The role of the genetic testing industry in patient education of hereditary cancer: An observational study assessing the quality of patient education videos.

OBJECTIVES: Genetic testing (GT) companies have developed patient education videos to supplement or replace pre-test genetic counseling (GC) by certified genetic counselors (CGC). The aim of this study was to assess the quality of these videos compared to the standard of care (SOC). METHODS: Videos from four major GT companies were selected from an internet search identifying pre-test patient education videos. A scoring rubric with 22 questions and 36 total points was devised to assess quality metrics, as described by the National Cancer Institute and National Society of Genetic Counselors. Twenty-two individuals with varying genetics expertise (3 gynecologic oncologists, 3 academic generalists, 4 CGC, a genetics community health worker, 3 cancer care navigators, and 8 medical students) scored each video. Scorers were blinded to others' assessments. RESULTS: Invitae had the highest median score (26/36), followed by Myriad (22/36), Ambry (17.5/36), and Color (15/36). All videos scored highly in explaining DNA basics, cancer development, and hereditary cancer predisposition. All addressed benefits of GT but failed to address potential disadvantages. All scored poorly in explaining medical terms and different GT options. There was variability in addressing patient concerns including cost, privacy, and procedure. CONCLUSIONS: There is significant variation in the content of pre-test patient education videos between GT companies. None of the videos met the SOC for pre-test GC, and none addressed disadvantages of GT, possibly due to a conflict of interest. With improvement in content, accessibility, and use of interactive platforms, these videos may serve as an adjunct to in-person pre-test GC.

Vulvar intraepithelial neoplasia: Risk factors for recurrence.

OBJECTIVE: We studied a large population of women with high-grade vulvar intraepithelial neoplasia (VIN) in order to identify patient and treatment-related risk factors for recurrence and progression to cancer. METHODS: For this retrospective cohort study of women with a histologic diagnosis of VIN within Southern California Permanente Medical Group between 1995 and 2007 medical records were reviewed; clinical, demographic and pathologic data were collected. Statistical analyses included Chi-squared and Student's t-tests, univariate and multivariate logistic regression, and cumulative incidence analysis. RESULTS: 914 patients with high-grade VIN were identified; 784 met inclusion criteria. We found 26.3% recurrences among treated women, with 2.2% progression to cancer (8.2% among those with recurrence). Risk factors for recurrence on multivariate analysis were: age >50years (OR, 1.44; 95%CI 1.01-2.07), immunosuppression (OR 2.08; 95%CI 1.42-3.06), metasynchronous VAIN or CIN (OR 1.76; 95%CI 1.08-2.88) in addition to margin status (OR 8.17; 95%CI 4.60-14.51) and adjacent LSA (OR 9.91; 95%CI 1.53-31.32) or HPV (OR 2.15; 95%CI 1.13-3.37) with excisional treatment. Recurrence rates did not differ significantly by smoking status and treatment modalities. Median time to recurrence was 16.9months; 25% had late recurrences (44-196months). Cumulative incidence analyses of time to recurrence shows a significantly higher risk among patients over age 50 (log-rank p=0.0031). CONCLUSION: We identified independent risk factors for recurrence including age >50years, immunosuppression, metasynchronous vaginal or intraepithelial neoplasia, positive excision margins, and adjacent lichen sclerosus or human papilloma-virus. Regardless of treatment modality, 25% of recurrences occurred late, highlighting the need for long-term surveillance in women treated for VIN.

The use of continuous infusion topotecan in persistent and recurrent ovarian cancer.

We retrospectively review our experience with continuous infusion topotecan for the treatment of persistent or recurrent ovarian cancer in this paper. Nine patients were identified who were treated at the University of California Los Angeles Medical Center between January 1997 and December 1999 using a 14-21 day continuous infusion schedule (0.3-0.7 mg/m2/d). Dose adjustments were performed for grade 3-4 toxicities and treatment was discontinued for persistent severe toxicity or progressive disease. Response to treatment was analyzed and stratified by platinum refractory, resistant, and sensitive disease. A total of 41 treatment cycles were given to nine patients with a median of five per patient (range 1-11). Median follow-up was 8 months. There were two partial responses (22%) and four patients had stable disease (44%), which included two patients with platinum-refractory tumors. No grade 3 or 4 hematologic toxicities were observed. However, two patients suffered grade 3 gastrointestinal toxicity during the first cycle leading to discontinuation of topotecan administration. There was no cumulative toxicity. Topotecan administered by continuous infusion demonstrated response rates comparable to other dosing schedules with minimal hematologic toxicity. Treatment of patients with persistent or recurrent ovarian cancer with continuous infusion topotecan warrants further investigation.

