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PubMed1997

Clinical behavior of borderline ovarian tumors: a study of 150 cases.

BACKGROUND: We evaluated the clinical features, treatment, and survival status of the patients with borderline ovarian tumors. METHODS: A retrospective review of the charts of 150 patients with borderline ovarian tumor registered at the Tokai Ovarian Tumor Study Group from January 1, 1980, to December 31, 1994, was conducted to obtain clinical and pathological information. RESULTS: In stage II and III disease, the numbers of patients with no residual tumor, residual tumor of <2 cm, 2-5 cm, and >5 cm were 9, 10, 3, and 3, respectively. The sizes of residual tumors and corresponding clinical response to chemotherapy were as follows: residual tumor of <2 cm, complete response (CR), 6 patients; no change (NC), 2; progressive disease (PD), 2; tumors 2-5 cm, NC, 1 patient, PD, 2; tumors >5 cm, PD, 3 patients. The survival for patients with residual tumor <2 cm was significantly better than for those with residual tumor from 2-5 cm and of >5 cm (P < 0.05). The survival for patients with stage II and III serous tumor was significantly longer than that for patients with stage II and III mucinous tumor (P < 0.05). CONCLUSION: In advanced borderline ovarian tumor, the prognosis of patients with gross residual tumor after initial surgery, and especially with mucinous tumor, was poor.

Adolescent↗
PubMed1998

Prognosis of patients with ovarian cancer and borderline tumours diagnosed in Norway between 1954 and 1993.

The Scandinavian countries exhibit some of the highest incidence rates of ovarian cancer in the world. Prognosis is poor, and the crude 5-year relative survival was 36% in the Nordic countries in the 1980s. Histology-specific prognostic trends in 5-year relative survival of patients with ovarian cancer and borderline tumours were examined, based on data from the population-based Cancer Registry of Norway. Relative risks (RRs) of dying were derived from Cox regression models. Logistic regression analysis on the proportion of cases with a localised tumour was performed. The 5-year relative survival rate of patients with ovarian cancer increased steadily from 1954 to 1993, being most pronounced in women below the age of 65 at the time of diagnosis. No improvement was seen for women older than 75. For all patients with ovarian cancer, an RR of dying of 0.48 (95% CI = 0.44-0.53) was estimated in 1989-1993 compared with 1954-1958. For patients with epithelial cancer, an RR of 0.63 (95% CI = 0.57-0.69) was seen in 1989-1993 compared with 1970-1973. Patients with mucinous, endometrioid and clear cell tumours had the highest odds of having a localised tumour. The age-adjusted 5-year relative survival rate of patients with borderline tumours was almost constant between 1970 and 1993, at about 93%. The prognosis of patients with ovarian cancer in Norway has improved since the 1950s. The very favourable prognosis of patients with borderline tumours has remained unchanged since the 1970s.

Adenocarcinoma↗
PubMed1999

Somatic genetic alterations (LOH) in benign, borderline and invasive ovarian tumours: intratumoral molecular heterogeneity.

Loss of heterozygosity (LOH) affects a number of chromosome regions in ovarian cancer, pointing to the possible involvement of tumour-suppressor genes in ovarian tumorigenesis. We performed comparative analysis of allelic loss at 6 frequently affected chromosome regions in a panel of 53 benign, borderline and malignant ovarian tumours. Precursor lesions could provide evidence that an accumulation of genetic events is required for normal ovarian epithelium to generate malignant tumours. LOH on chromosome 1p was relatively common in benign, borderline and malignant tumours, while at 11p and 7q it was observed not only in invasive but also in borderline tumours. Moreover, 17q and 18q were affected mainly in advanced malignant tumours and revealed a high frequency of clonal intratumoral heterogeneity. We encountered different spectra of genetic alterations in primary tumours and their metastasis, which may be the results of intratumoral heterogeneity leading to dissemination in only some sub-clones.

Chromosome Mapping↗
PubMed1994

Genotype of subjects with borderline hemoglobin A2 levels: implication for beta-thalassemia carrier screening.

In this study, we have defined by molecular analysis, the alpha, beta, and delta globin genotype in a group of individuals with normal or thal-like red cell indices but borderline hemoglobin (Hb)A2 levels, who were identified in a program for beta-thal carrier screening. In 37 of 125 individuals with borderline HbA2 levels, we detected a molecular defect in the beta, in both the delta and the beta, or in the alpha globin gene. Specifically seven of these subjects were carriers of the -101 C T mutation, ten of the IVSI nt6 T C mutation, 16 were double heterozygotes for delta and beta thal, and two had the triple alpha globin gene and two the single alpha globin gene deletion. From these results, we may conclude that subjects with borderline HbA2, particularly when they marry a typical beta-thal carrier, should be extensively investigated in order not to miss heterozygous beta-thalassemia.

