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Biomedical subjects

B Y Karlan

Publications and source records attributed to B Y Karlan.

At least 19 recordsLinked to original sources

Pattern of lymph node metastases in clinically unilateral stage I invasive epithelial ovarian carcinomas.

PURPOSE: There is controversy regarding the pattern of lymphatic spread in unilateral stage I invasive ovarian carcinomas. The purpose of this study is to describe the incidence and distribution of lymph node (LN) metastases in ovarian carcinomas clinically confined to one ovary. METHODS: Ninety-six patients with disease visibly confined to one ovary were identified. Pathology reports were reviewed to identify metastatic LN involvement, number of involved nodes, and their locations. Patients with gross disease in the pelvis or abdomen or those who had grossly positive LNs removed for debulking were excluded from this review. RESULTS: Fourteen of ninety-six patients (15%) had microscopically positive LNs on pathologic review. All of these 14 patients had grade 3 tumors. Grade 3 tumors were more commonly seen in LN-positive versus LN-negative patients (P < 0.001). Pelvic nodes were positive in 7 patients (50%), paraaortic nodes in 5 patients (36%), and both in 2 patients (14%). Forty-two patients had LN sampling only on the side ipsilateral to the neoplastic ovary, 4 of whom (10%) had LN metastases. Fifty-four patients had bilateral sampling performed, 10 of whom (19%) had LN metastases. Of these 10 patients, isolated ipsilateral LN metastases were seen in 5 (50%) cases. Isolated contralateral LN metastases were seen in 3 (30%) cases, and bilateral metastases were seen in 2 (20%). CONCLUSIONS: In this cohort of patients with clinical stage I ovarian carcinoma with disease limited to one ovary, bilateral LN sampling increased the identification of nodal metastases. Ipsilateral sampling may result in the understaging of patients. Bilateral pelvic and paraaortic LN sampling is recommended to accurately stage ovarian carcinoma.

Aorta, Abdominal↗

Allelotype of papillary serous peritoneal carcinomas.

OBJECTIVE: Papillary serous peritoneal carcinoma (PSPC) is histologically indistinguishable from papillary serous ovarian carcinoma (PSOC) with a similar clinical presentation, yet may differ in its carcinogenesis. The purpose of this study was to determine the incidence of allelic loss and the frequency of p53 mutation by p53 overexpression in PSPC compared to PSOC. METHODS: An allelotype analysis of 26 patients with PSPC was performed using 39 microsatellite markers from 25 chromosomal arms. Thirty-seven previously studied patients with PSOC served as the comparison. P53 mutations were detected by immunohistochemical protein overexpression. RESULTS: There was significantly less LOH in PSPC than PSOC. Both the number of chromosomes with LOH and the proportion of tumors with allelic loss were less frequent. Significant LOH, defined as >/=30% of informative tumors having loss at a chromosome locus, was seen on 4 chromosome arms in PSPC: 12p, 17p, 17q, and 18q, compared to 18 arms in PSOC: 4q, 5q, 6p, 6q, 9p, 9q, 12p, 12q, 13q, 15q, 16q, 17p, 17q, 18q, 19p, 19q, 22q, and Xq (P < 0.001). The median LOH frequency was higher in PSOC than PSPC, 43% versus 33%, respectively (P = 0.013), and more PSOC tumors had LOH than PSPC tumors, 91% versus 65% (P = 0.042). P53 overexpression was detected in 80% of PSPC tumors. CONCLUSIONS: LOH occurs less frequently in PSPC compared to PSOC. Chromosomal regions with high frequencies of LOH common to PSPC and PSOC, such as 12p, 17p, 17q, and 18q, may harbor tumor suppressor genes important in the carcinogenesis of both malignancies and likely include p53.

Aged↗

Genetic factors in ovarian carcinoma.

Recent evidence indicates that inherited and acquired genetic mutations are the driving force behind carcinogenesis and cellular transformation. This review examines a number of proto-oncogenes and tumor suppressor genes that are associated with ovarian carcinomas, including p53, BRCA1, and BRCA2; mismatch repair genes such as hMSH2 and hMLH1; and PTEN, HER-2/neu, K-ras, fms, and AKT2. Novel genes recently implicated in ovarian tumorigenesis are discussed, including NOEY2, OVCA1, and PIK3CA. Although no singular gene alteration has been shown to initiate transformation in the ovarian epithelium, elucidation of the complex molecular and cellular mechanisms involving these known gene mutations may result in new clinical management strategies.

