BRCA2 alteration is important in clear cell carcinoma of the ovary.

BRCA2 has been shown to play a significant role in hereditary ovarian carcinoma. Several cases of clear cell carcinoma (CCC) of the ovary containing BRCA2 mutations have been identified. We hypothesize that sequence variants of the BRCA2 gene are common in CCC of the ovary. Multiple methods were utilized to detect BRCA2 genetic alterations in a cohort of 13 ovarian CCC. These included an LOH analysis for copy number, real-time and methylation-specific polymerase chain reaction (PCR) to probe for BRCA2 promoter methylation, in addition to protein truncation testing (PTT) gel screening for nonsense BRCA2 mutations, and finally direct gene sequencing to either confirm the nonsense mutations or to detect candidate missense mutations in the remaining tumor samples. Whenever a sequence variation was detected in a tumor sample, the corresponding region was sequenced from a blood sample to determine germline status. Seven BRCA2 sequence variations were identified in 6 of the 13 CCC (46%); three tumors contained an alteration in BRCA2 copy number. Only one subject carried a germline sequence variation that might alter BRCA2 function despite the fact that a family history of breast, ovarian or colon cancer was common in this population. The 5-year disease-specific survival probability for patients with a BRCA2 alteration is 87.5%, compared to only 40% for those patients without a BRCA2 alteration (p = 0.39). Alterations in BRCA2 gene sequence, copy number, or expression are extremely common in CCC and may contribute to a paradoxical better clinical outcome.

Tunneled central venous catheters in a gynecologic oncology service: operative and short-term complications.

PURPOSE: To determine the difference in the immediate complication rate between placement of long-term central venous catheters (LTCVCs) by the percutaneous versus jugular venous cutdown method. METHOD: Case lists were examined to determine the number of LTCVCs placed during the designated time period. Medical records, operative reports, and chest roentgenograms were examined to extract pertinent information. Immediate complications included complications occurring in the operating room until 30 days postoperatively. Complications included misplacement of the catheter requiring an adjustment or a repeat procedure, pneumothorax, hydrothorax, or hemothorax, operative site or tunnel infection, and line migration requiring removal. RESULTS: Five hundred and one patients had LTCVCs placed during the period of this study. This included 399 totally implantable venous access devices (TIVADs) and 102 free access venous access devices (FAVADs) with 163 placed percutaneously into subclavian veins and 338 placed by cutdown into jugular veins. There was a significant increased risk in the overall immediate complication rate for the percutaneous placement compared to venous cutdown (p < 0.001). Also, pneumothorax was more common with the percutaneous approach compared to the venous cutdown approach (p < 0.001). CONCLUSIONS: Immediate complications, especially pneumothorax, were more common when placing catheters by the percutaneous approach as compared to the venous cutdown approach.

E-cadherin is a novel transcriptional target of the KLF6 tumor suppressor.

The tumor suppressor KLF6 is a member of the Krüppel-like family of transcription factors, which has been implicated in the pathogenesis of several human carcinomas. Uncovering the transcriptional targets relevant for its tumorigenic properties, including cellular proliferation and invasion, will be essential to understanding possible mechanisms by which KLF6 and its antagonistic splice form, KLF6-SV1, regulate this development. To begin defining possible metastatic-related pathways, we analysed the effect of KLF6 dysregulation on a recognized suppressor of cellular invasion, E-cadherin. Targeted KLF6 reduction in an ovarian cancer cell line, SKOV-3, resulted in a 50% reduction of E-cadherin expression (P<0.01) and conversely, KLF6-SV1 silencing upregulated E-cadherin approximately fivefold (P<0.0001). These changes resulted from KLF6 directly transactivating the E-cadherin promoter as demonstrated by luciferase promoter assay and chromatin immunoprecipitation (ChIP). KLF6-mediated changes in E-cadherin levels were accompanied by downstream changes in both the subcellular localization of beta-catenin and c-myc expression levels. Moreover, and consistent with these experimental findings, patient-derived epithelial ovarian tumors with low KLF6 and high KLF6-SV1 expression ratios had significantly decreased E-cadherin expression (P<0.0001). These combined findings highlight the E-cadherin pathway as a novel and functionally important mediator by which changes in KLF6 and KLF6-SV1 can directly alter ovarian tumor invasion and metastasis.

