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The original vision of the field of gynecologic oncology was to establish a multidisciplinary approach to the management of patients with gynecologic cancers. Fifty years later, scientific advances have markedly changed the overall practice of gynecologic oncology, but the profession continues to struggle to define its value-financial and otherwise. These issues were examined in full at the Society of Gynecologic Oncology (SGO) Future of the Profession Summit and the purpose of this document is to summarize the discussion, share the group's perceived strengths, weaknesses, opportunities, and threats (SWOT) for gynecologic oncologists, further educate members and others within the patient care team about the unique role of gynecologic oncologists, and plan future steps in the short- and long- term to preserve the subspecialty's critical mission of providing comprehensive, longitudinal care for people with gynecologic cancers., Competing Interests: Declaration of Competing Interest Dr. Huh reports personal fees from AstraZeneca, Roche, SeaGen and Inovio outside the submitted work. Dr. Hardesty reports personal fees from Immunogen, Axiom, GSK, Takeda, AZ-Mereck, and Intuitive outside the submitted work. Dr. Prendergast reports personal fees from Heron Therapeutics and AstraZeneca outside the submitted work. Dr. Rimel reports being an Advisory Board Participant for GSK, Merck, and Immunogen and a consultant for Deep 6AI. Dr. Shahin reports grants and personal fees from GSK, AstraZeneca, and Merck, personal fees from Eisai, Immunogen, and GenMab during the conduct of the study. All other authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: High-risk human papillomavirus (hrHPV) testing is utilized in primary cervical cancer screening, generally along with cytology, to triage abnormalities to colposcopy. Most screening-based hrHPV testing involves pooled detection of any hrHPV or of HPV16/18. Cervical neoplasia progression risks based on extended hrHPV genotyping-particularly non-16/18 hrHPV types-are not well characterized. HPV genotype-specific incidence of high-grade cervical intraepithelial neoplasia or more severe (CIN2+) following an abnormal screening result was examined., Methods: We assessed a US-based prospective, multiracial, clinical cohort of 343 colposcopy patients with normal histology (n = 226) or CIN1 (n = 117). Baseline cervical samples underwent HPV DNA genotyping, and participants were followed up to 5 years. Genotype-specific CIN2+ incidence rates (IR) were estimated with accelerated failure time models. Five-year CIN2+ risks were estimated nonparametrically for hierarchical hrHPV risk groups (HPV16; else HPV18/45; else HPV31/33/35/52/58; else HPV39/51/56/59/68)., Results: At enrollment, median participant age was 30.1 years; most (63%) were hrHPV-positive. Over follow-up, 24 participants progressed to CIN2+ (7.0%). CIN2+ IR among hrHPV-positive participants was 3.4/1,000 person-months. CIN2+ IRs were highest for HPV16 (8.3), HPV33 (7.8), and HPV58 (4.9). Five-year CIN2+ risk was higher for HPV16 (0.34) compared with HPV18/45 (0.12), HPV31/33/35/52/58 (0.12), and HPV39/51/56/59/68 (0.16) (P = 0.05)., Conclusions: Non-16/18 hrHPV types are associated with differential CIN2+ progression rates. HPV16, 33, and 58 exhibited the highest rates over 5 years. HPV risk groups warrant further investigation in diverse US populations., Impact: These novel data assessing extended HPV genotyping in a diverse clinical cohort can inform future directions to improve screening practices in the general population., (©2022 American Association for Cancer Research.)

Uterine fibroids (leiomyomas), the most common benign tumors in women of reproductive age, are a frequent cause of abnormal vaginal bleeding and other reproductive complaints among women. This study investigates the feasibility of using histotripsy, a non-invasive, non-thermal focused ultrasound ablation method, to ablate uterine fibroids. Human fibroid samples (n = 16) were harvested after hysterectomy or myomectomy procedures at Carilion Memorial Hospital. Histotripsy was applied to ex vivo fibroids in two sets of experiments using a 700-kHz clinical transducer to apply multicycle histotripsy pulses and a prototype 500-kHz transducer to apply single-cycle histotripsy pulses. Ultrasound imaging was used for real-time treatment monitoring, and post-treatment ablation was quantified histologically using hematoxylin and eosin and Masson trichrome stains. Results revealed that multicycle histotripsy generated diffuse cavitation in targeted fibroids, with minimal cellular ablative changes after treatment with 2000 pulses/point. Single-cycle pulsing generated well-confined bubble clouds with evidence of early coagulative necrosis on histological assessment in samples treated with 2000 pulses/point, near-complete ablation in samples treated with 4000 pulses/point and complete tissue destruction in samples treated with 10,000 pulses/point. This study illustrates that histotripsy is capable of fibroid ablation under certain pulsing parameters and warrants further investigation as an improved non-invasive ablation method for the treatment of leiomyomas., Competing Interests: Conflict of interest disclosure E.V. has financial ties and research collaborations with HistoSonics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited., Methods: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race., Results: Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36)., Conclusions: While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

