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issn:1048-891
1.  Factors Associated With Grade 3-4 Treatment-Related Toxicity In Women With Advanced Or Recurrent Cervical Cancer: An Exploratory Analysis Of NRG Oncology/Gynecologic Oncology Group Trials (GOG) 179 And 204 
Objective
To describe pretreatment patient characteristics and baseline quality of life (QoL) scores as they relate to the development of grade 3-4 toxicity in patients receiving chemotherapy for advanced/recurrent cervical cancer.
Methods
The study sample was drawn from Gynecologic Oncology Group (GOG) protocols 179 and 204. Grade 3 or 4 toxicities were considered in four specified categories: peripheral neuropathy, fatigue, hematologic and gastrointestinal. The data variables explored included age, stage, pretreatment radiation, performance status (PS) at treatment initiation and baseline FACT-Cx (Functional Assessment of Cancer Therapy-Cervix) score. A logistic regression model was developed with various adverse events as binary [0/1] outcomes.
Results
Six-hundred-seventy-three patient-reported questionnaires were used in the analyses. At baseline, pain was the most severe patient-reported symptom. Baseline line-item patient concerns did demonstrate specific correlations with the development of individual toxicities. In 401 patients were enrolled on GOG 204 (fatigue not measured on 179), a worse PS predicted the development of grade 3-4 fatigue (OR 2.78 95% CI 1.66-4.68). Exposure to prior radiation, treatment regimen and a worse FACT-Cx score were associated with the reporting of both grade 3-4 leukopenia (P<0.05) and anemia (p<.0005). PS and treatment regimen (p<0.05) were associated with the development of grade 3-4 thrombocytopenia. Age and treatment regimen (p<0.05) were associated with the development of grade 3-4 neutropenia. The FACT-Cx score (p=0.0016) predicted grade 3-4 GI toxicity.
Conclusions
The development of fatigue, hematologic and GI toxicity might be predictable based on factors other than treatment assignment such as age, PS and patient-reported QoL measurement.
doi:10.1097/IGC.0000000000000328
PMCID: PMC4506195  PMID: 25405577
Quality of life; Gynecologic Oncology Group; cervical cancer; grade 3; grade 4; toxicity
2.  Quality of Life, Body Mass Index, and Physical Activity among Uterine Cancer Patients 
Objective
The purpose of this study was to assess the independent and joint effects of body mass index (BMI) and physical activity (PA) on overall quality of life (QoL) in survivors of uterine cancer.
Methods
We conducted a survey among uterine cancer patients who received curative therapy at the University of Pennsylvania between 2006 and 2010. Surveys assessed weight, height, PA (college alumnus survey), and QoL (Functional Assessment of Cancer Therapy – Gyn).
Results
The response rate to the survey was 43%. Among 213 patients, the mean BMI was 31.1±8.9 kg/m2, and 48% reported ≥150 min·wk−1 of PA. Higher BMI was independently associated with poorer overall QoL (P=.050), including physical (P=.002) and functional well-being (P=.008). Higher min·wk−1 of PA was not independently associated with any QoL outcome. However, among patients who engaged in ≥150 min·wk−1 of PA, the negative association between BMI and overall QoL was attenuated (P=.558), whereas among patients who engaged in <150 min·wk−1 of PA, the negative association between BMI and overall QoL persisted (P=.025). Among patients who engaged in ≥150 min·wk−1 of PA, the negative association between BMI, and physical and functional well-being was attenuated (P=.765 and P=.284), whereas among patients who engaged in <150 min·wk−1 of PA, the negative association between BMI, and physical and functional well-being persisted (P<.001 and P=.010), respectively.
Conclusion
BMI is associated with poorer QoL among uterine cancer patients. The findings from this cross-sectional study are consistent with the hypothesis that endometrial cancer survivors who are able to perform 150 min/week of PA may be protected from the negative effects of BMI on QoL.
doi:10.1097/IGC.0000000000000166
PMCID: PMC4085571  PMID: 24927246
3.  Patient preferences for side effects associated with cervical cancer treatment 
Objectives
To assess patient preferences regarding side effects associated with cervical cancer treatment.
Methods/Materials
The visual analog scale (VAS) and modified standard gamble (SG) were used to elicit preferences of women with no evidence of disease following primary treatment for cervical cancer. Higher scores on VAS and SG indicated more favorable ratings for a given health state (HS). HS included: vaginal shortening (VAG), diarrhea, dietary changes (DIET), menopause, moderate nausea/vomiting (NV), rectal bleeding, sexual dysfunction, and urinary self-catheterization (USC). Descriptive statistics, Kruskal-Wallis, Mann Whitney U, Wilcoxon signed-ranks tests and correlation coefficients were used for statistical analysis.