FIGO stage III and IV uterine papillary serous carcinoma: impact of residual disease on survival.

The objective of this study was to assess the impact of surgical cytoreduction on the survival of patients with uterine papillary serous carcinoma (UPSC). Patients added to the institutional tumor registries between January 1980 and September 2001 with the diagnosis of UPSC were reviewed. The records of 43 patients who underwent surgical cytoreduction for FIGO stage III and IV disease were reviewed. The median survival of UPSC patients with microscopic residual disease was significantly improved compared to those with macroscopic residual disease following primary surgical cytoreduction. We conclude that primary surgical cytoreduction resulting in microscopic residual disease is associated with an improvement in recurrence-free survival and overall survival in women with UPSC.

Ovarian cancer: epidemiology, biology, and prognostic factors.

Ovarian cancer varies widely in frequency among different geographic regions and ethnic groups, with a high incidence in Northern Europe and the United States, and a low incidence in Japan. The majority of cases are sporadic, and only 5% to 10% of ovarian cancers are familial. The etiology of ovarian cancer is poorly understood. Models of ovarian carcinogenesis include the theory of incessant ovulation, in which a person's age at ovulation, i.e., lifetime number of ovulatory cycles, is an index of her ovarian cancer risk. Excessive gonadotropin and androgen stimulation of the ovary have been postulated as contributing factors. Exposure of the ovaries to pelvic contaminants and carcinogens may play a role in the pathogenesis of ovarian cancer. Epidemiologic and molecular-genetic studies identify numerous risk and protective factors. The most significant risk factor is a family history of the disease. Recent advances in molecular genetics have found mutations in the BRCA1 and BRCA2 tumor suppressor genes responsible for the majority of hereditary ovarian cancer. Additional risk factors include nulliparity and refractory infertility. Protective factors include multiparity, oral contraceptives, and tubal ligation or hysterectomy. With five years of oral contraceptive use, women can cut their risk of ovarian cancer approximately in half; this also holds true for individuals with a family history. Stage at diagnosis, maximum residual disease following cytoreductive surgery, and performance status are the three major prognostic factors. Using a multimodality approach to treatment, including aggressive cytoreductive surgery and combination chemotherapy, five-year survival rates are as follows: Stage I (93%), Stage II (70%), Stage III (37%), and Stage IV (25%).

A single-visit cervical carcinoma prevention program offered at an inner city church: A pilot project.

BACKGROUND: A single-visit cervical carcinoma prevention program was implemented, integrating screening, diagnosis, treatment, and health education in the familiar environment of the community church. METHODS: Nonpregnant women age 18 years or older, who had not received cervical carcinoma screening in the preceding year were eligible. Subjects provided information on personal demographics, health, and knowledge regarding cervical carcinoma prevention. Thereafter, cervical cytology was collected, processed, and interpreted on site. Participants attended small-group instruction on cervical carcinoma prevention. Screening results were given to each subject individually. Patients with abnormal cytology underwent immediate colposcopy with biopsies or loop electrosurgical excision procedure as indicated. Participant satisfaction and educational impact were evaluated. RESULTS: Ninety of the 98 participants reported that Spanish was their native language; 59 did not speak English. Fifty-four had had fewer than 6 years of education and 55 were unemployed. Seventy-eight did not have a regular physician or health insurance. Twenty-four either had never undergone cervical carcinoma screening or had let more than 5 years elapse since their previous examination. None of nine potential barriers assessed correlated with past compliance with cervical carcinoma screening. The mean time for processing and on-site interpretation of cervical cytology smears was 22.6 +/- 5.3 minutes. The median time patients spent in the program was 75 minutes. There was a significant improvement in the subjects' knowledge regarding cervical carcinoma prevention. All participants were highly satisfied. CONCLUSIONS: This parish-based, integrated, single-visit program for the prevention of cervical carcinoma was easily implemented and provided care to a substantial proportion of underserved patients.