Objective: Enhanced Recovery After Surgery (ERAS) protocols are designed to mitigate the physiologic stress response created by surgery, to decrease the time to resumption of daily activities, and to improve overall recovery. This study aims to investigate postoperative recovery outcomes following gynecologic surgery before and after implementation of an ERAS protocol., Methods: A retrospective chart review was performed of patients undergoing elective laparotomy at a major academic center following implementation of an ERAS protocol (11/4/2014-7/27/2016) with comparison to a historical cohort (6/23/2013-9/30/2014). The primary outcome was length of hospital stay. Secondary outcomes included surgical variables, time to recovery of baseline function, opioid usage, pain scores, and complication rates. Statistical analyses were performed using Wilcoxon rank sum, Fisher's exact, and chi squared tests., Results: One hundred and thirty-three women on the ERAS protocol who underwent elective laparotomy were compared with 121 historical controls. There was no difference in length of stay between cohorts (median 4 days; P = 0.71). ERAS participants had lower intraoperative (45 vs 75 oral morphine equivalents; P < 0.0001) and postoperative (45 vs 154 oral morphine equivalents; P < 0.0001) opioid use. ERAS patients reported lower maximum pain scores in the post-anesthesia care unit (three vs six; P < 0.0001) and on postoperative day 1 (four vs six; P = 0.002). There was no statistically significant difference in complication or readmission rates., Conclusions: ERAS protocol implementation was associated with decreased intraoperative and postoperative opioid use and improved pain scores without significant changes in length of stay or complication rates., Competing Interests: Competing interests: GB reports grants from National Institutes of Health, during the conduct of the study. FV reports personal fees from American Board of Obstetrics and Gynecology, personal fees from Elsevier, outside the submitted work. JMT reports other from Merck Advisory Council, other from Ethicon Advisory Council, other from Medtronic, other from Edwards LifeScience, outside the submitted work. LH reports grants from Astra Zeneca, grants from Tesaro, other from Bioventus, outside the submitted work., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The primary aim of this study was to pilot the use of an objective measurement technique to prospectively evaluate the incidence of lower extremity lymphedema (LEL) after minimally invasive staging surgery for endometrial cancer. Secondary objectives included observation of changes in lower extremity function and quality of life in this patient population., Methods: A prospective evaluation of LEL was performed in 97 women who underwent minimally invasive staging surgery for endometrial cancer using comparative circumferential volume measurements. Postoperative changes in lower extremity function and global quality of life were also assessed using patient-reported outcome measures., Results: Ninety-seven patients were included for lymphedema analysis. The rate of LEL was 25% at 4-6 weeks, 19% at 6-9 months, and 27% at 12-18 months postoperatively. The presence of LEL was associated with a significant worsening from baseline Lower Extremity Functional Scale (LEFS) scores at 4-6 weeks (-27.0% vs -3.7%, p = 0.02) and 6-9 months (-13.0% vs 0%, p = 0.01). LEL was not associated with a change in patient-reported global quality of life., Conclusions: Up to one in four women experience lymphedema following surgical staging for endometrial cancer, and its presence is associated with diminished lower extremity function. Larger, prospective trials using the objective methodology piloted in this study should better clarify risk factors and long-term outcomes of this morbidity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow-up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine-phosphate-guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non-regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time-point), adjusting for age, race, high-risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0-64.4 years), 39% were African-American, and 11% were current smokers. Most participants were hrHPV-positive at enrollment (80.5%). Over one-third of cases regressed (n = 53, 35.1%). Median time-to-regression was 12.6 months (range: 4.5-24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23-0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65-0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening., (© 2018 UICC.)