Genetic Carrier Screening↗
PubMed1985

Cardiovascular response to static contraction in borderline hypertension.

Nine young males with borderline hypertension (BH) (mean age +/- SD, 25 +/- 5 yr) and 13 young male normotensive controls (NT) (24 +/- 3 yr) were studied to determine their cardiovascular responses to small and large muscle static contractions. The subjects performed one-arm handgrip and two-leg extension in a randomly assigned order for 3 min at 30% of maximal voluntary contraction. Mean intra-arterial blood pressure (MABP), heart rate (HR), and tension were measured throughout the contractions. Borderline hypertensive patients had a higher MABP at rest (p less than 0.005) and at the end of both types of static contractions (p less than 0.05). The average increases in MABP from rest to the end of exercise (delta MABP) were slightly greater for the BH patients (6 mmHg), but these differences were not significant (p greater than 0.1). However, a greater percentage of BH patients were hyperreactive to handgrip (delta BP greater than 35 mmHg) and leg extension (delta BP greater than 40 mmHg) when compared to controls. These data indicate that, in general, young men with borderline hypertension demonstrate normal cardiovascular regulation in response to static contraction, but that a portion of this population may be hyperreactive to this type of circulatory stress.

Adult↗
PubMed2005

Different proportions of aneusomic cells in ovarian inclusion cysts associated with serous borderline tumours and serous high-grade carcinomas support different pathogenetic pathways.

Ovarian serous tumours may arise from the ovarian surface epithelium or from ovarian cortical epithelial inclusion cysts. However, little is known about the pathogenetic mechanisms involved in the progression from ovarian surface epithelium or inclusion cysts to neoplastic disease. In the present study, chromosomal aberrations typical of ovarian serous tumours were studied in ovarian surface epithelium and inclusion cysts. Ten ovaries with inclusion cysts obtained from patients without a gynaecological tumour, as well as 15 serous borderline tumours and 16 invasive high-grade serous carcinomas with inclusion cysts either in the ipsi- or in the contralateral ovary, were investigated by fluorescence in situ hybridization (FISH) using centromere enumeration probes directed against chromosomes 1, 6, 7, and X. The proportions of aneusomic cells were assessed. Trisomies 1 and 7 and monosomies 6 and X were present in the surface epithelium, inclusion cysts, and tumours, providing evidence for a link between the surface epithelium, and inclusion cysts, and serous neoplasia. Inclusion cysts generally harboured more aneusomic cells than the associated surface epithelium, suggesting an influence of the ovarian stroma on the development of chromosomal instability. Moreover, inclusion cysts associated with borderline tumours displayed a higher proportion of aneusomic cells than inclusion cysts associated with invasive high-grade carcinoma and than inclusion cysts in ovaries without neoplastic disease. These results suggest a genetic field defect of the inclusion cyst epithelium in serous borderline tumours. Invasive high-grade serous carcinomas, by contrast, may arise from single cell clones subject to a different set of genetic events.

Aneuploidy↗
PubMed1995

The significance of sweat Cl/Na ratio in patients with borderline sweat test.

Recently a few cystic fibrosis (CF) patients with borderline or normal sweat tests have been reported. These patients present a diagnostic challenge. We aimed to study the sweat Cl/Na ratio in cystic fibrosis patients and to assess whether this ratio could be used as a diagnostic criteria. The mean sweat Cl/Na ratio of 3 groups was compared: Group A: 71 CF patients carrying 2 mutations known to be associated with severe disease presentation (delta F508, W1282X, G542X, N1303K, 1717-1G --> A). Group B: 10 compound heterozygous patients who carry one mutation associated with mild clinical disease (3849 + 10 kb --> T). Group C: 142 normal subjects. Sweat chloride levels higher than those of sodium were found in 96% of patients in Group A as compared to 3% of patients in Group C. In Group B 40% of the patients had sweat chloride levels higher than or equal to sodium levels. The mean Cl/Na ratio of Group A (1.2 +/- 0.1) differed significantly from that of Group B (0.94 +/- 0.1) and both groups had significant higher mean Cl/Na ratio compared to Group C (0.7 +/- 0.4) (P < 0.001). Thus in individuals with a borderline sweat test and a Cl/Na ratio > or = 1 the diagnosis of CF should be considered. However, a Cl/Na ratio < 1 does not exclude CF, since patients carrying mild mutations may have sweat sodium levels higher than those of chloride. Our findings suggest that the sweat Cl/Na ratio in CF is genetically determined and it may be of help in establishing the diagnosis of CF in patients with a borderline sweat test.

