A 20-Centimeter Peritoneal Inclusion Cyst Presenting as Vaginal Prolapse.

This video shows the surgical excision of a 20-cm peritoneal inclusion cyst with laparoscopic repair of pelvic floor defects caused by the mass effect of the cyst. A 44-year-old woman presented with bulge symptoms and a reducible posterior prolapse extending 4 cm beyond the introitus inconsistent with an enterocele/rectocele. Dynamic MRI revealed a 20-cm cystic mass surrounding the uterine fundus extending down the posterior wall of the vagina, anterior to the rectum. Robotic-assisted laparoscopy revealed stage-IV endometriosis and a large peritoneal inclusion cyst extending from the pelvic brim to the rectovaginal septum. The cyst was mobilized through retroperitoneal dissection. Redundant peritoneum was excised down to the perineal body, and the distended posterior vaginal wall was plicated laparoscopically. The peritoneum was closed in a purse-string fashion, obliterating any potential space. Resolution of the prolapse was confirmed along with restoration of normal anatomy. We managed a unique case of a large peritoneal inclusion cyst presenting as vaginal prolapse. To correct defects after cystectomy, laparoscopic repair was performed similarly to closing an enterocele. Repair of a high posterior defect can be performed laparoscopically when working abdominally to avoid vaginal incisions, allowing for excellent visualization and access.

Racial disparities in histopathologic characteristics of uterine cancer are present in older, not younger blacks in an equal-access environment.

OBJECTIVE: We sought to determine whether racial disparities in tumor characteristics among uterine cancer patients persisted, and varied by age, in an equal-access healthcare population. METHODS: The distributions of tumor histology, stage and grade by race were compared for uterine cancers diagnosed from 1990 to 2003 using data from the U.S. Department of Defense's Automated Central Tumor Registry. Comparisons were conducted overall and stratified by age (<50, ≥50) using the Chi-square test. RESULTS: Of 2582 uterine tumors identified, 2057 (79.7%) were diagnosed among White women and 183 (7.1%) among Black women. Among all women analyzed, Blacks were more likely than Whites to present with non-endometrioid tumors (47.7% vs 23.5%, p<0.01), non-localized tumors (31.8% vs 24.5%, p=0.02), and poorly differentiated tumors (20.5% vs 15.0%, p<0.01). Among women 50 years and older, similar significant racial disparities were observed. However, no significant racial differences were observed among young patients. When comparisons were restricted to endometrioid histology adenocarcinomas, trends in age-specific disparities for older women were observed. CONCLUSIONS: Our study suggests that racial disparities in uterine cancers persist between Blacks and Whites in an equal-access population. Blacks endure higher stage and grade tumors, and more aggressive histologies. This disparity in clinicopathologic factors is confined to women older than 50 years. Multiple factors such as racial variation in age-related health knowledge/behavior and estrogen metabolism may be related to the racial disparity.

The impact of disease distribution on survival in patients with stage III epithelial ovarian cancer cytoreduced to microscopic residual: a Gynecologic Oncology Group study.

OBJECTIVE: To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual. METHODS: We reviewed data from 417 stage III EOC patients cytoreduced to microscopic disease and given adjuvant intravenous platinum/paclitaxel on one of three randomized Gynecologic Oncology Group (GOG) trials. We subdivided patients into three groups based on preoperative disease burden: (1) minimal disease (MD) defined by pelvic tumor and retroperitoneal metastasis (2) abdominal peritoneal disease (APD) with disease limited to the pelvis, retroperitoneum, lower abdomen and omentum; and (3) upper abdominal disease (UAD) with disease affecting the diaphragm, spleen, liver or pancreas. We assessed the survival impact of potential prognostic factors, focusing on initial disease distribution using a proportional hazards model and estimated Kaplan-Meier survival curves. RESULTS: The study groups had similar clinicopathologic characteristics. Median overall survival (OS) was not reached in MD patients compared to 80 and 56 months in the APD and UAD groups (P<0.05). The five-year survival percentages for MD, APD, and UAD were 67%, 63%, and 45%. In multivariate analysis, the UAD group had a significantly worse prognosis than MD and APD both individually and combined (Progression Free Survival (PFS) Hazards Ratio (HR) 1.44; P=0.008 and OS HR 1.77; P=0.0004 compared to MD+APD). CONCLUSION: Stage III EOC patients with initial disease in the upper abdomen have a worse prognosis despite cytoreductive surgery to microscopic residual implying that factors beyond cytoreductive effort are important in predicting survival.

