Obesity-related endometrial cancer: an update on survivorship approaches to reducing cardiovascular death.

As the rate of obesity increases worldwide, so will the number of women diagnosed with obesity-related malignancy. The strongest correlation between obesity and cancer is endometrial cancer (EC). Obesity is the most significant modifiable risk factor for development of EC and also contributes to the most common cause of death in EC survivors-cardiovascular disease (CVD). Most cancer survivors after diagnosis do not implement lifestyle changes aimed at weight-loss and CVD risk reduction. This selective review highlights recent novel and unique approaches for managing CVD co-morbidities in EC survivorship.

Self-efficacy, quality of life, and weight loss in overweight/obese endometrial cancer survivors (SUCCEED): a randomized controlled trial.

OBJECTIVE: More patient-centered programming is essential for endometrial cancer (EC) survivors needing to lose weight to reduce cardiovascular disease risk (CVD). The purpose of this study was to improve self-efficacy (SE) and quality of life (QOL) using a lifestyle intervention program designed for weight loss. METHODS: Overweight and obese early-stage EC survivors, n = 75, were randomized into two groups: 1) Survivors of Uterine Cancer Empowered by Exercise and Healthy Diet (SUCCEED), a six-month lifestyle intervention or 2) a usual care group (UC). Participants completed the Weight Efficacy Lifestyle Questionnaire (WEL) to assess SE and the Functional Assessment of Cancer Therapy-General (FACT-G) to measure QOL, and their body mass index (BMI) was calculated at baseline, 3, 6, and 12 months. Mixed, repeated-measures ANCOVA models with baseline covariates were employed using SPSS 20.0. RESULTS: Positive effects in every WEL domain, including the total score, were statistically significant in the SUCCEED group versus the UC group. A linear regression model demonstrated that, if BMI decreased by 1 unit, the total WEL score increased by 4.49 points. Significant negative correlations were found in the total WEL score and a change in BMI of R = -0.356 (p = 0.006). Between-group differences in the FACT-G were significant from baseline in the fatigue domain at three months (p = .008) and in the physical domain at six months (p = .048). No other significant differences were found. CONCLUSION: Overall, this study shows promise for targeted interventions to help improve SE, thus improving BMI.

Bariatric surgery in the field of gynecological oncology.

Obesity has become a foremost health problem. More than half of US adults are overweight or obese. This has been due to sedentary lifestyles, increased intake of refined carbohydrates, and fat-rich diets. Obese women are particularly susceptible to a variety of health risks including cancer, especially cancers of the breast, endometrium, and colon. Bariatric surgery appears to be a viable option for the treatment of severe obesity. As the role of surgery in the management of this condition becomes increasingly frequent, it is important for gynecological oncologists to recognize the potential for gynecological malignancies in this patient population.

A novel early-stage orthotopic model for ovarian cancer in the Fischer 344 rat.

The purpose of our study was to ascertain the progression of metastases in a novel ovarian cancer model designed to mimic early-stage disease by utilizing an orthotopic injection technique. Female Fischer 344 rats were injected with either 10(4) or 10(5) NuTu-19 cells by intraperitoneal or orthotopic injection. Peritoneal washings and histologic specimens were examined to correlate the incidence and extent of tumor growth. In a second phase, orthotopic injections of 10(2) and 10(3) cells were compared to that of 10(4) cells. Progression of ovarian cancer was observed by gross and microscopic examinations in both intraperitoneal and orthotopic models. Pelvic extension and abdominal adhesions uniquely characterized the orthotopically injected animals. Numbers of identifiable metastases declined with lower cell inocula, confirming that early-stage disease was extended to at least 14 days with 10(2) NuTu-19 cells. The orthotopic ovarian cancer model emulates early disease with the initiation of a primary tumor that is localized within the inherent microenvironment. The orthotopic model offers a clinically relevant alternative for future cancer research that allows for the investigation of therapeutic strategies against early stages of the disease process.

Rodent models for ovarian cancer research.

Animal models that are biologically and clinically relevant are essential for conducting research to investigate the pathophysiologic progression of disease and to develop diagnostic or therapeutic strategies. Several rodent models that vary in methods of induction allow appropriate in vivo evaluation for ovarian cancer. The types of rodent models discussed include chemically (nonhormonal and hormonal) induced, genetic (knockout and transgenic), xenograft, and syngeneic. A summary of the available rodent models is provided with a discussion of the advantages and disadvantages of each. Optimization and application of these rodent models to future research may benefit the detection and treatment of ovarian cancer.

A comparison of complementary and alternative medicine use by gynecology and gynecologic oncology patients.

