Major Gynecologic Cancer Research Articles

Expression and Humoral Response of A-Kinase Anchor Protein 4 in Cervical Cancer

Cervical cancer is one of the major gynecologic cancers. In developing countries, because of a lack of medical support and infrastructure, cervical cancer is the leading cause of cancer-related deaths. Therefore, there is a need to identify novel biomarkers for cervical cancers. In this context, cancer-testis (CT) antigens represent a unique class of tumor antigens that have been shown to be associated with various solid tumors. These antigens have restricted expression in testis and no expression in somatic tissues. Because of their restricted expression, CT antigens are novel candidate molecules for early detection and diagnosis and immunotherapy. In the present study, novel CT antigen A-kinase anchor protein 4 (AKAP4) expression and humoral response were investigated in patients with cervical cancer. In this study, 74 cervical cancer tissue specimens, which included different tumor stages (stage I [n = 35], stage II [n = 39]) and histologic grades (grade 1 [n = 17], grade 2 [n = 46], and grade 3[n = 11]) and 62 adjacent noncancerous tissue specimens were investigated for AKAP4 gene expression by using reverse transcriptase polymerase chain reaction and in situ RNA hybridization. Furthermore, AKAP4 protein expression was determined by immunohistochemistry. In addition, humoral response against purified recombinant AKAP4 protein was determined in available sera of 70 patients with cervical cancer by enzyme-linked immuno assay (ELISA). Our study revealed that AKAP4 gene and protein expression was detected in 86% of total patients with cervical cancer. Based on the AKAP4 immunoreactivity score, most of stage I (n = 22/29) and stage II (n = 30/35) specimens revealed high AKAP4 expression (≥50% AKAP4-positive cells). A-kinase anchor protein 4 expression was significantly associated with early grades tumor specimens (P = 0.023). In addition, humoral response was detected in 53% of patients irrespective of stages, lymph node positivity, and grades. Collectively, our data indicate the putative role of AKAP4 in early tumorigenesis and may be implicated as a biomarker and immunotherapeutic target for cervical cancer.

Perioperative care in gynecologic oncology

To review perioperative care in gynecologic oncology with special emphasis on areas of controversy. Major gynecologic surgery still represents the cornerstone of management among women diagnosed with gynecologic malignancies. The implementation of clinical guidelines can significantly impact perioperative morbidity and mortality. Preoperative evaluation and preparation allows the surgeon to identify patient risks and develop risk factor modification strategies decreasing delays in preparation and cost and improving patient safety. Preoperative areas of controversy include preoperative testing and evaluation, use of mechanical bowel preparation, prophylactic antibiotics, and use of anticoagulants, and the timing of postoperative feeding. In healthy women undergoing gynecologic cancer surgery preoperative evaluation requirements will be minimal. For women with extensive comorbid conditions a more detailed evaluation will be required to decrease perioperative morbidity and mortality. Mechanical bowel preparations should not be required preoperatively. Preoperative administration of antibiotics and anticoagulants should be provided to all patients undergoing major gynecologic cancer surgery.

The Role of Intraoperative Fluid Optimization Using the Esophageal Doppler in Advanced Gynecological Cancer: Early Postoperative Recovery and Fitness for Discharge

To determine the effect of fluid optimization using esophageal Doppler monitoring (EDM) when compared to standard fluid management in women who undergo major gynecological cancer surgery and whether its use is associated with reduced postoperative morbidity. From January 2009 to December 2010, women undergoing laparotomy for pelvic masses or uterine cancer had either fluid optimization using intraoperative EDM or standard fluid replacement without using EDM. Cases were selected from 2 surgeons to control for variability in surgical practice. Demographic and surgical details were collected prospectively. Univariate and multivariate analyses were performed to quantify the association between the use of EDM with "early postoperative recovery" and "early fitness for discharge." A total of 198 women were operated by the 2 prespecified surgeons; 79 women had fluid optimization with EDM, whereas 119 women had standard anesthetic care. The use of ODM was associated with earlier postoperative recovery (adjusted odds ratio, 2.83; 95% confidence interval, 1.20-6.68; P = 0.02) and earlier fitness for discharge (adjusted odds ratio, 2.81; 95% confidence interval, 1.01-7.78; P = 0.05). Women with advanced-stage disease in the "EDM" group resumed oral diet earlier than women in the "no EDM" group (median, 1 day vs 2 days; P = 0.02). These benefits with EDM did not extend to women with early-stage disease/benign/borderline tumors. No significant difference in postoperative complications was noted. Intraoperative fluid optimization with EDM in women with advanced gynecological cancer may be associated with improved postoperative recovery and early fitness for discharge. Studies with adequate power are needed to investigate its role in reducing postoperative complications.