Child↗
PubMed1995

Possible metaplastic origin of lymph node "metastases" in serous ovarian tumor of low malignant potential (borderline serous tumor).

A patient with a stage III serous ovarian carcinoma of low malignant potential (borderline serous tumor) is described who had extensive involvement of the pelvic and para-aortic lymph nodes by both borderline tumor and endosalpingiosis. Transition from endosalpingiosis to papillary serous borderline tumor was demonstrable in multiple intranodal sites, and in fully developed lesions, areas of metaplastic growth acquired a desmoplastic stroma. This finding suggests that the lymph node "metastases" may have arisen de novo by neoplastic transformation of preexistent metaplastic tubal-type epithelium (endosalpingiosis), and would lend further credence to the metaplastic (rather than metastatic) origin or extraovarian implants in serous ovarian carcinoma of low malignant potential.

Adult↗
PubMed2000

Contemporary surgical management of borderline ovarian tumors: a survey of the Society of Gynecologic Oncologists.

OBJECTIVE: The objective of this study was to review the current practice patterns regarding the surgical management of borderline ovarian tumors. METHODS: A one-page survey was mailed to the members of the Society of Gynecologic Oncologists (SGO), using the directory of the Society. The survey addressed the demographics of the respondent and the recommended staging procedure for presumed early-stage disease. RESULTS: Of the 660 surveys mailed, 274 (42%) were returned. Ninety-seven percent (267/274) of respondents advocate surgical staging. Of this group, 96% (257/267) perform peritoneal washings, 97% (259/267) sample the omentum, and 92% (245/267) submit random peritoneal biopsies. Eighty-eight percent (235/267) perform lymph node sampling: paraaortic biopsies by 89% (210/235) and pelvic biopsies by 97% (228/235). Of this latter group, 91% sample the external iliac chain, 82% submit hypogastric nodal tissue, and 70% remove obturator lymph nodes. CONCLUSION: Diversity exists in the surgical management of borderline ovarian tumors among members of the SGO who responded to this survey. Efforts to ensure a consistent approach to the management of borderline ovarian tumors are warranted.

Biopsy↗
PubMed1976

Comparison of the pharmacokinetics of intravenous dl-propranolol in borderline and permanent hypertension.

In borderline and permanent hypertensives after rapid i.v. injection of dl-propranolol 0.2 mg/kg plasma levels were measured and were fitted to a two-compartment open-model. In borderline patients, characterized by a high basal cardiac output (CO), plasma levels were always lower than in permanent hypertensives. The biological half-life was reduced and the central volume of distribution, volume of distribution at pseudo-equilibrium and total clearance (TC) were markedly increased. In the overall population, there was a significant positive correlation between CO and TC. Rapid achievement of a predetermined plateau in each group constituted experimental proof of the validity of the two-compartment open-model for kinetic analysis of propranolol i.v. If kinetic parameters from permanent hypertensive were applied to borderline hypertensives a lower plateau was obtained. Thus, in so far as beta-blockade is related to plasma level of propranolol, an increased intravenous dose may be required in patients with high CO.

Cardiac Output↗
PubMedDate not supplied

The borderline hypertensive rat (BHR): a new model for the study of environmental factors in the development of hypertension.

While many studies have attempted to produce hypertension through the use of various environmental stressors, few have succeeded in producing chronic elevations in blood pressure beyond levels considered to be borderline hypertensive (140-160 mm Hg systolic). The problem with most studies stems from the use of genetically normotensive animals and the selection of stressors to which animals readily adapt. A new approach is suggested, which recognizes the role of genetics in human essential hypertension. Animals with one hypertensive parent do not develop spontaneous hypertension but show a more sensitive cardiovascular response to environmental stressors than animals with normotensive parents. Preliminary studies revealed that animals with a mixed genetic history of hypertension develop spontaneous borderline hypertension. When subjected to shock-shock conflict, these borderline hypertensive rats (BHR) developed permanent hypertension that failed to abate even after a ten-week, shock-free recovery period. The hypertension was accompanied by elevated heart weight to body weight ratios and by significant cardiac pathology. Subsequent work has demonstrated that these animals also become hypertensive when fed a high-sodium diet. Finally, in a series of exercise studies, we found that BHRs subjected to a shock stressor were protected against stress-induced hypertension if they exercised daily. The potential of this model for studies of the mechanisms by which environmental variables produce permanent hypertension is discussed.

