverse prognostic factor for long-term outcome.

Acute Disease↗

Morphometry and digital AgNOR analysis in cytological imprints of benign, borderline and malignant serous ovarian tumours.

AIM: The aim of the study was to determine values of a quantitative morphometry analysis of nuclear characteristics and argyrophilic nucleolar organizer regions (AgNORs) in differential cytodiagnosis of benign, atypically proliferating (borderline) and malignant serous ovarian tumours. METHODS: Cytological imprints of benign (n = 20), borderline (n = 19) and malignant (n = 20) ovarian serous tumours were analysed. A computerized, digital analysis was used to determine morphometric nuclear features, the number and characteristics of single AgNORs, cluster AgNORs, total AgNOR and AgNOR area/nucleus (relative area) ratio. According to their size AgNORs were classified in three categories. A one-way variance analysis and post hoc test (Scheffé) were used for statistical analysis. RESULTS: The morphometric nuclear analysis showed that benign, borderline and malignant serous ovarian tumours are statistically different (P < 0.001) according to the area and outline, the values being highest in malignant tumours and lowest in the borderline group. Digital analysis of AgNORs in benign, borderline and malignant groups showed that the total AgNOR number increases with progression of the lesion (meaning tumour malignancy) significantly (P < 0.001) between benign and malignant as well as between borderline and malignant serous ovarian tumours (P < 0.001). The progression of the lesion malignancy was accompanied by a significant (P < 0.001) progressive increase of the total and relative AgNOR area per nucleus. The AgNOR size increases from benign to malignant tumours and a statistically significant difference (P < 0.001) was observed in all three groups regarding small and large AgNORs. CONCLUSION: Combining different markers of morphometric nuclear characteristics and AgNOR values could improve differential cytodiagnosis of benign, borderline and malignant serous ovarian tumours.

Cystadenocarcinoma, Serous↗

Structural cardiac changes in relation to 24-h ambulatory blood pressure levels in borderline hypertension.

OBJECTIVES: To investigate left ventricular hypertrophy (LVH) in relation to 24-h ambulatory blood pressure (24-ABPM) and insulin levels in borderline hypertension. DESIGN: A case-control study. SUBJECTS: Borderline hypertensive men (diastolic blood pressure (DBP) 85-94 mmHg, n = 69) and age-matched normotensive controls (DBP < or = 80 mmHg, n = 69) from a population screening programme. MAIN OUTCOME MEASURES: Echocardiography (M-mode), insulin (RIA) and 24-APBM (Del Mar P-IV) levels. RESULTS: The borderline group showed a significant increase in septal thickness (10.4 +/- 1.5 vs. 9.7 +/- 1.5 mm, P < 0.01), peak systolic wall stress (218 +/- 38 vs. 202 +/- 38 10(3) dynes cm-2, P < 0.05) and a decrease in LV ejection time (28.4 +/- 2.5 vs. 29.5 +/- 2.1s, P < 0.01). The septum vs. posterior wall thickness ratio was significantly higher in the borderline group (1.13 +/- 0.14 vs. 1.06 +/- 0.14, P < 0.01). Casual BP levels did not correlate with LVH indices, while 24-ABPM systolic levels correlated strongly with LVH indices in the borderline group (r = 0.22-0.52, P < 0.05) but not in the normotensive group. Insulin levels correlates strongly with LVH indices in the normotensive group (r = 0.34-0.47, P < 0.01) but not the borderline, group. CONCLUSIONS: Signs of asymmetric LVH and altered ventricular function are already detectable in borderline hypertension. The data also suggest that early structural cardiac changes are related to ambulatory blood pressure profile, but not to casual blood pressure or trophic factors such as insulin.

Adult↗

Borderline systemic lupus erythematosus (SLE): a separate entity or a forerunner to SLE?