Incidence of cervical, endometrial, and ovarian cancer in Korea, 1999-2010

ObjectiveTo investigate the recent incidence of and trends in cervical, endometrial, and ovarian cancer in Korean females.MethodsData from the Korea Central Cancer Registry between 1999 and 2010 were analyzed. Age-standardized rates (ASRs) and annual percent changes (APCs) were calculated.ResultsThe absolute incidence rates of the three major gynecologic cancers increased: 6,394 in 1999 to 7,454 in 2010. The ASR for gynecologic cancer was 23.7 per 100,000 in 1999 and decreased to 21.0 in 2010 (APC, -1.1%; 95% confidence interval [CI], -1.53 to -0.70) due to a definitive decrease in the incidence of cervical cancer (APC, -4.3%). Endometrial cancer has been definitively increasing (APC, 6.9% during 1999-2010), especially in females <30 years old (APC, 11.2%) and in females ≥80 years old (APC, 9.5%). The incidence of ovarian cancer is increasing gradually (APC, 1.5%).ConclusionASRs and APC for gynecologic cancers overall are decreasing due to the decrease in the incidence of cervical cancer. However, the incidence of endometrial and ovarian cancer has been increasing.

A prospective study of the feasibility and acceptability of a Web-based, electronic patient-reported outcome system in assessing patient recovery after major gynecologic cancer surgery

PurposeThe purposes of this study are to evaluate the feasibility of capturing patient-reported outcomes (PROs) electronically and to identify the most common distressing symptoms in women recovering from major gynecologic cancer surgery. MethodsThis was a prospective, single-arm pilot study. Eligible participants included those scheduled for a laparotomy for presumed or known gynecologic malignancy. Patients completed a Web-based “STAR” (Symptom Tracking and Reporting for Patients) questionnaire once preoperatively and weekly during the 6-week postoperative period. The questionnaire consisted of the patient adaptation of the NCI CTCAE 3.0 and EORTC QLQ-C30 3.0. When a patient submitted a response that was concerning, an automated email alert was sent to the clinician. The patient's assessment of STAR's usefulness was measured via an exit survey. ResultsForty-nine patients completed the study. The procedures included the following: hysterectomy±staging (67%), resection of tumor (22%), salpingo-oophorectomy (6%), and other (4%). Most patients (82%) completed at least 4 sessions in STAR. The CTC generated 43 alerts. These alerts resulted in 25 telephone contacts with patients, 2 ER referrals, one new appointment, and one pharmaceutical prescription. The 3 most common patient-reported symptoms generating an alert were as follows: poor performance status (19%), nausea (18%), and fatigue (17%). Most patients found STAR useful (80%) and would recommend it to others (85%). ConclusionApplication of a Web-based, electronic STAR system is feasible in the postoperative period, highly accepted by patients, and warrants further study. Poor performance status, nausea, and fatigue were the most common distressing patient-reported symptoms.

A prospective study of the feasibility and acceptability of a web-based, electronic patient-reported outcomes system in assessing patient recovery after major gynecologic cancer surgery

Objective: To evaluate the feasibility and patient (pt) acceptability of electronic capture of patient-reported outcomes (PROs) and to identify the most common reported distressing symptoms in women recovering from major gynecologic cancer surgery.

A prospective study of the feasibility and acceptability of a Web-based, electronic patient-reported outcome system in assessing patient recovery after major gynecologic cancer surgery

A prospective study of the feasibility and acceptability of a Web-based, electronic patient-reported outcome system in assessing patient recovery after major gynecologic cancer surgery

Incidence and timing of venous thromboembolism after surgery for gynecological cancer