CAG repeat length in exon 1 of the androgen receptor gene is related to age of diagnosis but not germ line BRCA1 mutation status in ovarian cancer.

It has been postulated that androgens, through their interaction with androgen receptors (AR), may play an important role in the development of ovarian cancer. Exon 1 of the AR gene contains three highly polymorphic trinucleotide repeats. The length of the (CAG)n repeat segment 1 is inversely correlated with the transactivation function of the AR. Recent studies have shown that BRCA1 may function as an AR coregulator or coactivator and play positive roles in androgen-induced cell death in cancer cells as well as other androgen/AR target organs. We hypothesize that the AR gene, involved in endocrine signaling, may modify BRCA1-associated ovarian cancer risk. To test this hypothesis, potential associations between the (CAG)n repeat length, germ line BRCA1 mutation status, and age of diagnosis for ovarian cancer were investigated. One hundred and eleven ovarian cancer patients (27 hereditary and 84 sporadic) were included. All the cases were allelotyped for CAG repeat length and genotyped for mutations in the BRCA1 gene by direct sequencing. No association between CAG repeat length and BRCA1 mutation status was identified. Furthermore, there were no differences between hereditary and sporadic ovarian cancer in the number of (CAG)n repeats of the short allele (P= 0.336), long allele (P= 0.875), or average allele length (P= 0.550). However, ovarian cancer patients from both groups (hereditary and sporadic) who carried any AR allele of (CAG)n < or = 22 repeats were diagnosed on average 8.17 years (95% confidence interval [1.3, 15.0]) earlier than the patients whose shortest AR allele (CAG)n was >22 (P= 0.020). In conclusion, it is suggested that the CAG repeat length in AR exon 1 may affect the age of diagnosis of ovarian cancer but does so independent of germ line BRCA1 carrier status.

Malignant mixed mullerian tumor of the ovary and bilateral breast cancer: an argument for BRCA3, or a coincidental cluster of unconnected cancers?

OBJECTIVES: Malignant mixed mullerian tumors (MMMTs) of the ovary are a rare, aggressive subtype of ovarian cancer without a clear relationship to familial breast-ovarian cancer syndromes. CASE: We present the case of a woman with bilateral breast cancers who subsequently developed a stage IIIc MMMT of the ovary. The patient had a first-degree female relative with breast and ovarian cancer (not MMMT), as well as second- and third-degree female relatives each with bilateral breast cancers. BRCA1 and BRCA2 sequencing of germline DNA revealed no evidence of a heritable mutation. CONCLUSIONS: Ovarian MMMTs may be a hallmark of breast/ovarian cancer secondary to genetic risk independent of classic BRCA1/2 pathways.

The role of p53 mutation in BRCA1-associated ovarian cancer.

Ovarian cancer remains the most deadly gynecologic malignancy, resulting in an estimated 23,300 new cases and 13,900 deaths in the United States in the year 2002. The discovery of the BRCA1 gene in 1994 has proven to be of great interest to the study of hereditary ovarian cancer. BRCA1 gene mutation confers a 16-42% lifetime risk of the development of ovarian cancer in those affected. Although BRCA1 functions as a tumor suppressor gene, conflicting studies have shown that BRCA1 dysfunction alone may not be sufficient for tumorigenesis. p53 is a tumor suppressor gene found to be dysfunctional in nearly 50% of all human cancers and in up to 80% of ovarian malignancies. The p53 protein product plays a crucial role in DNA surveillance and repair at the Gap 1-synthesis (G1-S) cell cycle checkpoint. Studies exhibiting the interaction of BRCA1 and p53 and the role of this interaction in DNA damage response led many investigators to suggest that p53 gene mutation is required for BRCA1-associated tumor development. This review explores the evidence for BRCA1 and p53 interplay, and outlines the crucial role p53 may play in BRCA1-related ovarian cancer.