Results
78 patients participated in the study. Median age was 44.1 years (range 24.9–67.8). Median time since treatment completion was 31.2 months (range 1.0–113.3). The health states rated as most favorable by VAS were also rated as most favorable by SG. Increasing age was associated with higher VAS scores for menopause and VAG (p=0.04 and 0.036). African-Americans had higher VAS scores for DIET (p=0.05), sexual dysfunction (p=0.028), and diarrhea (p=0.05) when compared to Hispanic and non-Hispanic white patients. Women receiving radiation had more favorable VAS scores for menopause compared to women undergoing radical hysterectomy (p=0.05). Women receiving chemotherapy rated USC less favorably by VAS score compared to those not receiving chemotherapy (p=0.045).
Conclusions
Multiple demographic and clinical factors influence the severity of treatment-related adverse effects perceived by women surviving cervical cancer. A better understanding of factors influencing patient preferences regarding treatment side effects will allow providers to formulate care better tailored to the individual desires of each patient.
doi:10.1097/IGC.0000000000000149
PMCID: PMC4287264  PMID: 24905618
Preferences; Quality of life; Cervical Cancer
4.  Bevacizumab shows activity in patients with low-grade serous ovarian and primary peritoneal cancer 
Objective
Low-grade serous (LGS) ovarian and primary peritoneal cancer is a rare disease with limited therapeutic options. Low response rates are observed with cytotoxic chemotherapy. However, significant responses have been reported in patients treated with bevacizumab. The objective of this study was to determine the response rate to bevacizumab with or without concurrent chemotherapy in patients with recurrent serous borderline or LGS ovarian or primary peritoneal cancer.
Methods
This single-institution, retrospective study examined the response rate to treatment with bevacizumab in patients with serous borderline or LGS cancer. Patients were treated at Memorial Sloan Kettering Cancer Center between 2005 and 2012. Best overall response was determined by RECIST criteria.
Results
A total of 17 patients were identified, 15 of whom were evaluable for the primary endpoint of best overall response. Two patients were treated with bevacizumab as a single agent and the remainder received bevacizumab in conjunction with chemotherapy (paclitaxel, topotecan, oral cyclophosphamide, gemcitabine, or gemcitabine and carboplatin). The median duration of bevacizumab administration in evaluable patients was 23 weeks (mean, 32.2; range, 6-79.4). There were no complete responses. Partial responses were observed in 6 patients (5 received concurrent paclitaxel, and 1 received concurrent gemcitabine). The overall response rate was 40%, with a response rate of 55% amongst the subgroup of patients with LGS cancer.
Conclusions
These results indicate that bevacizumab in combination with chemotherapy is an active treatment for recurrent LGS ovarian cancer. A prospective trial of bevacizumab in combination with paclitaxel for treatment of LGS ovarian cancer should be considered.
doi:10.1097/IGC.0000000000000190
PMCID: PMC4401424  PMID: 24978709
low-grade serous; ovarian cancer; serous borderline; low malignant potential; bevacizumab
5.  Risk Factors and Indications for 30-Day Readmission After Primary Surgery for Epithelial Ovarian Cancer 
Background
To identify patients at risk for postoperative morbidities, we evaluated indications and factors associated with 30-day readmission after epithelial ovarian cancer surgery.
Methods
Patients undergoing primary surgery for epithelial ovarian cancer between January 2, 2003, and December 29, 2008, were evaluated. Univariable and multivariable logistic regression models were fit to identify factors associated with 30-day readmission. A parsimonious multivariable model was identified using backward and stepwise variable selection.
Results
In total, 324 (60.2%) patients were stage III and 91 (16.9%) were stage IV. Of all 538 eligible patients, 104 (19.3%) were readmitted within 30 days. Cytoreduction to no residual disease was achieved in 300 (55.8%) patients, and 167 (31.0%) had measurable disease (≤1 cm residual disease). The most common indications for readmission were surgical site infection (SSI; 21.2%), pleural effusion/ascites management (14.4%), and thromboembolic events (12.5%). Multivariate analysis identified American Society of Anesthesiologists score of 3 or higher (odds ratio, 1.85; 95% confidence interval, 1.18–2.89; P = 0.007), ascites [1.76 (1.11–2.81); P = 0.02], and postoperative complications during initial admission [grade 3–5 vs none, 2.47 (1.19–5.16); grade 1 vs none, 2.19 (0.98–4.85); grade 2 vs none, 1.28 (0.74–2.21); P = 0.048] to be independently associated with 30-day readmission (c-index = 0.625). Chronic obstructive pulmonary disease was the sole predictor of readmission for SSI (odds ratio, 3.92; 95% confidence interval, 1.07–4.33; P = 0.04).