ObjectiveThis study aims to determine the incidence, timing, and risk factors of clinical venous thromboembolism. MethodsA cohort of patients who had major gynecologic cancer surgery between 1998 and 2008 was identified. Secondarily, a nested case–control design wherein patients who had clinical VTE within 90days after surgery were considered cases. Controls were matched on age, race, surgery date, and cancer site. Risk factors were evaluated for VTE within 90days, and late VTE between 8 and 90days. ResultsWe identified 4158 women, 18years or older, without a history of recent thrombosis. We observed 126 cases of clinical VTE within 90days of surgery (incidence 4%) of which 96 (76%) occurred after post-operative day 7. In a multivariable model including age, ASA, BMI, race, and site of cancer, only ovarian cancer was a significant predictor for VTE within 90days (HR 2.8; 95% CI 1.6, 5.0).In the nested case–control study, we identified hospital stay≥5days (OR 2.8; 95% CI 1.5, 5.1) and prior VTE (OR 2.6; 95% CI 1.1, 6.1) as significant risk factors for VTE within 90days. Only hospital stay ≥5days (OR 2.5; 95% CI 1.3, 4.7) was significantly associated with late VTE between 8 and 90days. ConclusionIn gynecologic cancer patients, over 75% of VTE are detected more than 7days after surgery. Patients with ovarian cancer, prolonged hospitalization, or a history of VTE are at highest risk of developing clinical VTE. Such patients would be optimal candidates for clinical trials evaluating extended VTE prophylaxis.

Transversus Abdominis Plane Block Does Not Provide Additional Benefit to Multimodal Analgesia in Gynecological Cancer Surgery

The transversus abdominis plane (TAP) block is a recently described technique involving injecting local anesthetic between the internal oblique and transversus abdominis layers of the abdominal wall. It has been shown to be effective in reducing morphine consumption and improving postoperative pain relief in several clinical settings. We performed a randomized placebo-controlled trial comparing bilateral ultrasound-guided TAP blocks (2 x 20 mL 0.5% ropivacaine or 0.9% saline) in adult female patients undergoing midline laparotomy for known or presumed gynecological malignancy. Both groups received multimodal IV analgesia. The primary outcomes for the study were defined as the incidence of "inadequate" analgesia (defined as a score >50 mm on a visual analog scale) with forced expiration at 2 hours postoperatively and total postoperative morphine consumption at 2 hours and 24 hours. Data from 65 patients were included in the study. The groups were comparable in terms of age, weight, surgical duration, and intraoperative morphine doses. There were no significant differences between the control and treatment groups in the proportion of patients with inadequate analgesia either at rest (39% vs. 22%, P = 0.13) or with coughing (61% vs. 53%, P = 0.54) at 2 hours. There was no significant difference in postoperative morphine consumption between the placebo and treatment groups at 2 hours (13.5 mg vs. 11.87 mg, P = 0.53) or 24 hours (34.0 mg vs. 36.1 mg, P = 0.76). There were no significant differences in the incidence of opioid side effects or patient satisfaction. This study demonstrated that TAP blockade conferred no benefit in addition to multimodal analgesia in women undergoing major gynecological cancer surgery.

PRO: Therapy for a Patient with Platinum-Resistant/Refractory Recurrent Ovarian Carcinoma Should Be Selected Based on the Result of an In Vitro Chemoresistance Assay

General Debate Background Ovarian cancers are the second most frequent group of invasive malignancies of the female genital tract (an estimated 21,650 new cases in 2008); however, the lack of an effective early diagnostic test for ovarian cancer results in ovarian cancers accounting for more deaths than the other 2 major gynecologic cancers combined (an estimated 15,520 deaths in 2008).1 Stage distribution at diagnosis explains the lethality of ovarian cancer because 75%-80% of cases present as stage 111-IV (advanced) disease and require systemic therapy as the mainstay of treatment. Although the success rate with initial systemic therapy has improved, the majority of patients will exhibit recurrent or persistent disease during the course of their disease and will require management beyond initial therapy. There are 4 distinct patient populations with newly diagnosed disease: large-volume residual advanced disease, small-volume residual advanced disease, high-risk limited disease, and low-risk limited disease. The recurrent disease population will come from these 4 groups. Patients with large-volume residual advanced disease (2 1 residual neoplastic masses > 2 centimeters in diameter) have a probability of recurrence at 10 years that ranges from 80% to 90%. Those with small-volume residual advanced disease (no residual masses > 2 centimeters in diameter) exhibit a recurrence rate at 10 years of 60% to 70%. Patients with limited disease at high risk for recurrence (1 of the following high-risk features: grade 2 or 3 disease, disease on the surface of the ovary, disease outside the ovary, positive peritoneal cytology, or the presence of ascites) have a probability of recurrence by 10 years of 20%-25%, whereas those at low risk for recurrence (none of the high-risk features) exhibit a probability of recurrence of only 10% by 10 years. If the relative frequencies of each