A posterior uteroperitoneal fistula: an unexpected finding.

OBJECTIVE: To demonstrate a unique presentation and surgical treatment of a posterior uteroperitoneal fistula with excision of the fistula tract and repair in multiple layers. DESIGN: Illustrative video presentation. A case report is used to describe potential causes of an uteroperitoneal fistula found in a patient during evaluation of secondary infertility and to highlight surgical technique and management using the principles of fistula repair through a minimally invasive approach. The Institutional Review Board reviewed this video article and it was deemed "not human subject research." SETTING: Tertiary medical center. PATIENT(S): A 33-year-old G1P1001 woman with a history of a cesarean section presented with secondary infertility, pelvic pain, and dysmenorrhea and was found to have a posterior uteroperitoneal fistula at the time of hysterosalpingography. INTERVENTION(S): The patient underwent an uncomplicated robot-assisted laparoscopic excision of a posterior uteroperitoneal fistula with the use of careful dissection of the fistula tract, continuous reassessment, and tension-free closure in layers. MAIN OUTCOME MEASURE(S): Preoperative diagnosis and surgical management displaying intraoperative techniques for robot-assisted excision of fistula tract and repair of defect. RESULT(S): The patient underwent robot-assisted operative laparoscopy that revealed a 4-cm mass on the right posterior aspect of the uterus independent from her adnexa. Concomitant hysteroscopy revealed normal endometrium without an evident fistula. During chromopertubation, extravasation was seen into the peritoneal cavity from this mass. The mass and fistula tract were excised without a connection found from her cesarean scar, and reconstruction was performed in multiple layers. Endometriotic lesions were noted intraperitoneally in locations distant from the mass. The patient had significant improvement in her symptoms after surgery. CONCLUSION(S): We present a unique case of a suspected spontaneous posterior uteroperitoneal fistula in the presence of endometriosis without evidence of a connection to her prior hysterotomy scar. Possible etiologies include an undiagnosed, unrepaired hysterotomy extension or a result of chronic inflammation from deep infiltrating endometriosis. Adverse effects on fertility from uteroperitoneal fistulas may be due to disruption of sperm function or endometrial quality secondary to presence of old blood products sequestered in the fistula or due to resultant inflammation from the same. As in this video case, successful treatment of symptoms resulting from an uteroperitoneal fistula requires removal of the fistula tract. The constellation of pelvic pain, dysmenorrhea, postmenstrual bleeding, and infertility should raise suspicion for an uteroperitoneal fistula.

A stepwise approach to robotic assisted excision of a cesarean scar pregnancy.

OBJECTIVE: To develop a stepwise approach to robotic assisted excision of cesarean scar pregnancy (CSP) with metroplasty. METHODS: This illustrative video presentation demonstrating CSP, the criteria for ultrasound diagnosis, and a step-by-step approach for robotic assisted excision of CSP and multi-layer hysterotomy closure at a tertiary medical center. RESULTS: Robotic assisted resection is a safe and feasible method to treat cesarean scar ectopic pregnancies. Key ultrasonographic characteristics of CSP are highlighted to facilitate its diagnosis, thus allowing for early intervention with a minimally invasive surgical treatment as necessary. Our patient was a 30-year-old gravida 2 para 1 woman with a history of 1 prior-term low transverse cesarean delivery, who presented with vaginal bleeding in the first trimester and was ultimately diagnosed with CSP. After unsuccessful methotrexate therapy, the patient underwent an uncomplicated robotic assisted excision of her CSP and metroplasty in 2 layers using a stepwise approach: Step 1-Creation of a bladder flap; Step 2-Isolation and excision of CSP; Step 3-Hysterotomy closure in 2 layers; and Step 4-Hysteroscopy. CONCLUSION: When diagnosed late, cesarean scar ectopic pregnancy can cause a significant hemorrhage from rupture. Early radiologic diagnosis does not only indicate minimally invasive surgery as a treatment option but also assists with related surgical planning. This video demonstrates a stepwise approach to the robotic assisted excision of CSP with metroplasty. With these 4 simple steps, surgical procedure can be safe and efficient.

