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OBJECTIVE Vietnam, Indonesia, and Ukraine have major burdens of IDU and HIV. We estimated the prevalence of depressive symptoms at baseline among people living with HIV who inject drugs, evaluated associations between depression at baseline and 12-month HIV care outcomes and medication-assisted treatment (MAT), and evaluated the study intervention effect by baseline depression subgroups. DESIGN HPTN 074 was a randomized study. The study intervention included psychosocial counseling, systems navigation, and antiretroviral treatment (ART) at any CD4+ cell count. METHODS Moderate-to-severe depression was defined as a Patient Health Questionnaire-9 score of 10 or above. ART and MAT were self-reported. Eligibility criteria were: 18-60 years of age, active IDU, and viral load of at least 1000 copies/ml. Adjusted probability differences (aPD) were estimated using inverse-probability weighting. RESULTS A total of 502 participants enrolled from April 2015 to June 2016. Median age was 35 years; 85% identified as men. Prevalence of baseline moderate-to-severe depression was 14% in Vietnam, 14% in Indonesia, and 56% in Ukraine. No evident associations were detected between baseline depression and ART, viral suppression, or MAT at 12-month follow-up. The study intervention improved the proportions of people who inject drugs achieving 12-month viral suppression in both the depressed [intervention 44%; standard of care 24%; estimated aPD = 25% (95% confidence interval: 4.0%, 45%)] and nondepressed subgroups [intervention 38%; standard of care 24%; aPD = 13% (95% confidence interval: 2.0%, 25%)]. CONCLUSION High levels of depressive symptoms were common among people living with HIV who inject drugs in Ukraine but were less common in Vietnam and Indonesia. The study intervention was effective among participants with or without baseline depression symptoms.

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.

Background Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. Methods and findings HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted. Conclusions In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. Trial registration ClinicalTrials.gov NCT02732730., Connie Celum and co-workers report on use of pre-exposure prophylaxis by young women in Southern Africa., Author summary Why was this study done? HIV incidence remains high (4%) in young African women. Pre-exposure prophylaxis (PrEP) has over 90% efficacy in preventing HIV infection when used consistently and could reduce HIV incidence in young African women. Adherence was low in placebo-controlled efficacy trials of oral PrEP among young African women. Qualitative research among a subset of women at unblinding of the efficacy trials indicated that women thought drug level feedback would support their adherence and foster open discussions with counselors about adherence. Drug level feedback should be evaluated as a strategy to increase PrEP adherence among young African women. What did the researchers do and find? A cohort of 451 young women in South Africa and Zimbabwe who were at risk for HIV were recruited and offered PrEP, among whom 95% initiated PrEP. Half were randomized to receive drug level feedback at months 2 and 3 plus the standard adherence support package (2-way SMS, brief counseling, and optional PrEP adherence clubs), and half received the standard adherence support package without drug level feedback. The majority had detectable intracellular drug levels through the first 6 months, and 21% had high adherence at month 6, defined as intracellular tenofovir-diphosphate (TFV-DP) ≥700 fmol/punch. PrEP adherence did not differ based on whether they were randomized to receive drug level feedback at months 2 and 3 or to standard of care (SOC) PrEP adherence support without drug level feedback. What do these findings mean? Drug level feedback was not associated with improved PrEP adherence among young African women. Additional strategies need to be evaluated for their effectiveness in increasing adherence with oral PrEP for young African women. Longer-acting and less user-dependent PrEP formulations may also overcome adherence challenges with daily oral PrEP.

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.

Background People who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention. Methods Participants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention. Results The intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (, HPTN 074 was an intervention for HIV and opioid use disorder treatment among people who inject drugs living with HIV. In the study extension, viral suppression declined for initial intervention group, yet viral suppression improved for those new to intervention.

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.

Summary Background People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use. Methods This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18–45 years (updated to 18–60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12–24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new participants. Findings Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4–1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3–2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3–2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0–1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4–2·1; incidence rate difference −1·0 per 100 person-years, 95% CI −2·1 to 1·1). No severe adverse events due to the intervention were recorded. Interpretation This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered. Funding US National Institutes of Health.

