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PubMed2004

Current challenges and opportunities for research on borderline ovarian tumors.

This article summarizes key issues for future research on borderline ovarian tumors that emerged at a National Cancer Institute-sponsored Borderline Ovarian Tumor Workshop held in August 2003 in Bethesda, MD. Limitations in existing research and opportunities for future advances have been highlighted. The application of new molecular techniques in combination with improved study designs holds promise for elucidating the pathogenesis of these tumors and revealing the source of the extra-ovarian lesions ("implants") with which they are frequently associated. Clarification of the etiology of borderline tumors and the pathogenesis of their associated implants is critical for improving pathological diagnosis, revising the classification system of ovarian neoplasms, and developing optimal, evidence-based clinical management algorithms.

Cystadenocarcinoma, Mucinous↗
PubMed2005

Analysis of the beta-lactamase plasmid of borderline methicillin-susceptible Staphylococcus aureus: focus on bla complex genes and cadmium resistance determinants cadD and cadX.

Borderline methicillin-susceptible Staphylococcus aureus strains are a rather homogeneous group, characterized by MICs of penicillinase-resistant penicillins (PRPs) at or just below the susceptibility breakpoint. Other features unique to this group include the presence of a pBW15-like beta-lactamase plasmid, the association with phage complex 94/96, and the production of a PRP-hydrolyzing beta-lactamase activity in addition to the classical penicillinase activity. The four HindIII fragments of pBORa53, a pBW15-like plasmid from the well-studied borderline S. aureus strain a53, were cloned in Escherichia coli, sequenced and analyzed. The plasmid (17,334 bp in size) contains 14 open reading frames (ORFs) and a complete copy of transposon Tn552, which harbors the three genes of the bla complex (blaZ, blaR1, and blaI) necessary for penicillinase production. Among the other 11 ORFs identified, two were homologous to cadmium resistance determinants of Staphylococcus lugdunensis and to the cadD and cadX genes recently detected in S. aureus. Consistent with this, strain a53 was found to be cadmium resistant. From a collection of 30 S. aureus isolates with borderline PRP MIC levels, 27 matched strain a53 in the positive amplification reactions with all of the four primer pairs targeting the cadD-cadX region, the presence of the 17.3-kb plasmid, and the level of cadmium resistance. The well-established S. aureus laboratory strain ATCC 29213 was also found to express cadD-cadX-mediated cadmium resistance. pBORa53 could be re-isolated from transformants obtained by transferring it into a PRP-susceptible recipient. However, while the transformants demonstrated levels of cadmium and penicillin resistance similar to those of strain a53, they remained fully susceptible to PRPs.

Bacterial Proteins↗
PubMed2004

Borderline changes in the Banff schema: rejection or no rejection?

The relationship between acute renal allograft rejection and histopathologic biopsy alterations recognized by the Banff Schema as "borderline changes" is not clear. Some evidence supports the contention that about one third of patients with borderline infiltrates and clinical evidence of graft dysfunction do indeed have acute rejection, which, if left untreated, progresses to a histologically more advanced stage of rejection. Several investigators recognize that not all patients with mild tubulitis respond clinically to antirejection therapy; a significant number of these biopsy specimens display additional histological alterations. The most common concurrent lesions are chronic allograft nephropathy, arteriolar lesions consistent with calcineurin inhibitor toxicity, acute tubular necrosis, and obstructive nephropathy. Management of patients with borderline changes must tightly correlate the pathologic features and the clinical information.

Diagnosis, Differential↗
PubMed2004

Are borderline tumors of the ovary safely treated by laparoscopy?

OBJECTIVES: To evaluate the risk of the laparoscopic approach to patients with borderline ovarian tumors compared to the laparotomic management. METHODS: We treated or followed in our institution 479 women with borderline ovarian tumor. Sixty-two patients had fertility-sparing surgery followed by restaging or follow-up intervention: 30 operated by laparoscopy, 32 by laparotomy. Restaging surgery was performed in five cases and second-look surgery in 57. RESULTS: The diameter of the cyst is significantly lower in patients treated by laparoscopy, especially in women who underwent cystectomy (4.7 cm) compared to oophorectomy (10 cm, P = 0.008). Rupture of the cyst and stage IC were more frequent in the laparoscopic group. After a median follow-up of 61 months for the laparoscopic group and 77 months for the laparotomic group, we observed 11 patients (37%) with persistent disease after primary laparoscopy (adnexa, five cases; peritoneal implants, three cases; both patterns, three cases). After primary laparotomy, no patients showed early persistence of tumor, and ovarian relapses were diagnosed in seven women (22%) 33-138 months after laparotomy. The univariate analysis for the risk of neoplastic persistence after primary laparoscopy shows that patients with cysts greater than 5 cm have a higher risk (odds ratio 9.7, P = 0.02) compared to smaller cysts. No other factors proved significant, but the odds ratios for patients with serous tumor (5.8), stage IC (2.0), and those undergoing cystectomy (1.9) suggest a relationship to the probability of persistence. CONCLUSION: Laparoscopic treatment in borderline ovarian tumors should be reserved to masses not greater than 5 cm. When conservative therapy is desired, the entire affected ovary should be removed. If the neoplasia is bilateral, cystectomy could be allowed in women who wish to preserve fertility, although they are at high risk of relapse.

