Phase II trial evaluating efficacy of a Fitbit program for improving the health of endometrial cancer survivors.

BACKGROUND: Despite the favorable prognosis of early stage endometrial cancer, mortality from cardiovascular disease is high. We aimed to evaluate the efficacy of a Fitbit program to improve physical activity in endometrial cancer survivors. METHODS: Eligible patients were diagnosed with stage IA-IIIA endometrial adenocarcinoma, ≥3 months out from treatment. Participants received a Fitbit Alta and were randomized to receive communication via telephone or electronic methods (email/text). Communication was every two weeks for two months, then once during months four and five. Average daily steps were assessed weekly for nine months. RESULTS: The 46 analyzable patients demonstrated a baseline of 5641 median daily average steps. Average steps increased by 22% at 6 months but decreased to baseline by nine months. Baseline activity level (daily steps and walks per week) was the greatest predictor of activity level. Only the telephone intervention participants demonstrated increased activity level at several timepoints, although not maintained by nine months. BMI was unchanged. There was mild improvement in physical and social well-being in those with low baseline well-being (p = 0.009 and 0.014, respectively), regardless of intervention group. Emotional well-being correlated with step count (p = 0.005). CONCLUSIONS: Activity level was low and mildly improved on the Fitbit program with the telephone intervention, but effects did not persist by study completion. The program had the greatest impact on a select group of telephone intervention patients with high baseline walking frequency and low baseline step count. Others may require more intense intervention to promote more robust/persistent lifestyle changes.

Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield.

PURPOSE: To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield. METHODS: Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age > 2 years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p < 0.05). RESULTS: Measures of age were negatively correlated with number of oocytes (chronological age Pearson ρ = - 0.45, biologic age Pearson ρ = - 0.46) and AMH was positively correlated with number of oocytes (Pearson ρ = 0.91). Patients with AgeAccel were noted to have lower AMH values (1.29 ng/mL vs. 2.29, respectively (p = 0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p = 0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (- 6.9 oocytes (CI - 11.6, - 2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (- 3.1; 95% CI - 6.5, - 0.1; p = 0.036). CONCLUSIONS: In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve.

Ovarian carcinoma glyco-antigen targeted by human IgM antibody.

Epithelial Ovarian Cancer (EOC) cells expression of a novel carbohydrate antigen was defined using a human VH4-34 encoded IgM monoclonal antibody (mAb216). MAb216 binds to a poly N-acetyllactosamine epitope expressed on B cells and kills normal and malignant B cells in vitro and in vivo. EOC patient ascites and EOC cell lines were used to study the anti tumor effect of mAb216. Various assays were used to characterize the epitope and demonstrate antibody-mediated binding and cytotoxicity in EOC. Drug and antibody combination effects were determined by calculating the combination index values using the Chou and Talalay method. MAb216 displays direct antibody mediated cytotoxicity on a population of human EOC tumor and ascites samples and EOC cell lines, which express high amounts of poly N-acetyllactosamine epitope, carried by CD147/CD98. Eighty four percent of patient samples, including platin resistant, had a tumor population that bound the monoclonal antibody. The binding pattern of mAb216 and mechanism of cytotoxicity was similar to that seen on normal and malignant B cells with unique general membrane disruption and "pore" formation. In vitro incubation with mAb216 and cisplatin enhanced killing of OVCAR3 cell line. In EOC cell lines percent cytotoxicity correlated with percent expression of epitope. Although in vitro data shows specific EOC cytotoxicity, for possible treatment of EOC MAb216 would need to be evaluated in a clinical trial with or without chemotherapy.

Targeting FOXM1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer.

OBJECTIVE: Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. METHODS: Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative reverse transcriptase-polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets. RESULTS: Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1 and CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo. CONCLUSION: Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.

Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma.

High-grade epithelial ovarian carcinomas containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and PARP inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pretreatment and postprogression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase II study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed ovarian carcinoma. In 6 of 12 pretreatment biopsies, a truncation mutation in BRCA1, RAD51C, or RAD51D was identified. In five of six paired postprogression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51CIn vitro complementation assays and a patient-derived xenograft, as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.Significance: Analyses of primary and secondary mutations in RAD51C and RAD51D provide evidence for these primary mutations in conferring PARPi sensitivity and secondary mutations as a mechanism of acquired PARPi resistance. PARPi resistance due to secondary mutations underpins the need for early delivery of PARPi therapy and for combination strategies. Cancer Discov; 7(9); 984-98. ©2017 AACR.See related commentary by Domchek, p. 937See related article by Quigley et al., p. 999See related article by Goodall et al., p. 1006This article is highlighted in the In This Issue feature, p. 920.