High-risk sharing practices among people who inject drugs (PWID) are associated with high rates of HIV transmission in several parts of the world. PWID in these regions face significant barriers to HIV testing and engagement in care, highlighting the need to develop and test interventions aimed at overcoming these barriers. Drug use and HIV are often highly stigmatized in these same settings, which raises safety concerns during the conduct of research. In preparing to address concerns about the safety and well-being of participants in an international research study, HPTN (HIV Prevention Trials Network) 074, we developed participant safety plans (PSPs) at each site to supplement local research ethics committee oversight, community engagement and usual clinical trial procedures. The PSPs were informed by systematic local legal and policy assessments as well as interviews with key stakeholders. Following PSP refinement and implementation, we assessed social impacts at each study visit to ensure continued safety. Throughout the study, five participants reported a negative social impact, with three resulting from study participation. Future research with stigmatized populations should consider using and assessing this approach to enhance participants’ safety and welfare.

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.

Resistance to reverse transcriptase and protease inhibitors was frequently detected in HIV from black men who have sex with men (MSM) enrolled in the HIV prevention trials network (HPTN) 061 study. In this study, integrase strand transfer inhibitor (INSTI) resistance was analyzed in black MSM enrolled in HPTN 061 (134 infected at enrollment and 23 seroconverters) and a follow-up study, HPTN 073 (eight seroconverters). The ViroSeq HIV-1 Integrase Genotyping Kit (Abbott Molecular) was used for analysis. Major INSTI resistance mutations were not detected in any of the samples. HIV from 14 (8.4%) of the 165 men, including 4 (12.9%) of 31 seroconverters, had accessory or polymorphic INSTI-associated mutations. The most frequently detected mutation was E157Q. These findings are promising because INSTI-based regimens are now recommended for first-line antiretroviral treatment and because long-acting cabotegravir is being evaluated for pre-exposure prophylaxis.

Background African women face overlapping HIV and STI risks. PrEP programs among men who have sex with men have seen high STI incidence, but few data from African women taking PrEP are available Methods HPTN 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) to evaluate uptake and adherence to daily oral PrEP in young African women. Sexually active HIV-negative women ages 16–25 were enrolled. Enrollment vaginal swabs were tested for gonorrhea (GC) and chlamydia (CT) by nucleic acid amplification, and trichomonas (TV) by rapid test. Syphilis serology was assessed. All women with positive test results received treatment. Repeat testing was conducted at 6 and 12 months. Results Of the 412 women who initiated PrEP, median age was 21 years, 84% reported a primary sex partner and a median of 4 vaginal sex acts (IQR 2,8) in the prior month; 35% reported that they never or rarely used condoms. At enrollment 29% of women had CT, 8% GC, 7% TV and 2% reactive syphilis serology. STI incidence was 29.6 per 100 person-years (py) for CT (95% CI 24.3, 35.4), 11.8 per 100 py for GC (95% CI 8.7, 15.7), and 7.1 per 100 py for TV (95% CI 4.7, 10.2). The majority of incident STIs were new infections: 79 of 119 CT infections, 41 of 48 GC infections, and 23 of 29 TV infections diagnosed were in women who did not have these infections at enrollment. The majority of these infections were asymptomatic. Conclusion The prevalence and incidence of treatable STIs were high among young African women initiating PrEP. Diagnostic STI testing is important and innovative strategies that reduce STI acquisition, complications, and their potential impact on future fertility, need evaluation within the context of PrEP services where currently syndromic STI management is the standard of care. Disclosure No significant relationships.

People who inject drugs (PWID) face barriers to engagement in antiretro-viral treatment (ART) and medication-assisted treatment (MAT). We detail the design, rapid preparation and adaptation, and systematic implementation of a flexible, individually tailored intervention for PWID in multiple settings: Indonesia, Ukraine, and Vietnam. HPTN 074 integrated systems navigation and counseling to facilitate entry and adherence to ART and MAT. Site-level guidance on the intervention involved in-depth interviews (IDIs) among PWID and their supporters and site-specific document review. IDIs emphasized ART misinformation and importance of social support for adherence. The document review revealed differences in health care system barriers, requiring an intervention that was flexible and tailored enough to address key outcomes. Implementation included regular debriefs for iterative adaptations based on participants' needs, including booster counseling sessions and subsidizing pre-ART testing. HPTN 074 provides a unique framework implementing a flexible and scalable intervention to improve ART and MAT outcomes among PWID across multiple settings.