AIM: To compare a subgroup of patients with borderline systemic lupus erythematosus (SLE) with those with classic lupus in order to determine whether the former subset is a separate entity or a forerunner to SLE. METHODS: A retrospective survey was undertaken of a database containing the clinical information of a total of 71 patients in an Abu Dhabi hospital setting over a 12-year period. Data of interest were criterial and non-criterial features of SLE together with relevant laboratory tests. RESULTS: Fifty-six patients had SLE and 15 were considered to have borderline SLE as they satisfied less than four criteria of classification. Age and female sex distribution were no different in the two subgroups, but the disease duration was shorter in patients with borderline lupus. The occurrence of arthropathy (non-erosive), serositis, thrombocytopenia, hemolytic anemia, and malar eruption was common to both subgroups. Patients with borderline SLE lacked other mucocutaneous manifestations of lupus and major organ disease involvement. A number of other clinical features were also observed in the latter subgroup, including antiphospholipid (APL) syndrome. In addition, patients with borderline SLE expressed a multiple autoantibody profile, but had lower titers of antinuclear factor (ANF) and anti-double-stranded DNA (anti-dsDNA) antibodies than those with classic SLE. None progressed to full-blown SLE after a mean period of follow-up of 21.2 months. CONCLUSIONS: In our patients, borderline SLE was milder than classic lupus, yet shared a wide spectrum of non-criterial features and also produced clinical subsets. The clinical heterogeneity and multiple antibody profile may suggest that borderline SLE is a forerunner to SLE rather than a separate entity. A regular and longer period of follow-up is required, however, to ultimately determine the fate of these patients.

Adult↗

Renal allograft biopsies with borderline changes: predictive factors of clinical outcome.

The clinical outcome and appropriate management for patients showing 'borderline changes' on allograft biopsy after renal transplantation is still controversial. In an attempt to identify predictive factors of clinical outcome of patients with such lesions, we reviewed the clinical course of 91 patients with borderline changes. Multivariate analysis revealed significant and independent effects of histological stage (i + t < or = or > 2) and time to borderline changes (< or = or > 3 months after transplant) on serum creatinine levels at 1 year from borderline changes episodes (respectively, p = 0.04 and p = 0.02) and only a significant effect of time to borderline changes on serum creatinine levels at 2 years (p = 0.005). Renal function at 1 year and 2 years as 5- and 8-year graft survival were not significantly different in the group of patients treated with antirejection therapy (T group, n = 49) compared with the untreated group (UT group, n = 42). This study strongly suggests that borderline changes with histological score (i + t) > 2 and late episodes of borderline changes should be considered to be of poor prognosis.

Adult↗

Augmented sympathetic nerve activity in response to stressors in young borderline hypertensive men.

To determine whether there may be an abnormality in sympathetic nerve activity in response to physical and psychological stressors, we microneurologically recorded muscle sympathetic nerve activity in 11 normotensive and 9 borderline hypertensive, age-matched men. Supine blood pressure, plasma levels of epinephrine and norepinephrine and muscle sympathetic nerve activity were measured before and during a cold pressor test or a mental arithmetic test. The resting basal values of muscle sympathetic nerve activity, blood pressure and plasma epinephrine were significantly higher in the borderline hypertensives than in the normotensives (P less than 0.05). Plasma norepinephrine levels tended to be higher in the borderline hypertensives than in the normotensives but not to a significant extent (P less than 0.10). The cold test produced significantly exaggerated pressor and muscle sympathetic nerve responses (P less than 0.05) with a trend towards an increase in plasma norepinephrine (P less than 0.10) in the borderline hypertensives as compared with normotensives. The mental arithmetic test produced significantly enhanced pressor and plasma epinephrine responses in the borderline hypertensives as compared with the normotensives (P less than 0.05). During the mental arithmetic test the muscle sympathetic nerve activity decreased significantly in the normotensives (P less than 0.05) but not in the borderline hypertensives. These findings indicate that in people with borderline hypertension an abnormality exists in sympathetic nerve activity at rest and in response to stressors.

Adult↗

Cardiac and vascular remodeling in older adults with borderline isolated systolic hypertension: the ICARe Dicomano Study.

Although borderline isolated systolic hypertension (ISH), defined as a blood pressure of 140 to 159/<90 mm Hg, is a proven cardiovascular risk factor, the major clinical trials on treatment of ISH have used a cutoff of 160 mm Hg. Moreover, no data exist on the cardiovascular modifications associated with borderline ISH. Therefore, we compared subjects with borderline ISH to subjects with diastolic hypertension (diastolic blood pressure > or =90 mm Hg) or ISH. Community-dwelling residents (age > or =65 years) of a small town in Italy (Dicomano) underwent extensive clinical examination, echocardiography, carotid ultrasonography, and applanation tonometry. Only untreated subjects were included in this analysis: 95 with diastolic hypertension, 87 with borderline ISH, and 43 with ISH. Despite lower systolic and mean pressures in borderline ISH, left ventricular mass was similar to that in diastolic hypertension. In univariate and multivariate analysis, pulse pressure but not systolic pressure was related to left ventricular mass. Borderline ISH subjects had a tendency to greater carotid cross-sectional area and stiffness index than did diastolic hypertensive subjects despite lower mean carotid pressure, whereas the number of atherosclerotic plaques was similar in the 2 groups. Pulse pressure but not systolic pressure was independently related to carotid remodeling. In our community-based, older population, individuals with borderline ISH had a similar prevalence of left ventricular hypertrophy and carotid atherosclerosis as that of subjects with diastolic hypertension, despite lower systolic and mean pressures. Among blood pressure values, pulse pressure was the single or strongest independent predictor of cardiovascular remodeling.