BRCA1 Protein↗

Differential gene expression between normal and tumor-derived ovarian epithelial cells.

The majority of ovarian tumors arise from the transformation of the ovarian surface epithelial cells, a single layer of cells surrounding the ovary. To identify genes that may contribute to the malignant phenotype of ovarian cancers, cDNA representational difference analysis was used to compare expressed genes in primary cultures of normal human ovarian surface epithelium (HOSE) and ovarian tumor-derived epithelial cells from the Cedars-Sinai Ovarian Cancer (CSOC) repository. A total of 255 differentially expressed genes were identified, of which 160 and 95 were specifically expressed in HOSE and CSOC cells, respectively. Using cDNA array hybridization, the expression profiles of the genes identified by cDNA-representational difference analysis were examined in an additional 5 HOSE and 10 CSOC lines. The comparison of average signal of each gene revealed 44 HOSE-specific and 16 CSOC-specific genes that exhibited at least a 2.5-fold difference in expression. A large number of genes identified in this study encode membrane-associated or secreted proteins and, hence, may be useful as targets in the development of serum-based diagnostic markers for ovarian cancer. Very few genes associated with protein synthesis or metabolism were identified in this study, reflecting the lack of observable differences in phenotypic or growth characteristics between HOSE and CSOC cells. Northern blot analysis on a subset of these genes demonstrated comparable levels of gene expression as observed in the cDNA array hybridization.

Blotting, Northern↗

BRCA1 promoter region hypermethylation in ovarian carcinoma: a population-based study.

There is a clear association between germ-line BRCA1 mutations and inherited ovarian cancer; however, the association between BRCA1 mutations and sporadic ovarian cancer remains ambiguous. The frequency of BRCA1 promoter hypermethylation as an epigenetic means of BRCA1 inactivation was determined for a large, population-based cohort of ovarian cancer patients. BRCA1 promoter hypermethylation was determined by methylation-specific restriction digestion of tumor DNA, followed by Southern blot analysis and confirmed by methylation-specific PCR. BRCA1 promoter hypermethylation was observed in 12 of 98 ovarian tumors. BRCA1 methylation status of the primary tumor was conserved in six recurrent tumors after interim chemotherapy. None of the 12 tumors with BRCA1 promoter hypermethylation demonstrated BRCA1 protein expression by immunohistochemistry. BRCA1 methylation was only seen in ovarian cancer patients without a family history suggestive of a breast/ ovarian cancer syndrome. Therefore, the 12 BRCA1 methylated tumors represented 15% (12 of 81) of the sporadic cancers analyzed in this study. Although the clinical significance of BRCA1 promoter hypermethylation is yet to be determined, promoter hypermethylation may be an alternative to mutation in causing the inactivation of the BRCA1 tumor suppressor gene in sporadic ovarian cancer.

Alleles↗

Splenectomy and surgical cytoreduction for ovarian cancer.

OBJECTIVE: The aim of this study was to evaluate the role of splenectomy, as a surrogate marker for aggressive tumor cytoreduction in ovarian cancer, and its impact on patient morbidity and survival. METHODS: A retrospective cohort study of 35 patients who underwent splenectomy for ovarian cancer cytoreduction between August 1986 and May 1998 was performed. Data abstracted from the medical record included patient demographics, preoperative imaging, surgical procedures, tumor distribution, postoperative complications, chemotherapy treatment, and follow-up information. RESULTS: Splenectomy was performed in 13 patients at the time of primary cytoreduction and in 22 patients at the time of secondary cytoreduction. Preoperative diagnosis of splenic involvement was frequently made prior to secondary surgery, 77.3% compared to 15.4% of primary cases. In addition, parenchymal splenic involvement was more commonly observed at recurrence, 59.1% vs 23.1% at initial presentation. Disease distribution in secondary cytoreduction cases tended to be more focal, macronodular, and have no ascites. Cytoreduction to less than 1 cm disease was achieved in 100% of primary patients and 86% of secondary patients. Major morbidity (pneumonia, PE, sepsis, pancreatitis, MI) occurred in 23.1% of primary patients and 28.6% of secondary patients. Combining splenectomy with other cytoreductive procedures may make splenectomy itself seem more morbid. With a 17-month median follow-up, median progression-free interval was 24 months in primary patients and 14 months in secondary patients. Among secondary patients, median survival time after splenectomy and cytoreduction was 41 months. CONCLUSIONS: Splenectomy at the time of primary and secondary cytoreduction for ovarian cancer can be performed with acceptable morbidity. Secondary cytoreduction patients may be selected preoperatively by their progression-free interval, prior degree of cytoreduction, and macronodular tumor involvement on imaging studies. Identification of splenic involvement allows for appropriate counseling and preoperative preparation.