Adult↗
PubMed2005

Results after laparoscopic management of serous borderline tumor of the ovary with peritoneal implants.

OBJECTIVE: The aim of this study is to assess the clinical outcomes of laparoscopic treatment of borderline ovarian tumor (BOT) with peritoneal implants. METHODS: Retrospective analysis of patients treated initially and/or for recurrent disease using a laparoscopic approach for a stage II or stage III BOT between January 2001 and January 2004. RESULTS: Nine patients underwent a laparoscopic pure treatment of stage II/III serous borderline tumor. Three of them had a previous history of BOT. Three patients had a stage II and 6 a stage III disease. A conservative management was performed in 7 patients. Laparoscopic treatment of peritoneal implants included: omentectomy (or omental biopsies) in 4 patients and/or large peritoneal resection in 5 patients (pelvic peritoneum in all patients associated with peritonectomies of paracolic gutters in 2 and of the peritoneum of the right diaphragmatic peritoneum in 3). Implants were nonivasive in 8 patients. Each of implant had a size <5 mm. Four patients recurred, 3 of them had a borderline ovarian recurrence after conservative management. Two patients had peritoneal disease found during a second-look surgery (associated with ovarian recurrence in 1). Three spontaneous pregnancies were observed. All patients are alive without evidence of disease with a median time of follow-up of 35 months following the laparoscopic treatment. CONCLUSION: Our series suggests that laparoscopic treatment of patients with BOT associated with small size non-invasive implants is feasible and seem to be safe. The main indication of this management consists in young patients treated conservatively to preserve their fertility.

Adolescent↗
PubMed2005

Fertility and recurrence results of conservative surgery for borderline ovarian tumors.

OBJECTIVES: To evaluate the fertility and recurrence outcomes in women treated with fertility-sparing surgery for borderline ovarian tumors. METHODS: A total of 142 patients with borderline ovarian tumors managed surgically from 1993 to 2004 were identified from gynecologic oncology and pathology files of SSK Ankara Maternity and Women's Health Teaching Hospital. Sixty-two of those patients who had conservative surgery were eligible for the study. Information was acquired by retrospective medical record review and patient interview. RESULTS: The observed recurrence rates after radical and fertility-sparing surgery were 0.0% and 6.5%, respectively. Four patients from the conservative surgery group developed recurrence, in contrast to none of the patients from the non-conservative surgery group. No disease-related deaths occurred in any group. In the conservatively managed group, ten women had successful pregnancies, with a total of 10 live births and 3 abortions. The mean duration of follow-up for the conservative surgery group was 44.3 months (range, 3-128). CONCLUSION: Fertility-sparing surgery for borderline ovarian tumors should be considered for women in the reproductive age group who desire preservation of fertility. Recurrence is noted significantly more often after this type of treatment and close follow-up is needed to detect recurrent disease.

Adolescent↗
PubMed2005

Recurrence and prognostic factors in borderline ovarian tumors.