Aged↗

The pupillary light reflex in borderline diabetics.

Computerized IR videopupilography, using an open-loop photic stimulator, was used to compare the reflexes of borderline diabetics with overt non-insulin-dependent diabetics and with age- and sex-matched non-diabetic healthy controls. The patients were all male, aged 41-59 years. Overt non-insulin-dependent diabetics in their 40s had a smaller pupillary area and pupillary diameter prior to photic stimulus compared with borderline diabetics and healthy controls. Overt non-insulin-dependent diabetics in their 50s had a lower pupillary area and pupillary diameter prior to photic stimulus, maximum velocity and acceleration of constriction and maximum velocity of dilation than did borderline diabetics or controls. The only abnormality observed among borderline diabetics compared to controls was a smaller amplitude of constriction in response to light in patients in their 50s. Amplitude of constriction in response to light and velocity of constriction measurements of borderline diabetics, however, were considerably more frequently abnormal than were those of controls. The frequency of abnormal pupillary diameter prior to photic stimulus, maximum velocity of dilation and acceleration of constriction was higher in overt non-insulin-dependent diabetics than in borderline diabetics. The results indicate that borderline diabetics have autonomic neuropathy before the disease becomes overt. The importance of the pupillary light reflex examination is discussed.

Adult↗

Increased urinary C-peptide and albumin excretion in juvenile borderline hypertensives.

The study was designed to evaluate the urinary excretion of C-peptide and albumin, and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in juvenile borderline hypertensives. The second aim was to examine the relationship between these variables and ambulatory blood pressure level and variability. The study group consisted of 21 non-obese males consecutively chosen from patients with borderline hypertension, defined by sphygmanometer readings, examined in our outpatient clinic. All subjects collected separately their day-time and night-time urines during the period of ambulatory blood pressure monitoring. In 16 patients, who were considered to have "sustained" borderline hypertension, both 24-h urinary C-peptide excretion and 24-h UAE were significantly increased in comparison to those of the controls, while NAG activity did not differ significantly between the two groups. UAE was significantly lower at night than during the day in both borderline hypertensives and controls. Twenty-four-hour UAE in borderline hypertensives correlated significantly with the ambulatory blood pressure variability, but not with the average blood pressure level. These results suggest that the 24-h insulin secretion rate estimated by means of urinary C-peptide excretion is significantly increased in "sustained" borderline hypertensives. Elevated UAE in juvenile borderline hypertensives can be explained by a possible direct effect of systemic blood pressure variability on albuminuria.

Acetylglucosaminidase↗

Inter-relationship of sympathetic nervous system and renin-angiotensin-aldosterone system in three renin subgroups of borderline and persistent essential hypertension.

Plasma renin activity (PRA), dopamine beta-hydroxylase (DBH) activity, and plasma aldosterone concentration were determined in 51 patients categorized as borderline or persistent hypertensives and as high, normal, or low renin. Basal DBH activity correlated with diastolic blood pressure in borderline but not in persistent hypertensives. In borderline patients with normal or high renin activity standing plus furosemide caused a marked rise in diastolic blood pressure but little change in systolic and increased PRA and DBA. In contrast this stimulation procedure depressed both systolic and diastolic blood pressure and resulted in blunted PRA and DBH responses in the low renin borderline and the three groups of persistent hypertensives. After dietary sodium restriction, the decrease in systolic blood pressure correlated with the decrease in urinary sodium excretion in persistent, but not in the borderline patients. The data suggest that both borderline an persistent hypertensive patients respond to volume depletion with an increase in sympathetic and renin activity, and the increase of these two vasoconstrictive systems is greater in borderline hypertensives.

Adult↗

Catecholamines, angiotensin II and sodium concentrations in cerebrospinal fluid in young men with borderline hypertension.