Objective: To evaluate the perceptions of fellowship program directors of incoming clinical fellows for subspecialty training., Methods: A validated survey by the American College of Surgeons was modified and distributed to all fellowship program directors in four subspecialties within obstetrics and gynecology: female pelvic medicine and reconstructive surgery, gynecologic oncology, maternal-fetal medicine, and reproductive endocrinology-infertility. The 59-item survey explored five domains concerning preparedness for fellowship: professionalism, independent practice, psychomotor ability, clinical evaluation, and academic scholarship. A Likert scale with five responses was used and tailored to each subspecialty. Standard statistical methods were used to compare responses between subspecialties and to analyze data within each subspecialty individually., Results: One hundred thirty directors completed the survey, for a response rate of 60%. In the domain of professionalism, more than 88% of participants stated that incoming fellows had appropriate interactions with faculty and staff. Scores in this domain were lower for gynecologic oncology respondents (P=.046). Responses concerning independent practice of surgical procedures (hysterectomy, pelvic reconstruction, and minimally invasive) were overwhelmingly negative. Only 20% of first-year fellows were able to independently perform a vaginal hysterectomy, 46% an abdominal hysterectomy, and 34% basic hysteroscopic procedures. Appropriate postoperative care (63%) and management of the critically ill patient (71%) were rated adequate for all subspecialties., Conclusion: Graduating residents may be underprepared for advanced subspecialty training, necessitating an evaluation of the current structure of resident and fellow curriculum., Level of Evidence: III.

To study anxiety levels in first-year medical students taking gross anatomy. Thirty medical students per year, for 2 years, completed the Beck Anxiety Inventory (BAI) 10 times during a 13-week gross anatomy course. In addition, behavioral observations were made by a psychiatrist during gross anatomy for demonstrations of assertive, destructive, neutral, or passive behavior. Additional qualitative outcome measures were group exit interviews with the faculty and students. The mean BAI for all 60 students per year, for 2 years, was 2.19 ± 3.76, 93% of the scores indicated minimal anxiety, and 89% of BAI values were less than five which confirmed a minimal level of anxiety. The low level of reported BAI contrasted sharply with verbal reports by the same students and face-to-face exit interviews with the psychiatrist. Symptoms of stress and anxiety emerged as a result of these conversations. The high levels of subjective stress and anxiety revealed by the interviews were unknown to the gross anatomy faculty. The low scores of students on the BAI's stand in sharp contrast to the BAI's reported for medical students in other published reports. Although it is possible that our students were truthfully devoid of anxiety, it is more likely that our students were denying even minimal anxiety levels. There have been reports that medical students feel that admitting stress, depression, or anxiety put their competitiveness for a residency at risk. We conclude that students may be in frank denial of experiencing anxiety and, if so, this behavior is not conducive to good mental health., (© 2014 Wiley Periodicals, Inc.)

Purpose: For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women., Methods: Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status., Results: Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs., Conclusions: Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

Objectives: (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures., Methods: A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, >1 hospitalization in the last 30 days, >1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤3 days., Results: One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p=0.003), >1 hospitalization in the last 30 days (p<0.001), ICU admission in the last 30 days (p=0.005), dying in acute care setting (p=0.01), admitted to hospice ≤3 days (p=0.02). EOL discussion as outpatient was associated with fewer patients hospitalized >1 in the last 30days of life (p<0.001)., Conclusions: End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Our goals were to (1) define a set of descriptive health states related to adverse events (AEs) associated with gynecologic cancer treatment with radical surgery and chemoradiation and (2) derive a set of quality of life-related utility scores corresponding to these health states., Methods: We developed a list of health states for grade 3/4 AEs related to gynecologic cancer treatment. Using the visual analog scale score and time trade-off (TTO) methods, valuation of each health state was obtained through interviews of 60 volunteers (15 cervical cancer survivors treated with surgery and/or chemoradiation and 45 women without a cancer diagnosis). Health states were ranked by mean/median TTO scores. Wilcoxon rank sum test was used to compare central tendencies related to patient and volunteer characteristics., Results: Patients and volunteers agreed on their preference rankings, with highest preference given to infection (median TTO = 1.0) and thrombosis (median TTO = 0.97). Lowest preference was assigned to radiation proctitis (median TTO = 0.87) and gastrointestinal fistula formation (median TTO = 0.83). Utility scores for the majority of health states were not significantly associated with age, race, parity, patient or volunteer status, history of abnormal Pap smear, stage of cervical cancer diagnosis, or personal experience of a serious treatment-related AE., Conclusions: This study helps establish preferences and quality-of-life utility scores for health states related to toxicities from surgery, radiation, and chemotherapy for gynecologic cancer treatment. Such information can be used to inform medical decision making/counseling and may be applied to future comparative effectiveness models in which radical surgery and/or chemoradiation are considered.