Targeting Foxm1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer.

OBJECTIVE: Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. METHODS: Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative real-time polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets. RESULTS: Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1, CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo. CONCLUSION: Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.

Radiation Therapy for Recurrent Clear-Cell Cancer of the Ovary.

OBJECTIVE: Given the relative chemo-resistant nature of clear-cell gynecologic cancers, we investigated the utility of radiation therapy (RT) to treat recurrent clear-cell carcinoma (CCC) of the ovary. METHODS: A retrospective chart review of patients with recurrent CCC managed from 1994-2012 was conducted at 2 academic medical centers. Demographic and clinicopathologic factors were abstracted and evaluated using Pearson χ or t tests, Kaplan-Meier and Cox regression analyses. RESULTS: Fifty-three patients had recurrent CCC, and 24 (45.3%) of these patients received RT. There were no significant differences in age, stage, optimal cytoreduction, platinum response, or the percentage of patients that received more than 3 regimens of chemotherapy between the 2 groups. Patients who received RT for recurrent CCC were more likely to have had a focal recurrence (62.5% vs 10.3%, P ≤ 0.001) and to have undergone secondary cytoreduction (70.8% vs 10.3%, P ≤ 0.001). Of patients who received RT, 73.9% underwent surgery with or before their treatment. Five-year survival after recurrence was significantly higher in the group that received RT, 62.9% versus 18.8% (P = 0.002). In a multivariate analysis, platinum-sensitive disease and RT were associated with improved survival from recurrence, (hazard ratio, 0.26; 95% confidence interval, 0.08-0.81; P = 0.02 and hazard ratio, 0.28; 95% confidence interval, 0.09-0.90, P = 0.03, respectively). CONCLUSIONS: In this cohort of patients with recurrent CCC, platinum-sensitive disease and RT are associated with improved survival. However, it is important to note that the majority of these patients underwent surgery along with RT, and it may be that the benefit of RT is limited to those who undergo secondary cytoreduction.

Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34-Encoded Natural IgM Antibodies.

B cell binding and cytotoxicity by human VH4-34-encoded Abs of the IgM isotype has been well documented. A VH4-34-IgM has recently shown a favorable early response in a phase 1 trial for treatment of B cell acute lymphoblastic leukemia. Although its B cell ligand has been identified as straight chain poly-N-acetyl-lactosamine (SC-PNAL), the carrier of the sugar moiety has not been identified. Using nanoelectrospray ionization mass spectrometry, we identify the metabolic activation related protein complex of CD147-CD98 as a major carrier of poly-N-acetyl-lactosamine (SC-PNAL) on human pre-B cell line Nalm-6. Previous studies have suggested CD45 as the SC-PNAL carrier for VH4-34-encoded IgG Abs. Because Nalm-6 is CD45 negative, human peripheral blood B lymphocytes and human B cell line, Reh, with high CD45 expression, were examined for SC-PNAL carrier proteins. Western blot analysis shows that the CD147-98 complex is indeed immunoprecipitated by VH4-34-encoded IgMs from human peripheral blood B lymphocytes and human B cell lines, Reh, OCI-Ly8, and Nalm-6. However, CD45 is immunoprecipitated only from peripheral B lymphocytes, but not from Reh despite the high expression of CD45. These results suggest that human B cells retain SC-PNAL on the CD147-98 complex, but modulate the sugar moiety on CD45. Because the carbohydrate moiety may act as a selecting Ag for VH4-34 autoantibody repertoire, its differential expression on proteins may provide a clue to the intricate atypical regulation of the VH4-34 gene.

Differentiating between borderline and invasive malignancies in ovarian tumors using a multivariate logistic regression model.