OBJECTIVE: The purpose of this study was to evaluate the survival estimates and clinico-pathological variables in patients treated for borderline ovarian tumors. METHODS: The patients treated for borderline ovarian tumors were evaluated retrospectively. Data were obtained from hospital records and special gynecologic oncology forms. RESULTS: Overall, 100 patients were evaluated. The mean age at the time of diagnosis was 41.7 (range, 19-84). Seventy one (71%) patients underwent surgical staging including 49 (49%) of them with comprehensive surgical staging, 22 (22%) with fertility-sparing surgery. Only 30 (30%) patients were unstaged. The histopathological diagnosis was serous, mucinous, and the other types of borderline ovarian tumor in 54 (54%), 39 (39%), and 7 (7%) of the patients, respectively. Seventy patients had stage IA (70%), 10 had stage IB (10%), 9 had stage IC (9%), 3 had stage IIIA (3%), and 8 had stage IIIC (8%) disease. The stage of only four patients in which disease confined to ovary was upgraded as stage IIIC following surgical staging procedure. The recurrence rate was found 3% (3). The overall disease-free survival rates of BOT in surgically staged (comprehensive, fertility-sparing surgery) and unstaged patients were 97.92%, 95.00%, and 96.30%, respectively. But, the overall tumor-free survival was significantly found to be decreased in cases of young age (<30 years old), performing fertility-sparing surgery and presence of micropapillary architecture or peritoneal implants. Overall survival rates of BOT in surgically staged (comprehensive, fertility-sparing surgery) and unstaged patients were 97.9%, and 100% and 100%, respectively. CONCLUSION: Low malignant potential ovarian tumors have excellent survival, and the patients can be treated safely by conservative surgery.

Adult↗
PubMed2006

Cystic clear cell tumor of borderline malignancy of the ovary lacking fibromatous components: report of two cases and a possible new histological subtype.

BACKGROUND: All of the ovarian borderline clear cell tumors ever reported had, without exception, an adenofibromatous pattern. CASE: We report two cases of borderline cystic clear cell tumor of the ovary without apparent invasive lesions or adenofibromatous components. CONCLUSION: This is the first report of cystic clear cell tumors of borderline malignancy, indicating a possible new histological subtype.

Adenocarcinoma, Clear Cell↗
PubMed2006

CHEK2 variants predispose to benign, borderline and low-grade invasive ovarian tumors.

OBJECTIVE: Three founder alleles of the CHEK2 gene have been associated with predisposition to a range of cancer types in Poland. Two founder alleles (1100delC and IVS2 + 1G >A) result in a truncated CHEK2 protein and the other is a missense substitution, leading to the replacement of a threonine with an isoleucine (I157T). METHODS: To establish if these variants play a role in the etiology of ovarian tumors, we genotyped 1108 Polish women with various types of ovarian tumors and 4000 controls for the three CHEK2 variants. We included 539 Polish women with benign ovarian cystadenomas, 122 women with borderline ovarian malignancies and 447 women with invasive ovarian cancer. RESULTS: Positive associations were seen with the CHEK2 I157T missense variant and ovarian cystadenomas (OR = 1.7; P = 0.005), with borderline ovarian cancers (OR = 2.6; P = 0.002) and with low-grade invasive cancers (OR = 2.1; P = 0.04). There was no association with ovarian cancer of high grade (OR = 1.0). The association between the I157T missense variant was then confirmed in a second sample of Russian patients with borderline ovarian cancers (OR = 2.7; P = 0.06). CONCLUSION: These data indicate that CHEK2 variants may predispose to a range of ovarian tumor types of low malignant potential, but not to aggressive cancers.

Checkpoint Kinase 2↗
PubMed2000

Clinical impact of borderline and undiagnosed diabetes mellitus in patients with coronary artery disease.

The present study was aimed to evaluate the prevalence and prognostic significance of unrecognized and newly defined borderline diabetes (with fasting blood sugar 126 to 139 mg/dl) by the American Diabetes Association criteria in coronary patients over a 7.7-year follow-up. Both undiagnosed and newly diagnosed borderline diabetes were associated with an unfavorable metabolic profile. The mortality of the borderline diabetics tended to be higher than in their nondiabetic counterparts. but this tendency did not reach statistical significance. A significant excess in long-term mortality was observed among the undiagnosed diabetes group.

Aged↗
PubMed2003

Molecular genetic evidence for monoclonal origin of bilateral ovarian serous borderline tumors.

Patients with serous borderline tumors of the ovary often present with multiple tumors at different sites in the abdominal cavity. Whether different foci of ovarian serous borderline tumors are monoclonal in origin, arising as a consequence of spread from a single ovarian site, or whether such deposits are polyclonal and explained by independent molecular genetic alterations on the background of a field defect, is unknown. So far, only X-chromosome inactivation studies were performed to study this issue. We used a genome-wide allelotyping to assess clonality in 47 metachronous and/or synchronous multifocal tumors from 22 patients, using 59 microsatellite markers. Loss of heterozygosity (LOH) was observed in only 34 of 1969 informative markers in 9 of 22 serous borderline cases studied. Of these cases, 7 showed concordant LOH for at least one polymorphic marker in more than one tumor site. Flanking microsatellite markers enabled identification of identical chromosomal breakpoints in 6 of 7 cases. The LOH results strongly favor a common origin indicated by a likelihood ratio (possibility common origin/possibility independent origin) ranging from 39 to 14,163. Strong additional evidence for monoclonality is provided by the finding of identical microsatellite alterations in all three-tumor sites in one case.