Objectives: To determine utility scores for health states relevant to the treatment of early-stage, high-risk cervical cancer., Methods: Seven descriptive health states incorporating the physical and emotional aspects of medical treatment, recovery, and prognosis were developed. Forty-five female volunteers valuated each health state using the visual analogue score (VAS) and time trade off (TTO) methods. Treatment options were ranked by mean and median TTO scores. The 95% confidence intervals were calculated to determine the statistical significance of ranking preferences. The Wilcoxon rank-sum test was used to compare central tendencies related to age, race, parity, and subject history of abnormal cervical cytology., Results: VAS and TTO scores were highly correlated. Volunteers ranked minimally invasive radical hysterectomy with low-risk features as most preferred (mean TTO = 0.96; median TTO = 1.00) and aborted radical hysterectomy followed by chemoradiation as least preferred (mean TTO = 0.69; median TTO = 0.83). Health states that included radical surgery were ranked higher than those that included chemoradiation, either in the adjuvant or primary setting. When survival was comparable, volunteers rated radical hysterectomy with high-risk pathology followed by adjuvant chemoradiation (mean TTO = 0.78; median TTO = 0.92; 95% CI: 0.69-0.87) similarly to chemoradiation alone (mean TTO = 0.76; median TTO 0.90; 95% CI: 0.66-0.86; p = NS). Utility scores for the majority of health states were not significantly associated with age, race, parity, or subject history of abnormal cervical cytology., Conclusion: Subjects consistently preferred surgical excision to treat early-stage, high-risk cervical cancer and chose a minimally invasive approach. Such utility scores can be used to incorporate quality-of-life effects into comparative-effectiveness models for cervical cancer., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Reports of female reproductive tract neoplasia are infrequent in great apes., Methods: Two captive-born, female western lowland gorillas (Gorilla gorilla gorilla) housed at the North Carolina Zoological Park were diagnosed with reproductive neoplasia., Results: The first gorilla had uterine endometrial thickening and uterine fibroids diagnosed during a routine annual examination. Subsequently, the animal underwent several uterine curettage procedures in an attempt to debulk the uterine mass. Biopsy results indicated uterine adenocarcinoma. The animal was treated with an ovariohysterectomy followed by a combination of megestrol acetate and medroxyprogesterone acetate. The second gorilla was diagnosed with squamous cell carcinoma of the vagina, cervix, and uterus after presenting for intermittent vaginal bleeding of 1-month duration. This animal underwent palliative radiation therapy, receiving two rounds of radiation treatment 8 weeks apart., Conclusions: The following report describes the diagnosis and management of the two cases., (© 2010 John Wiley & Sons A/S.)

Objective: The objective of this study was to compare tolerance of treatment of ovarian cancer patients > or = 70 years to those < or =55., Materials and Methods: A retrospective review of all data relevant to comparison of clinical course in 31 women > or =70 years (Study Group) and 44 women < or =55 (Control Group), who received primary therapy for ovarian cancer between 1996 and 2001 was performed. The tolerance of the entire treatment plan was then compared using SAS 8.1 (Gary, IN), chi(2) test with Yates correction or Fischer's exact test, and the Student t test as appropriate., Results: The mean age for the study group was 73, and for the control group 49. Statistically significant differences were as follows: the study group had a lower hemoglobin and serum albumin, higher performance status postoperatively, and received lower carboplatin dose and dose intensity. The groups were similar in stage at presentation, medical comorbidities, estimated blood loss, optimal cytoreduction rates, dose intensity of paclitaxel, completed number of chemotherapy cycles, time intervals from surgery to completion of therapy, and posttreatment performance status and nutritional status. The rate of grade 3 and 4 toxicities was low in both groups, and did not hinder delivery of therapeutic dose of chemotherapy., Conclusion: Women in the study group tolerated aggressive cytoreductive surgery and therapeutic doses of chemotherapy, despite poorer nutritional status and general health at time of diagnosis. Although older women are more likely to have chemotherapy dose reduction, the treatment remained within the recommended standard dosage.