See-and-treat in the management of high-grade squamous intraepithelial lesions of the cervix: a resource utilization analysis.

OBJECTIVE: To use activity-based costing techniques to compare see-and-treat with conventional evaluation and treatment of women presenting with a screening Papanicolaou smear demonstrating high-grade squamous intraepithelial lesion (SIL). METHODS: A total of 4000 theoretical patients were assumed to be evaluated and treated following one of four management algorithms: conventional algorithm I, with colposcopy and directed biopsies, followed by cryotherapy or cold-knife conization; conventional algorithm II, substituting the loop electrosurgical excision procedure for cold-knife conization; conventional algorithm III, substituting the loop electrosurgical excision procedure for cold-knife conization and cryotherapy; or see-and-treat algorithm IV, using the loop electrosurgical excision procedure. Costs associated with patient management in each algorithm were calculated including those for the procedure, patient time, physician time, and disposable expenses, as well as costs to manage complications, treatment failures, and follow-up for 1 year. RESULTS: Algorithm I was the most expensive, costing $899,405 for 1000 patients with high-grade SIL. Substituting the loop electrosurgical excision procedure for cold-knife conization (algorithm II) decreased the cost by 32%, whereas substituting it for cryotherapy also (algorithm III) reduced the cost by only 25%. The most cost-effective management was the see-and-treat single visit of algorithm IV. This strategy cost $531,281, offering a 41% cost reduction compared with algorithm I. CONCLUSION: A see-and-treat approach to the management of women with high-grade SIL, although incorporating more procedures, offers significant cost savings over conventional management algorithms.

Immunomodulation with interleukin-10 and interleukin-4 compared with ketorolac tromethamine for prevention of postoperative adhesions in a murine model.

OBJECTIVE: To assess the effects of two macrophage down-regulating cytokines (interleukin [IL]-10 and IL-4) and the nonsteroidal anti-inflammatory drug ketorolac tromethamine on postoperative adhesion formation. DESIGN: Randomized controlled trial. SETTING: Research center vivarium. ANIMAL(S): Six-week-old Swiss Webster mice. INTERVENTION(S): One hundred eighty animals were randomized to serve as nonsurgical controls or to undergo a standardized adhesion-inducing procedure. Subsequently, animals were randomized to nine different treatment groups to receive no injections, phosphate-buffered saline (PBS) only, IL-10, IL-4, ketorolac, IL-10 plus IL-4, IL-10 plus ketorolac, IL-4 plus ketorolac, or all three agents. MAIN OUTCOME MEASURE: Adhesion scores on postoperative day 10. RESULT(S): Postoperative adhesion scores were significantly reduced in all groups of animals treated with IL-10 or ketorolac. Animals treated with IL-4 showed a nonsignificant trend toward reduction of adhesions. There were significantly more animals with adhesion scores of < or = 3 in the IL-10 and ketorolac treatment groups than in the control groups receiving no treatment or PBS only. CONCLUSION(S): Although treatment with IL-10 and ketorolac did not completely prevent adhesion formation, treatment with these drugs did lead to a significant reduction in adhesion formation. Adhesions also tended to be thin and filmy rather than thick and vascular. Addition of IL-4 did not augment these effects.

Endogenous versus exogenous IL-10 in postoperative intraperitoneal adhesion formation in a murine model.