Adult↗

A phase I trial of a 3-day topotecan Q 21 days for recurrent epithelial cancers of the ovary, fallopian tube, and peritoneum.

OBJECTIVE: This trial was undertaken to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of topotecan that can be administered for 3 days q 21 days. A 3-day schedule is more convenient and less expensive than standard 5-day dosing. METHODS: Patients with recurrent epithelial ovary, tubal, or peritoneal carcinoma were treated with escalating doses of topotecan beginning at 2.50 mg/m(2) as an outpatient days 1-3 q 21 days. Colony stimulating factors were not employed prophylactically, but could be added for grade 4 marrow toxicity. RESULTS: Twenty patients with a median age of 61 (range 46-80) and performance status of 0 or 1 were entered. All patients had received at least one prior paclitaxel/platinum regimen; 6 had received two. Ninety-one cycles were delivered (median = 6) and 98.9% were on schedule. Grade 4 neutropenia was seen in 17 of 20 patients (85%) in cycle 1 and in 38 of 91 (41.8%) total cycles. Sixteen of 20 patients (80%) started G-CSF on cycle 2. Two of 91 (2.2%) cycles had grade 4 thrombocytopenia. Four cycles (4.4%) were associated with febrile neutropenia. Two patients experienced grade 4 neurotoxicity (DLT) at 4.25 mg/m(2). Other nonhematologic toxicity was mild. CONCLUSIONS: Topotecan can be safely administered on schedule as an outpatient days 1-3 q 21 days. Neurotoxicity was the DLT when G-CSF was added; the MTD was 3.75 mg/m(2). There was minimal other nonhematologic toxicity. Neutropenia was predictable and easily managed with G-CSF. Febrile neutropenia was uncommon and thrombocytopenia was rare at the doses evaluated.

Aged↗

Ovarian cancer tumor marker behavior in asymptomatic healthy women: implications for screening.

Ovarian cancer screening protocols generally have been limited by inadequate recognition of the normal behavior of tumor markers in women at risk of ovarian cancer. We have characterized the behavior of five serum tumor markers in a large cohort of healthy women and examined the implications for screening. Serial measurements of CA125, HER-2/neu, urinary gonadotropin peptide, lipid-associated sialic acid, and Dianon marker 70/K were obtained during 6 years of follow-up of 1257 healthy women at high risk of ovarian cancer. We analyzed individual-specific tumor marker behavior and explored methods that can exploit this information to develop individual-specific screening rules. These five tumor markers behaved approximately independently. Substantial heterogeneity was observed among women in the behavior of each tumor marker, particularly CA125. Intraclass correlation (ICC), or the proportion of total variability that occurs between individuals, was approximately 0.6 for log-transformed CA125 and urinary gonadotropin peptide, and less than 0.4 for the other markers. This degree of tumor marker heterogeneity among healthy women, and the relative independence of these markers, has important implications for screening and diagnostic tests. Independence of markers results in the clinically useful fact that the combined false positive rate from screening with multiple markers may be estimated by the sum of individual false positive rates. Heterogeneity of tumor marker patterns in healthy women implies that a fixed screening cutoff level is suboptimal to a degree that depends strongly on ICC. Using information on longitudinal measurements and ICC, individual-specific screening rules may be developed with the potential to improve early detection of ovarian cancer.

Adult↗

Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas.

Comparative hybridization of cDNA arrays is a powerful tool for the measurement of differences in gene expression between two or more tissues. We optimized this technique and employed it to discover genes with potential for the diagnosis of ovarian cancer. This cancer is rarely identified in time for a good prognosis after diagnosis. An array of 21,500 unknown ovarian cDNAs was hybridized with labeled first-strand cDNA from 10 ovarian tumors and six normal tissues. One hundred and thirty-four clones are overexpressed in at least five of the 10 tumors. These cDNAs were sequenced and compared to public sequence databases. One of these, the gene HE4, was found to be expressed primarily in some ovarian cancers, and is thus a potential marker of ovarian carcinoma.

Biomarkers, Tumor↗

Altered expression of transforming growth factor-beta ligands and receptors in primary and recurrent ovarian carcinoma.