Aging↗
PubMed2006

Methylation profile in benign, borderline and malignant ovarian tumors.

PURPOSE: Promoter hypermethylation is a common phenomenon in neoplasm. The aims of this study were (a) to compare the methylation profiles in different types of ovarian tumors and (b) to determine the possible relationship between the methylation status and different clinicopathologic characteristics. METHODS: We examined the promoter methylation status of 9 tumor suppressor genes (RARbeta2, TMS1, RIZ1, P15, P16, PTEN, MINT31, APC and HIC1) in 89 ovarian cancers, 16 borderline ovarian tumors, 19 benign ovarian tumors, 16 normal ovarian tissue and 5 ovarian cancer cell lines. The methylation status was examined with respect to clinicopathologic characteristics of the ovarian cancer patients. RESULTS: Methylation indices for ovarian cancer, borderline ovarian tumor, benign ovarian tumor, normal ovarian tissue and ovarian cancer cell lines were 28.8, 20.1, 10.5, 11.8 and 42.2%, respectively. It was significantly higher in ovarian cancer, borderline ovarian tumor and ovarian cancer cell lines (X (2) test, P < 0.001, P = 0.01 and P < 0.001, respectively) than benign or normal ovarian tissues. In ovarian cancer, concurrent methylation of at least two genes (CM2) was associated with early stage disease (X (2) test, P = 0.035) and less recurrence (X (2) test, P = 0.020). When the methylation statuses of the nine genes as well as CM2 were included in multivariate Cox Regression analysis, CM2 was the only independent predictor for survival (P = 0.013). CONCLUSION: CM2 was an independent predictor for survival in ovarian cancer.

Cell Line, Tumor↗
PubMed2005

Borderline resectable pancreatic cancer.

Rigorous criteria to define "borderline resectable" pancreatic cancer are required for appropriate patient accrual into clinical trials that examine the utility of chemotherapy and/or chemoradiation that will be delivered prior to pancreatic resection for exocrine cancer. At our institution, tumor abutment of less than or equal to 180 degrees (< or = 50% of the vessel circumference) of the superior mesenteric artery, short segment abutment or encasement (> or = 50% of the vessel circumference) of the common hepatic artery (typically at the gastroduodenal artery origin), or segmental venous occlusion are used to categorize a pancreatic tumor as borderline resectable. These patients are at a high risk for margin positive resection with initial surgery; therefore, we favor a treatment schema that incorporates preoperative (neoadjuvant) therapy with systemic chemotherapy and chemoradiation. Patients whose tumors show radiographic stability or regression that are often accompanied by an improvement in serum tumor markers are candidates for pancreaticoduodenectomy. A prospective multicenter clinical trial with well-defined eligibility criteria may help decide the best overall treatment strategy for these patients. Vascular resection and reconstruction may be required in patients with borderline resectable tumors, and surgery should be performed at centers with expertise in such complex pancreatic resections.

Journal Article↗
PubMed1975

Vascular reactivity to norepinephrine and hemodynamic parameters in borderline hypertension.

Pressor response to norepinephrine, cardiopulmonary blood volume, and hemodynamic parameters were studied in 41 borderline hypertensive patients in comparison with 42 permanent essential hypertensive patients and 28 normal subjects. Borderline hypertensive subjects had high cardiac index (p less than 0.0001), normal total peripheral resistance, and low total blood volume (p less than 0.005). The ratio between cardiopulmonary blood volume (CPBV) and total blood volume (TBV) was significantly higher in comparison with normal subjects (p less than 0.01) and permanent hypertensive subjects subjects (p less than 0.0001). The pressor dose of norepinephrine was elevated (p less than 0.0001) and was directly correlated with the basal values of the cardiac output (p less than 0.005), the cardiopulmonary blood volume (p less than 0.001), and the CPBV/TBV ratio (p less than 0.01). None of these results was observed in permanent hypertensive subjects: the only significant result was a negative correlation between the pressor dose of norepinephrine and the basal diastolic arterial pressure (p less than 0.0001). This study provides evidence that the cardiac output elevation in borderline hypertensive subjects was related to increased venous return and enhanced sympathetic venous tone.

Adult↗
PubMed1984

Impaired systemic arterial compliance in borderline hypertension.