Papillary serous carcinoma of the uterus: increased risk of subsequent or concurrent development of breast carcinoma.

OBJECTIVE: Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. METHODS: The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and chi(2) tests. RESULTS: Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC (P < 0.001). CONCLUSION: Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.

Simultaneously detected endometrial and ovarian carcinomas--a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study.

OBJECTIVES: The coexistence of carcinomas of the endometrium and ovary occurs in about 10% of women with ovarian carcinoma. It is often unclear whether this represents synchronous primary tumors or metastasis from endometrium to ovary, or from ovary to endometrium; consequently, staging, therapy, and expected outcome are uncertain. The Gynecologic Oncology Group sought to study patients with simultaneously detected adenocarcinomas in the endometrium and ovary with disease grossly confined to the pelvis to explore the possible correlation among discrete tumor subsets, natural history, and survival. METHODS: Between 1985 and 1991, 85 patients were prospectively enrolled, of whom 74 were eligible. All were initially treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and staging laparotomy, with radiation and chemotherapy left to the discretion of the treating physician and patient. Fifteen pathologic variables were examined to identify differences in tumor behavior. RESULTS: Of the 74 patients, 23 (31%) had microscopic spread of tumor in the pelvis or abdomen. Sixty-four (86%) patients had endometrioid carcinomas in both the endometrium and the ovary, and endometriosis was found in the ovary of 23 (31%) patients. There was concordance between the histologic grade of the tumor in the ovary and the uterus in 51 (69%) patients. The estimated probability of recurrence 5 years following staging surgery is 15.1% (95% confidence interval (CI): 8.7-25.2%). The presence of metastasis discriminated two groups of patients that experienced different probabilities of recurrence within 5 years: 10.0% (95% CI: 4.32-21.3%) for those with tumors confined to the uterus and ovary and 27.1% (95% CI: 13.0-48.5%) for those with metastasis (hazard ratio = 4.6, P = 0.006). The histologic grades of ovarian and uterine tumors also distinguished groups of patients with different probabilities of recurrence at 5 years: 8.0% (95% CI: 2.8-21.3%) for those patients with no more than grade 1 disease at either site and 22.4% (95% CI: 11.8-38.4%) for those with a higher grade in either the ovary or the endometrium (hazard ratio = 3.1, P = 0.047). The estimated overall probability of surviving 5 years is 85.9% and that of surviving 10 years is 80.3%. CONCLUSION: The prognosis for women with simultaneously detected carcinomas in the uterus and ovary with gross disease confined to the pelvis is surprisingly good, particularly for those with disease microscopically limited to the uterus and ovary or of low histologic grade.

Ovarian cancer BRCA1 mutation detection: Protein truncation test (PTT) outperforms single strand conformation polymorphism analysis (SSCP).

Recent studies have shown that the BRCA1 tumor suppressor gene plays a role in the development of both hereditary and sporadic ovarian cancer. Since several different mechanisms may give rise to tumor gene defects, a better understanding of these mechanisms may identify BRCA1 as an attractive therapeutic target in ovarian cancer. Sequencing this large gene is not practical on a population-wide basis. The optimal screening strategy is yet to be determined. The purpose of our study is to compare two common screening techniques: the protein truncation test (PTT) and single strand conformational polymorphism analysis (SSCP). Ninety-four patients with epithelial ovarian cancer and available snap-frozen tissue were screened for BRCA1 mutations by both PTT (five individual PCR reactions with complete translation of the product in the TNT System (Promega, Madison, WI)) and SSCP (41 individual PCR reactions covering the entire coding sequence). All abnormal results were confirmed by sequencing. A paired peripheral blood DNA sample was utilized to determine if the sequence abnormality was a germline mutation. Twenty-three mutations in BRCA1 were found in 22 patients (14 germline, eight somatic, one unknown) including four novel mutations: E489X, 3558delT, 3871delGTCT, del exon 7-10. Although the predictive value of a negative test was close for the two methods (PTT 99.1%, SSCP 99.8%), the comparison of positive predictive value overwhelmingly favored PTT (100.0%, vs. 26.4%, respectively). The specificity for PTT was 100.0% while the sensitivity was 82.6%. While for SSCP, the specificity was 99.0% and the sensitivity was only 60.9%. The concordance rate for the two screening tests was 88.9%. Only SSCP can detect missense mutations. PTT is a superior screening test for truncating BRCA1 mutations that are expected to be of clinical significance.