OBJECTIVE: The objective of this study was to build a model to differentiate between borderline and invasive ovarian tumors. MATERIALS AND METHODS: We performed a retrospective study involving 148 patients with borderline or invasive ovarian tumors in our institute between 1997 and 2012. Clinical and pathologic data were collected. Logistic regression was used to build the model. RESULTS: The model was created based on the following variables (p < 0.05): menopausal status; preoperative serum level of cancer antigen 125; the greatest diameter of the tumor; and the presence of solid parts on ultrasound imaging. The sensitivity and specificity of the model were 94.6% [95% confidence interval (CI), 0.887-1] and 78.3% (95% CI, 0.614-0.952) for patients aged ≥ 50 years, and 76.0% (95% CI, 0.622-0.903) and 60.0% (95% CI, 0.438-0.762) for those aged < 50 years, respectively. The performance of the model was tested using cross-validation. CONCLUSION: Differentiation between borderline and invasive ovarian tumors can be achieved using a model based on the following criteria: menopausal status; cancer antigen 125 level; and ultrasound parameters. The model is helpful to oncologists and patients in the initial evaluation phase of ovarian tumors.

In silico investigation of FOXM1 binding and novel inhibitors in epithelial ovarian cancer.

OBJECTIVE: Using TCGA database, we had demonstrated that aberrantly activated Forkhead box M1 (FOXM1) correlates to worse overall survival in a subgroup of platinum resistant patients. Application of thiostrepton, a natural thiazole antibiotics that inhibits FOXM1 transcription activity in the clinic is hampered by difficulties in synthesis, degradation potential, and solubility. In this study, we aim to identify potential FOXM1 small molecule inhibitors to develop a new class of therapeutic agents to address the challenges in treating chemotherapy resistant EOC. METHODS: We used in silico screening of compounds against a solved structure of FOXM1 and subsequently to derive a list of possible compounds that could inhibit FOXM1. Three compounds were tested for in vitro cytotoxicity and FOXM1 expression level was confirmed by RT-PCR and Western blot in EOC cell lines. RESULTS: The FOXM1 structure obtained from 3G73 represented the DNA binding region of FOXM1 and possessed the winged helix fold representative of the Forkhead family of enzymes with two wings in direct contact with DNA. For ease of representation, we described both wings as a dimer and a single wing as a monomer. From this structure, we hypothesized two main models of how thiostrepton binding to FOXM1 could possibly curtail its transcriptional activity. In the first model thiostrepton could bind either of the wings or both wings and prevent association to DNA. In the second model thiostrepton bind the FOXM1/DNA complex and weaken association of FOXM1 to DNA. Subsequently, small molecular inhibitors could also use either of the models to inhibit transcription. To account for both models, the NCI diversity set was screened against the FOXM1 dimer:DNA complex (39 hits), dimer (11 hits) and monomer (14 hits). Those hits were further classified by chemical structure, biological function and chemical similarities to known molecules that target FOXM1. In cellular cytotoxicity assays, N-phenylphenanthren-9-amine (related to hit #225) successfully showed cytotoxicity to all three cell lines with IC50 around 1µM, and downregulate FOXM1 and transcription of its downstream molecules such as CCNB1. CONCLUSION: By a combination of in silico screening coupled to cellular cytotoxicity studies, we have taken the first step towards identifying potential inhibitors of FOXM1 that can replace thiostrepton.

IgG Subclasses and Isotypes of VH4-34 Encoded Antibodies.

VH4-34 gene encoded autoantibodies are elevated in systemic lupus erythematosus (SLE) and in other diseases associated with B-cell hyperproliferation/dysfunction. One of the autoantigens recognized by VH4-34-encoded antibodies are branched/linear poly N-acetyl lactosamine chains. Since the anti-carbohydrate response in humans is dominated by the IgG2 subclass, here we tested whether VH4-34 encoded IgG showed similar subclass segregation. Serum samples from SLE, infectious mononucleosis, nasopharyngeal carcinoma and hepatitis-C were analyzed. Levels of VH4-34-encoded IgM and IgA isotypes were also tested. VH4-34-IgM and IgA were elevated in all four clinical conditions. VH4-34-IgG was detected in the IgG1 and IgG3 subclass but not in the IgG2 and IgG4 subclass. Interestingly, VH4-34-IgG3 was also detected in serum samples of normal healthy adults. These observations are discussed in context of the VH4-34 gene regulation. VH4-34 repertoire development is of interest since it is the only human VH gene profoundly overrepresented in the naïve repertoire but counter-selected for antibody secretion. VH4-34 B-cell could thus become a unique tool to inspect germinal center independent/dependent pathways of subclass and isotype-specific antibody secretion.