Despite recent advances in HIV prevention and treatment, high HIV incidence persists among people who inject drugs (PWID). Difficult legal and political environments and lack of services for PWID likely contribute to high HIV incidence. Some advocates question whether any HIV prevention research is ethically justified in settings where healthcare system fails to provide basic services to PWID and where implementation of research findings is fraught with political barriers. Ethical challenges in research with PWID include concern about whether research evidence will be translated into practice; concerns that research might exacerbate background risks; and ethical challenges regarding the standard of HIV prevention in research. While these questions arise in other research settings, for research with PWID, these questions are especially controversial. This paper analyses four ethical questions in determining whether research could be ethically acceptable: (1) Can researchers ensure that research does not add to the burden of social harms and poor health experienced by PWID? (2) Should research be conducted in settings where it is uncertain whether research findings will be translated into practice? (3) When best practices in prevention and care are not locally available, what standard of care and prevention is ethically appropriate? (4) Does the conduct of research in settings with oppressive policies constitute complicity? We outline specific criteria to address these four ethical challenges. We also urge researchers to join the call to action for policy change to provide proven safe and effective HIV prevention and harm reduction interventions for PWID around the world.

BACKGROUND Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited. METHODS HIV Prevention Trials Network 058 (HPTN 058) was a randomized controlled trial designed to compare the impact of 2 medication-assisted treatment (MAT) strategies on HIV incidence or death among opioid-dependent people who inject drugs (PWID). HIV-negative opioid-dependent PWID were recruited from 4 communities in Thailand and China with historically high prevalence of HIV among PWID. A total of 1251 participants were randomly assigned to either (1) a 1-year intervention consisting of 2 opportunities for a 15-day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling [short-term medication-assisted treatment (ST-MAT)] or (2) thrice-weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions [long-term medication-assisted treatment (LT-MAT)] followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact. RESULTS Although the study was stopped early due to lower than expected occurrence of the primary end points, sufficient data were available to assess the impact of the interventions on drug use and injection-related risk behavior. At week 26, 22% of ST-MAT participants had negative urinalyses for opioids compared with 57% in the LT-MAT (P < 0.001). Differences disappeared in the year after treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection-related risk behaviors were significantly reduced in both groups after randomization. CONCLUSIONS Participants receiving BUP/NX 3 times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection-related risk behavior. These data support the use of thrice-weekly BUP/NX as a way to reduce exposure to HIV risk. Continued access to BUP/NX may be required to sustain reductions in opioid use.

Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection.

To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual.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.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 (P0.05). 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).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.

OBJECTIVE: The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection. METHODS: A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types. An independent set of endometrial cancer specimens from 394 patients were used to externally validate the differential expression of select proteins. RESULTS: 209 differentially expressed proteins were identified in a comparison of stage I endoimetrial cancers and normal post-menopausal endometrium controls (Q

Author(s): Lancaster, Kathryn E; Hoffman, Irving F; Hanscom, Brett; Ha, Tran Viet; Dumchev, Kostyantyn; Susami, Hepa; Rose, Scott; Go, Vivian F; Reifeis, Sarah A; Mollan, Katie R; Hudgens, Michael G; Piwowar-Manning, Estelle M; Richardson, Paul; Dvoriak, Sergii; Djoerban, Zubairi; Kiriazova, Tetiana; Zeziulin, Oleksandr; Djauzi, Samsuridjal; Ahn, Chu Viet; Latkin, Carl; Metzger, David; Burns, David N; Sugarman, Jeremy; Strathdee, Steffanie A; Eshleman, Susan H; Clarke, William; Donnell, Deborah; Emel, Lynda; Sunner, Lisa E; McKinstry, Laura; Sista, Nirupama; Hamilton, Erica L; Lucas, Jonathan P; Duong, Bui D; Van Vuong, Nguyen; Sarasvita, Riza; Miller, William C; HPTN 074 Study Team | Abstract: IntroductionPeople who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention.MethodsWe present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two-arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV-positive index and their HIV-negative network injection partner(s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours.ResultsThe majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self-reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test - Alcohol Consumption Questions (AUDIT-C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions.ConclusionsWhile regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations.