Chromosome Mapping↗
PubMed2001

Fertility and tumor recurrence rate after conservative laparoscopic management of young women with early-stage borderline ovarian tumors.

OBJECTIVE: To evaluate the efficacy of laparoscopic conservative surgery in young women with borderline ovarian tumors who want to preserve their childbearing potential, and to assess whether pregnancy influences the recurrence rate during the follow-up evaluation period. DESIGN: Retrospective study. SETTING: Center for Reconstructive Pelvic Endosurgery, Reproductive Medicine Unit, S. Orsola Hospital, University of Bologna, Italy. PATIENT(S): Nineteen women (mean age 27.4 +/- 4.7) with borderline ovarian tumors who underwent laparoscopy between January 1995 and January 1998. All of the women wanted to preserve their fertility. INTERVENTION(S): A standardized conservative laparoscopic approach and a strict follow-up schedule. MAIN OUTCOME MEASURE(S): A complete preoperative examination. RESULT(S): Follow-up evaluations (mean 42 +/- 19 months) were made available to all patients. Among 19 patients, 10 attempted pregnancy and 6 conceived spontaneously. All six pregnancies went to term and the disease did not affect the gestation or the follow-up period after the pregnancy (24.5 +/- 15.7 months). CONCLUSION(S): Conservative laparoscopic management of borderline ovarian tumors is a potentially safe alternative in young women who want to retain their childbearing potential. Fertility and pregnancy outcome remain excellent in these women. Our preliminary data seem to indicate that the recurrence rate after pregnancy is not influenced by this approach.

Adult↗
PubMed2000

Three-year follow-up of borderline congenital hypothyroidism.

The purpose of this study was to determine whether children with borderline hypothyroidism in the neonatal period had persistent hypothyroidism after 3 years of levothyroxine replacement therapy. Fourteen term infants with slightly abnormal newborn screening results (thyroxine <10th percentile, thyroid stimulating hormone ¿TSH <40 microU/mL) were identified. The subsequent serum confirmatory TSH results of 12 subjects were modestly elevated (5.3 to 18.8 microU/mL, normal 0.6 to 4.6), whereas 2 subjects who had borderline confirmatory TSH (4.6 and 4.7 microU/mL) had abnormal TSH responses to thyrotropin releasing hormone testing. After 3 years of therapy, levothyroxine was discontinued in 13 patients, and repeat thyroid function tests were obtained 1 month later. Levothyroxine was not discontinued in one patient because he had an elevated random TSH (10 microU/mL) while receiving therapy. At 3 years of age, 13 patients had persistently abnormal thyroid function tests (TSH >4.6 microU/mL or a thyroid releasing hormone test result consistent with primary hypothyroidism), and levothyroxine was reinitiated. Only one patient had normal thyroid function studies. Although prospective studies are still lacking, we recommend levothyroxine replacement in newborns with borderline hypothyroidism.

Body Height↗
PubMed1977

Borderline hypertension. An overview.

Borderline hypertension is widespread. Though the increased blood pressure appears to be innocent, and upon rest frequently returns to the normal range, signs of complex and profound alteration of the physiologic control of the circulation can already be found. The pathophysiology of borderline hypertension is of particular interest since it may reveal clues about the processes which initiate the hypertension rather than the consequences of the primary blood pressure elevation. Patients with borderline hypertension are at a higher risk of developing future sustained hypertension and its consequences. The risk, however, is not sufficient to justify treatment in all cases. Patients must be followed to observe blood pressure trends and treatment attempted in the selected minority which has the highest risk. The determination of risk is based on repeated measurements of blood pressure and on the assessment of risk factors for atherosclerosis and for future hypertension.

Adolescent↗
PubMed1998

Effects of naloxone on hemodynamic and sympathetic nerve responses to pain in normotensive vs. borderline hypertensive men.