Background: It is clear that morbid obesity presents a serious risk to women undergoing major intra-abdominal gynecologic surgery. Unfortunately, many gynecologic malignancies and benign conditions are best treated surgically. Thus, the gynecologic surgeon must choose an incision that permits adequate exposure with acceptables rates of complications. Panniculectomy as an approach to the peritoneal cavity is becoming increasingly popular. Recent reports suggest that panniculectomy is reasonably straightforward to perform, provides adequate exposure and is associated with an acceptable rate of manageable complications. In these circumstances, panniculectomy is not a cosmetic procedure, but medically necessary to perform indicated major gynecologic intra-abdominal surgery., Aims: To present our experience with panniculectomy in morbidly obese women undergoing major intra-abdominal surgery on a gynecologic oncology service., Methods: The medical records of 48 morbidly obese women (Quetelet Index > 40 kg/m2) with a large dependent pannus who underwent major intra-abdominal surgery via a panniculectomy between May 1990 and October 1999 were reviewed. Data regarding demographics, concomitant medical conditions, operative indications and results, and postoperative outcomes were abstracted for analysis., Results: The mean age was 54.9 years, the mean body mass was 130.2 kg, the mean height was 1.63 m and the mean Quetelet Index was 49.3 kg/m2. The mean operating time was 188 min and the mean estimated blood loss was 615 ml. Two patients suffered intraoperative urologic injuries which were repaired without sequelae; there were no bowel, vascular or neurologic injuries. Eighteen patients had a suprafascial wound breakdown (3 complete and 15 superficial) and 15 patients developed an infection. There were no documented deep venous thromboses, pulmonary emboli or fascial dehiscences. Two patients died in the postoperative period; one from a myocardial infarction on Day 2 and one from overwhelming sepsis on Day 76., Conclusions: Morbid obesity is associated with substantial operative and postoperative risks. Panniculectomy provides operative exposure with acceptable risks of complications.

Background: To evaluate the efficacy of a miniaturized portable transcutaneous electrical nerve stimulation (TENS) unit (ReliefBand) as an adjunct to standard antiemetic therapy for controlling nausea and vomiting induced by cisplatin-based chemotherapy in gynecologic oncology patients., Methods: Forty-two patients were enrolled in a randomized, double-blind, placebo-controlled parallel-subjects trial with a follow-up crossover trial. All patients received a standardized antiemetic protocol, then wore the ReliefBand continuously for 7 days., Results: Thirty-two patients were evaluable for the parallel-subjects component, 16 in each group. The percentage of patients with absent or minimal nausea was 59% overall, which was similar to that for both the active (56%) and placebo (62%) groups. The incidence and severity of nausea and vomiting was similar for each group. Eighteen patients completed two consecutive cycles and were evaluable for the crossover component. The average age of the crossover patients and their dose intensity were comparable with those of the overall study population (56.3 versus 58.6 years and 22.7 versus 22.7 mg/m2/week, respectively). The percentage of cycles with absent or minimal nausea was 47% overall, which was similar to that of the active (50%) and placebo (44%) cycles. However, the severity of nausea was significantly lower in the active cycles during days 2 to 4. Patients averaged less than one episode of vomiting daily in each cycle., Conclusions: The ReliefBand is an effective adjunct to standard antiemetic agents for controlling nausea induced by cisplatin-based chemotherapy in gynecologic oncology patients.

Background: We reviewed the outcomes of panniculectomy and supraumbilical vertical midline incisions in morbidly obese women undergoing gynecologic operations., Study Design: Medical records were reviewed for 62 morbidly obese women with a large dependent pannus who underwent gynecologic operations on the Gynecologic Oncology Service at the State University of New York at Stony Brook between May 1990 and July 1997. Thirty-five patients underwent panniculectomy and 27 had a supraumbilical vertical midline incision, forming the study groups. The patient charts were abstracted for demographic, perioperative, and postoperative data., Results: For the entire study population, the average age was 56 years, the mean body mass was 128.6 kg, and the mean Quetelet Index was 48.3 kg/m2. The mean operative time and estimated blood loss were similar for both groups. Eight percent of the patients had urologic injuries, evenly distributed between the groups. Postoperative infections, wound breakdowns, and hospital stay were greater for the panniculectomy group than for the supraumbilical vertical midline incision group (p < 0.05). Uniform use of subcutaneous closed-suction drains (since 1995) was associated with a significant reduction in the incidence of wound breakdowns and a shorter hospital stay in the panniculectomy group., Conclusions: Panniculectomy and supraumbilical vertical midline incision provide reasonable peritoneal access with acceptable rates of postoperative complications for morbidly obese women undergoing gynecologic operations.