BACKGROUND: Modulation of the immune response to peritoneal injury may prevent postoperative adhesion formation. Exogenous interleukin-10 (IL-10) limits postoperative adhesion formation. The objective of the present study is to determine (I) the IL-10 dose most effective at adhesion prevention, (II) the presence of endogenous IL-10 in peritoneal fluid, and (III) the ability of an anti-IL-10 monoclonal antibody to modify postoperative intraperitoneal adhesion formation. MATERIALS AND METHODS: Within parts I, II, and III of the study 8-week-old Swiss Webster mice were randomized to have no surgery or to undergo a standardized adhesion-inducing peritoneal injury. Animals were further randomized to different dosing schedules of IL-10 (10 ng/kg to 100 micrograms/kg; part I), different times of euthanasia and peritoneal lavage after surgery (part II), or intraperitoneal (i.p.) treatment with phosphate-buffered saline vehicle (1 ml), IL-10 (1 microgram/kg), or anti-IL-10 (1 microgram/kg; part III). All i.p. injections were given immediately after surgery and then every 24 hr for a total of four injections. Animals were sacrificed 7 days after surgery and adhesion formation was assessed. RESULTS: Maximal adhesion-limiting effects of exogenons IL-10 were reached at doses of 1 microgram/kg. Mean detectable endogenous IL-10 levels in the peritoneal fluid varied from 145 to 220 pg/ml throughout the postoperative course. There were significant (P < 0.0005) differences in adhesion scores between mice treated with IL-10 (3.39; 95% CI 0.39-6.39) or PBS postoperatively (7.46; 95% CI 5.28-9.64), untreated surgical control animals (5.98; 95% CI 2.55-9.41), or anti-IL-10-treated animals (10.11; 95% CI 8.50-11.72). CONCLUSION: Interleukin 10 is effective at reducing postoperative intraperitoneal adhesion formation. Low levels of endogenous IL-10 are detectable in peritoneal fluid throughout the postoperative course, not correlating with adhesion scores. Anti-IL-10, when administered daily postoperatively in pharmacologic doses, does not appear to significantly increase postoperative adhesion formation. This puts into question if endogenous IL-10 production indeed plays a role in nonadhesiogenic peritoneal healing.

Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature.

BACKGROUND: The standard treatment for endometrial carcinoma is staging laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy. In an attempt to preserve childbearing potential, selected patients with endometrial carcinoma were treated with progestin alone as primary therapy. METHODS: Patients were identified through searches of tumor registries and solicitation of consulting gynecologic oncologists at the affiliated institutions of the University of California-Los Angeles Center for the Health Sciences. Only those patients with a diagnosis of endometrial carcinoma treated with progestin alone as primary therapy were included in the study. Independent pathologic review was performed by a recognized expert gynecologic pathologist to exclude cases of endometrial hyperplasia. A MEDLINE search was conducted to identify reports of similarly treated patients. RESULTS: Seven patients were treated with progestin alone for endometrial carcinoma at the study institution. Fourteen additional patients were identified through the literature search. Combining the data for all patients, 13 of 21 patients (62%) had an initial response to progestins. Three initial responders later developed recurrent disease, one of whom was found to have extrauterine disease at laparotomy. Eight of 21 patients (38%) did not respond to progestins and underwent more definitive treatment. None of these patients later developed recurrent disease. Six viable infants were delivered of three patients after therapy. Nineteen of 21 patients were alive without evidence of disease at last follow-up. CONCLUSIONS: The results of this study show that premenopausal women with endometrial carcinoma may be treated successfully with progestin therapy alone as primary therapy to preserve childbearing potential.

Incisional hernia following laparoscopy: a survey of the American Association of Gynecologic Laparoscopists.

OBJECTIVE: To estimate the risk factors for and incidence of post-laparoscopy incisional hernia. METHODS: A questionnaire was sent to all individuals on a mailing list from the American Association of Gynecologic Laparoscopists. Adequately completed responses were entered into a computer-based data bank for analysis. Of the 11,500 surveys mailed, 3293 were returned; of these, 3217 were evaluable. RESULTS: A total of 933 hernias was reported from an estimated 4,385,000 laparoscopic procedures (an incidence of 21 per 100,000); 167 (17.9%) were reported to have occurred despite fascial closure. Six hundred sixty-five patients (71:3%) had subsequent surgical repair. Seven hundred twenty-five (86.3%) of the 840 hernias in which the size of the original fascial defect was noted, occurred in sites where ports 10 mm in diameter or larger had been placed. The occurrence of hernias is a function of the number of laparoscopies performed (P < .0001) and is not related to the length of the surgeon's career (P = .41). In at least 157 instances (16.8%), the presenting symptom or morbidity of the hernia was directly related to the involvement of the large or small intestine. CONCLUSION: Post-laparoscopy incisional hernias occur at an approximate incidence of 21 per 100,000 and are associated with significant morbidity. These hernias are most likely to occur when large ports are used. As currently practiced, closure is not completely protective. Further methods or devices should be developed to minimize the risk of hernia formation.

Interleukin 10: ability to minimize postoperative intraperitoneal adhesion formation in a murine model.