Clinical decision making using ovarian cancer risk assessment.

OBJECTIVE: Although any adnexal abnormality found at imaging can be concerning for an ovarian malignancy, the clinician must perform an evaluation to decide if the actual likelihood of malignancy justifies the risk of surgery. When determining the likelihood of an asymptomatic, incidental adnexal mass being malignant, the provider must answer one important question: Do the clinical findings warrant the potential morbidity of surgery? This article will focus on the decision making that goes into such an evaluation. CONCLUSION: A patient's medical history, physical examination, CA-125 level, and imaging characteristics are all factors that impact the ultimate decision of whether a patient can be observed with repeat imaging or should proceed to surgical evaluation.

The use of acellular dermal allograft for vulvovaginal reconstruction.

BACKGROUND: Many different techniques that require the surgeon to harvest autologous tissue to create a neovagina have been described in the literature. TECHNIQUE: We describe a technique for creating a neovagina with the use of an acellular dermal allograft as a replacement for split-thickness skin graft. Three patients are presented who had a successful creation of a neovagina with this technique. The indications for vaginoplasty include vaginal agglutination from lichen planus, squamous cell carcinoma of the vagina, and vaginal agenesis. CONCLUSION: The creation of a neovagina using an acellular dermal allograft can be successfully accomplished in patients undergoing constructive and exenterative procedures. The use of an acellular dermal allograft decreases operative time and decreases the incidence of postoperative morbidity because harvesting autologous tissue for the neovagina is not required.

A four step strategy for robot assisted abdominal cerclage placement prior to pregnancy.

OBJECTIVE: To demonstrate a simple, stepwise strategy for robot-assisted abdominal cerclage placement before pregnancy. DESIGN: Demonstrative video presentation. Surgical footage surrounding a case report is used to describe a four-step technique for robot-assisted abdominal cerclage placement in women with recurrent pregnancy loss or other anatomic variants before pregnancy. This video article was reviewed by the Investigational Review Board and further investigation was waived because the study was "not considered human subject research." SETTING: Tertiary medical center. PATIENT(S): A 38-year-old G4P0220 (Gestations: 4, Term deliveries: 0, Preterm deliveries: 2, Abortions: 2, Living children: 0) with a history of two second trimester losses who had failed a prior history-indicated transvaginal cerclage (Fig. 1). INTERVENTION(S): The patient underwent an uncomplicated robot-assisted abdominal cerclage using a four-step strategy: Step 1, create the bladder flap; Step 2, identify pertinent anatomy; Step 3, place the cerclage; and Step 4, hysteroscopy. MAIN OUTCOME MEASURE(S): Intraoperative technique presenting a four-step method to ensure successful robot-assisted abdominal cerclage placement. RESULT(S): Robot-assisted abdominal cerclage is a safe, viable alternative to traditional abdominal cerclage placed via laparotomy. This video outlines four critical steps to facilitate placement and decrease patient morbidity. This patient did well operatively without increased blood loss or operative time and was discharged home on postoperative day 1. She went on to have a successful future pregnancy and currently is scheduled for an elective cesarean section at term. CONCLUSION(S): Abdominal cerclages significantly improve pregnancy and neonatal outcomes in women who previously have failed transvaginal cerclage. Robot-assisted abdominal cerclage placement allows a minimally invasive approach with enhanced dexterity and better visualization for the surgeon compared with conventional laparoscopy or laparotomy, as well as decreased pain and shorter recovery time for patients. This video demonstrates placement of a robot-assisted abdominal cerclage in a patient with recurrent pregnancy loss using a simple four-step strategy to ensure successful, correct, and easy placement. To our knowledge, this is the first video demonstrating a stepwise approach to robot-assisted abdominal cerclage placement.

A Gynecologic Oncology Group Study of serum CA-125 levels in patients with stage III optimally debulked ovarian cancer treated with intraperitoneal compared to intravenous chemotherapy: an analysis of patients enrolled in GOG 172.