BACKGROUND: The purpose of this study was to confirm whether black and white women with endometrial cancer are equally tolerant of chemotherapy and identify factors that impact survival. METHODS: A retrospective review of 169 black women and 982 white women with the International Federation of Gynecologists and Obstetricians stage III, stage IV, or recurrent endometrial carcinoma was performed. All patients received doxorubicin combined with cisplatin. Chemotherapy parameters that were reviewed included relative dose, relative time, and relative dose intensity. Treatment cycles ≥7 were defined as treatment completion. RESULTS: Although black patients were more likely to experience grades 3-4 anemia (20% vs 14%) and genitourinary (5% vs 1%) toxicity, and less likely to experience severe gastrointestinal toxicity (10% vs 17%), the overall incidence of grades 3-4 treatment-related chemotoxicity was the same between the 2 groups (82% vs 82%). There were no differences in the number of cycles received, relative dose (0.57 vs 0.58), relative time (0.77 vs 0.78), or relative dose intensity (0.76 vs 0.76) for black and white patients. CONCLUSIONS: Black patients with advanced stage or recurrent endometrial cancer, treated on 4 Gynecologic Oncology Group (GOG) protocols, had similar dose intensity and severe chemotherapy-related toxicity compared with white patients, suggesting that previously described racial disparities in survival among patients in GOG trials may have an novel etiology. Cancer 2010. © 2010 American Cancer Society.

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.

The objectives of this study were to confirm whether racial disparity exists with regard to outcome between black women and white women with ovarian cancer and to identify factors associated with the administration of adjuvant treatment that had an impact on survival.A retrospective review of 97 black women and 1392 white women with International Federation of Gynecology and Obstetrics stage III/IV ovarian carcinoma was performed. All patients received paclitaxel combined with cisplatin while participating in 1 of 7 Gynecologic Oncology Group clinical trials. The treatment parameters that were reviewed included relative dose, relative time, and relative dose intensity. The treatment parameters and outcomes were compared between black patients and white patients.There were no differences in relative dose (0.90 vs 0.89), relative time (1.02 vs 0.99), or relative dose intensity (0.90 vs 0.91) received between black patients and white patients. Black women had less grade 3 and 4 leukopenia (53% vs 63%; P.05) and gastrointestinal toxicity (10% vs 19%; P.05) than white women. Performance status0, ageor=70 years, and mucinous histology were associated with not completing treatment (P.001). The median progression-free survival was 16.2 months for black patients and 16.1 months for white patients, and the median overall survival was 37.9 months and 39.7 months, respectively (P.05 for all).When they received similar treatment, there was no difference in clinical outcome between black women and white women with advanced stage epithelial ovarian cancer when they received similar treatment as participants in Gynecologic Oncology Group clinical trials. Black patients may experience less severe gastrointestinal toxicity or leukopenia compared with whites when treated with platinum-based chemotherapy.

Objective To examine whether preschool children with Attention deficit/hyperactivity disorder (ADHD) utilize more speech and language therapy (ST), occupational therapy (OT), and physical therapy (PT) services and are more likely to be placed in special education (SPED) classrooms as compared to their peers. Corresponding financial consequences were also examined. Methods The amount of ST, OT, and PT, as well as SPED placements, was examined in 3- and 4-year-old children with and without ADHD (n = 109 and n = 97, respectively) during the baseline portion of an ongoing, 5-year longitudinal study. Costs for individual services and aggregate cost were determined per child and compared across groups. Results Preschool children with ADHD were more likely to receive individual and multiple services. Higher rates of service utilization translated into increased costs for each individual service with the exception of PT. Conclusions A comprehensive understanding of service utilization in the early years of development is important in addressing the increased service use in the preschool years and assist in guiding allocation of resources.

Purpose To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC). Patients and Methods A retrospective review of 360 patients with International Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS). Results The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively. Conclusion Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.