Cervical Cancer, Version 2.2015.

The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.

Does omentectomy in epithelial ovarian cancer affect survival? An analysis of the Surveillance, Epidemiology, and End Results database.

OBJECTIVE: Although omentectomy is part of the staging and treatment of epithelial ovarian cancer (EOC), its performance in a patient with a grossly normal omentum­acknowledging its role in debulking gross tumor deposits­has never been definitively shown to improve survival. METHODS/MATERIALS: Using Surveillance, Epidemiology, and End Results data from 1998 to 2010, we identified patients with EOC and assessed their age, race, year of diagnosis, tumor grade, histologic subtype, International Federation of Gynecology and Obstetrics stage, lymph node dissection, nodal findings, and performance of omentectomy. We compared disease-specific survival (DSS) based on the presence or absence of omentectomy using log-rank univariate analysis, Cox multivariate analysis, and Kaplan-Meier survival curves. RESULTS: A total of 20,975 patients with invasive EOC underwent surgical treatment. Initial univariate analysis indicated a lower mean DSS with performance of omentectomy. However, multivariate analysis demonstrated no significant association between DSS and performance of omentectomy (hazard ratio, 0.978; P = 0.506). The DSS was improved if lymphadenectomy was performed (hazard ratio, 0.60; P < 0.001). In recent years, there was a trend toward decreased performance of omentectomy.To look specifically at patients without bulky omental disease, a subset analysis was done looking at patients with stage I-IIIA disease who had had lymphadenectomy performed. There were 5454 patients in the group who underwent an omentectomy and 2404 patients in the group who did not. No difference in DSS was seen between the groups based on performance of omentectomy (P = 0.89). However, the analysis was limited by the lack of Surveillance, Epidemiology, and End Results data on the extent of omentectomy, amount of residual disease, and adjuvant chemotherapy. CONCLUSIONS: In this analysis, performance of omentectomy in patients with EOC without bulky disease (≤stage IIIA) did not seem to confer improvement in survival. A randomized control trial would be needed to fully address this question.

Impact of navigation on knowledge and attitudes about clinical trials among Chinese patients undergoing treatment for breast and gynecologic cancers.

Racial, ethnic and economic disparities in cancer rates, outcomes, and clinical trials participation persist despite significant research. We examined barriers to clinical trials enrollment among Chinese patients, and developed a navigation program for Chinese gynecologic and breast cancer patients. Six bilingual navigators were trained and a navigator assigned to each patient for at least 2 months. All patients received a clinical trials booklet in Chinese and English. Data collection included pre-and post-navigation surveys, intake forms, and documentation of navigation encounters. Between July 2010 and May 31, 2011, we recruited 28 breast and gynecologic cancer patients. Patients averaged 317 min of navigation (range 63-1,852) during 8 sessions (range 3-28). They improved in 4 of 10 true-false knowledge statements about clinical trials. A patient navigation program for Chinese-speaking cancer patients is feasible. It results in high patient satisfaction rates and modest improvements in clinical trials knowledge and participation.

Cell-penetrating, guanidinium-rich molecular transporters for overcoming efflux-mediated multidrug resistance.

Multidrug resistance (MDR) is a major cause of chemotherapy failure in the clinic. Drugs that were once effective against naïve disease subsequently prove ineffective against recurrent disease, which often exhibits an MDR phenotype. MDR can be attributed to many factors; often dominating among these is the ability of a cell to suppress or block drug entry through upregulation of membrane-bound drug efflux pumps. Efflux pumps exhibit polyspecificity, recognizing and exporting many different types of drugs, especially those whose lipophilic nature contributes to residence in the membrane. We have developed a general strategy to overcome efflux-based resistance. This strategy involves conjugating a known drug that succumbs to efflux-mediated resistance to a cell-penetrating molecular transporter, specifically, the cell-penetrating peptide (CPP), d-octaarginine. The resultant conjugates are discrete single entities (not particle mixtures) and highly water-soluble. They rapidly enter cells, are not substrates for efflux pumps, and release the free drug only after cellular entry at a rate controlled by linker design and favored by target cell chemistry. This general strategy can be applied to many classes of drugs and allows for an exceptionally rapid advance to clinical testing, especially of drugs that succumb to resistance. The efficacy of this strategy has been successfully demonstrated with Taxol in cellular and animal models of resistant cancer and with ex vivo samples from patients with ovarian cancer. Next generation efforts in this area will involve the extension of this strategy to other chemotherapeutics and other MDR-susceptible diseases.