Objective: The objective of the study was to determine the response rate and associated toxicity of 5-fluorouracil and high-dose leucovorin in patients with recurrent adenocarcinoma of the cervix., Methods: Between December 1993 and October 1995, 53 patients with recurrent adenocarcinoma of the cervix were entered into a Phase II trial utilizing 200 mg/m2 of intravenous (iv) leucovorin with 370 mg/m2 of i.v. 5-fluorouracil daily for 5 days every 4 weeks for two courses, then every 5 weeks until disease progression. Eligibility criteria were a Gynecologic Oncology Group (GOG) performance status of 0-2, adequate bone marrow reserve, adequate liver function with bilirubin < or = 1.5 x normal and SGOT and alkaline phosphatase < or = 3 x normal, serum creatinine < or = 2 mg%, and signed informed consent. Standard GOG toxicity and response criteria were employed., Results: Six patients were ineligible because of wrong cell type (N = 3), insufficient pathology materials (N = 2), or a second primary (N = 1); therefore 45 were evaluable for toxicity. Two patients did not have adequate response assessment; thus, 43 were evaluable for response. The median age was 50 (range, 28-79). Prior chemotherapy had been administered to 16 patients and radiotherapy to 40 patients. The median number of courses delivered was three (range, 1-22). The site of evaluable disease was pelvic in 25 patients and extra-pelvic in 18. Grade 3 neutropenia was seen in 17.8% (8/45) patients and 35.5% (16/45) developed grade 4 neutropenia. Grade 3 or 4 thrombocytopenia was seen in 1 patient each (2.1%). Grade 3 gastrointestinal toxicity with nausea, vomiting, diarrhea, dehydration, or stomatitis was of grade 3 severity in 11.1% (5/45) and grade 4 in 6.7% (3/45). There were four partial responses and two complete responses for an overall response rate of 14%. The duration of the complete responses was 17.3 and 8.8+ months. None of the patients with responses had previously received chemotherapy., Conclusion: The schedule of 5-fluorouracil and leucovorin exhibits moderate activity in patients with previously treated adenocarcinoma of the cervix and should be considered for a trial in chemotherapy-naive patients.

Although the clinicopathologic features of primary peritoneal carcinoma (PPC) in women are relatively well defined, the molecular pathogenesis of the disease has not been examined. The object of this study was to assess the biological significance of p53 alterations in PPC. Twenty-nine PPCs studied for p53 protein accumulation with monoclonal antibody DO-7 consisted of 26 serous carcinomas, one clear cell carcinoma, one tumor with endometrioid features, and one malignant mixed müllerian tumor. P53 was overexpressed in 83% of all PPCs and in 81% of the serous PPCs. Among eight immunopositive tumors with at least two distinct anatomic sites sampled, six tumors showed concordance, whereas two tumors showed discordance for p53 immunopositivity. The latter two tumors support the concept of a multifocal origin of PPC. This is the first report to suggest that loss of p53 function plays an important role in the development of PPC and might contribute to the poor prognosis of this disease. Parallels to serous papillary carcinomas of the uterus and ovary are discussed.

Objective: The objective of this study was to assess the clinical utility of a pretreatment barium enema in women with endometrial cancer., Methods: The medical records of 249 patients with endometrial cancer who underwent a pretreatment barium enema were retrospectively reviewed. The patients' charts were abstracted for demographic information, stage, grade, histology, current disease status, and barium enema results., Results: The pretreatment barium enema was normal in 122 (49%) patients. Diverticulosis was the most common abnormality, reported in 112 (45%) patients. Apparent intraluminal abnormalities were found in 15 (6.0%) patients. Each of these patients underwent colonoscopy prior to treatment for endometrial carcinoma. During colonoscopy, benign colonic polyps were removed from 11 (4.4%) patients. Primary colonic adenocarcinoma was discovered in polypoid lesions removed from 2 (0.8%) patients. Significant luminal narrowing from extrinsic lesions was noted in 2 (0.8%) patients, one at the rectosigmoid and the other at the cecum. No patient was found to have colonic mucosal involvement by endometrial cancer., Conclusion: The results of this study do not justify routine pretreatment barium enema to assess the colonic mucosa for metastatic involvement by endometrial cancer or as a screening tool for colorectal cancer in women with endometrial cancer.