Oligonucleotide array and tissue microarray analysis (TMA) by our group has revealed that folate binding protein (FOLR1) is overexpressed in some types of uterine cancer, particularly tumors with serous histology. Since FOLR1 overexpression is a frequent event in some types of endometrial carcinoma, we examined the relationship between FOLR1 overexpression and clinical and pathologic features to determine its prognostic relevance.A tissue microarray (TMA) comprised of primary tumor specimens from 485 patients diagnosed with endometrial adenocarcinoma was used to identify cases characterized by FOLR1 overexpression. A proportional hazards model was used to evaluate the association of FOLR1 overexpression with progression-free survival while accounting for confounding influences.Overexpression of FOLR1 was observed in 50/292 (17%) cases and was seen more often in poorly differentiated cancers (22/90 [24%], p=0.051) and tumors with serous histology (16/32 [50%], p0.001). A shorter progression-free survival was noted in patients with FOLR1 overexpression (log-rank p=0.016) that persisted when the data were limited to patients with stage III/IV disease (log-rank p=0.021) or serous tumors (log-rank p=0.020). Multivariate Cox regression analysis revealed that patients with FOLR1 overexpression had a shorter progression-free survival (H.R. 2.14; 95% CI 1.07-4.28) even when controlling for stage, grade, myometrial invasion and adjuvant chemotherapy.Our data show that FOLR1 overexpression is not only a biomarker associated with endometrial cancer, but it also appears to be a prognostic factor associated with adverse outcome. These findings suggest that FOLR1 may be an appealing target for biological therapies in some types of endometrial carcinomas.

Folate receptor alpha (FOLR1) is a membrane bound receptor involved in the transport of folate as well as other regulatory cellular processes. The purpose of this study was to examine the expression of FOLR1 in uterine cancers and to identify changes in gene expression that are associated with overexpression of FOLR1.Fifty-eight frozen uterine cancer specimens were stained for FOLR1 using immunohistochemistry and results were correlated with transcript expression noted on quantitative PCR. Total RNA from 16 cases of uterine serous carcinoma (USC) was analyzed for gene expression using the Affymetrix HG-U133A and HG-U133B GeneChip set. USCs overexpressing FOLR1 were compared to cancers with an absence of FOLR1 using binary comparison and template matching of data was used to identify genes that correlate with FOLR1 expression. Selected targets from this analysis were evaluated by quantitative PCR as well as in an independent set of USC represented in quadruplicate on a tissue microarray (TMA).Overexpression of FOLR1 was observed in 11/16 (69%) of USC and 0/10 normal endometrium cases using frozen tissue specimens. Binary comparison between FOLR1 positive and negative cases identified 121 genes altered by 2-fold at p0.01 of which 45 are well correlated with FOLR1 expression pattern. Using quantitative PCR, both mesothelin (MSLN) and PTGS1 (COX1) were significantly increased in FOLR1 overexpressing tumors (p=0.014 and p=0.006 respectively). TMA confirmed that overexpression of FOLR1 and MSLN respectively occurred in 23/48 (48%) and 17/54 (32%) of pure USC.Both FOLR1 and MSLN are cell surface targets that are co-expressed at high levels in USC and are appealing targets for biologic therapy.

A prospective observational study of HIV seroincidence among high-risk injection drug users (IDU) was carried out in Guangxi, China. The primary objectives of this study were (1) to estimate HIV seroincidence (2) to estimate participant retention rate and (3) to evaluate changes in drug use and sexual behavior over a one year period.Five hundred HIV seronegative IDU were enrolled. HIV-1 incidence and retention rates were analyzed as a function of sociodemographic, behavioral, and recruitment variables. Changes in drug use and sexual behavior were analyzed at the baseline, 6-month and 12-month follow- up visits.At 12 months of follow-up, the HIV-1 incidence rate was 3.1 per 100 person years, [95% CI: (1.6%; 5.2%)] and participant retention rate was 87%. Reported changes in high-risk behaviors over 12-months included significant decreases in the frequency of heroin injection, in direct or indirect sharing of injection equipment, and in the number of sexual partners.HIV incidence is high among IDU in Guangxi, China despite a self-reported decrease in some high risk behaviors over the course of the study.