Arterial compliance was evaluated by pulse wave velocity, pulse pressure/stroke volume, and by an exponential analysis of the diastolic blood pressure decay curve in three groups of normotensive, borderline hypertensive, and established essential hypertensive patients. Two of the above three indices reflected significantly impaired arterial compliance in borderline hypertension, and all three indices were distinctly abnormal in patients with established hypertension. A close correlation among the three indices was observed in the entire study population. Multiple regression analysis indicated that age (p less than 0.005), systolic (p less than 0.005) and diastolic (p less than 0.025) pressure were independent determinants of pulse wave velocity; other factors such as total peripheral resistance, pulse pressure, and stroke volume were not. We conclude that arterial compliance becomes impaired early in hypertensive cardiovascular disease at the time when arterial pressure may be only slightly elevated. Thus structural alteration of the arterial wall can be demonstrated in borderline hypertension. Age, systolic and, to a lesser degree, diastolic pressures are the best determinants of arterial compliance in large vessels and are therefore important risk factors for evolving systemic arterial disease in essential hypertension.

Adult↗
PubMed1979

Echocardiographic dimensions in borderline and sustained hypertension.

Echocardiographic dimensions and hemodynamic indexes were determined in 42 patients with borderline hypertension and in 22 with sustained hypertension and the results were compared with findings in 33 normal subjects. In patients with borderline hypertension the thickness of the interventricular septum (IVS) was significantly increased (P less than 0.001), whereas the posterior wall PW) thickness remained within normal range. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). In patients with sustained hypertension a symmetric cardiac hypertrophy was observed, and there was a significant positive correlation between the IVS/PW ratio and diastolic pressure (P less than 0.05). The study suggested that (1) in sustained hypertension the symmetric cardiac hypertrophy was secondary to a progressive increase in pressure load, whereas (2) in borderline hypertension the asymmetric cardiac hypertrophy could not be directly related to the level of blood pressure and was probably associated with abnormalities of the sympathetic nervous system.

Blood Pressure↗
PubMed1978

Repeat hemodynamic determinations in borderline hypertension.

Repeat hemodynamic determinations were performed in 37 young men with borderline hypertension. The duration of the follow up study was 47 +/- three months. At each determination, those with borderline hypertension were compared to a group of matched normal subjects. Blood pressure increased from the first to the second determination, but the increase was significant only for systolic (P less than 0.001) and mean (P less than 0.01) arterial presssures. Cardiac index and heart rate, which were initially increased, decreased significantly (P less than 0.02; P less than 0.01, respectively) and decreased to normal values; total peripheral resistance increased (P less than 0.01); blood and plasma volumes decreased (P less than 0.01). At the first determination, the cardiac index-heart rate correlation was significant (P less than 0.01) and the cardiac index-blood volume correlation was not. At the second determination, on the contrary, the cardiac index-total blood volume correlation was significant (P less than 0.001) whereas the cardiac index-heart rate correlation was not. The study provides evidence that patients with borderline hypertension, over a short-term period, show (1) a greater increase in systolic than in diastolic pressure, (2) a return of cardiac output toward normal values through a decrease both in heart rate and blood volume, and (3) an increased importance of volume factors in the cardiac output control.

Adult↗
PubMed1983

Effects of two doses of methylphenidate on cross-situational and borderline hyperactive children's evoked potentials.

This study involved 27 children displaying cross-situational hyperactivity and 14 youngsters with borderline hyperactivity. For all patients, evoked potentials were recorded after receiving 0 (placebo), 0.3 and 0.6 mg/kg methylphenidate. Under each pharmacologic condition, subjects were administered: a photic stimulation procedure; two versions of the Continuous Performance Test (CPT), which varied in difficulty level; and a discrimination ('oddball') test. Under photic stimulation, methylphenidate reduced the impact of increasing brightness levels on the rates of amplitude increment and latency decrease in the P208 component of the visual evoked response. These results are similar to those obtained by Buchsbaum and Wender (1973) for hyperactive patients with a positive clinical response to amphetamine. In CPT and the discrimination test, the two active dosages of methylphenidate brought about a comparable reduction of placebo levels of errors and reaction time. Analogously, in both versions of CPT, the two active dosages resulted in comparable increases in the amplitude of two components of the late positive complex (LPC; P510 and P740). P510 was identified as a classical P300. In the discrimination test, the effect of the stimulant on the response evoked by the visual non-target was to increase the amplitude of a component (P463) previously identified as P300. These pharmacologic results were nearly identical for borderline and cross-situational patients. In general, the results confirmed previous observations that methylphenidate improves hyperactive children's performance and increases the amplitude of their LPC. Further, these findings support previous observations that hyperactive patients' cognitive processing is optimized by a dosage of 0.3 mg/kg methylphenidate. Finally, the similarity between findings for cross-situational and borderline hyperactive patients is consistent with other evidence that stimulant effects are not limited to classically hyperactive children.

Attention Deficit Disorder with Hyperactivity↗