OBJECTIVE: To determine the ability of interleukin 10 (IL-10) to suppress postoperative intraperitoneal adhesion formation. DESIGN: Randomized, controlled trial. SETTING: University animal research facility. ANIMALS: Six-week-old Swiss Webster mice undergoing a standardized intraperitoneal operative procedure. INTERVENTIONS: Animals were randomized to "surgery" or "no surgery" and then further randomized to receive intraperitoneal injections of 1 mL phosphate-buffered saline (PBS) or 1 microgram/kg IL-10 in 1 mL PBS. Vehicle-only doses were given immediately after surgery and then every 24 hours for a total of four injections. Interleukin 10 injections were similarly given but with an added preoperative injection 30 minutes before surgery in one half of the animals. MAIN OUTCOME MEASURE: Adhesion formation. RESULTS: Animals treated with vehicle or IL-10 but not undergoing surgical intervention had no intraperitoneal adhesions. Animals undergoing surgery who were treated with IL-10, with or without a preoperative dose, had significantly lower postoperative adhesion scores than did control animals who postoperatively received PBS only. CONCLUSION: Interleukin-10 is effective at limiting postoperative intraperitoneal adhesion formation with minimal evident systemic side effects.

The modified Pereyra procedure in recurrent stress urinary incontinence: a 15-year review.

OBJECTIVE: To assess the effectiveness and perioperative morbidity of the modified Pereyra procedure in the treatment of recurrent stress urinary incontinence. METHODS: Data of 54 patients who underwent a modified Pereyra procedure for the treatment of recurrent stress urinary incontinence between January 1, 1978, and August 1, 1992, were analyzed retrospectively regarding presenting symptoms, preoperative evaluation, surgical procedure, complications, and cure and failure rates. The patients were divided into two groups depending on the preoperative absence (group I) or presence (group II) of risk factors for repeated failure (detrusor instability, low-pressure urethra, fibrotic urethra, negative Q-tip test, and neurogenic incontinence). RESULTS: After a mean follow-up of 36.3 months, the cure rate of 81.6% in group I (N = 38) was significantly (P = .005) higher than that in group II (N = 16; 43.8% cured). The mean time of occurrence of failure was 11.9 months for group I and 6.8 months for group II. The incidence of intraoperative complications (Pereyra suture in bladder, hemorrhage) for both groups was 7.4%. Immediate postoperative complications were found in 25.9% of all patients; these were mainly infectious processes. Late postoperative complications occurred in 33.3%, with the most prevalent being new-onset urge incontinence and de novo detrusor instability (11.1%) and obstructive voiding dysfunction (9.3%). The rates of perioperative morbidity were not significantly different between the groups. CONCLUSION: The modified Pereyra procedure is well suited for the treatment of uncomplicated recurrent stress urinary incontinence, with a long-term cure rate of over 80%. However, success rates are significantly lower for recurrent stress incontinence in association with persistent risk factors for failure. In either instance, the procedure is associated with appreciable perioperative morbidity.

Small bowel obstruction following radical hysterectomy: risk factors, incidence, and operative findings.

Our objective was to determine the incidence, risk factors, and outcome of small bowel obstruction in patients undergoing radical hysterectomy as therapy for a nonadnexal gynecologic malignancy. Using a computerized search of discharge data from January 1, 1981 to January 1, 1991, 113 patients were identified who had undergone a radical hysterectomy as part of initial therapy for a nonadnexal gynecologic malignancy. Complete records were available for 98 patients who comprised the study population. For purposes of data accrual, patients were separated into three groups: radical hysterectomy without concomitant radiotherapy (Group I, n = 60), patients receiving pelvic radiation following radical hysterectomy (Group II, n = 20), and a third group with preceding pelvic radiation (Group III, n = 18). Postoperative small bowel obstruction (SBO) occurred in 3 (5%) of Group I patients, all of which required surgical management. The incidence of SBO was significantly higher (P < 0.05) in the groups that had received concomitant radiotherapy (4 of 20 (20%) in Group II; 4 of 18 (22%) in Group III). Importantly, none of these patients had recurrent disease noted at the time of SBO occurrence. Three Group II patients and no Group III patients received operative management of their SBO. Findings at surgery for the SBO were similar in all cases: minimal incisional adhesions but extensive matted small bowel adherent to the pelvic operative sites. We concluded that small bowel obstructions due to intraperitoneal adhesions are frequent sequelae of radical hysterectomy, being more common if concomitant radiotherapy is given. Further investigations as to ways to limit post-radical hysterectomy adhesion formation are needed.