Conclusions
Clinically significant risk factors for 30-day readmission include American Society of Anesthesiologists score of 3 or higher, ascites and postoperative complications at initial admission. The SSI and pleural effusions/ascites are common indications for readmission. Systems can be developed to predict patients needing outpatient management, improve care, and reduce costs.
doi:10.1097/IGC.0000000000000339
PMCID: PMC4487916  PMID: 25611896
Readmission; Ovarian cancer; Primary cytoreduction
6.  Adrenomedullin Up-regulates the Expression of Vascular Endothelial Growth Factor in Epithelial Ovarian Carcinoma Cells via JNK/AP-1 Pathway 
Objective
Adrenomedullin (AM), a potent vasodilator peptide, presents in various kinds of tumors and promotes angiogenesis. We have previously reported that AM is expressed in epithelial ovarian carcinoma tissue. Here, we investigated the hypothesis that AM might regulate production of vascular endothelial growth factor (VEGF) in epithelial ovarian carcinoma and further promote angiogenic processes.
Methods
The messenger RNA expression of VEGF in human epithelial ovarian carcinoma cells (HO-8910) was examined by real-time polymerase chain reaction. Transcriptional control was analyzed by transient transfection assay of VEGF promoter-luciferase hybrid genes and chromatin immunoprecipitation assay. Activation of c-Jun N-terminal kinase (JNK) was detected by Western blotting. The formation of capillarylike structures by EA.hy926 cells cocultured with HO-8910 cells on Matrigel was also studied.
Results
We found that in HO-8910 cells, AM (10−10 to 10−7 mol/L) enhanced VEGF messenger RNA expression in a time- and concentration-dependent manner, as well as promoter activity. Furthermore, JNK was activated by AM stimulation. The AM-induced increase in VEGF expression was significantly attenuated by SP600125, a specific JNK inhibitor. Chromatin immunoprecipitation assay and promoter activity analysis showed that VEGF expression induced by AM required the activator protein 1 motif on the VEGF promoter. In an in vitro angiogenesis system for endothelial cells (EA.hy926) cocultured with HO-8910 cells, we observed that the addition of AM stimulated endothelial cell tube formation, which could be abolished by VEGF neutralizing antibody.
Conclusions
Our findings suggest that the JNK/Activator protein 1 pathway is involved in AM-induced VEGF expression in HO-8910 cells.
doi:10.1097/IGC.0000000000000465
PMCID: PMC4485736  PMID: 26098087
Adrenomedullin (AM); Vascular endothelial growth factor (VEGF); Epithelial ovarian carcinoma; c-Jun N-terminal kinase (JNK); Activator protein 1 (AP-1)
7.  Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer 
Supplemental digital content is available in the text.
Objective
Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting.
Methods
Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively.
Results
Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses.
Conclusions
Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment.
doi:10.1097/IGC.0000000000000448
PMCID: PMC4485738  PMID: 25962114
Ovarian cancer; Platinum refractory; Platinum resistant; Chemotherapy
8.  Cervical Cancer Awareness and Screening in Botswana 
Objective
Cervical cancer remains a leading cause of death in many developing countries due to limited screening by Papanicolaou (Pap) smear. We sought to better understand women’s beliefs about cervical cancer and screening in Botswana, a middle income African country with high rates of cervical cancer.
Methods
We interviewed 289 women attending general medicine or human immunodeficiency virus (HIV) clinics, where Pap testing was available, in Gaborone, Botswana in January 2009.
Results
About three-quarters (72%) of respondents reported having ever had a Pap smear. HIV-positive women were more likely to have had a Pap smear than HIV-negative women (80% vs. 64%, OR=1.97, 95% CI: 1.10, 3.55). Screening was also more common among women who were older, had higher incomes, or had heard of cervical cancer. Almost all participants reported a desire to have a Pap smear. Reasons included to determine cervical health (56%), to improve overall health (33%), and to obtain early treatment (34%). About half (54%) of respondents said they did not know what causes cervical cancer, and almost none attributed the disease to HPV infection.
Conclusion
Study findings can inform interventions that seek to increase cervical cancer awareness and uptake of screening as it becomes more widely available.
doi:10.1097/IGC.0b013e318249470a
PMCID: PMC4437542  PMID: 22367370
cervical cancer; Pap smear; screening; Africa; prevention
9.  Oncogenic Viral Prevalence in Invasive Vulvar Cancer Specimens from HIV Positive and Negative Women in Botswana 
Objective
The primary aim of this study is to describe the prevalence of select oncogenic viruses within vulvar squamous cell carcinoma (VSCC) and their association with Human Immunodeficiency Virus (HIV) status in women in Botswana, where the national HIV prevalence is the third highest in the world.