Application of the National Cancer Institute international criteria for determination of microsatellite instability in ovarian cancer.

Recently, the National Cancer Institute (NCI) established criteria for determination of microsatellite instability (MSI) in colorectal tumors. Although the best panel of markers for ovarian tumors is not known, we evaluated epithelial ovarian cancers for MSI based on the NCI recommendations. One hundred and nine ovarian tumors were analyzed for MSI by gel analysis of paired germ-line and tumor DNA. PCR amplification was performed using the panel of five microsatellite markers recommended by the NCI (BAT25, BAT26, D5S346, D2S123, and D17S250) and nine additional markers picked based on their genomic location (NME1, D10S197, D11S904, D13S175, DXS981, DXS6800, DXS6807, AR, and D3S1611). Tumors were characterized on the basis of: high-frequency MSI (MSI-H) if two or more of the five NCI markers showed instability or there was instability at 30% or more of all markers tested; or low-frequency MSI (MSI-L) if only one of the five NCI markers showed instability or <30% of all of the markers. All of the other tumors were considered microsatellite stable. On the basis of the NCI markers, 12 (11%) tumors demonstrated MSI-H, and 8 (7%) additional tumors had MSI-L. When all of the 14 markers were considered together, 13 (12%) tumors demonstrated MSI-H (based on 30% or more unstable loci), and 26 (24%) tumors had MSI-L. A single tumor identified to have MSI-H based upon all of the markers tested would have been classified as MSI-L based upon the NCI markers alone. Inclusion of an additional dinucleotide marker (NME1) to the NCI panel allowed detection of all of the tumors with MSI-H using only six markers. MSI-H occurs in approximately 12% of invasive ovarian tumors. For optimal detection of microsatellite instability in ovarian cancer, an additional marker (NME1) may be required, along with the five recommended by the NCI.

Molecular determinants of ovarian cancer plasticity.

During development, the formation and remodeling of primary vascular networks occurs by vasculogenesis and angiogenesis. Recently, the term "vasculogenic mimicry" has been used by our laboratory and collaborators to reflect the embryonic-like ability of aggressive, but not nonaggressive, melanoma tumor cells to form a pattern of matrix-rich networks (containing channels) surrounding spheroids of tumor cells in three-dimensional culture, concomitant with their expression of vascular cell markers. Ovarian cancer is usually diagnosed as advanced stage disease in most patients when widespread metastases have already been established within the peritoneal cavity. In this study, we explored whether invasive ovarian carcinoma cells could engage in molecular vasculogenic mimicry reflected by their plasticity, compared with their normal cell counterparts. The data revealed that the invasive ovarian cancer cells, but not normal ovarian surface epithelial cells, formed patterned networks containing solid and hollow matrix channels when grown in three-dimensional cultures containing Matrigel or type I collagen, in the absence of endothelial cells or fibroblasts. Immunohistochemical analysis showed that matrix metalloproteinases (MMP)-1, -2, and -9, and MT1-MMP were discretely localized to these networks, and the formation of the networks was inhibited by treatment with MMP inhibitors. Furthermore, the RNase protection assay revealed the expression of multiple vascular cell-associated markers by the invasive ovarian cancer cells. In patient tumor sections from high-stage, high-grade ovarian cancers, 7 to 10% of channels containing red blood cells were lined by tumor cells. By comparison, all vascular areas in benign tumors and low-stage cancers were endothelial lined. These results may offer new insights and molecular markers for consideration in ovarian cancer diagnosis and treatment strategies based on molecular vascular mimicry by aggressive tumor cells.

