TP53 mutations and the association with platinum resistance in high grade serous ovarian carcinoma.

OBJECTIVES: Alterations in the tumor suppressor TP53 gene are the most common mutations in high grade serous ovarian carcinoma. The impact of TP53 mutations on clinical outcomes and platinum resistance is controversial. We sought to evaluate the genomic profile of high grade serous ovarian carcinoma and explore the association of TP53 mutations with platinum resistance. METHODS: Next generation sequencing data was obtained from our institutional database for patients with high grade serous ovarian carcinoma undergoing primary treatment. Sequencing data, demographic, and clinical information was reviewed. The primary outcome analyzed was time to recurrence or refractory diagnosis. Associations between the primary outcome and different classification schemes for TP53 mutations (structural, functional, hot spot, pathogenicity scores, immunohistochemical staining patterns) were performed. RESULTS: 209 patients met inclusion criteria. TP53 mutations were the most common mutation. There were no differences in platinum response with TP53 hotspot mutations or high pathogenicity scores. Presence of TP53 gain-of-function mutations or measure of TP53 gain-of function activity were not associated with platinum resistance. Immunohistochemical staining patterns correlated with expected TP53 protein function and were not associated with platinum resistance. CONCLUSIONS: TP53 hotspot mutations or high pathogenicity scores were not associated with platinum resistance or refractory disease. Contrary to prior studies, TP53 gain-of-function mutations were not associated with platinum resistance. Estimation of TP53 gain-of-function effect using missense mutation phenotype scores was not associated with platinum resistance. The polymorphic nature of TP53 mutations may be too complex to demonstrate effect using simple models, or response to platinum therapy may be independent of initiating TP53 mutation.

Incidence of postoperative venous thromboembolism in patients with vulvar carcinoma undergoing vulvectomy with or without lymphadenectomy.

OBJECTIVES: The incidence of venous thromboembolism (VTE) following radical surgery for vulvar carcinoma remains poorly characterized, and recommendations for postoperative chemoprophylaxis are varied. Our objective was to assess the incidence of postoperative VTE in patients undergoing surgery for vulvar carcinoma and to determine if VTE incidence differs by radical vulvectomy with or without lymph node assessment. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients with a diagnosis of vulvar cancer undergoing radical vulvectomy with or without lymph node assessment from 2012 to 2020. Clinical characteristics and 30-day incidence of VTE as well as other postoperative outcomes were abstracted. Variables were compared using Chi-square test and Fischer's exact test, as well as Kruskal-Wallis and Wilcoxon rank sum tests where appropriate. RESULTS: A total of 1672 patients underwent radical vulvectomy for vulvar carcinoma. 11 patients (0.7%) experienced postoperative VTE within 30 days of surgery. The incidence of VTE was similar when radical vulvectomy was performed alone or with lymph node dissection by any method (p = 0.116). Longer operative times (p = 0.033) and greater postoperative length of stay (p = 0.001) were associated with increased risk of postoperative VTE. CONCLUSIONS: The incidence of postoperative VTE is low in patients undergoing radical vulvar surgery in this national cohort. Inguinofemoral lymph node dissection by any method does not appear to be a risk factor for VTE when compared to radical vulvectomy alone. Further research is needed to determine if extended VTE prophylaxis is beneficial in this population.

Bone health and osteoporosis screening in gynecologic cancer survivors.

Cancer treatment-induced bone loss is a known side effect of cancer therapy that increases the risk of osteoporosis and bone fracture. Women with gynecologic cancer are at increased risk of bone loss secondary to the combined effect of oophorectomy and adjuvant therapies. Data regarding bone loss in women with gynecologic cancers are overall lacking compared to other cancer populations. Consequently, guidelines for osteoporosis screening in women with cancer are largely based on data generated among non-gynecologic cancer survivors. This article reviews current available data of bone health in women with gynecologic cancer, summarizes best-available guidelines for screening for osteoporosis in women with cancer, and provides guidance for osteoporosis screening in women with gynecologic cancers based on best available evidence.

Postoperative venous thromboembolism in gynecologic oncology patients undergoing minimally invasive surgery: Does modality matter?