Methods/materials
A cross-sectional study of biopsy-confirmed VSCC specimens and corresponding clinical data was conducted in Gaborone, Botswana. Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) viral testing were done for Epstein-Barr Virus (EBV), Human Papilloma Virus (HPV) strains, and Kaposi's Sarcoma Herpesvirus (KSHV), and PCR viral testing alone was done for John Cunningham Virus (JCV).
Results
HPV prevalence by PCR was 100% (39/39 35/35) among tested samples. HPV16 was the most prevalent HPV strain (82.9% by PCR, 94.7% by either PCR or IHC). KSHV prevalence by PCR had a significant association with HIV status (p = 0.013), but not by IHC (p = 0.650).
Conclusions
The high burden of HPV, specifically HPV16, in VSCC in Botswana suggests a distinct HPV profile that differs from other studied populations, which provides increased motivation for HPV vaccination efforts. Oncogenic viruses KSHV and EBV were also more prevalent in our study population though their potential role in VSCC pathology is unclear.
doi:10.1097/IGC.0000000000000111
PMCID: PMC3999226  PMID: 24651632
human immunodeficiency virus; human papilloma virus; molecular viral testing; oncogenic viruses; vulvar squamous cell carcinoma
11.  High Pretreatment Plasma D-dimer Levels Are Associated With Poor Prognosis in Patients With Ovarian Cancer Independently of Venous Thromboembolism and Tumor Extension 
Objective
Elevated plasma D-dimer (DD) is associated with decreased survival among patients with breast, lung, and colon cancers. The present study clarifies the prognostic significance of pretreatment plasma DD levels in patients with epithelial ovarian cancer (EOC).
Methods
We investigated pretreatment DD levels and other variables for overall survival using univariate and multivariate analyses in 134 consecutive patients with EOC stages II to IV who were initially treated between November 2004 and December 2010.
Results
The median follow-up period was 53 (7–106) months. Univariate analysis significantly associated elevated pretreatment DD (≥2.0 μg/mL) levels to poor 5-year overall survival rates irrespective of previously treated venous thromboembolism (72.2% vs 52.6%, P = 0.039). Cancer antigen 125 levels of 200 U/mL or higher (P = 0.011), distant metastases (P = 0.0004), residual tumors (P < 0.0001), and International Federation of Gynecology and Obstetrics stage III/IV (P = 0.0033) were also poor prognostic factors. Multivariate analysis independently associated DD levels of 2.0 μg/mL or higher (P = 0.041), distant metastases (P = 0.013), and residual tumors (P < 0.0001) with poor overall survival.
Conclusions
High pretreatment DD levels are associated with poor overall survival in patients with EOC independently of venous thromboembolism and tumor extension and might comprise a promising prognostic biomarker for patients with EOC.
doi:10.1097/IGC.0000000000000415
PMCID: PMC4406979  PMID: 25756402
Plasma D-dimer; Epithelial ovarian cancer; Prognosis
12.  IQGAP1 Is Involved in Enhanced Aggressive Behavior of Epithelial Ovarian Cancer Stem Cell-Like Cells During Differentiation 
Background
Wide metastasis is one of characteristics of ovarian cancer. Cancer stem cells, as a source in cancer invasion and metastasis, possess powerful potential of differentiation. Scaffolding IQ domain GTPase-activating protein 1 (IQGAP1) plays a key role in the invasion and metastasis of cancer cells, but IQGAP1’s role in cancer stem cells including ovarian cancer was unclear.
Methods
Spheroid culture with serum-free medium was used for enriching ovarian cancer stem cell-like cells (CSC-LCs) from 3AO cell line, and a medium with 10% fetal bovine serum was used to induce the differentiation of CSC-LCs. Immunofluorescence was for detecting the stem markers OCT4 and SOX2. The quantitative real-time-polymerase chain reaction and Western blotting were performed to determine the messenger RNA and protein expression of IQGAP1, respectively. The capacity of cell invasion was evaluated by transwell chamber assay.
Results
Ovarian CSC-LCs obtained through spheroid culture showed irregularly elongated appearance, CD24 negative, and OCT4 and SOX2 positive. IQGAP1 expression was decreased in ovarian CSC-LCs compared with parental 3AO cells, but increased de novo during the differentiation of CSC-LCs. Knockdown of IQGAP1 by specific small interfering RNA remarkably weakened invasion capacity of 2-day differentiated ovarian CSC-LCs.
Conclusions
Increased IQGAP1 expression during the differentiation of CSC-LCs is involved in an aggressive cell behavior, which may contribute to metastasis of ovarian cancer.
doi:10.1097/IGC.0000000000000394
PMCID: PMC4406980  PMID: 25675045
IQGAP1; Ovarian cancer; Cancer stem cell-like cells; Differentiation; Invasion
13.  Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment 
Objective
We propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.