To evaluate the role of central nervous mechanisms and their relationships to the peripheral sympathetic nervous system in borderline hypertension, we measured catecholamines, angiotensin II (AII) and sodium (Na) concentrations in cerebrospinal fluid (CSF) with plasma catecholamines concomitantly in 12 young men with borderline hypertension and 7 age-matched healthy normotensive men on ordinary salt intake. Plasma norepinephrine (NE) and epinephrine (E) were higher in the borderline hypertensives than in the normotensives (NE: 239 +/- 15 vs 190 +/- 11 pg/ml, p less than 0.05, E: 83 +/- 9 vs 43 +/- 6 pg/ml, p less than 0.01). NE levels in CSF were also higher in the borderline hypertensives than in the normotensives (200 +/- 15 vs 150 +/- 18 pg/ml, p less than 0.05). In most of the subjects, CSF E and plasma and CSF dopamine levels were below the sensitivity of the assay. CSF NE correlated positively with both plasma NE (p less than 0.01) and mean blood pressure (p less than 0.05) in all subjects. Immunoreactive AII and Na concentrations in CSF did not differ between the borderline hypertensives and normotensives. These results suggest that peripheral sympathoadrenal overactivity in young subjects with borderline hypertension may be related to an altered function of central noradrenergic neurons. AII and Na in the central nervous system do not appear to have an important role in borderline hypertension.

Adolescent↗

Relative importance of borderline and elevated levels of coronary heart disease risk factors.

BACKGROUND: Clinical trials indicate that a sizable proportion of adults have multiple borderline coronary risk factors and may benefit from treatment. OBJECTIVE: To estimate the relative and absolute contributions of borderline and elevated risk factors to the population burden of coronary heart disease (CHD) events. DESIGN: A prospective cohort study and a national cross-sectional survey. SETTING: The Framingham Study and the Third National Health and Nutrition Examination Survey (NHANES III). PARTICIPANTS: White non-Hispanic persons in the Framingham Study and in NHANES III who were between 35 to 74 years of age and had no CHD. MEASUREMENTS: Occurrence of first CHD events according to 5 major CHD risk factors: blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, glucose intolerance, and smoking. Three categories-optimal, borderline, and elevated-were defined for each risk factor per national guidelines. Sex-specific 10-year CHD event rates from the Framingham Study were applied to numbers of at-risk individuals estimated from NHANES III and the 2000 U.S. Census. RESULTS: Twenty-six percent of men and 41% of women had at least 1 borderline risk factor in NHANES III. According to estimates, more than 90% of CHD events will occur in individuals with at least 1 elevated risk factor, and approximately 8% will occur in people with only borderline levels of multiple risk factors. Absolute 10-year CHD risk exceeded 10% in men older than age 45 years who had 1 elevated risk factor and 4 or more borderline risk factors and in those who had at least 2 elevated risk factors. In women, absolute CHD risk exceeded 10% only in those older than age 55 years who had at least 3 elevated risk factors. LIMITATIONS: The generalizability of the findings to persons of other ethnic backgrounds is unknown. CONCLUSIONS: Borderline CHD risk factors alone account for a small proportion of CHD events.

Adult↗

Borderline epithelial tumours of the ovary--a retrospective analysis of 31 cases.

Thirty one cases of epithelial borderline tumours of the ovary recorded over a period of six years were reviewed. The incidence of borderline tumours was 6% in relation to ovarian epithelial malignancies, with serous and mucinous types comprising three fourth of the lesions. The serous tumours were bilateral in 39%, revealed surface growth in 17% and had peritoneal implants in 11% of cases. The mucinous tumours were bilateral in 11% and had associated pseudomyxoma peritonei in 22% of cases. Nuclear grade appeared to correlate with extraovarian spread and surface growth in the serous borderline tumours, but not in the mucinous borderline tumours. The endometrioid borderline tumours and mixed epithelial borderline tumours were rare lesions. Twenty one patients (68%) presented in Stage-la. Surface growth correlated with recurrences. The prognosis remained good in serous borderline tumours even in the presence of implants as these were non-invasive. The mean disease free survival was 43.03 months. There was no statistical difference in disease free survival of patients with and without implants.

Adenofibroma↗

Apoptotic and proliferative activity in ovarian benign, borderline and malignant tumors.