Objective. Oxaliplatin and topotecan have demonstrated activity as single agents against recurrent platinum-sensitive and -resistant ovarian cancer, as well as synergy in vitro. This was a dose-finding study of combination therapy with weekly topotecan and alternating-week oxaliplatin in patients with recurrent epithelial ovarian cancer. Methods. Eligible patients had a diagnosis of recurrent ovarian or primary peritoneal carcinoma, a performance status of 0–2, and normal bone marrow, renal, and hepatic function. On days 1 and 15 of a 28-day cycle, patients received a fixed dose of oxaliplatin (85 mg/m 2 ) via intravenous infusion. On days 1, 8, and 15, patients received an escalating dose of intravenous topotecan (2.0–4.0 mg/m 2 ). Five dose levels were planned with a minimum cohort of 3 patients at each level. Results. Thirteen patients were enrolled and received a total of 50 cycles of chemotherapy. The maximum tolerated dose was 85 mg/m 2 of oxaliplatin and 3.0 mg/m 2 of topotecan, and grade 3 neutropenia was the dose-limiting toxicity. Four of nine (44%) evaluable patients had stable disease or a partial response to the drug combination as assessed by cancer antigen-125 levels. Conclusions. A 28-day schedule of oxaliplatin and topotecan is safe and well tolerated. Because of the in vitro synergy observed between topoisomerase I inhibitors and platinum derivatives and the tolerability reported in the current study, this regimen warrants further investigation.

BACKGROUND. Previous studies have reported shorter survival of black women compared with white women who had advanced/recurrent endometrial cancer. It has been suggested that this may reflect racially based differences in treatment. METHODS. The authors retrospectively reviewed data from 169 black women and 982 white women with International Federation of Gynecologic Oncology (FIGO) Stage III, Stage IV, or recurrent endometrial carcinoma who were participants in 1 of 4 Gynecologic Oncology Group randomized treatment trials of doxorubicin alone or combined with paclitaxel and/or cisplatin. Demographic, histologic, treatment, and outcome data were analyzed to estimate survival, and between-group comparisons were performed. RESULTS. The pooled data revealed that black women were more likely to have papillary serous histology (P < .001), Stage IV disease (P < .001), and higher tumor grade (P < .001) compared with white women, and survival was worse among black women than among white women (median survival, 10.6 months vs. 12.2 months, respectively; P < .001). A Cox proportional hazards regression analysis that was adjusted for performance status, disease stage, tumor histology, tumor grade, and treatment demonstrated worse survival for black women (hazards ratio, 1.26, 95% confidence interval, 1.06–1.51; P = .010). CONCLUSIONS. The data from a large group of women with advanced/recurrent endometrial cancer suggested that a racial disparity in survival persists, despite the finding that black women and white women received similar treatment. Although the causes of racial disparity in endometrial cancer remain to be elucidated, socioeconomic, biologic, and cultural factors should be investigated to identify the etiologic origins of this multifactorial healthcare problem. Cancer 2006. Published 2006 by the American Cancer Society

The liquid-based cytology Pap test was adopted as the exclusive collection method for cervical cytology in military treatment facilities within the National Capital Area in 2001. We sought to determine the impact of converting from conventional to liquid-based cervical cytology.A retrospective population-based study was performed to analyze the cervical cytology results from the National Capital Area for fiscal years 1999, 2000, 2002, and 2003. Using a computer database, the results of 78,738 conventional and 76,675 liquid-based cervico-vaginal cytology examinations were reviewed. All cytology samples during the study period were collected with the same collection device and were processed in a single laboratory.An increase of 116% (P0.005) in the mean rate of LSIL detection and a 38% (P0.005) increase in HSIL detection were noted with conversion to liquid-based cytology. A 65% (P0.005) decrease in the mean rate of atypical glandular cell detection was also observed. However, a mean increase of 46% (P0.005) per year was noted in the unsatisfactory rate with conversion to liquid-based cytology. The incidence of cervical carcinoma did not change during the study period.Consistent with previous reports, conversion from conventional to liquid-based Pap testing in this population resulted in a significant increase in the detection rates of both LSIL and HSIL. Contrary to earlier studies, we noted an almost 50% increase in the number of unsatisfactory samples after conversion. Further studies are warranted to determine the potential etiology of these findings to include the role of collection devices.

Five dogs with unilateral thoracic limb lameness, neurologic deficits, muscle atrophy, and pain, or a combination of these signs, were examined using ultrasonograghy. Large, hypoechoic tubular masses that displaced vessels and destroyed the normal architecture were found in each dog. The affected axilla of each patient was then imaged with computed tomography or magnetic resonance to fully assess the extent of the masses. We describe the use of ultrasound in screening patients for brachial plexus tumors.