Twenty-eight patients with advanced, persistent or recurrent leiomyosarcoma of the uterus not previously exposed to cytotoxic drugs were entered into a study of single-agent intravenous etoposide 100 mg/m2 daily for 3 days every 3 weeks. No complete or partial responses were observed. Thirteen patients demonstrated stable disease, while 15 exhibited increasing disease. Median progression-free interval was 2.1 months, median survival 9.2+ months. The most frequent and severe adverse effects were the result of myelosuppression and manifested primarily as leukopenia and neutropenia. Based on the absence of activity, no further study of intravenous etoposide in leiomyosarcoma of the uterus at the dose and schedule tested is planned.

A case of primary retroperitoneal mucinous cystadenocarcinoma of low malignant potential in the presence of normal ovaries is reported. The precise etiology of these neoplasms has not been defined; however, they may arise from heterotopic ovarian tissue, monodermal teratomas, embryonal urogenital remnants, intestinal duplication, or coelomic metaplasia. Although minimal data exist to define the appropriate management, it seems reasonable to extrapolate from the treatment of analogous ovarian neoplasms.

Previous clinical investigations using interferons (IFNs) have shown activity against epithelial ovarian cancer. The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) IFN-alpha 2b which could be administered in combination with intravenous (iv) cis-platinum plus cyclophosphamide chemotherapy. After comprehensive surgical staging and maximal cytoreduction, previously untreated patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels. IFN-alpha 2b (5-30 x 10(6) units) was administered ip on Day 1 (+/- Day 8). cis-Platinum (75 mg/m2) plus cyclophosphamide (750 mg/m2) were administered iv on Day 2 with prophylactic hydration and anti-emetics. Courses were repeated every 3 weeks for 8 cycles. Adverse effects were recorded using standard Gynecologic Oncology Group toxicity scales. Fifteen patients with mean age 56 years (range 43-73) were entered and received a combined total of 100 treatment cycles. Catheter-related complications occurred in 8 patients, and in three cases lead to catheter removal and discontinuation of ip therapy. Two patients experienced grade 2-3 nephrotoxicity and 1 experienced grade 2 peripheral neuropathy. There was a single episode of chemical peritonitis. Myelosuppression was the dose-limiting toxicity with grade 3-4 leukopenia complicating 6, 5, 12, 11, and 17 cycles at dose levels 1-5, respectively. No patient completed planned treatment without interruption or dose reduction. Planned cis-platinum dose intensity was most compromised at the fifth IFN-alpha 2b dose level. The maximum tolerated dose of IFN-alpha 2b was determined to be 20 x 10(6) units repeated on Days 1 and 8 of this 21-day cis-platinum plus cyclophosphamide chemotherapy cycle.

Objective: The purpose of this study was to determine and compare the expression of the alpha 2-, alpha 3-, alpha 4- and alpha 5-subunits of the beta 1-family of integrins in both the normal and the carcinomatous cervix., Study Design: A total of 22 solid tissue specimens (18 cancer and 4 normal) were analyzed immunohistochemically. The double-stain technique used an avidin-biotin complex kit to identify the various integrins and alkaline phosphatase-anti-alkaline phosphatase kit to identify the epithelial cells. Staining intensity, the main outcome measured, was graded as absent, weak, moderate, or strong. Statistical analysis was performed with the Wilcoxon rank sum test for nonparametric data., Results: The alpha 2- and alpha 3-integrins stained the normal cervix epithelium more intensely than the stroma (p = 0.03). The alpha 4- and alpha 5-integrins stained both the stroma and the normal epithelium similarly. The alpha 2-integrin was absent in the stroma of all 18 cancer specimens despite being present in the epithelial regions of 14 to 18 cancers. The alpha 3-integrin had a greater staining intensity in the stroma of the cancers than in the epithelial regions (p = 0.002). Both alpha 4- and alpha 5-integrins were absent in the epithelial regions of the cancers but present in the stroma., Conclusions: The distribution and intensity of integrin expression in cervical cancer differ from their expression in the normal cervix. In particular, the fibronectin receptors, alpha 4 and alpha 5, were absent in the epithelial regions of the cervical cancers, and alpha 3 also had diminished expression in the malignant epithelium. These changes correlate well with the changes expected in malignant transformation.