A prospective randomized trial comparing patient-controlled epidural analgesia to patient-controlled intravenous analgesia on postoperative pain control and recovery after major open gynecologic cancer surgery

Objective To determine the effect of perioperative patient-controlled epidural analgesia (PCEA) compared to postoperative intravenous (IV) patient-controlled analgesia (PCA) on postoperative recovery parameters after major open gynecologic surgery. Methods A randomized controlled clinical trial included women undergoing laparotomy for a gynecologic disorder. Patients were randomized to postoperative IV morphine PCA (control arm) or to postoperative morphine–bupivacaine PCEA (treatment arm). Postoperative outcomes such as pain, and length of hospital stay were compared with an intention-to-treat analysis. The primary endpoint was postoperative pain at rest and when coughing — assessed by a 10-point visual analog scale (VAS). Results Between 9/04 and 6/07, 153 patients were randomized and 135 were evaluable (PCEA = 67; PCA = 68). Over 75% of the women in this study had gynecologic cancer. Patients in the PCEA arm had significantly less postoperative pain at rest on Day 1 and during the first 3 postoperative days when coughing compared to the PCA arm ( P < 0.05). The mean pain score at rest on Day 1 was 3.3 for the PCEA group compared to 4.3 for the PCA group ( P = 0.01). Overall, postoperative pain at rest and while coughing in the first 6 days was less in women treated with PCEA compared to PCA ( P < 0.003). Conclusions PCEA offers superior postoperative pain control after laparotomy for gynecologic surgery compared to traditional IV PCA. Women requiring major open surgery for gynecologic cancer should be offered PCEA for postoperative pain management if there are no contraindications.

A Population-Based 5-Year Cohort Study Including All Cases of Epithelial Ovarian Cancer in Western Sweden: 10-Year Survival and Prognostic Factors

Epithelial ovarian cancer (EOC) is the major gynecologic cancer mortality cause in Sweden. The aim of the present study was to investigate the long-term survival and prognostic factors of a complete population-based 5-year cohort of 682 patients with invasive EOC in western Sweden (population around 1.6 million). Data relating to residual tumor after surgery, FIGO stage, grade, histopathologic subtype, ploidy status, adjuvant chemotherapy (the prepaclitaxel period), and disease state (recurrence and death) were reported to a quality register in a prospectively kept database and were controlled against the Swedish National Cancer Registry for completeness. The median follow-up durations for the prospectively collected data in the Cox analysis and for the survival analysis that was made for all patients were 81 months (range, 52-109 months) and 11.7 years (range, 8.7-14.1 years), respectively. No patient was lost to follow-up. The relative 10-year survival rate was 38.4% (95% confidence interval, 34.5%-42.8%). The median relative survival time was 4.3 years (95% confidence interval, 3.6%-5.2%). In the univariate Cox regression analysis, prognostic significances for age, stage, residual tumor, histopathologic subtype of serous cystadenocarcinoma, grade, CA-125, and ploidy status were seen. In the multivariate analysis, age, stage, residual tumor after surgery, and postoperative CA-125 were of prognostic significance. In conclusion, 4 major prognostic factors were found for EOC in this population-based cohort study that also presents nearly accurate long-term survival owing to the nonselective nature and completeness regarding patients and follow-up of the study.

Clear cell carcinoma of the cervix: A multi-institutional review in the post-DES era