OBJECTIVE: Serum CA-125 values have been advocated in the monitoring of ovarian cancer patients receiving intravenous (IV) chemotherapy. This evaluation sought to determine if the CA-125 test can be used to monitor treatment effect among patients receiving intraperitoneal chemotherapy (IP). METHODS: Patient charts from a phase III clinical trial (GOG 172) were retrospectively reviewed. Serum CA-125 levels prior to each cycle of therapy were collected and compared between the IV and IP chemotherapy delivery. The association between CA-125 and progression-free survival (PFS) or overall survival (OS) was estimated and the homogeneity of the results between IP and IV chemotherapy was assessed. RESULTS: A total of 177 patients were treated with IV chemotherapy and 165 patients with IP chemotherapy with CA-125 data available were included in this analysis. The observed difference was not statistically significant in median CA-125 levels between the IV and IP arms at any time point (P>0.05 for all). Following surgery and adjuvant chemotherapy, patients with an abnormal CA-125 >35 U/ml were 2.45 times more likely to have disease progression (95% CI: 1.52-3.95, P<0.001) and 2.78 times more likely to die of disease (95% CI: 1.66-4.65, P<0.001), compared to those with a CA-125 <35 U/ml. These results were consistent with IP and IV chemotherapy. CONCLUSION: Serum CA-125 levels decrease in a similar manner during IP chemotherapy when compared to IV chemotherapy. Serum CA-125 algorithms for monitoring treatment effect that have been established for IV chemotherapy may also be applied for patients receiving IP chemotherapy.

Incidental gynecological findings on computed tomographic colonography: prevalence and outcomes.

OBJECTIVES: Computed tomographic colonography (CTC) is an investigational method for detecting colorectal polyps. Our objectives were to determine the prevalence of gynecologic findings found incidentally on CTC, and to determine the incidence of additional radiological studies and surgical procedures. METHODS: An electronic database identified female patients who underwent CTC at Walter Reed Army Medical Center from January 2002 to July 2005. CTC reports were pared down using gynecologic keywords. Subsequent radiological studies and pathology reports were evaluated for women with gynecological findings. RESULTS: Gynecologic extracolonic findings (ECF) were identified in 71 (9.5%) of the 749 women who underwent CTC. Of these 71 women, 14 (20%) underwent additional radiological and/or surgical evaluation. Nine (13%) of these women underwent surgical evaluation; all pathologic diagnoses were benign. CONCLUSION: Gynecologic extracolonic findings are common in women undergoing CTC. These gynecologic ECF identified on CTC may lead to additional investigative studies and procedures.

Diffuse laminar endocervical glandular hyperplasia: a case report.

BACKGROUND: Diffuse laminar endocervical glandular hyperplasia is extremely rare with only 14 cases reported in the literature. Diffuse laminar endocervical glandular hyperplasia is a benign lesion that is easily confused with malignancy. CASE REPORT: We present a 22-year-old woman referred to our gynecologic oncology service with a 2.0 x 4.0-cm exophytic cervical mass. Colposcopic-directed cervical biopsies were diagnosed as adenocarcinoma, suggestive of minimal deviation adenocarcinoma. Computed tomographic scans of the abdomen and the pelvis failed to reveal any metastatic foci. A radical abdominal hysterectomy with pelvic and para-aortic lymph node sampling was performed without complications. Final pathology revealed diffuse laminar endocervical glandular hyperplasia. CONCLUSIONS: Diffuse laminar endocervical glandular hyperplasia is an uncommon histological type of pseudoneoplastic glandular lesions that may be found in the cervix, and this entity should be considered in the differential diagnosis of a potentially malignant endocervical glandular lesion.

Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer.

BACKGROUND: Malignant ascites often has a profound impact on the quality of life of patients with refractory ovarian cancer. Current treatments, including dietary, medical, and procedural are often temporary and unsatisfactory options in patients approaching the end of life. CASE: We present a case of an 88 year-old receiving home hospice care with refractory ovarian cancer and severe symptomatic ascites. We performed a paracentesis and treated her with intraperitoneal bevacizumab with dramatic improvement in her ascites and the quality of her final weeks of life. CONCLUSION: Intraperitoneal bevacizumab may be a useful tool in the palliation of malignant ascites and is worthy of further study.