OBJECTIVES: Minimally invasive surgery (MIS) is increasingly utilized for gynecologic cancers. While incidence of venous thromboembolism (VTE) after MIS is low, some guidelines recommend extended chemoprophylaxis for these patients undergoing MIS. Our objectives were to determine incidence of postoperative VTE in patients undergoing MIS, evaluate differences in the incidence by MIS modality and assess the need for extended chemoprophylaxis. METHODS: We conducted a retrospective cohort study including all patients undergoing MIS (robot-assisted, multi-port laparoscopy, single-port laparoscopy) for gynecologic cancers between January 2014 and December 2018 at our institution. Demographic and perioperative variables were collected. Patients <18 years, with benign pathology, or on preoperative anticoagulation were excluded. Chi-square, Fisher's exact test, and one-way ANOVA were performed to determine risk factors related to VTE occurrence. RESULTS: We identified 806 patients who underwent MIS with median age 61. Most had Stage I disease (81.5%) and uterine cancer (81.5%). Five VTE events occurred within 90 days following surgery (0.6%). Incidence of 90-day VTE did not differ between MIS modalities (p = 0.6). Patients with longer OR times (p = 0.004) were more likely to experience VTE. Age, smoking status, BMI, type of cancer and stage were not significant risk factors for VTE. CONCLUSIONS: The incidence of postoperative VTE in patients with gynecologic cancers undergoing MIS is low and does not appear to differ by MIS modality. Given the very low incidence of postoperative VTE, extended chemoprophylaxis is unlikely to benefit patients with gynecologic malignancies undergoing MIS procedures.

Preoperative obstructive sleep apnea screening in gynecologic oncology patients.

BACKGROUND: Women with a gynecologic cancer tend to be older, obese, and postmenopausal, characteristics that are associated with an increased risk for obstructive sleep apnea. However, there is limited investigation regarding the condition's prevalence in this population or its impact on postoperative outcomes. In other surgical populations, patients with obstructive sleep apnea have been observed to be at increased risk for adverse postoperative events. OBJECTIVE: We sought to estimate the prevalence of obstructive sleep apnea among gynecologic oncology patients undergoing elective surgery and to investigate for a relationship between obstructive sleep apnea and postoperative outcomes. STUDY DESIGN: Patients referred to an academic gynecologic oncology practice were approached for enrollment in this prospective, observational study. Patients were considered eligible for study enrollment if they were scheduled for a nonemergent inpatient surgery and could provide informed consent. Enrolled patients were evaluated for a preexisting diagnosis of obstructive sleep apnea. Those without a prior diagnosis were screened using the validated, 4-item STOP questionnaire (ie, Snore loudly, daytime Tiredness, Observed apnea, elevated blood Pressure). All patients who screened positive for obstructive sleep apnea were referred for polysomnography. The primary outcome was the prevalence of women with obstructive sleep apnea or those who screened at high risk for the condition. Secondary outcomes examined the correlation between body mass index (kg/m2) with obstructive sleep apnea and assessed for a relationship between obstructive sleep apnea and postoperative outcomes. RESULTS: Over a 22-month accrual period, 383 eligible patients were consecutively approached to participate in the study. A cohort of 260 patients were enrolled. A total of 33/260 patients (13%) were identified as having a previous diagnosis of obstructive sleep apnea. An additional 66/260 (25%) screened at risk for the condition using the STOP questionnaire. Of the patients who screened positive, 8/66 (12%) completed polysomnography, all of whom (8/8 [100%]) were found to have obstructive sleep apnea. The prevalence of previously diagnosed obstructive sleep apnea or screening at risk for the condition increased as body mass index increased (P < .001). Women with untreated obstructive sleep apnea and those who screened at risk for the condition were found to have an increased risk for postoperative hypoxemia (odds ratio, 3.5; 95% confidence interval, 1.8-4.7; P = .011) and delayed return of bowel function (odds ratio, 2.1; 95% confidence interval, 1.3-4.5; P = .009). CONCLUSION: The prevalence of obstructive sleep apnea or screening at risk for the condition is high among women presenting for surgery with a gynecologic oncologist. Providers should consider evaluating a patient's risk for obstructive sleep apnea in the preoperative setting, especially when risk factors for the condition are present.

Maintaining sexual health throughout gynecologic cancer survivorship: A comprehensive review and clinical guide.