The p53 mutational spectrum associated with BRCA1 mutant ovarian cancer.

PURPOSE: Cancer-specific p53 mutational spectra have been identified. Data from murine models and human BRCA1-related hereditary breast cancers suggest that both unique and specific BRCA1-associated p53 mutations may be found in BRCA1-related ovarian cancers. EXPERIMENTAL DESIGN: The p53 mutational spectrum from ovarian cancers containing either somatic or germ-line BRCA1 mutations was compared with that of sporadic ovarian cancers defined as those diagnosed with a negative family history for breast/ovarian cancer in a three-generation pedigree. Tumor DNA was screened over exons 2-11 of the p53 gene by the PCR and single-strand confirmation polymorphism analysis of the amplimers. Cycle-based DNA sequencing from separate reactions was used to confirm p53 mutations. RESULTS: p53 gene mutations were detected in 42 of 86 sporadic ovarian cancers, compared with 13 of 15 cancers with somatic BRCA1 mutations (P = 0.007) and 16 of 20 cancers with germ-line BRCA1 mutations (P = 0.01). p53 null mutations were found in 31.4% of BRCA1 mutant cancers, compared with only 9.3% of the sporadic cancers (P = 0.002). The p53 mutational spectrum of germ-line BRCA1-related cancers was shifted toward transversions, frameshifts, and non-CpG transitions relative to the spectrum of sporadic ovarian cancers. Thirty-three unique ovarian cancer p53 mutations were sequenced. However, the specific p53 mutations in the BRCA1 mutant cancers were no more unique to this cohort than the p53 mutations of the sporadic cancers. CONCLUSIONS: Ovarian cancers containing somatic or germ-line BRCA1 mutations are uniformly accompanied by p53 dysfunction. This finding offers additional support to observations regarding the importance of p53/BRCA1 interactions in ovarian carcinogenesis.

p53 Mutations and microsatellite instability in ovarian cancer: Yin and yang.

OBJECTIVE: We tested the hypothesis that p53 frameshift mutations in ovarian cancer occur as a result of genomic instability rather than as a proximal cause of this process. STUDY DESIGN: Sequencing of the p53 tumor suppressor gene has been carried out on 305 ovarian, fallopian tube, and peritoneal cancers. Two groups of p53 null mutations were identified: (1) those caused by frameshift insertion or deletion mutations (n = 31) and (2) those caused by nonsense mutations (n = 28). As a control group 59 tumors with p53 missense mutations were selected by matching with the p53 null tumors on the basis of patient age at diagnosis, stage and grade of cancer, cancer site, and year of diagnosis. Microsatellite instability was determined from paired normal and tumor tissue deoxyribonucleic acid by means of the following different markers: D2S123, D5S346, D17S250, BAT25, and BAT26. Amplimers from polymerase chain reactions were evaluated on 7% polyacrylamide gels. RESULTS: The p53 null tumors were more likely to be of higher stage and grade. Fallopian tube cancers were more common (P =.02) in the p53 frameshift group. The overall incidence of microsatellite instability was 39%, 36%, and 25% for tumors with p53 frameshift nonsense and missense mutations (P =.30). Microsatellite instability was seen almost exclusively with ovarian cancer (P =.04). CONCLUSIONS: Microsatellite instability is a relatively common event in ovarian cancer and is dependent on marker selection. The p53 frameshift mutations do not appear to occur as a consequence of genomic instability.

Ovarian function after surgical treatment for cervical cancer.