Methods
We analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:
Low-grade carcinoma with less than half myometrial invasion
Negative nodes
No nodes removed
High-grade carcinoma with no myometrial invasion
Negative nodes
No nodes removed
Low-grade carcinoma with half or greater myometrial invasion
Negative nodes
No nodes removed
High-grade carcinoma with any myometrial invasion
Negative nodes
No nodes removed
Results
Data from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.
Conclusions
By incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).
doi:10.1097/IGC.0b013e3182a5055e
PMCID: PMC4405774  PMID: 24126219
Endometrial cancer; Stage I; FIGO
14.  RETRACTION 
doi:10.1097/IGC.0000000000000255
PMCID: PMC4384811  PMID: 25153679
15.  The limited utility of magnetic resonance imaging in determining the primary site of disease in patients with inconclusive endometrial biopsy 
Objective
To evaluate the utility of preoperative magnetic resonance imaging (MRI) in determining whether primary disease site is cervical or endometrial in patients with inconclusive preoperative endometrial biopsy.
Methods
We retrospectively identified all patients who underwent pelvic MRI and who had a preoperative diagnosis of cervical or endometrial cancer at MD Anderson Cancer Center between 1990 and 2006. The subset in which endometrial biopsy did not clarify the primary disease site were analyzed. MRI results were compared with postoperative histopathologic findings.
Results
A total of 168 patients who underwent MRI who had a preoperative diagnosis of cervical or endometrial cancer were identified. Of these, 51 had an inconclusive endometrial biopsy. MRI suggested an endometrial primary tumor without cervical invasion in 28 patients, of whom 21 (75%) actually had such a tumor and 7 had an endometrial primary tumor with cervical invasion. MRI suggested an endometrial primary tumor with cervical invasion in 3 patients, all of whom had such a tumor. MRI suggested a cervical primary tumor in 6 patients, of whom 5 had such a tumor and 1 had an endometrial primary tumor without cervical invasion. MRI was inconclusive (did not clarify primary disease site or no lesion visualized) in 14 (27%) of 51 patients, 6 of whom had an endocervical primary tumor or an endometrial tumor with cervical involvement. Overall, preoperative MRI was either inaccurate or unhelpful in 22 (43%) of 51 patients.
Conclusion
Preoperative MRI in patients with inconclusive endometrial biopsy is inaccurate or unhelpful in nearly half of patients.
doi:10.1111/IGC.0b013e3181f30c1b
PMCID: PMC4361062  PMID: 21051975
16.  Rate of port-site metastasis is uncommon in patients undergoing robotic surgery for gynecologic malignancies 
Objective
To describe the rate of port-site metastasis in patients who underwent robotic surgery for suspected gynecologic malignancy.
Methods
Using a prospective database, we identified all patients who underwent robotic surgery performed by the Gynecologic Oncology service at 1 institution between December 2006 and March 2010. Records of patients with confirmed malignancy were reviewed for clinicopathologic data and information about port-site metastasis.
Results
One hundred eighty-one patients met the inclusion criteria. The median age was 55.4 years (range, 19–82), and the median body mass index was 29.6 kg/m2 (range, 17.9–70.7). Port-site metastases were detected in two patients (1.1%) at 3 weeks (patient 1) and 11 months (patient 2) after surgery. Patient 1 underwent surgery for an adnexal mass and pathologic examination revealed gallbladder adenocarcinoma metastatic to the ovary. She had a recurrence in the right lateral-abdominal-wall robotic-trocar site with concurrent metastases in the gallbladder fossa and liver. Patient 2 was diagnosed with adenocarcinoma of unclear (cervical vs. endometrial) origin. Imaging showed metastases in pelvic and paraaortic lymph nodes. She underwent laparoscopy and was found intraoperatively to have gross disease on the right ovary. The patient underwent right salpingo-oophorectomy and chemoradiation. She had residual disease in the cervix and subsequently underwent robotic hysterectomy and left salpingo-oophorectomy. Pathologic examination revealed endometrial cancer. She had a recurrence at the transumbilical trocar site concurrent with retroperitoneal lymphadenopathy and carcinomatosis. There were no cases of isolated port-site metastasis.
Conclusions
The rate of port-site metastasis after robotic surgery in women with gynecologic cancer is low and similar to the rate for laparoscopic procedures.
doi:10.1097/IGC.0b013e3182174609
PMCID: PMC4361068  PMID: 21633306
Robotic; laparoscopy; port-site metastasis/recurrence; ovarian cancer; cervical cancer; uterine cancer
17.  Laparoscopic Versus Abdominal Hysterectomy for Endometrial Cancer 
Objective
To compare the demographics, cancer characteristics, and hospital outcomes of endometrial cancer patients undergoing a laparoscopically assisted vaginal hysterectomy (LAVH) versus a total abdominal hysterectomy (TAH).