Uterine neoplasms, version 1.2014.

Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.

Hedgehog signaling regulates drug sensitivity by targeting ABC transporters ABCB1 and ABCG2 in epithelial ovarian cancer.

A major challenge of successful chemotherapy in ovarian cancer is overcoming intrinsic or acquired multi-drug resistance caused by active drug efflux mediated by ATP-binding cassette (ABC) transporters. Regulation of these transporters in ovarian cancer is poorly understood. We have found that abnormal expression of the hedgehog (Hh) signaling pathway transcription factor Gli1 is involved in the regulation of ABC transporters ABCB1 and ABCG2 in ovarian cancer. Hh is a known regulator of cancer cell proliferation and differentiation in several other types of invasive and metastatic malignancies. Our work has demonstrated that Gli1 is abnormally activated in a portion of ovarian cancers. Inhibition of Gli1 expression decreases ABCB1 and ABCG2 gene expression levels and enhances the response of ovarian cancer cells to certain chemotherapeutic drugs. The underlying mechanism is a direct association of Gli1 with a specific consensus sequence located in the promoter region of ABCB1 and ABCG2 genes. This study provides new understanding of ABC gene regulation by Hh signaling pathway, which may lead to the identification of new markers to detect and to anticipate ovarian cancer chemotherapy drug sensitivity.

Ovarian cancer, version 2.2013.

These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made.

The omentum and omentectomy in epithelial ovarian cancer: a reappraisal. Part I--Omental function and history of omentectomy.

OBJECTIVE: This article reviews the literature concerning the function of the omentum and how omentectomy came to be part of the staging and treatment of epithelial ovarian cancer. METHODS: A review of the English language literature based on a MEDLINE (PubMed) database search using the key words: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers. RESULTS: Descriptions of the omentum can be found as far back as the time of the ancient Egyptians. An immunologic role of the omentum was confirmed in 1980s when "milky spots" were described. Omentectomy arrived as part of the ovarian cancer guidelines in the 1960s after observing that the omentum was a frequent site of metastasis and that patients with removal of all diseased tissue did better. The exact role of the omentum in immunology and cancer remains incompletely understood. CONCLUSIONS: Historically, occult omental metastases in otherwise early disease have led to the inclusion of omentectomy for the purpose of accurate staging and for a possible therapeutic benefit. Laboratory studies on the role in cancer of the omental fat and milky spots are controversial.

The omentum and omentectomy in epithelial ovarian cancer: a reappraisal: part II--The role of omentectomy in the staging and treatment of apparent early stage epithelial ovarian cancer.

OBJECTIVE: This article reviews the literature concerning the role of omentectomy in the staging and treatment of clinically apparent early stage epithelial ovarian cancer. METHODS: A review of the English language literature based on a MEDLINE (PubMed) database search using the keywords: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers. RESULTS: Historically, the realization that ovarian cancer cells have a predisposition to metastasize to the omentum has led to the inclusion of omentectomy, both for the purpose of accurate staging of ovarian cancer and for its possible therapeutic benefit. In apparently early stage epithelial ovarian cancer, microscopic disease in the omentum is found in 0-22% of the cases; however extra-ovarian disease isolated to the omentum is found in 2-7% of cases at most. There are no specific guidelines as to how much of the omentum should be removed, but pathology studies show that for the purpose of staging and detecting microscopic disease, omental biopsies are probably sufficient in a grossly normal appearing omentum. In cases where adjuvant chemotherapy is planned, the role of omentectomy appears to be primarily for staging, while its therapeutic role remains unclear in microscopic omental disease. CONCLUSIONS: In apparent early stage ovarian cancer, the presence of isolated omental metastases is relatively rare. For staging purposes in such cases, random omental biopsies rather than total omentectomy may suffice. Furthermore, chemotherapy appears to effectively treat microscopic disease and therefore if this is already planned the benefit of omentectomy is unclear.