BACKGROUND: Resistance to the potent growth inhibitory effects of transforming growth factor-beta (TGF-beta) is a characteristic of many malignancies. TGF-beta insensitivity has been attributed to alterations in the number and function of the TGF-beta receptors as well as disturbances of downstream signal transduction. Paradoxically, increased levels of TGF-beta ligand have been demonstrated in several types of malignant tumors. TGF-beta also may play a role in ovarian carcinogenesis; however, the nature of this interaction has yet to be defined completely. METHODS: To explore the potential role of TGF-beta-mediated autocrine and paracrine influences in epithelial ovarian carcinoma, mRNA expression levels of the three TGF-beta ligand isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) and the three TGF-beta receptors (TbetaR-I, T/betaR-II, and TbetaR-III) were examined by Northern blot analysis in both primary and recurrent ovarian carcinoma specimens. Immunohistochemical analysis was performed to localize expression of TbetaR-I and TbetaR-II, whereas the presence of genetic alterations in TbetaR-1 was examined through Southern blot analysis. RESULTS: Compared with normal ovarian tissue, both primary and recurrent ovarian carcinomas demonstrated significant overexpression of the TGF-beta1 and TGF-beta3 mRNA transcripts. TGF-beta2 expression was detectable in 75% of primary and only 53% of recurrent tumor specimens. Alterations also were detected in TbetaR mRNA expression. Expression levels of TbetaR-III were significantly reduced in both primary and recurrent ovarian carcinomas. Furthermore, detectable levels of TbetaR-I and TbetaR-III mRNA transcripts were present in only 47% and 50% of recurrent ovarian tumors, respectively. Immunohistochemical staining demonstrated that TbetaR-I and TbetaR-II expression localized to tumor cells; however, receptor staining in stromal tissue also was detected. Southern blot analysis of TbetaR-I did not reveal any major genetic changes to account for the absence of TbetaR-I expression. CONCLUSIONS: Alterations in expression of TGF-beta ligands and receptors consistently were greater in recurrent ovarian carcinomas compared with primary tumors, and may reflect a phenotype that promotes tumor recurrence or chemoresistance. Together, these data suggest that enhanced expression of TGF-betaI and TGF-beta3, as well as the loss of expression of TbetaR-I and TbetaR-III, contribute to ovarian carcinogenesis and/or tumor progression.

Blotting, Northern↗

Survival impact of surgical cytoreduction in stage IV epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to evaluate the influence of surgical cytoreduction on survival in patients with Stage IV epithelial ovarian cancer and to determine the survival impact of debulking extrahepatic disease in the subgroup of patients with liver metastasis. METHODS: Medical records were retrospectively reviewed for all women with International Federation of Gynecology and Obstetrics Stage IV ovarian cancer treated between 1/1/82 and 12/31/94. Clinical information abstracted included age at diagnosis, performance status, histologic subtype, tumor grade, Stage IV criteria, ascites volume, predominant peritoneal tumor pattern, surgical procedures performed, hepatic tumor residuum, extrahepatic tumor residuum, and postoperative complications. Optimal surgical status was defined as residual disease </=1 cm. Chemotherapy treatment and follow-up were recorded. Survival analysis and comparisons were performed using the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression model was used to identify independent variables associated with an improved survival rate. RESULTS: There were 84 women with Stage IV ovarian cancer and complete operative and postoperative information available. Median age at diagnosis was 61 years (range 26-85 years). Performance status was </=2 in 83% of patients (70/84). Papillary serous histology was found in 44/84 patients (52%) and 55 patients (65%) had grade 3 tumors. Thirty-seven of 84 patients (44%) had parenchymal liver metastasis and 32/84 (38%) had malignant pleural effusion. Overall median survival was 18.1 months and was highly correlated with performance status (P = 0.002), predominant peritoneal tumor pattern (P = 0.0002), and the number of chemotherapy regimens received (P = 0.0039). Primary surgical cytoreduction was attempted in all patients and 25/84 (30%) achieved optimal status. Median survival of optimally cytoreduced patients was 38.4 months, compared to 10.3 months for patients with suboptimal residual disease (P = 0.0004). In patients with liver metastasis, optimal extrahepatic cytoreduction was achieved in 46% (17/37). Six of 37 patients (16%) underwent optimal resection of both extrahepatic and hepatic disease and had a median survival of 50.1 months, compared to a median survival of 27.0 months for the 11 patients (30%) with optimal extrahepatic disease but suboptimal residual hepatic tumor. Twenty patients (54%) were left with both suboptimal residual extrahepatic and hepatic disease and had a median survival of 7.6 months (P = 0.0001). Optimal debulking surgery and performance status retained significance as independent predictors of survival on multivariate analysis. CONCLUSIONS: Optimal surgical debulking and performance status appear to be important determinants of survival in patients with Stage IV epithelial ovarian cancer. Even in patients with unresectable liver metastasis, optimal debulking of extrahepatic disease is associated with a significant survival advantage.