OBJECTIVE: Our previous analysis found a high rate of early menopause in cervical cancer patients with ovarian transposition (OT) compared to a group that underwent radical hysterectomy (RH) alone. The current study evaluates ovarian function in the same group for a prolonged follow-up period and analyzes predictive factors for early menopause. METHODS: One hundred two cervical cancer patients were treated with RH and/or lymphadenectomy and ovarian preservation from 1982 to 1989. A retrospective chart review was conducted, followed by a survey to determine the time of menopause. RESULTS: Eighty-three patients underwent RH and 19 patients underwent a staging laparotomy. Eighty procedures included OT. Twenty-six patients received postoperative radiation therapy. The mean follow-up for premenopausal patients was 87.0 months. The average age of menopause for the 13 nonradiated patients without unilateral oophorectomy (UO) or OT was 50.6 years. After OT without radiation therapy, 98.0% of patients retained ovarian function for a mean of 126 months with menopause at a mean of 45.8 years. When OT and radiation therapy were added, 41% retained ovarian function for a mean of 43 months and a mean age at menopause of 36.6 years. A multivariate analysis of nonradiated patients correlated age at diagnosis and a combination of OT procedure and UO with earlier ovarian failure. CONCLUSIONS: RH with bilateral ovarian preservation and without OT does not significantly reduce the age of menopause. The addition of UO or OT to this treatment reduces ovarian function appreciably. The addition of radiation therapy after OT dramatically shortens ovarian function.

Asymptomatic lung carcinoma presenting with a large vulvar lesion.

OBJECTIVE: Metastases to the vulva are infrequent, accounting for less than 10% of vulvar tumors. Vulvar metastases from lung carcinoma have been reported in two other cases. METHODS: A case of lung carcinoma metastatic to the vulva is reported. RESULTS: A 71-year-old woman was referred to The University of Iowa Hospitals and Clinics with a lung nodule on chest x-ray and a 12-cm, necrotic, left vulvar mass. A lung biopsy showed poorly differentiated carcinoma, and a palliative resection of the vulvar mass showed metastatic lung carcinoma. The patient died from sepsis on postoperative day 10. CONCLUSIONS: Lung carcinoma metastatic to the vulva is rare and portends a poor prognosis.

SSCP and Sequence Analysis of p53 Mutations in Ovarian Tumors.

The p53 tumor suppressor gene encodes a 53-kD nuclear phosphoprotein and is the most commonly altered gene in human cancers (1). There are a large variety of methods currently employed for detection of alterations in thep53 gene. The reported abnormalities in p53 have been detected with a variety of techniques including immunohistochemical staining (IHCS) as a primary screening modality and less frequently single-strand conformation polymorphism (SSCP) screening. However, certain mutations such as frameshift mutations may not be detectable by IHCS, and most studies using SSCP have limited their search to exons 5-8 (2). As shown previously by our lab, this strategy can lead to underreporting of the true frequency of p53 null mutations (3). We routinely perform a complete evaluation of the p53 open reading frame (exons 2-11) using SSCP analysis with an estimated sensitivity of over 90% (3). This approach significantly enhances the detection of null mutations, especially insertion/deletion type mutations.

The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma.

BACKGROUND: The prognostic significance and nature of p53 dysfunction in ovarian carcinoma is unclear. The relation between p53 overexpression, p53 mutations, and their effects on overall survival in primary ovarian carcinoma is explored. METHODS: Tumor specimens from 171 consecutive epithelial ovarian carcinomas were examined for overexpression of p53 protein with DO7 antibody. P53 mutations were determined by direct sequencing. The influences of conventional histopathologic prognostic factors and various p53 molecular alterations on overall survival were assessed. RESULTS: Overall, 48.5% and 57.3% of the samples showed p53 overexpression and p53 mutation, respectively. Although neither p53 overexpression nor the mere presence of a p53 mutation impacted overall survival, the combination did prognosticate survival both in univariate and multivariate models. The authors' results suggest 4 mechanisms that may affect p53 dysfunction in nearly 100% of advanced stage ovarian carcinomas. These include null mutation, nonresponsive p53 (wild-type [wt] p53 sequence, DO7 negative), sequestration (wt p53 sequence, DO7 positive), and missense mutation. Median survival for these groups that constitute sequentially 21.3%, 20.5%, 12.3%, and 45.9% of the 122 Stage III or IV (International Federation of Gynecology and Obstetrics) cancers was 1.49, 1.31, 3.09, and 3.6 years, respectively. The nonresponsive p53 and null sequence tumors grouped together as functionally null convey the worst prognosis relative to missense mutations in a univariate model (P = 0.006). Functionally null p53 (P = 0.002), stage (P = 0.008), and optimal cytoreduction (P = 0.008) were independent prognostic factors by multivariate analysis. CONCLUSIONS: Sequestration of wt p53 is unique to advanced stage ovarian carcinoma. Functionally null p53 represents an independent molecular predictor of compromised survival.