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.

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.

BACKGROUND In the current study, the authors sought to examine the prognosis and recurrence risk for patients with cervical squamous intraepithelial lesions (SILs) diagnosed during pregnancy. METHODS A retrospective review of all women who gave birth at Walter Reed Army Medical Center (Washington, DC) or the National Naval Medical Center (Bethesda, MD) between 1986 and 1997 was performed. One hundred fifty-seven patients with SILs who underwent antepartum and postpartum evaluation were identified from a total of 6248 records of birth at these two institutions. Patient demographics and cervical cytology and histology were reviewed. RESULTS One-hundred twenty-nine patients were diagnosed with low-grade squamous intraepithelial lesions (LSILs) antepartum. Of these patients, 49 (38%) had a previous history of abnormal cervical cytology (30 LSILs and 19 high-grade squamous intraepithelial lesions [HSILs]). Twenty-eight patients were diagnosed with HSIL antepartum. Of these patients, 24 (86%) had a history of abnormal cervical cytology. Sixty-two percent of patients with antepartum LSILs had disease regression postpartum, 32% had persistent LSILs postpartum, and 6% experienced progression of an LSIL to an HSIL. All cases of HSIL that were diagnosed antepartum persisted on postpartum cytologic examination. Three patients were found to have microinvasive squamous cell carcinoma after postpartum conization. Five years of follow-up data were available for 98 patients (60%), 78 of whom had antepartum LSILs and 20 of whom had antepartum HSILs. Sixty percent of patients with antepartum LSILs detected on Pap smear developed recurrent LSILs within 5 years, and all 20 patients with antepartum HSILs developed recurrent HSILs within 5 years. CONCLUSIONS Most cases of LSIL regressed or remained stable during pregnancy. All cases of HSIL diagnosed antepartum persisted in the postpartum period, and 11% of patients with antepartum HSILs were found to have invasive carcinoma postpartum. High rates of recurrence for both LSIL and HSIL were noted 2–5 years after the diagnosis of SIL in the antepartum. Cancer (Cancer Cytopathol) 2004. Published 2004 by the American Cancer Society.

Introduction Gastrointestinal obstruction is a common complication of recurrent ovarian cancer. Proximal intestinal obstruction, at the level of the duodenum or proximal jejunum, can result from bulky intraperitoneal or retroperitoneal disease. Classic management has been palliation of symptoms with a gastrostomy or jejunostomy tube. Cases We describe a series of four patients with recurrent ovarian carcinoma and proximal intestinal obstructions treated with a bypass stapled side-to-side gastrojejunostomy at the time of secondary cytoreduction or surgical palliation. The clinical history, preoperative evaluation, surgical technique, and outcomes of each patient are reviewed. Discussion Gastrojejunostomy may offer patients with ovarian cancer and a proximal intestinal obstruction symptomatic relief and an opportunity for resumption of enteral feedings.

Objective The Department of Defense health care system provides access to care without respect to age, race, or socioeconomic status. We sought to determine the effect of race as a predictor of survival in patients with endometrial cancer treated in the Department of Defense medical system. Methods Information on patients with endometrial carcinoma was extracted from the Department of Defense centralized tumor registry for the period 1988 to 1995. Data included age at diagnosis, military status, race, tumor histology, grade, FIGO surgical stage, adjuvant therapies, and disease-free survival. The χ 2 test was used for analysis of prognostic factors and adjuvant treatments between racial groups. Actuarial survival curves were calculated by using the method of Kaplan and Meier and compared by the log-rank test. Variables found to be significant on univariate analysis ( P Results Of 1811 patients meeting criteria for the study, racial distribution was 90% Caucasian, 4.4% African-American, and 5.5% Asian-Pacific Islander. African-Americans had more advanced stages of disease compared to Caucasians ( P P P = 0.007). Additional poor prognostic factors included age >60 years, grade, unfavorable histology, and stage. On multivariate analysis age >60 years, stage, and Asian-Pacific Islander race remained significant prognostic factors. Conclusion African-Americans and Asian-Pacific Islanders had worse survivals than Caucasians. After controlling for imbalances in clinicopathologic factors, Asian-Pacific Islander race was found to be a newly identified poor prognostic factor.