Adenocarcinoma↗

Primary ovarian cancer cultures are resistant to Fas-mediated apoptosis.

OBJECTIVES: Fas, a primary mediator of cellular apoptosis, is expressed by the normal ovarian epithelium. We analyzed the levels of Fas and soluble Fas (sFas) expression in ovarian cancer tissue and determined the susceptibility of primary ovarian cancer cell (CSOC) cultures to Fas-mediated apoptosis. METHODS: Fas mRNA levels were detected by RT-PCR, and Fas protein levels were determined by immunohistochemistry and Western blot analysis. Secreted sFas levels were measured by ELISA. Localization of Fas to the cell surface was demonstrated by flow cytometry. The effect of Fas on cell proliferation was measured by MTT assay. RESULTS: Intense Fas staining was detected on the cell surface and in the cytoplasm of ovarian carcinoma specimens. We also found that mean levels of sFas, which can function as a Fas agonist, were significantly increased in 18 sera from cancer patients (0.98 ng/ml) compared to those of 8 healthy individuals (0.61 ng/ml, P = 0.004). Fas mRNA and protein were expressed in all primary ovarian cancer cell cultures. Despite abundant Fas expression, CSOC cultures were significantly less sensitive to Fas-mediated apoptosis (11.3%) than primary cultures of normal ovarian epithelial cells (HOSE) (50.0%) (P = 0.00001). The sFas level in CSOC-conditioned medium was minimal (0.07 ng/ml) and not significantly different from that of HOSE-conditioned medium (0. 09 ng/ml). The small amount of sFas secreted by CSOC does not likely account for the observed resistance to Fas-mediated apoptosis. CONCLUSION: Decreased sensitivity to Fas-mediated apoptosis could contribute to ovarian tumorigenesis through resistance to cytotoxic T lymphocyte-mediated cytotoxicity and may play a role in ovarian tumorigenesis.

Apoptosis↗

Ovarian carcinoma cell cultures are resistant to TGF-beta1-mediated growth inhibition despite expression of functional receptors.

OBJECTIVE: The purpose of this study was to determine the response of ovarian carcinoma cells to TGF-beta1 and to examine components of the TGF-beta signaling pathway. METHODS: Twenty-three primary ovarian cancer cell (CSOC) cultures established from solid ovarian carcinomas were treated with TGF-beta1 and assayed for growth response by MTT assay. Expression of TGF-beta receptor I (TbetaR-I) and receptor II (TbetaR-II), essential for effective signaling, was determined by Western analysis of CSOC cultures. TGF-beta1 ligand-induced phosphorylation of TbetaR-I was determined by immunoprecipitation of TbetaR-I followed by a protein kinase assay to assess TbetaR-I phosphorylation, an essential first step in TGF-beta signal transduction. Gelatin zymography performed on 5 CSOC cultures incubated with TGF-beta1 was used to determine TGF-beta's effect on matrix metalloproteinase production. Normal ovarian surface epithelial cells were used for comparison. RESULTS: Eighteen of twenty-three (78%) CSOC cultures demonstrated no significant growth inhibition in response to TGF-beta1 treatment. All cell cultures expressed TbetaR-I and TbetaR-II and exhibited TbetaR-I phosphorylation following TGF-beta1 treatment. CSOC cultures produced significantly higher levels of matrix metalloproteinase-2 (MMP-2) than normal ovarian surface epithelial cells; however, the level of MMP-2 expression was not regulated by TGF-beta1. CONCLUSION: These results indicate that TGF-beta1 resistance and higher levels of MMP-2 production may be inherent properties of the ovarian cancer phenotype. The initial steps in the TGF-beta signaling pathway, receptor expression, ligand binding, and TbetaR-I phosphorylation, appear to be functional in primary ovarian cancer cell cultures. Therefore, the mechanism of growth resistance is downstream of TbetaR-I phosphorylation.

Cell Division↗

Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian cancer: implications for ovarian cancer screening.