OBJECTIVE: The diagnosis and treatment of gynecologic cancer can cause short- and long-term negative effects on sexual health and quality of life (QoL). The aim of this article is to present a comprehensive overview of the sexual health concerns of gynecologic cancer survivors and discuss evidence-based treatment options for commonly encountered sexual health issues. METHODS: A comprehensive literature search of English language studies on sexual health in gynecologic cancer survivors and the treatment of sexual dysfunction was conducted in MEDLINE databases. Relevant data are presented in this review. Additionally, personal and institutional practices are incorporated where relevant. RESULTS: Sexual dysfunction is prevalent among gynecologic cancer survivors as a result of surgery, radiation, and chemotherapy-negatively impacting QoL. Many patients expect their healthcare providers to address sexual health concerns, but most have never discussed sex-related issues with their physician. Lubricants, moisturizers, and dilators are effective, simple, non-hormonal interventions that can alleviate the morbidity of vaginal atrophy, stenosis, and pain. Pelvic floor physical therapy can be an additional tool to address dyspareunia. Cognitive behavioral therapy has been shown to be beneficial to patients reporting problems with sexual interest, arousal, and orgasm. CONCLUSION: Oncology providers can make a significant impact on the QoL of gynecologic cancer survivors by addressing sexual health concerns. Simple strategies can be implemented into clinical practice to discuss and treat many sexual issues. Referral to specialized sexual health providers may be needed to address more complex problems.

Impact of histology and surgical approach on survival among women with early-stage, high-grade uterine cancer: An NRG Oncology/Gynecologic Oncology Group ancillary analysis.

OBJECTIVES: We sought to analyze the clinicopathologic features, recurrence patterns and survival outcomes of women with high-grade uterine cancer (UC) enrolled on The Gynecologic Oncology Group (GOG) LAP2 trial. METHODS: This is a post-hoc analysis of LAP-2 patients with grade 3 endometrioid adenocarcinoma (ENDO), uterine serous (USC), clear cell (CC) and carcinosarcoma (CS). Demographics, clinicopathologic features, and recurrence patterns, were compared by histology and surgical approach. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Of the 2600 patients enrolled in LAP-2, 753 patients had high-grade UC: 350 had ENDO, 289 had USC, 42 had CC and 72 had CS. Compared with the ENDO cohort, those with other high-grade subtypes were older (p<0.001) and were more likely to have positive peritoneal cytology (p<0.001), positive lymph nodes (p=0.05) and higher disease stage on final pathology (p<0.001). With a median follow-up time of 60months, compared to patients with ENDO, those with USC, CCC and CS subtypes had higher recurrence rates (p<0.001), extra-pelvic recurrences (p<0.001) and poorer PFS (p<0.001) and OS (p<0.001). Those diagnosed with USC and CS experienced the worst survival outcomes (p=0.003). Patterns of recurrence and survival were not different in those staged with LSC vs LAP. On multivariable analysis, age, stage, pelvic washings and Type II histology were independently and adversely associated with survival. CONCLUSIONS: Women with apparent early-stage, USC and CS histologies have poorer outcomes than women with grade 3 endometrioid adenocarcinoma. Patterns of recurrence and survival were not impacted by surgical approach.

Thrombocytosis is Predictive of Postoperative Pulmonary Embolism in Patients With Gynecologic Cancer.

OBJECTIVES: The prompt diagnosis of postoperative pulmonary embolism (PE) in gynecologic oncology patients is imperative, but the clinical presentation is nonspecific in this high-risk group. We sought to determine risk factors and clinical findings that may assist clinicians in diagnosing PE in the inpatient setting. METHODS: Radiology data were queried to identify patients with gynecologic cancer who had a postoperative PE evaluation with computed tomography pulmonary angiography (CT-PA). Patient clinical findings at the time of the PE evaluation were abstracted, and univariate and multivariate regression analyses were performed to identify predictors of PE. RESULTS: For 6 years, there were 2498 major gynecologic oncology surgical procedures performed at our institution. Within 14 days of surgery, 107 CT-PA studies were obtained with a positive study rate of 24.3%. In patients with and without PE, there was no significant difference noted for age, oxygen saturations, body mass index and heart rate. After controlling for stage, history of venous thromboembolism (VTE), heart rate, and oxygen saturation, platelet count (odds ratio, 1.26 per 50 counts increase; 95% confidence interval, 1.07-1.48; P = 0.006) and history of VTE (odds ratio, 17.1; 95% confidence interval, 1.77-Inf, P = 0.014) were identified as independent predictors of PE in the multivariate model. CONCLUSIONS: Although clinicians often use tachycardia and low oxygen saturation as triggers to order PE imaging studies, these signs have a very low specificity. Given the findings of our study, accounting for high platelet count and history of VTE increases the pretest probability of CT-PA study.