Methods
Two California population databases (Office of Statewide Health Planning and Development and the California Cancer Registry) were linked using patient identifiers. Patients who underwent endometrial cancer surgery from 1997 to 2001 were identified. The combined database was queried for type of surgery, patient demographics, hospital outcomes, comorbidities, and cancer characteristics. Statistical analyses included the t test, χ2 test, and logistic regression.
Results
In this study, 978 endometrial cancer patients (7.7%) had an LAVH and 11,765 (92.3%) had a TAH. The mean ages for the 2 groups were 63.3 and 64.8 years, respectively. Lymphadenectomy was performed more frequently in LAVH patients compared with TAH patients (45.6 vs 41.1%; P = 0,006). Patients undergoing LAVH were more likely to be younger and healthier and have stage 1 or grade 1 disease (P < 0.0001). Total abdominal hysterectomy patients were more likely to have significant medical comorbidities. Mean length of stay for LAVH was 2.40 versus 4.36 days for TAH (P < 0,001), but mean hospital charges were comparable. Perioperative complications such as vascular and bowel injuries, pulmonary embolism, wound problems, and transfusions were significantly more common in TAH patients.
Conclusion
Surgeons seem to carefully select endometrial cancer patients for laparoscopic surgery. Although surgical staging was performed in less than 50% of endometrial cancer patients, the rate was not worse in laparoscopic procedures. Short-term hospital complications were less common in the laparoscopy group.
doi:10.1111/IGC.0b013e3181a83db8
PMCID: PMC4357489  PMID: 20009892
Laparoscopy; Abdominal hysterectomy; Endometrial cancer; Patient outcomes
18.  Lifestyle modification in cervical cancer survivors: an ongoing need 
Objective
With the introduction of multimodality therapy for cervical cancer, many women will be long-term survivors in need of comprehensive surveillance care. Our goal was to evaluate patterns of obesity and smoking in a cohort of cervical cancer survivors, and to assess the potential influence of these comorbidities on subsequent follow-up.
Methods
We reviewed the records of patients treated for invasive cervical cancer at our institution from 2000–2003 who had no evidence of disease ≥ 3 years. Demographic and clinical data were collected, including smoking history and anthropometric measurements. Body mass index (BMI) was categorized according to World Health Organization criteria. Logistic regression, Wilcoxon rank sum, and chi-square analyses were performed.
Results
298 women had complete follow-up data at three years. The median age at diagnosis was 43.5 years (range 17.6–87.1). At diagnosis, 31.9% had a normal BMI, 28.2% were overweight, and 34.6% were obese compared with 31.7%, 21.1%, and 30.2% at 3 years, respectively. Of the 51 women whose BMI categorization changed, 33 (64.7%) had weight gain, and 18 (35.3%) had weight loss. By paired analyses, increase in BMI was significant over the three-year interval (p<0.001). Seventy (70) patients actively smoked at diagnosis. Compared with nonsmokers, current smokers had a greater odds of referral to the pain service [OR6.56, CI 6.26–16.43, p<0.001], physical therapy [OR 4.74, CI 1.29–17.36, p=0.02], and gastroenterology [OR 2.25, CI 1.14–4.24, p=0.02].
Conclusion
Obesity and smoking are significant comorbidities which may complicate care in cervical cancer survivors. Interventions aimed at modifying these risk factors should be routinely undertaken in this population.
doi:10.1097/IGC.0000000000000081
PMCID: PMC4279702  PMID: 24469324
obesity; cervical cancer; smoking
19.  Risk of Ovarian Cancer Relapse Score 
Objective
The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC).
Methods
A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score.
Results
Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (<0.33), intermediate (0.34–0.67), and high (>0.67) probability of relapse.
Conclusions
The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support.
doi:10.1097/IGC.0000000000000361
PMCID: PMC4340599  PMID: 25647256
CA-125; Ovarian cancer; Prognostic factors; Relapse; ROVAR
20.  Preoperative Tumor Size at MRI Predicts Deep Myometrial Invasion, Lymph Node Metastases, and Patient Outcome in Endometrial Carcinomas 
Supplemental digital content is available in the text.
Objective
The aim of this study was to explore the relation between preoperative tumor size based on magnetic resonance imaging (MRI) and the surgical pathologic staging parameters (deep myometrial invasion, cervical stroma invasion, and metastatic lymph nodes) and to assess the prognostic impact of tumor size in endometrial carcinomas. Interobserver variability for the different tumor size measurements was also assessed.