This study was done to measure the effect on inspiratory carbon dioxide (CO2) levels of infants exposed to the infant Crib Air (ICA) apparatus, a novel device which circulates room air within the infant's crib. Twenty-one healthy, sleeping infants and neonates (mean age = 14.7 weeks) were studied in a prospective crossover trial. All infants were studied lying face down or with the face placed passively to the side in their cribs. Inspiratory CO2 levels were recorded over a 30 minute period by measuring the concentration of CO2 immediately adjacent to the infants' nose and mouth. During the first 15 minute period, the baseline concentration of inspiratory CO2 was recorded. The infants were then exposed to the ICA apparatus in their cribs for 15 minutes and the concentrations of inspiratory CO2 were measured. Mean inspiratory CO2 levels in infants lying face down decreased from 8.5 to 1.4 mm Hg after ICA exposure (P < 0.001). Infants studied with their face placed passively to the side experienced a similar decrease in inspired CO2 concentrations. We conclude that the level of inspired CO2 by sleeping infants can be significantly reduced by the ICA regardless of the position of the infant's head.

The purpose of this study was to correlate the presence of matrix metalloproteinase (MMP)-9 and MMP-2 and tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 mRNAs, detected in serial sections using the reverse transcriptase in situ PCR technique, with prognosis in 23 cases of cervical carcinoma. PCR-amplified MMP and TIMP cDNA were restricted to the invasive cancers cells and the surrounding stromal cells. The ratios of cancer and stromal cells expressing MMP-9 and MMP-2 to those expressing TIMP-1 and TIMP-2 were approximately 1 in those cancers with a good prognosis. This MMP:TIMP ratio in the cancer and stromal cells with a poor prognosis was significantly increased to 5.4 and 3.4 (P < 0.0001), respectively, reflecting a marked reduction in the TIMP detection rate in cancers with a poor prognosis. In cervical cancer cell lines SiHa and HeLa, the MMP:TIMP ratio was also close to 1 and, interestingly, these cell lines are invasive but rarely metastatic in nude mice. These data suggest that the balance of MMP-9 and MMP-2 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of cervical cancer.

Patients with a palpable mass often benefit most from aspiration. As the clinician tries to aspirate, fluid may be obtained if the lesion is cystic. A solid lesion can be assessed with FNA biopsy with a very high degree of accuracy. Excisional biopsy should be used when a cystic lesion recurs, the mass does not disappear after the cyst is aspirated, or if the fluid obtained is bloody. A solid lesion may need to be excised if the aspirate is negative. The overall detection rate of breast cancer is approximately 20% for excisional biopsies. Mammographically detected lesions can be evaluated with needle-localization biopsies and stereotactic biopsies. The detection rates for breast carcinoma averages approximately 30%, with at least 20% of these lesions being noninvasive. The role of core needle biopsy of palpable lesions is limited; however, histologic confirmation of positive cytologic results from aspirate is possible with this approach. Stereotactic needle biopsy appears to correlate well with the specimen obtained at incisional biopsy and may decrease the need for needle-localized excisional biopsy.

The purpose of this report was to review second-line hexamethylmelamine (HMM) chemotherapy of epithelial ovarian cancer to determine if HMM was active in cisplatin-resistant disease. Forty-four women with measurable disease received 100-300 mg/day HMM for 14 days, courses repeated every 4 weeks. There were 6 complete and 3 partial responses for an objective response rate of 20%. Among responding patients disease-free survival was 55% and overall survival was 88% at 3 years. Five of the 6 patients with a complete response remained disease-free at 10-117 months. Only 7/35 (20%) nonresponding patients were alive with mean follow-up of 16 months, and all had persistent cancer. Five women manifesting disease progression during cisplatin or carboplatin were subsequently treated with HMM, and none responded. Seventeen patients developing progressive cancer while receiving HMM were subsequently treated with cisplatin or carboplatin and objective responses occurred in 5 (29%). HMM was an active drug against epithelial ovarian cancer previously treated with cisplatin, but further study is needed to determine its activity against cisplatin-resistant ovarian cancer.