Preservation of the saphenous vein during inguinal lymphadenectomy decreases morbidity in patients with carcinoma of the vulva.

BACKGROUND: Traditional inguinal lymphadenectomy includes the removal of a portion of the saphenous vein. The authors hypothesized that preserving the saphenous vein would decrease morbidity without affecting treatment outcome. METHODS: A retrospective review of 83 patients with carcinoma of the vulva who underwent inguinal lymphadenectomy between 1990-1998 was performed. Postoperative short term and long term complications were evaluated. RESULTS: A total of 139 inguinal dissections were performed in 83 patients. The saphenous vein was preserved in 62 patients and ligated in 77 patients. The clinical characteristics of the patients, the operating time, and the estimated blood loss were not significantly different between the two groups. The incidence rate of short term complications including fever, seroma, phlebitis, lymphocyst, and deep venous thrombosis also was similar. Cellulitis occurred in 39% of the patients who underwent vein ligation compared with 18% of the patients who underwent a vein-sparing procedure (P = 0.006). Short term (< 6 months) lower extremity lymphedema occurred in 70% of the vein-ligated group compared with 32% of the vein-spared group (P < 0. 001). Chronic edema (>/= 2 years) was present in only 3% of the patients who underwent saphenous vein preservation compared with 32% of those who underwent vein ligation (P = 0.003). Chronic lymphedema in the vein-spared group was observed in only one patient who received postoperative radiation. Overall, individuals with preservation of the saphenous vein were less likely to develop complications (56% vs. 23%; P < 0.001). There was no difference in the rate of incidence of recurrent disease between the two groups. CONCLUSIONS: Preservation of the saphenous vein during inguinal lymphadenectomy reduces both the short term and long term postoperative complications without affecting treatment outcome. The saphenous vein should be preserved routinely in patients undergoing inguinal lymphadenectomy.

Longterm central venous access in gynecologic cancer patients.

BACKGROUND: To assess the utility and safety of three different longterm indwelling intravenous catheters in patients with gynecologic malignancies. STUDY DESIGN: A retrospective review was performed of the records of all women with gynecologic malignancies who required longterm venous access catheters and ports between 1990 and 1997. RESULTS: Two hundred sixty-eight women underwent placement of 308 indwelling catheters, of which 305 were available for analysis. Of those, 68 (22%) were Hickman catheters, 162 (53%) were infusaports, and 75 (25%) were Peripheral Access System (PAS) ports. Venous access was obtained percutaneously in 152 (50%) patients and by cutdown in 153 (50%). Prophylactic anticoagulation was used with 96 catheters (31%). Catheter placement was associated with 12 (4%) immediate complications and 87 (29%) delayed complications. The average duration of a catheter in place was 5.6 months for the Hickman, 12.5 months for the infusaport, and 16.0 months for the PAS port (p < 0.001). Bacteremia was more likely to develop in patients with Hickman catheters when compared with those with infusaports and PAS ports (19% versus 6% and 5%, respectively, p = 0.002). Thrombosis was significantly less likely to develop in patients receiving prophylactic anticoagulation (11% versus 4%, p = 0.004). Overall, the complication rate was lower with cutdown versus percutaneous access (p = 0.004). There was no statistically significant difference between the frequency of complications when correlated with the stage of disease, patient age, body mass index, or type of malignancy. CONCLUSIONS: Infusaports and PAS ports were associated with a lower risk of infection and have a longer life than Hickman catheters. The cutdown approach was associated with a lower complication rate. Low-dose prophylactic anticoagulation should be given to all patients with longterm central venous catheters.