A new diagnostic test for endometrial cancer?: Cytology analysis of sonohysterography distention media.

OBJECTIVE: During saline-infused sonohysterography (SIS), the distension fluid is typically discarded. If cytology analysis could identify those patients with endometrial cancer, many women would be spared from further procedures. METHODS: Thirty consecutive patients with clinical stage I or II endometrial adenocarcinoma were prospectively recruited preoperatively. Saline-infused sonohysterography was performed by instilling 5 mL of saline, withdrawing and sending for analysis. Saline was reinfused until complete SIS images were obtained and sent separately for cytology. RESULTS: Of the 30 women enrolled, SIS was technically successful in 29. Demographics included mean age (60.5 ± 6.99 years), body mass index (35.55 ± 8.18 kg/m), endometrioid histology (76%), and grade (grade 1, 67%). Prestudy diagnostic method included biopsy (70%), dilatation and curettage (17%), and hysteroscopy (10%). Adequate cytology specimens were obtained in 66% of the 5 mL flushes and 72% of the complete SIS collections. Of adequate specimens, the sensitivities to detect endometrial cancer for the 5-mL, complete, and combined fluid samples were 26% (95% confidence interval, 9%-51%), 36% (17%-59%), and 42% (22%-63%). Sensitivity based on the whole study sample (N = 30) was 33% (17%-53%). Statistical significance was not found in the association between a positive test and age, body mass index, grade, diagnostic method, or volume instilled or aspirated. CONCLUSIONS: Most patients with early endometrial cancer can undergo SIS procedures with adequate cytology specimens obtained from distention media. However, the sensitivity is low, and refinements are necessary before utilizing as a diagnostic test. In cases with positive results, the patient may be able to avoid other costly and painful procedures.

Phase III Trial of Carboplatin and Paclitaxel Compared With Cisplatin and Paclitaxel in Patients With Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study.

Purpose: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population.Patients and Methods: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II).Results: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02).Conclusion: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Cervical Cancer.

Cervical cancer is the most common gynecologic cancer worldwide. Almost all are related to human papillomavirus exposure. Cervical cancer treatment is associated with significant morbidity that is likely to require support from palliative care teams. In these pearls on cervical cancer, we hope to inform providers about the common treatments and issues for cervical cancer patients. Treatment modalities include surgery for early-stage disease, radiation therapy for locally advanced disease, and pelvic exenteration, chemotherapy, or immunotherapy for recurrent disease. Cervical cancer causes pain and bleeding. Radiation can affect ovarian, urinary, and bowel function. Chemotherapy and immunotherapy are associated with fatigue and nausea. Fistulas between the vagina and bowel or bladder can occur due to cancer or to cancer treatments. Physical and emotional supportive care is important for women with cervical cancer.

Peripartum Blood Transfusion Among Rural Women in the United States.

OBJECTIVE: To evaluate the peripartum transfusion rates for rural women compared with urban women in the United States. METHODS: In this population-based retrospective cohort study, geocoded birth records from 2014 to 2016 from the National Center for Health Statistics were used to examine the rural-urban differences in blood transfusion among nulliparous women delivering singleton, vertex pregnancies at term. We compared transfusion rates across the counties on a continuum from urban to rural. We generated a multivariable logistic regression model controlling for age, race, nativity, education, insurance, prenatal care, maternal health, gestational age, intrapartum care, mode of delivery, peripartum factors, and county of delivery. RESULTS: Among 3,346,816 births, the transfusion rates based on maternal county of residence increased as the counties became more rural: large metropolitan-center (1.9/1,000 live births); large metropolitan-fringe (2.4); medium metropolitan (2.6); small metropolitan (2.6); micropolitan (4.5); and noncore rural (5.3). Rural women living and delivering in a rural county had more transfusions (8.5/1,000 live births) than women in more urban counties (2.5/1,000). After adjusting for key covariates, the odds of transfusion were higher among women living in micropolitan (adjusted odds ratio [aOR] 2.25, 95% CI 2.09-2.43) and noncore rural (aOR 2.59, 95% CI 2.38-2.81) counties when compared with women living in large metropolitan counties. County of delivery had a higher association with transfusion than resident county. After adding delivery county to the regression model, the association of transfusion and living in a micropolitan (aOR 1.39, 95% CI 1.19-1.63) or noncore rural (aOR 1.32, 95% CI 1.12-1.55) county diminished. CONCLUSION: The odds of blood transfusion were higher for women in rural areas. The results indicate that the rurality of the county where the birth occurred was associated with more transfusion. This may reflect differences in maternity and blood banking services in rural hospitals and warrants further study to identify opportunities for intervention.