Objective To conduct an outcome analysis of patients with cervical clear cell carcinoma (CCCC) in the post-DES era. Methods A retrospective review was conducted at 3 major gynecologic cancer centers of all primary CCCC between 1982 and 2004. Results CCCC was confirmed in 34 patients. Median age was 53 years. DES exposure was confirmed in 2 (6%) patients. A history of smoking was elicited in 22%, and of abnormal Pap smear 18% patients. Primary surgical resection was performed in all stage I or IIA patients ( n = 26); they displayed superior 3-year overall survival (OS) compared to advanced stage ( n = 8) patients (91% vs. 22%, p < 0.001). Pelvic lymph node involvement was noted in 25%; all patients with positive para-aortic nodes (20% of patients sampled) had positive pelvic nodes. All node positive patients were treated with adjuvant radiation, but nevertheless displayed reduced progression free (31% vs 92%, p < 0.001) and overall survival (80% vs. 100%, p = 0.02). Adjuvant radiotherapy did not appear to impact OS in patients with negative lymph nodes. Discussion This series provides insight into the management of early stage CCCC in the post-DES era. Although these patients may be at slightly higher risk of nodal spread, clear cell histology by itself does not appear to portend a worse prognosis than squamous cell carcinoma of the cervix in the absence of traditional risk factors. Our data suggest that patients with low risk early stage CCCC may be managed with radical surgery alone, without the need for adjuvant chemotherapy or radiation.

Surgical management and adjuvant therapy for patients with uterine clear cell carcinoma: A multi-institutional review

Objective To assess the role of surgical staging, adjuvant therapy, and cytoreduction in uterine clear cell carcinoma (UCCC). Methods A retrospective review was conducted at 2 major gynecologic cancer centers of all primary UCCC between 1982 and 2004. Results UCCC was confirmed in 99 patients. The 5-year overall survival (OS) was 79%, 77%, 47%, and 21% for stages I–IV respectively. 69 patients had no gross evidence of extra-uterine disease, but 36 (52%) were upstaged at surgery. For those 22 patients with stages I and II disease who had a systematic lymphadenectomy (LND) (> 20 lymph nodes), no lymphatic (LF), peritoneal (PF), or hematological (HF) failures were noted. Radiation (RT) improved PFS (67 vs. 36%, p = 0.02), and reduced pelvic sidewall recurrences (18 vs. 53%, p = 0.04) and vaginal failures (VF) (7 vs. 35%, p = 0.04) for 45 patients at risk for LF (positive nodes or suboptimal LND). 39 patients with stages IIIC and IV disease were separately analyzed. Patients with no visible residual disease after cytoreduction had a significant improvement in median PFS (17 vs. 7months, p < 0.001), and OS (40 vs. 18months, p = 0.02) compared to patients with any residual disease after surgery. Conclusion Comprehensive surgical staging with a systematic LND is essential to accurately define early stage UCCC. Vaginal brachytherapy may be adequate adjuvant therapy for stages I and II UCCC confirmed by systematic LND. Patients at risk for LF appear to benefit from pelvic RT. An effort at cytoreduction to no visible residual disease should be made in advanced UCCC when feasible.

Primary prevention of gynecologic cancers

A shift from treatment to prevention of the three major gynecologic cancers is overdue. The traditional approach to cervical, endometrial, and ovarian cancers has been secondary or tertiary prevention — early detection and treatment or mitigation of damage, respectively. We reviewed the literature on these cancers to identify strategies for primary prevention. Cervical cancer behaves as a sexually transmitted disease. As with other such diseases, barrier and spermicidal contraceptives lower the risk of cervical cancer; the risk reduction approximates 50%. Combination oral contraceptives help prevent both endometrial and epithelial ovarian cancers. The risk of endometrial cancer among former oral contraceptive users is reduced by about 50% and that of ovarian cancer by about 30% to 80%. Weight control confers strong protection against endometrial cancer. Breast-feeding and tubal sterilization also appear to protect against ovarian cancer. Although women have a range of practical, effective measures available to reduce their risk of these cancers, few are aware of them. Without this information, women cannot make fully informed decisions about their health.

End results, interhospital differences, and trends in patterns of care for gynecologic cancer.

Survival rates represent one measure of population-wide progress in cancer control. Data from the Surveillance, Epidemiology and End Results (SEER program of the National Cancer Institute (NCI) document that, during the 1970s, survival rates for several cancers improved. For the major gynecologic cancers and breast cancer, improvements are evident for some sites but, areas of decline also are observed. Black women in the US have a poorer survival rate than white women and the trend in recent years suggest that this gap may be widening. Comparisons of survival rates from comprehensive cancer centers and population-based rates indicate differences in outcomes associated with the treatment setting. Data from the American College of Surgeons (ACS) patterns of care surveys suggest substantial interhospital variability in cancer survival which is largely explained by characteristics of the patient populations served. Recent studies of patterns of care document major shifts in treatment practices in the US and provide insight concerning the rate at which treatment changes are adopted at the community level.