The ability of endometrial biopsies with atypical complex hyperplasia to guide surgical management.

OBJECTIVE: This study was undertaken to determine the clinical relevance of "qualifying comments" on pathology reports of complex atypical endometrial hyperplasia. STUDY DESIGN: A retrospective review of endometrial biopsy specimens with atypical hyperplasia at our institutions was performed if subsequent hysterectomy results were available for review. Endometrial biopsy results were graded on an ordinal scale (complex atypical endometrial hyperplasia vs atypical endometrial hyperplasia "cannot rule out a more severe lesion") and compared with pathology obtained at hysterectomy. Data were analyzed by using Fisher's exact test. RESULTS: Endometrial biopsy specimens were associated with carcinoma in 37.5% (18/48) of complex atypical endometrial hyperplasia cases and in 60% (18/30) of atypical endometrial hyperplasia-cancer cases. Atypical endometrial hyperplasia-cancer on biopsy was associated with an increased risk of discovering a malignancy at intermediate/high-risk for lymph node involvement (odds ratio 4.71, P = .0256). CONCLUSION: Biopsy specimens that show atypical endometrial hyperplasia-cancer are associated with an increased risk of finding a cancer at intermediate or high risk for nodal metastasis.

Cervical biopsy and excision procedure specimens lack sufficient predictive value for lymph-vascular space invasion seen at hysterectomy for cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether lymph-vascular space invasion (LVSI) that is discovered in cervical biopsy and excision specimens is associated with LVSI in the hysterectomy specimen of patients with cervical cancer. STUDY DESIGN: A retrospective pathologic review to determine the presence of LVSI in cervical biopsy specimens, cold-knife cone biopsy (CKC biopsy), and loop electrical excision procedure (LEEP) specimens that contained cervical cancer was performed if subsequent hysterectomy results were available for review. Data were analyzed with chi-square analysis testing. RESULTS: One hundred six patients were identified. The negative predictive value of the biopsy is lower at 0.45 than either the CKC biopsy (0.83) or LEEP (0.57); however, the positive predictive value (0.83) is higher than either CKC biopsy (0.50) or LEEP (0.75). LVSI, when present in cervical biopsy (odds ratio, 4.13; 95% CI, 0.414-98.446), CKC biopsy (odds ratio, 4.8; 95% CI, 0.542-46.280), and LEEP (odds ratio, 4.0; 95% CI, 0.439-43.793) specimens, is associated with a statistically insignificant increased risk of LVSI in the hysterectomy specimen. CONCLUSION: Cervical biopsy and excision specimens lack sufficient negative predictive value for the detection of LVSI in the hysterectomy specimen.

Suppression of ovarian cancer cell tumorigenicity and evasion of Cisplatin resistance using a truncated epidermal growth factor receptor in a rat model.

The overexpression of the epidermal growth factor receptor (EGFR) is associated with a poor prognosis in ovarian cancer. The dominant-negative EGFR (EGFR-DNR) is a truncated receptor that lacks the tyrosine kinase domain and is devoid of signaling capability. This study tested the effects of a EGFR-DNR approach in ovarian cancer cells. NuTu-19, a rat ovarian cancer cell line was rendered resistant to cisplatin. Both NuTu-19 and resistant cells were infected with a retroviral vector containing the EGFR-DNR. NuTu-19 and NuTu-DNR (NuTu-19 cells expressing the EGFR-DNR) were injected into Fisher 344 immunocompetent rats. Western blot analyses were used to assess signal transduction pathways. All rats injected with NuTu-DNR cells remained healthy following tumor injection. In contrast, 100% of the rats injected with the NuTu-19 and NuTu-Sham (NuTu-19 cells expressing an empty vector) died of disease progression at the end of 15 weeks (P = 0.00009). On Western blot analysis, both NuTu-19 and NuTu-Sham cells showed a strong activation of mitogen-activated protein kinase (MAPK) after exposure to EGF. Cisplatin-resistant cell lines showed an enhanced EGF stimulatory effect via the MAPK pathway compared with parental cells. The EGFR-DNR significantly reduced the ability of EGF to induce cell signaling through the MAPK pathway. Lastly, the EGFR-DNR can partially reverse cisplatin resistance in drug-resistant cells. The EGFR-DNR approach suggests that EGFR confers a growth advantage to NuTu-19 cells in vivo. Thus, EGFR blockade may ultimately prove to be a useful therapeutic tool in the treatment of cisplatin-sensitive and cisplatin-resistant ovarian cancers.