Phase I trial of the treatment of high-risk endometrial cancer with concurrent weekly paclitaxel and cisplatin and whole abdominal radiation therapy: a Gynecologic Oncology Group study.

OBJECTIVES: To determine the maximum tolerated dose (MTD) and feasibility of weekly cisplatin and paclitaxel chemotherapy administered concurrently with whole abdominal radiation therapy (WART) in women with high-risk endometrial cancer. METHODS: Following surgery, patients with stage III-IV endometrial cancer (any histology) or with stage I-II serous or clear cell histology, and with largest residual disease

Sunitinib malate in the treatment of recurrent or persistent uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study.

PURPOSE: New agents are needed for patients with metastatic uterine leiomyosarcoma who progress after treatment with doxorubicin or gemcitabine-docetaxel. Agents targeting tumor vasculature have potential for activity in leiomyosarcoma. We aimed to assess the activity of sunitinib in patients with recurrent uterine leiomyosarcoma who had received one or two prior therapies by determining the frequency of patients who survived progression-free for at least 6 months or who achieved objective tumor response. We also aimed to characterize the toxicity of sunitinib and to estimate time-to-progression. PATIENTS AND METHODS: Eligible patients with uterine leiomyosarcoma were treated with sunitinib 50 mg by mouth daily for 4 weeks, with 2 weeks rest. Tumor response and progression-free status were assessed every 6 weeks. RESULTS: Twenty-three of 25 patients enrolled were evaluable for efficacy (two wrong histologies). The median number of cycles was one. Two of 23 patients achieved a partial response (8.7%, 90% two-sided, binomial confidence interval (CI) 1.6-24.9%). Four patients remained progression-free at 6 months (17.4%, 90% two-sided, binomial confidence interval 6.2-35.5%). Toxicities included: grade 3 neutropenia (17.4%); grade 3 thrombocytopenia (13%); grade 3 anemia (17.4%); grades 3-4 lymphopenia (8.7%); grades 3-4 fatigue (30%); grade 3 vomiting/diarrhea (21.7%); skin rash/hand-foot syndrome, grade 2 (13%), grade 3 (4.3%); hypertension, grade 2 (39%), grade 3 (4.3%); grade 2 decrease in cardiac ejection fraction (4.3%), and grade 3 thrombosis (4.3%) Median progression-free survival (PFS) was 1.5 months. CONCLUSION: Sunitinib fails to achieve sufficient objective response or sustained disease stabilization as second- or third-line treatment for uterine leiomyosarcoma.

A protocol of dual prophylaxis for venous thromboembolism prevention in gynecologic cancer patients.

OBJECTIVE: To evaluate a quality improvement protocol for venous thromboembolism prevention in postoperative gynecologic cancer patients. METHODS: On January 1, 2006, we initiated a universal protocol of dual prophylaxis with sequential compression devices and three times daily heparin (or daily low molecular weight heparin) until discharge in gynecologic cancer patients having major surgery. Patients with both malignancy and age over 60 years (or history of prior clot) were discharged on 2 weeks of anticoagulant. Before January 2006, all patients were given sequential compression devices starting before the induction of anesthesia, continuing until discharge from the hospital. Records of gynecologic cancer service patients admitted in 2005 and 2006 were reviewed, excluding patients with a history of heparin-induced thrombocytopenia or those admitted on an anticoagulant. Any pulmonary embolism or deep vein thrombosis diagnosed within 6 weeks of surgery was identified. We performed chi2 and Wilcoxon rank sum tests as well as multivariable regression analysis for confounders. RESULTS: Six of the 311 women meeting inclusion criteria in 2006 (1.9%) and 19 of 294 (6.5%) in 2005 had venous thromboembolism (odds ratio 0.33, 95% confidence interval 0.12-0.88, multivariable analysis adjusting for baseline differences between the groups). Heparin was given to 98.1% of patients in the hospital in 2006, and 91.1% of those meeting high-risk criteria were discharged on an anticoagulant. No differences in major bleeding complications were seen between years. CONCLUSION: A protocol of dual prophylaxis with prolonged prophylaxis in high-risk patients was successfully implemented and was associated with a significant reduction in the rate of venous thromboembolism without increasing bleeding complications. LEVEL OF EVIDENCE: II.