Methods/Materials
Preoperative pelvic MRI of 212 patients with histologically confirmed endometrial carcinomas was read independently by 3 radiologists. Maximum tumor diameters were measured in 3 orthogonal planes (anteroposterior, transverse, and craniocaudal planes [CC]), and tumor volumes were estimated. Tumor size was analyzed in relation to surgical staging results and patient survival. The multivariate analyses were adjusted for preoperative risk status based on endometrial biopsy. Intraclass correlation coefficients and receiver operating characteristics curves for the different tumor measurements were also calculated.
Results
Anteroposterior tumor diameter independently predicted deep myometrial invasion (P < 0.001), whereas CC tumor diameter tended to independently predict lymph node metastases (P = 0.06). Based on receiver operating characteristic curves, the following tumor size cutoff values were identified: anteroposterior diameter greater than 2 cm predicted deep myometrial invasion (unadjusted odds ratio [OR], 12.4; P < 0.001; adjusted OR, 6.7; P < 0.001) and CC diameter greater than 4 cm predicted lymph node metastases (unadjusted OR, 6.2; P < 0.001; adjusted OR, 4.9; P = 0.009). Large tumor size was associated with reduced progression/recurrence-free survival (P ≤ 0.005 for all size parameters), and CC diameter had an independent impact on survival (adjusted hazards ratio, 1.04; P = 0.009). The interobserver variability for the different size measurements was very low (intraclass correlation coefficient, 0.78–0.85).
Conclusions
Anteroposterior tumor diameter greater than 2 cm predicts deep myometrial invasion, and CC tumor diameter greater than 4 cm predicts lymph node metastases. Tumor size is a strong prognostic factor in endometrial carcinomas. Preoperative tumor measurements based on MRI may potentially improve preoperative risk stratification models and thus enable better tailored surgical treatment in endometrial cancer.
doi:10.1097/IGC.0000000000000367
PMCID: PMC4340601  PMID: 25628109
Endometrial carcinoma; Tumor size; Magnetic resonance imaging; Prognosis
21.  Increased Association Between Endometriosis and Endometrial Cancer 
Objective
Association between endometriosis and ovarian cancer has been well established. Nonetheless, endometriosis may also be associated with endometrial cancer because of shared etiological mechanisms of both estrogen stimulation and chronic inflammation; however, the association between these 2 disorders has rarely been investigated.
Methods
The National Health Insurance Research Databases in Taiwan were retrieved and analyzed. The case cohort consisted of patients with a diagnosis of endometriosis between January 1997 and December 2000 (N = 15,488). For the construction of control cohort, 8 age- and sex-matched control patients for every patient in the case cohort were selected using a random sampling method (n = 123,904). All subjects were tracked for 10 years from the date of entry to identify whether they had developed endometrial cancer. The Cox proportional hazards regression model was used to evaluate 10-year event occurrence of endometrial cancer.
Results
During the 10-year follow-up period, 392 participants developed endometrial cancer, with 104 (0.7%) distributed in the case cohort and 288 (0.2%) in the control cohort. Multivariable Cox regression modeling demonstrates a higher risk for developing endometrial cancer in the case cohort than in the control cohort (adjusted hazard ratio [aHR], 2.83; 95% confidence interval [CI], 1.495.35; P < 0.01). Age at diagnosis of endometriosis shows a moderator effect: when 40 years or younger, the risk for developing endometrial cancer was comparable between the case cohort and the control cohort (aHR, 1.42; 95% CI, 0.55–3.70; P = 0.226), whereas when older than 40 years, the risk for developing endometrial cancer was higher in the former group than in the latter group (aHR, 7.08; 95% CI, 2.33–21.55; P = 0.007).
Conclusions
Patients diagnosed with endometriosis may harbor an increased risk for developing endometrial cancer in their later life. Closer monitoring is advised for this patient population.
doi:10.1097/IGC.0000000000000384
PMCID: PMC4340602  PMID: 25695548
Endometrial cancer; Endometriosis; Population-based cohort study
22.  The Expression of Tumor-Derived and Stromal-Derived Matrix Metalloproteinase 2 Predicted Prognosis of Ovarian Cancer 
Objective
To evaluate the association of tumor-derived matrix metalloproteinase 2 (MMP-2) and stromal-derived MMP-2 expression with the prognosis of patients with ovarian cancer, a meta-analysis study was performed, which was aimed to comprehensively review the evidence of MMP-2 as prognostic biomarkers in ovarian cancers.
Methods
All relevant studies were searched in PubMed and Web of Science until May 30, 2014. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were used to assess the association between MMP-2 expression (tumor-derived or stromal-derived) and prognosis of patients with ovarian cancer. Pooled odds ratios (ORs) and their 95% CIs were used to assess the correlation of MMP-2 expression with the clinicopathological features of patients with ovarian cancer.