Cost-effectiveness analysis of liquid-based cytology and human papillomavirus testing in cervical cancer screening.

OBJECTIVE: To compare the outcomes of several cervix cancer screening strategies in a military population using a model that considers both direct and indirect costs of health care. METHODS: A Markov model of the natural history of cervical cancer was used to simulate an age-stratified cohort of 100,000 active duty women in the U.S. Army. Total costs and incremental cost-effectiveness ratios were estimated for different modalities of screening: liquid-based cytology with testing for human papillomavirus (HPV) irrespective of cytologic results compared with liquid-based cytology with HPV detection for cytologic results of atypical cells of undetermined significance (reflex HPV). The costs and outcomes of these screening methods were evaluated separately as well as in combination (liquid-based cytology and reflex HPV before age 30 years and DNA and Pap test every 3 years thereafter). Each of these screening methods was evaluated at 1-, 2-, and 3-year intervals. RESULTS: A screening strategy of liquid-based cytology and reflex HPV every 2 or 3 years is the least costly strategy among active duty women irrespective of age, especially when accounting for time costs associated with screening, diagnosis, and treatment of cervix cancer. A strategy of liquid-based cytology and HPV testing irrespective of cytology results is the most effective strategy; however, it is also the most costly of the strategies tested, even when performed in patients older than 30 years of age. CONCLUSION: In the U.S. Army, cervix cancer screening performed with liquid-based cytology and reflex HPV testing of atypical squamous cells of undetermined significance performed every 2 years is cost-effective, especially when indirect costs are considered.

The use of acellular dermal graft for vulvovaginal reconstruction in a patient with lichen planus.

BACKGROUND: Vulvovaginal lichen planus is an inflammatory dermatosis that can progress to an erosive form with scarring of the vulva, resorption of the labia minora, vaginal synechiae, and vaginal obliteration secondary to desquamative vaginitis. Traditionally, conservative medical therapy has consisted of topical corticosteroids and immunosuppressants. CASE: A 61-year-old woman with a history of refractory erosive vulvovaginal lichen planus presented with complete obliteration of the vaginal vault. The patient failed both medical and conservative surgical management and desired definitive management. After performing a skinning vulvectomy and simple vaginectomy, acellular dermal graft was used for grafting the vulva and creating a neovagina. CONCLUSION: Acellular dermal graft is a suitable graft material for vulvar and vaginal reconstruction in select patients, and it avoids the postoperative pain associated with graft harvest sites.

Gynecologic malignancies in women aged less than 25 years.

OBJECTIVE: To describe the epidemiologic characteristics of gynecologic malignancies in patients 25 years of age or younger. METHODS: The Automated Central Tumor Registry (ACTUR), the cancer registry for the Department of Defense, was used to identify children, adolescents, and young adults diagnosed with gynecologic malignancies. Specifically, primary ovarian, uterine, cervical, vaginal, and vulvar malignancies diagnosed between 1990 and 2002 were included in the analysis. Data from the Department of Defense tumor registry were then compared with results obtained from the national Surveillance, Epidemiology, and End Report (SEER) program database. RESULTS: Two hundred fifty-one cases were identified in the Department of Defense tumor registry. The most common primary site was ovary, with 116 cases (46%), followed by cervix, with 108 cases (43%). The most common histological types were germ cell (35%) for ovary, squamous cell (52%) for cervix, choriocarcinoma (18%) for uterus, and squamous cell (30%) for vulva/vagina. The 21- to 25-year-old age group had the greatest number of cases for the entire cohort (23%). Most patients had only local disease at time of diagnosis, and the 5-year survival percentage was 86% (95% confidence interval 80-91) for all patients with ovarian and cervical carcinoma. Data from the SEER program demonstrated a similar distribution and incidence pattern. CONCLUSION: The ovary and cervix are the most common primary sites of gynecologic malignancies in patients 25 years of age or younger. Health maintenance programs for patients in this age group should continue to include pelvic exams and Pap test screening.