OBJECTIVE: To determine the apoptotic and proliferative activities in various ovarian epithelial tumors. METHODS: Formalin-fixed, paraffin-embedded tissues of 86 ovarian epithelial tumors, including 52 adenocarcinomas, 23 borderline tumors and 11 cystadenoma, were retrieved. Apoptotic (AI) and proliferative (PI) index were estimated using the monoclonal antibodies: M30, Ki-67 and Ki-S1 in these tumors. Quantitative assessment of AI and PI was estimated by calculating the percentage of positive cells among no less than 1000 tumor cells. RESULTS: Statistically significant difference in AI was found between benign and borderline tumors or carcinomas (P = 0.028, 0.001, respectively). Significant differences in PI, as assessed by both Ki-67 and topo IIalpha, were demonstrated between carcinomas and benign or borderline tumors (both P < 0.001). Benign tumors had both low PI and AI; borderline tumors had lower PI but higher AI, while adenocarcinomas had both high proliferative and high apoptotic rates. Among borderline tumors, serious tumors had significantly lower AI and higher PI than mucinous ones. CONCLUSION: The results suggest that apoptotic and proliferative activities play important roles in the pathogenesis and development of ovarian borderline and malignant tumors. The high apoptotic rate in borderline tumor may explain its relatively indolent behavior while the high proliferative rate in carcinomas tends to explain its aggressive behavior.

Antigens, Neoplasm↗

[Ovarian epithelial tumors of borderline malignancy].

Ovarian tumor is known to show histological variation. Each tumor shows various clinical behavior. Ovarian epithelial tumors consist of several types of histological findings. Epithelial tumors can be classified into benign, borderline malignancy and malignant for their biological behavior. Recently the therapeutic effectiveness against ovarian cancer is increasing in order to establish the operation technique and development of chemotherapeutic method with cisplatin. Therefore it is important that borderline malignant tumors which are said to have a good prognosis be defined from obviously malignant tumors to evaluate accurately the effectiveness of the therapy against the ovarian cancer. On the other hand, borderline malignant tumors with characters of a malignant tumor, must be distinguished from benign adenoma because long-term follow up is required. However, it is difficult to make an exact histological diagnosis of benign adenoma, borderline malignancy and malignancy because the histological criteria of borderline malignancy is lacking in concreteness. The histological criteria should be defined more clearly and concretely. For example, mitotic counts per 10 HPF of borderline malignancy and DNA ploidy. Next, because of good prognosis, we need a quick therapeutic guide line for borderline malignancy, especially for stage I and young women.

Adult↗

Conservative treatment of borderline ovarian tumors.

Of 61 patients with stage IA borderline ovarian tumors, 41 were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, and 20 were treated by a variety of more limited operations, including cystectomy with (one patient) and without (three patients) a contralateral ovarian wedge biopsy, and unilateral salpingo-oophorectomy with (six patients) and without (ten patients) a contralateral wedge biopsy. In the group treated conservatively, there were 11 serous, seven mucinous, and two mixed seromucinous borderline tumors, whereas in the total abdominal hysterectomy and bilateral salpingo-oophorectomy treatment group there were 26 serious, 12 mucinous, and three mixed seromucinous borderline tumors. After a mean follow-up of 89 months (range 36 to 244 months), subsequent borderline neoplasms had developed in three patients (15%) with serious borderline tumors initially treated conservatively and in two patients (5%) with serous or mixed seromucinous borderline tumors initially treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patient with a mucinous borderline tumor treated either conservatively or with total abdominal hysterectomy and bilateral salpingo-oophorectomy developed a subsequent neoplasm. All 61 patients in the study group are alive and free of disease, including those who developed recurrent neoplasm.

Adult↗

Mucin histochemistry of ovarian borderline tumors of mucinous and mixed-epithelial types.

Mucin histochemistry was studied in 23 intestinal-type mucinous borderline tumors, 21 endocervical-like mucinous borderline tumors, and 24 mixed-epithelial borderline tumors. The latter two tumors, which are of müllerian type, had a mucin composition similar to that of normal endocervix, with abundant neutral and acidic mucins in approximately equal amounts and a slight predominance of sialomucins over sulfomucins. Intestinal-type mucinous borderline tumors showed several patterns that most closely resembled gastric mucosa with varying degrees and types of intestinal metaplasia. In conclusion, mucin histochemistry shows striking differences between these two types of müllerian borderline tumors compared with intestinal-type mucinous borderline tumors and confirm the subclassification of mucinous borderline tumors into intestinal and endocervical types.

Colonic Neoplasms↗