Our objective was to describe and compare the use of complementary and alternative medicine (CAM) in gynecology and gynecological oncology patients. Five hundred and twenty-nine gynecology and gynecological oncology patients completed a questionnaire regarding CAM use. Overall, 56.3% of gynecology and gynecological oncology patients reported current use of CAM. Therapies used included nutritional supplements (20%), prayer as medical therapy (17%), exercise as medical therapy (12%), megavitamins (10%), and green tea (10%). While 69.5% believed CAM to be beneficial, only 31.6% discussed these therapies with their physician. The women spent a mean of $656.22 on CAM (range $0-$7,000), with 31.7% receiving some insurance reimbursement. Gynecologic oncology patients (n = 161) used CAM significantly more than gynecology patients (n = 368) (66% vs. 52%, 95% CI = 0.046-0.230, P = 0.004). Gynecological oncology patients also spent more for CAM, with a mean expenditure of $711 versus $622 by gynecology patients. Within the gynecological oncology patient group, there were 69 patients currently receiving modern medical treatments for cancer; among these patients, 58% reported using CAM; of these, 39.3% communicated their use of CAM to their physician. Patients in this group spent an average of $1,178 on CAM during their illness, with only 6.3% receiving insurance reimbursement. Benefits from CAM were perceived by 54.5% in this group. We concluded that cancer patients have a higher usage rate and expenditure for CAM, particularly while they are receiving medical therapy, and are more likely to discuss the use of alternative therapies with their physicians. CAM was perceived as helpful by patients despite the lack of scientific data about its effect.

Complementary and alternative medicine use in the Amish.

OBJECTIVE: To examine the rate of utilization of complementary and alternative medicine (CAM) in Amish women, a population that traditionally uses non-mainstream medicine. METHODS & RESULTS: Sixty-six Amish women completed a survey concerning their use of CAM. Thirty-six percent of the Amish women used at least one form of CAM, primarily reporting a use of diet and nutrition programs, herbal therapies, and chiropractic medicine. In addition, ten pregnant Amish women reported using echinacea, St. John's Wort, red clover, garlic and ginseng. CONCLUSION: This survey highlights the need to address potential adverse effects of herbal therapies in young women who are a member of a group that may use non-mainstream medicine.

Bacteriology and treatment of malodorous lower reproductive tract in gynecologic cancer patients.

OBJECTIVE: To determine the bacteriology of lower genital tract cancers to direct potential treatment modalities and to determine the impact of treatment on quality of life. METHODS: Gram stain, saline preparations, tumor pH determinations, and anaerobic and aerobic tumor cultures were obtained from 13 consecutive patients with malodorous gynecologic cancers and 13 patients (controls) with nonmalodorous tumors. All patients with odor were treated with topical metronidazole for 7 days. Odor assessment questionnaires were administered daily in the treatment group. Quality-of-life evaluation was assessed using the Functional Assessment of Cancer Therapy questionnaire before and after treatment. RESULTS: Cancer of the cervix (n = 21) was the most common primary site and accounted for 81% (95% confidence interval 61%, 93%) of malodorous gynecologic cancers. Eight of 13 (62%) patients with malodorous tumors had bacterial vaginosis compared with four of 13 (31%) of those without odor (P =.11). Aerobic and anaerobic bacteria were isolated with equal frequency from malodorous gynecologic cancers. Results of odor assessment questionnaires showed a graded improvement with topical antibiotic therapy (P <.001). The Functional Assessment of Cancer Therapy questionnaire indicated improved quality of life after therapy (P =.02). CONCLUSION: Most patients with odor had bacterial vaginosis and had an improvement in odor with topical metronidazole. Therefore, this treatment might be useful for patients with malodorous pelvic tumors.

Alternative medicine in gynecologic oncology: A case report.

A patient with Stage IIB squamous cell cancer of the cervix presented 10 days into her primary radiation therapy with neutropenic fever and diarrhea requiring hospitalization and delay in treatment. The patient's history revealed extensive use of alternative therapies including potential toxic botanicals. This case raises the possibility that a patient's use of alternative therapies may have caused toxicity and delayed primary therapy. Gynecologic oncology patients may be using alternative therapies justifying the need for incorporating this classification into the historical exam.

Abdominal compartment syndrome in gynecologic surgery.

BACKGROUND: Abdominal compartment syndrome is a rare condition in which increased intra-abdominal pressure adversely affects perfusion and viability of the viscera, and the cardiovascular, respiratory, and renal systems. The syndrome follows acute abdominal events such as abdominal trauma, intraperitoneal hemorrhage, or intra-abdominal infection. CASES: Two women who had abdominal hysterectomies postoperatively developed clinical features of multisystem failure with markedly elevated intra-abdominal pressures. The women, one with intra-abdominal infection and diffuse intestinal edema and one with intra-abdominal hemorrhage, were diagnosed by clinical exam and intravesical pressure measurements. Both had follow-up exploration and temporary placement of the small bowel and colon into an intestinal bag until adequate resuscitation was achieved. CONCLUSION: Abdominal compartment syndrome is a rare complication in gynecology that can be diagnosed early and decompressed promptly.