Costs and effectiveness of alternative strategies for cervical cancer screening in military beneficiaries.

OBJECTIVE: To estimate the potential effects, on costs and outcomes, of changes in sensitivity and specificity associated with new screening methods for cervical cancer in the military. METHODS: A Markov model of the natural history of cervical cancer was created to simulate a cohort of 100,000 military beneficiaries aged 18-85. Probability estimates for various outcomes and the accuracy of screening tests were obtained from the literature. Cost estimates were obtained from military sources where available; otherwise, civilian costs were used. The outcomes and costs of conventional cytology, liquid-based cytology, and liquid-based cytology with human papillomavirus (HPV) triage were compared at 1-, 2-, and 3-year screening frequencies. RESULTS: Marginal reductions in the incidence of cervical cancer from increasing screening sensitivity are greater than reductions in cancer mortality at every screening interval. Incremental improvements in both cancer incidence and mortality are higher at less frequent screening intervals. Increases in the ratio of low- to high-grade lesions result from increasing the sensitivity of the screening test or shortening the screening interval. Both liquid-based cytology and liquid-based cytology with HPV testing are cost effective (less than $50,000 per life-year saved) when performed at 3-year screening intervals. However, neither strategy is cost-effective when performed more frequently than every 3 years. CONCLUSION: Use of a more sensitive cervical cancer screening test increases costs. However, a more sensitive test performed less frequently may be more effective and less expensive than conventional cytology done annually. In the military setting, this has significant implications for both expense reduction and readiness enhancement.

Intraperitoneal photodynamic therapy in the Fischer 344 rat using 5-aminolevulinic acid and violet laser light: a toxicity study.

OBJECTIVE: Our study was designed to investigate 5-aminolevulinic acid (ALA) as a candidate for intraperitoneal photodynamic therapy (IP-PDT). The toxicity of IP-PDT and the effects of IP-PDT on abdominal and pelvic organs, particularly the small intestine, were investigated after ALA administration and illumination with violet laser light. STUDY DESIGN AND RESULTS: The toxicity of IP-PDT was evaluated in Fischer 344 rats in two ways. In the first part of the study local PDT effects on the intestine were analyzed histologically. Violet laser light (lambda: 406-415 nm) was applied as a 2 cm diameter spot on the intestine 3 h after intraperitoneal (i.p.) administration of 50 mg/kg ALA. (A) Histological tissue samples were taken 0 min, 6 h and 1, 2 and 3 days after treatment (optical dose 3.2 J/cm(2)). Immediately after local PDT (3.2 J/cm(2), 50 mg/kg ALA) showed no effect on the intestine. However, 6 h post PDT there was complete destruction of the mesothelial lining and the outer (longitudinal) smooth muscle. Ganglion cells of the myenteric (Auerbach) plexus were also destroyed. The inner circular smooth muscle, the muscularis mucosa and the lamina propria were unharmed. Marked lymphectasia was present at this time. (B) To determine the threshold light dose of tissue destruction caused by PDT, different optical doses (1.6, 3.2, 6.4 J/cm(2)) were administered and histologic analysis of tissue samples were obtained 1 day post treatment. Destruction of the entire external musculature, submucosal structures and muscularis mucosa of the intestine at the illumination site could be observed above 1.6 J/cm(2) (50 mg/kg ALA). In the second part of the study whole peritoneal cavity PDT (WPC-PDT) was performed by illumination of the whole peritoneal cavity with 1.6 J/cm(2) violet light 3 h after ALA administration using different drug doses (200, 100 and 50 mg/kg). WPC-PDT showed lethal toxicity with a drug dose above 50 mg/kg ALA at 1.6 J/cm(2). The probable cause of death in the first 3 days after IP-PDT was rhabdomyolysis, whereas when death occurred at longer time intervals, megaintestine associated with significant damage could be observed; however, without perforation of the intestinal wall. CONCLUSION: In rats WPC-PDT with 50 mg/kg ALA, 1.6 J/cm2 at lambda=415 nm was the maximum tolerable light dose. This dose is likely to be above the threshold of destruction of ovarian cancer micrometastasis.