Pain sensitivity decreases with increasing resting blood pressure. This blood pressure-pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during 2 min periods of noxious mechanostimulation (skin fold pinching) in nine young (26 +/- 2 year), male normotensive (NT) subjects and in 12 age and weight matched males with borderline hypertension (BHT). Measurements were performed before and after the i.v. administration of naloxone (0.15 mg/kg) and placebo in a randomized double-blind cross-over trial. In the pre-naloxone trials, pain led to similar changes in MAP, CVP, MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group (3 +/- 1 vs. 1 +/- 1 bpm; P < 0.005). Opioid blockade with naloxone increased MSNA responses to pain in the NT group (from 5 +/- 1 to 9 +/- 1 bursts/min, and, from 100 +/- 23 to 204 +/- 36 units/min, respectively; P < 0.05) but did not significantly affect the MSNA response to pain in the BHT group. Pain induced responses of MAP, CVP, and catecholamines were not altered by naloxone in either group. Overall, there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone. The BHT subjects exhibited a lower pain perception compared to the NT subjects (P < 0.005). Naloxone increased pain rating in the NT group (from 194 +/- 9 to 218 +/- 13; P < 0.005) but not in the borderline hypertensive group (160 +/- 8 vs. 168 +/- 10; P = 0.36). Except for a decreased HR response in the BHT group, placebo had no effect on the responses to pain. Our data do not indicate a major role of the endogenous opioid system for the blood pressure-pain interaction in man. Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects. Therefore, the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.

Adult↗
PubMed1999

Echocardiographic features and QT dispersion in borderline isolated systolic hypertension in the elderly.

The aim of our study was to examine the structure of left ventricle, diastolic filling indexes and QT dispersion in elderly patients (aged 60 years and over) with borderline isolated systolic hypertension in a population screening program and to compare them with age matched controls. One hundred and four subjects (66 female, 38 male, mean age 66+/-5) and 110 normotensive age and sex matched controls (64 female, 46 male, mean age 66+/-5) were included in the study. Echocardiographic features of left ventricle, left atrium and cardiac valves, diastolic filling indexes and QT dispersion in 12 lead electrocardiographic examination were studied. In borderline hypertensive elderly, left ventricular hypertrophy was a more frequent finding compared with the controls (33% versus 15% respectively). Diastolic filling indexes were impaired, presence of left atrial enlargement and cardiac valve calcification were also more frequent in the patients group. In the electrocardiographic examination, the duration of QT and corrected QT interval and dispersion of QT and QTc were significantly prolonged compared with the controls. It is concluded that patients with borderline isolated systolic hypertension have more unfavourable echocardiographic and electrocardiographic findings compared with the normotensive elderly and especially those with end organ damage should be treated as defined for isolated systolic hypertension.

Aged↗
PubMed2000

Comparison of several methods to determine methicillin-resistance in Staphylococcus aureus with focus on borderline strains.

We compared the performance of several phenotypic tests to detect methicillin-resistant Staphylococcus aureus, with special focus on borderline strains. The reliability of the agar screen oxacillin and BBL Crystal tests was asserted for all methicillin-susceptible (n = 25), -resistant (n = 29) and borderline beta-lactamase-hyperproducer (n = 10) strains. Whereas these tests failed to detect 4 of 5 rare borderline strains containing few cells with high-level methicillin resistance (i.e., a frequency of 10(-7)-10(-8)), a "two-temperature" disk diffusion method, performed simultaneously at 35 and 42 degrees C, detected all of such strains.

Ampicillin↗
PubMed1990

"Borderline" myocarditis: an indication for repeat endomyocardial biopsy.

Repeat endomyocardial biopsy was performed in 28 patients with dilated cardiomyopathy of less than or equal to 12 months' duration and either symptomatic heart failure or life-threatening ventricular arrhythmias. Myocarditis was strongly suspected clinically in all cases, yet was unconfirmed on initial right ventricular biopsy. Seventeen patients underwent both right and left ventricular biopsy, seven patients had a repeat right ventricular biopsy and four patients underwent repeat left ventricular biopsy alone. The interval between initial and repeat biopsy averaged 31 +/- 6 days. Myocarditis was confirmed on repeat biopsy in 4 of 6 patients whose initial biopsy revealed "borderline" myocarditis (that is, interstitial inflammation but absence of myocyte necrosis) compared with none of the 22 patients whose initial biopsy showed either myocyte hypertrophy or interstitial fibrosis, or both (p = 0.0007). "Borderline" myocarditis on initial biopsy was the only clinical or histologic finding predictive of myocarditis on subsequent biopsy. Repeat endomyocardial biopsy can identify and potentially modify the treatment of an additional group of patients with dilated cardiomyopathy and nondiagnostic initial endomyocardial histologic features. Right ventricular sampling should be repeated in patients whose initial biopsy demonstrates "borderline" myocarditis.

Azathioprine↗