Efficacy of intraperitoneal adenovirus-mediated p53 gene therapy in ovarian cancer.

The purpose of this study was to determine the efficacy of adenovirus-based p53 gene therapy in the treatment of ovarian cancer using an intraperitoneal microscopic tumor animal model system. Adenovirus-mediated wild-type p53 gene was introduced into the NIH:OVCAR-3 human ovarian cancer cell line in vitro and in vivo. In order to study microscopic intraperitoneal tumor, athymic nude mice were inoculated intraperitoneally (i.p.) with 1 x 107 OVCAR-3 cells and observed for tumor growth. Three days after inoculation with OVCAR-3 cells, the mice were divided into 3 treatment groups. One group received three daily i.p. injections of 1 x 108 pfu Ad-CMV-p53, a second group received three daily i.p. injection of 1 x 108 pfu of the control adenovirus construct expressing beta galactosidase (Ad-CMV-betagal) and a third group received three daily i.p. injections of normal saline. Adenovirus-mediated introduction of the wild-type p53 gene in the ovarian cancer cell line resulted in transient high levels of p53 protein for 24-48 h. Cell cycle analysis revealed G1 arrest, as well as the appearance of apoptosis. In vitro cell growth assays showed growth inhibition of cancer cells infected with Ad-CMV-p53 compared to cells infected with Ad-CMV-betagal or normal saline. There was a significant increase in survival in the Ad-CMV-p53 adenovirus treated animals compared to the PBS treated animals (P = 0.004). Likewise, the survival in Ad-CMV-p53 treated mice was also significantly greater than mice treated with Ad-CMV-betagal (P < 0.0001). These results demonstrated that Ad-CMV-p53 treatment is effective in inhibiting tumor growth and prolonging survival in this microscopic cancer xenograft model. The results of this study constitute a step in translating promising in vitro and in vivo data from an adenovirus-based gene therapeutic model system into practical and scientifically based human cancer therapeutic trials.

In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer.

OBJECTIVES: To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (i.p.) 2774 human ovarian cancer cell line that contains a p53 mutation. STUDY DESIGN: An initial study of adenovirus tolerance was determined in nude mice by a single i.p. injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD100 dose of 1 x 10(7) cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-beta gal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 x 10(8) pfu of Ad-CMV-p53. RESULTS: The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 x 10(8) pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P = 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-beta gal-treated mice. CONCLUSIONS: These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibition in vivo. Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.

The effect of intermittent-release intraperitoneal chemotherapy on wound healing.

OBJECTIVE: Our purpose was to study the effect on wound healing when intraperitoneal chemotherapy was instilled on a daily basis. STUDY DESIGN: Intraperitoneal carboplatin, Taxol, or saline solution was instilled daily into 70 rats after they underwent laparotomy. The animals were killed and analyzed for adhesions. An area measuring 5 x 5 cm including the incision was also harvested for biomechanical testing. The wound thickness was measured, and the Shore Western Materials Testing System (Monrovia, Calif.) was used to test the force required to break the wound, the stress, and the stiffness. RESULTS: Groups of 10 rats received saline solution control, carboplatin 6 mg/kg, 7 mg/kg, 8 mg/kg, or Taxol 2.5 mg/kg, 3.0 mg/kg, or 3.5 mg/kg. The total dose was divided into seven equal amounts, administered daily. No significant adhesions developed in any of the animals. The carboplatin group experienced no significant decrease in wound thickness whereas the higher-dose Taxol group had a significant decrease in thickness from 1.06 mm to 0.72 mm (p = 0.02). The wound-breaking strength (force) also decreased for the highest-dose Taxol group from 710 gm to 411 gm (p = 0.02). The wound stiffness was also decreased from 69 gm/mm to 46 gm/mm (p = 0.01). The other measured parameters for both the Taxol and carboplatin groups were not significantly decreased when compared with those of controls. CONCLUSION: The immediate instillation of divided daily carboplatin did not influence wound strength whereas the use of Taxol on a similar schedule significantly decreased wound strength.

Carcinoma of the endometrium.

Carcinoma of the endometrium is the most common gynecologic malignancy. The majority of women present with stage I disease, and the most common presenting symptom is postmenopausal bleeding. Early detection of endometrial cancer is important, because up to 90 percent of patients with stage I disease can be successfully treated. Certain risk factors, such as obesity, hypertension and diabetes mellitus, are associated with the development of this malignancy. Office endometrial sampling has a sensitivity of up to 97 percent for diagnosing carcinoma of the endometrium and can often eliminate the need for dilatation and curettage. Endometrial cancer is treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy and, in many cases, postoperative radiation therapy.