Bullatacin--in vivo and in vitro experience in an ovarian cancer model.

The cytotoxicity and antitumor effects of the acetogenin Bullatacin were evaluated in vitro in multiple ovarian cancer cell lines and in vivo in a murine ovarian teratocarcinoma (MOT) model in C3HeB/FeJ mice. The in vitro cytotoxicity of Bullatacin against four human ovarian epithelial tumor cell lines (OC-194, OC-222, OVCAR-3, and A-2780) was assessed in 48- and 72-h tetrazolium-dye (MTT) cytotoxicity assays. The percentage of cytotoxicity was determined on the basis of the mean optical density of the respective untreated cells and the dose effective against 50% of the cells (ED50) was calculated for each cell line. In vivo experiments were performed on adult female C3HeB/FeJ mice, which were injected i.p. with 10(5) MOT cells and varying amounts of Bullatacin given either in a single dose or in 5 subsequent doses over 72 h. All mice were observed for survival relative to that of the control groups, which were injected either with 10(5) MOT cells with or without serial injections of vehicle or with vehicle only. All four epithelial ovarian cancer cell lines displayed sensitivity to Bullatacin. The relative cytotoxic effects were very heterogeneous, with the ED50 value ranging between 10(-7) micrograms/ml for OC-194 and 4 micrograms/ml for the cisplatin-resistant cell line OVCAR-3 in a 72-h MTT cytotoxicity assay. All mice that had been injected i.p. with 10(5) MOT cells and 1.4 mg/kg or more of Bullatacin died within the first 24 h after injection, whereas all mice that had received 600 micrograms/kg of Bullatacin or less survived equally as long as the controls that had been injected with MOT only (21.1 +/- 0.9 days). Mice that had received Bullatacin at a dose ranging from 600 micrograms/kg to 1.4 mg/kg either died during the 1st day postinjection or survived, but not longer than the MOT control group. Serial i.p. injections of Bullatacin again either led to death of the mice within 24-48 h of the last dose of Bullatacin or did not have any effect on the survival of the mice as compared with the respective control groups, which had been injected with the tumor and serial injections of vehicle (22.5 +/- 2.2 days). In summary, Bullatacin showed no effect on MOT-caused animal death in C3HeB/FeJ mice at nonlethal dose ranges, whether it was given as a single i.p. dose or serially over 72 h. In vitro, however, it proved to be a very potent cytotoxic agent in a variety of ovarian cancer cell lines.(ABSTRACT TRUNCATED AT 400 WORDS)

Large-loop excision of the transformation zone: effect on the pathologic interpretation of resection margins.

OBJECTIVE: To determine the effect of large-loop excision of the transformation zone (LLETZ) on the ability to interpret adequately the pathologic specimen and surgical margins. METHODS: Fifty consecutive LLETZ specimens were used for repeat histopathologic assessment with emphasis on the interpretability of the surgical specimen and margin. All reevaluations were performed by a single pathologist. Complete lesion evaluability was defined as satisfactory accuracy of the histologic diagnosis and the ability to evaluate thoroughly all surgical margins. Medical records of the patients from whom the specimens were obtained were reviewed and analyzed for possible correlates to the status of specimen interpretability. RESULTS: Histologic accuracy was sufficient in 46 cases (92%). Extensive heat distortion precluded full assessment of the ectocervical margins in ten (20%) and the endocervical margins in 22 (44%) of the cases. There was no difference in complete lesion evaluability whether LLETZ was performed solely for treatment in cases suitable for ablative procedures or for both diagnosis and treatment in patients who traditionally would have undergone a cone biopsy. If the latter group (N = 25) was analyzed separately, extensive heat distortion made histopathologic diagnosis impossible in four cases (16%) and precluded full assessment of the ectocervical margin in eight (32%) and the endocervical margin in 12 (48%). CONCLUSION: The high rate of surgical-margin thermal destruction, with related limitation of interpretability, may represent a serious diagnostic and therapeutic limitation of the LLETZ procedure when considered as an alternative to cold knife conization.