OBJECTIVE: Our purpose was to report the cancers arising during a familial ovarian cancer screening program and investigate the tumor's clonality and association with BRCA1 and BRCA2 mutations. STUDY DESIGN: Program participants with a diagnosis of ovarian cancer or peritoneal serous papillary carcinoma were identified and their demographic characteristics, ultrasonographic findings, CA 125 results, operative reports, and pathology slides reviewed. Immunohistochemical analysis of p53, bcl-2, HER-2/neu, and nm23 H1 expression was performed on tumor tissues from multiple metastatic sites, and germline BRCA1 and BRCA2 mutations were identified. RESULTS: Three stage I ovarian cancers and 7 cases of peritoneal serous papillary carcinoma were diagnosed from among 1261 program participants. Ultrasonographic abnormalities triggered surgical exploration in all 3 cases of stage I disease. Elevated levels of CA 125 were the harbinger in 2 of 7 cases of peritoneal serous papillary carcinoma, abnormal ultrasonographic findings prompted diagnosis in 2 of 7 cases, and 3 of 7 women had abdominal symptoms 5, 6, and 16 months after screening. Results of immunohistochemical studies suggested multifocal disease in 5 of 7 patients with peritoneal serous papillary carcinoma. At least 3 of the patients with peritoneal serous papillary carcinoma carry BRCA1 185delAG mutations. CONCLUSION: Multifocal peritoneal serous papillary carcinoma may be a phenotypic variant of familial ovarian cancer, and screening strategies for these women cannot rely on ultrasonography and CA 125 testing to detect early disease.

Adult↗

Molecular advances in gynecologic oncology.

Cancer is a genetic disease, and inherited or acquired genetic defects contribute to the initiation and progression of cancer. Improved molecular techniques have lead to the identification of many of these genetic mutations in gynecologic malignancies. The molecular characterization of cancer has provided a better understanding of tumor formation and the clinical behavior of different tumor types, with important implications for developing screening tests and prognostic markers. Applications of these findings have led to novel targeted gene therapies that correct the critical genetic defects seen in gynecologic cancers. Future research will focus on the clinical translation of these genetic alterations as targets of cancer prevention, screening, and treatment.

Female↗

[Is ultrasound screening for ovarian cancer possible in 1998?].

Ovarian cancer is the most common cause of gynecologic cancer death, as most patients present with advanced disease, in which the prognosis is poor. Five year-survival is only 35% for all stages, while it exceeds 90% in stage I. Consequently, there has been heightened interest in the development of screening modalities that can detect ovarian cancer at an early stage to reduce the mortality of this disease. Unfortunately, transvaginal sonography and color Doppler imaging still have a high false positive rate and low specificity increasing the number of surgical procedures, even among women with a strong family history of ovarian cancer. Psychological impact and economical cost has also to be discussed when considering such programs.

Abdomen↗

Surgical intensive care unit care after ovarian cancer surgery: an analysis of indications.

OBJECTIVE: Our purpose was to develop a profile of preoperative and perioperative characteristics that would enable gynecologic oncologists to identify those patients with ovarian cancer who would benefit most from postoperative surgical intensive care unit care and thereby optimize resource utilization and cost effectiveness. STUDY DESIGN: A retrospective analysis was performed of 85 patients admitted to the surgical intensive care unit after cytoreductive surgery between Jan. 1, 1989, and Dec. 31, 1993. Fifty-three patients admitted to the surgical intensive care unit for < 24 hours were compared with 32 patients admitted for > 24 hours. Five preoperative characteristics (age, American Society of Anaesthesiology classification, body mass index, albumin, primary versus recurrent disease) and six perioperative characteristics (estimated blood loss, ascites, surgical time, bowel resection, Swan-Ganz catheter, ventilator dependence) were compared across the two groups by univariate analysis and multivariate logistic regression analyses. RESULTS: All preoperative variables were similar across the two groups. Ascites volume and length of surgery were not significant, whereas estimated blood loss was significant in the univariate analysis but not in the logistic regression analysis. Three perioperative variables were found to be predictive of extended surgical intensive care unit care by logistic regression analysis: placement of a Swan-Ganz catheter (odds ratio 4.31, 95% confidence interval 1.13 to 16.4), bowel resection (odds ratio 13.0, 95% confidence interval 1.96 to 86.5), and ventilator dependence (excluded from logistic regression analysis for mathematic reasons). CONCLUSIONS: The patient's preoperative medical condition proved to be less important than how she fares during surgery. The patient most likely to benefit from surgical intensive care unit care had undergone bowel resection, required invasive hemodynamic monitoring, or was ventilator dependent postoperatively. This patient profile may prove to be a useful screening tool to optimize resource utilization and cost effectiveness, but it cannot replace clinical judgment.

Age Factors↗