Results
A total of 965 patients in 8 studies were included in this analysis. Among them, tumor-derived and stromal-derived MMP-2 expression was detected in 7 and 5 articles, respectively. The results revealed that ovarian cancer patients with positive tumor-derived MMP-2 expression showed a worse prognosis than did the ones with negative tumor-derived MMP-2 expression (HR, 1.52; 95% CI, 1.06–2.20). However, ovarian cancer patients with positive stromal-derived MMP-2 expression had not. In addition, we also found that tumor-derived MMP-2 expression was associated with distant metastasis (absent vs present; pooled OR, 4.52; 95% CI, 1.56–13.09; P = 0.001).
Conclusions
These results suggested that positive tumor-derived MMP-2 expression could predict a lower overall survival rate and could be an independent dangerous prognostic factor in patients with ovarian cancer.
doi:10.1097/IGC.0000000000000386
PMCID: PMC4340603  PMID: 25695542
Tumor-derived; Stromal-derived; MMP-2; Ovarian cancer; Prognosis
23.  [No title available] 
PMCID: PMC3946897  PMID: 24407585
24.  Incidence and Predictors of Venous Thromboembolism After Debulking Surgery for Epithelial Ovarian Cancer 
Objective
The aim of this study was to determine the incidence and the risk factors of venous thromboembolism (VTE) within 30 days after primary surgery for epithelial ovarian cancer (EOC).
Methods
In a historical cohort study, we estimated the postoperative 30-day cumulative incidence of VTE among consecutive Mayo Clinic patients undergoing primary cytoreduction for EOC between January 2, 2003, and December 29, 2008. We tested perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program, >130 variables) as potential predictors of postoperative VTE using the Cox proportional hazards modeling.
Results
Among 569 cases of primary EOC cytoreduction and/or staging and no recent VTE, 35 developed symptomatic VTE within 30 days after surgery (cumulative incidence = 6.5%; 95% confidence interval, 4.4%–8.6%). Within the cohort, 95 (16.7%) received graduated compression stockings (GCSs), 367 (64.5%) had sequential compression devices + GCSs, and 69 (12.1%) had sequential compression devices + GCSs + postoperative heparin, with VTE rates of 1.1%, 7.4%, and 5.8%, respectively (P = 0.07, χ2 test). The remaining 38 (6.7%) received various other chemical and mechanical prophylaxis regimens. In the multivariate analysis, current or past tobacco smoking, longer hospital stay, and a remote history of VTE significantly increased the risk for postoperative VTE.
Conclusions
Venous thromboembolism is a substantial postoperative complication among women with EOC, and the high cumulative rate of VTE within 30 days after primary surgery suggests that a more aggressive strategy is needed for VTE prevention. In addition, because longer hospital stay is independently associated with a higher risk for VTE, methods to decrease length of stay and minimize factors that contribute to prolonged hospitalization are warranted.
doi:10.1097/IGC.0b013e3182a80aa7
PMCID: PMC4307403  PMID: 24172104
Venous thromboembolism; Deep vein thrombosis; Ovarian cancer; Surgery
25.  The Impact of Perioperative Packed Red Blood Cell Transfusion on Survival in Epithelial Ovarian Cancer 
Objective
Perioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC.
Methods
Perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program) were retrospectively abstracted from 587 women who underwent primary EOC staging between January 2, 2003, and December 29, 2008. Associations with receipt of PRBCT were evaluated using univariate logistic regression models. The associations between receipt of PRBCT and disease-free survival and overall survival were evaluated using multivariable Cox proportional hazards models and using propensity score matching and stratification, respectively.
Results
The rate of PRBCT was 77.0%. The mean ± SD units transfused was 4.1 ± 3.1 U. In the univariate analysis, receipt of PRBCT was significantly associated with older age, advanced stage (≥IIIA), undergoing splenectomy, higher surgical complexity, serous histologic diagnosis, greater estimated blood loss, longer operating time, the presence of residual disease, and lower preoperative albumin and hemoglobin. Perioperative packed red blood cell transfusion was not associated with an increased risk for recurrence or death, in an analysis adjusting for other risk factors in a multivariable model or in an analysis using propensity score matching or stratification to control for differences between the patients with and without PRBCT.
Conclusions
Perioperative packed red blood cell transfusion does not seem to be directly associated with recurrence and death in EOC. However, lower preoperative hemoglobin was associated with a higher risk for recurrence. The need for PRBCT seems to be a stronger prognostic indicator than the receipt of PRBCT.
doi:10.1097/01.IGC.0000436089.03581.6b
PMCID: PMC4306564  PMID: 24172098
Perioperative red blood cell transfusion; Ovarian cancer; Disease-free survival; Overall survival

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