Sonohysterography and endometrial cancer: incidence and functional viability of disseminated malignant cells.

OBJECTIVE: The purpose of this study was to evaluate sonohysterography in patients with endometrial cancer and to determine whether (1) transtubal fluid spill occurs during routine sonohysterography, (2) a critical infusion volume for spill exists, or (3) disseminated cancer cells demonstrate viability. STUDY DESIGN: At laparotomy, sonohysterography was performed on 16 patients with endometrial adenocarcinoma. Volumes at which tubal spill occurred were recorded. Collected specimens were processed and incubated. After evaluation for viable cells, cytologic analysis was undertaken. RESULTS: The median volume that was required for adequate sonohysterography was 8.5 mL. Five patients (31%) had transtubal spill. With an additional saline solution flush, the median total volume for a spill was 20.5 mL. Two patients (12.5%) had viable benign cells that were cultured after routine sonohysterography. One patient (6%) had nonviable carcinoma cells that were identified. CONCLUSION: Transtubal spill occurs during sonohysterography. No critical spill volume was identified. A highly diagnostic tool when abnormal bleeding is evaluated, sonohysterography has a low probability of cancer cell dissemination.

Frequency-dependent complex modulus of the uterus: preliminary results.

The frequency-dependent complex moduli of human uterine tissue have been characterized. Quantification of the modulus is required for developing uterine ultrasound elastography as a viable imaging modality for diagnosing and monitoring causes for abnormal uterine bleeding and enlargement, as well assessing the integrity of uterine and cervical tissue. The complex modulus was measured in samples from hysterectomies of 24 patients ranging in age from 31 to 79 years. Measurements were done under small compressions of either 1 or 2%, at low pre-compression values (either 1 or 2%), and over a frequency range of 0.1-100 Hz. Modulus values of cervical tissue monotonically increased from approximately 30-90 kPa over the frequency range. Normal uterine tissue possessed modulus values over the same range, while leiomyomas, or uterine fibroids, exhibited values ranging from approximately 60-220 kPa.

Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. PATIENTS AND METHODS: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). RESULTS: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02). CONCLUSION: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.

Use of a bupivacaine continuous wound infusion system in gynecologic oncology: a randomized trial.

OBJECTIVE: The aim of the current study was to evaluate the safety and efficacy of a widely available bupivacaine continuous wound infusion system in gynecologic oncology patients undergoing laparotomy. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was performed. After closure of the fascia, flexible soaker catheters were placed in the deep subcutaneous space. The infusion pump was filled with 290 mL of either 0.5% bupivacaine or normal saline, to infuse over 72 hours. Daily assessments of pain scores utilized the Wisconsin Brief Pain Inventory. All patients received intravenous narcotics via patient-controlled devices. RESULTS: Eighty surgeries were evaluated in a total of 79 women (40 per arm). Mean age was 56 years, with 79% having invasive gynecologic pathology. The two groups were not significantly different in terms of type of surgery, length of incision, estimated blood loss, operative time, or medical history. Postoperative outcomes, including wound toxicity, time to flatus, and hospital stay, did not differ. Study patients averaged 75 mg intravenously and 107 mg total narcotic use (morphine equivalent), whereas controls averaged 60 mg intravenously and 86 mg total (P = .40 intravenously; P = .25 total). Acetaminophen and intravenous ketorolac consumption were equal between groups. The Brief Pain Inventory score for "current pain" was 2.84 for bupivacaine patients and 3.14 for controls (P = .46; least = 0, most = 10). There was no individual postoperative day when "current pain" BPI scores differed. "Worst pain" and "least pain" Brief Pain Inventory scores showed similar results. CONCLUSION: The results suggest that although the continuous infusion system seems safe, it is not efficacious in this patient population.