BACKGROUND The objective of this study was to compare survival between patients with adenocarcinoma and patients with adenosquamous carcinoma of the cervix. METHODS Patients who were diagnosed with invasive cervical carcinoma from 1988 to 1999 were identified from the Automated Central Tumor Registry for the United States Military Health Care System. Clinical data, including race, age at diagnosis, histology, tumor grade, disease stage, lymph node status, treatment modality, and survival, were collected. Survival analysis was performed with Kaplan–Meier survival curves and compared using the log-rank test. RESULTS A total of 273 women were identified, 185 women with a histologic diagnosis of adenocarcinoma (AC) and 88 women with a diagnosis of adenosquamous carcinoma (ASC). Among the women with ASC, only 5% had Grade 1 tumors, and 66% had Grade 3 tumors. By comparison, among the women with AC, 37% had Grade 1 tumors, and 26% had Grade 3 tumors (P < 0.001). There was no difference in the incidence of positive lymph nodes or in the number of patients who underwent radical hysterectomy as primary treatment between patients with ASC and patients with AC. More patients with ASC received radiation therapy (51% vs. 28%) or chemotherapy (29% vs. 12%) as treatment (P < 0.001). Patients who had tumors with ASC histology had a significantly decreased 5-year survival rate compared with patients who had tumors with AC histology (65% vs. 83%; P < 0.002). When patients with early-stage cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage I) were examined separately, there was no statistically significant difference in the 5-year survival rate (AC, 89%; ASC, 86%; P = 0.644). However, when patients with advanced-stage disease (FIGO Stages II–IV) were analyzed, ASC was associated with a significant decrease in median and overall survival (P = 0.01). When the results were analyzed by grade, patients who had tumors with ASC histology had a shorter survival compared with patients who had AC histology of any grade; however, this was a significant difference only for patients with Grade 1 tumors: The 5-year survival rate for patients with Grade 1 AC was 93%, compared with 50% for patients with Grade 1 ASC (P < 0.01). CONCLUSIONS ASC histology appears to be an independent predictor of poor outcome in women with cervical carcinoma compared with their counterparts who have pure AC. The significant decrease in survival was observed only in patients with advanced-stage cervical carcinoma. This decreased survival may be related mainly to the grade of ASC. Cancer 2003;97:2196–202. Published 2003 American Cancer Society. DOI 10.1002/cncr.11371

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.

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 I 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/ka 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. (C) 2002 Elsevier Science BY All rights reserved

Objective. The expression status of p27 and cyclin D1 was examined in 21 uterine papillary serous carcinoma (UPSC) specimens to determine the role of these genes in the development of this disease. The status of p53, p16, Rb, and K-ras was also determined in these tissues so that a marker profile for UPSC could be compared with the published marker profile for other forms of endometrial and ovarian cancer. Methods. Immunohistochemistry was performed on 21 UPSC tissue sections to determine the expression status of p27, cyclin D1, p53, p16, and Rb. K-ras mutations were identified by restriction fragment length polymorphism analysis of DNA isolated from the UPSC sections. Results. All specimens displayed at least one molecular abnormality. A high incidence of p27 alterations were observed, with reduced p27 expression measured in 16 of 21 (76%) tumors, followed by p53 alterations observed in 13 of 21 (62%) tumors. The p27 abnormalities occur at an early stage of the disease, with 63% (5/8) of Stage I cases displaying reduced p27 expression. Cyclin D1 overexpression was observed in 4 of 21 (19%) specimens, whereas p16, Rb, and K-ras abnormalities were each observed in 2 of 21 specimens (10%). Both K-ras mutations were at codon 12. The p16 and Rb abnormalities coexisted in the same specimens. Conclusion. UPSC tumors display a high incidence of p27 abnormalities, suggesting that p27 abnormalities play an important role in the development of this disease. Our results also indicate that cyclin D1 overexpression is involved in the development of a small number of UPSC cases. A comparison of our results with reports by other authors suggests that UPSC shares molecular marker alterations with both ovarian cancer and endometrioid adenocarcinoma.

Background. Spontaneous pregnancy is rare after radical cytoreduction and intraperitoneal chemotherapy. Case. We present a case of a 28-year-old female with extensive, bulky malignant peritoneal epitheliod mesothelioma who underwent optimal cytoreduction with peritonectomy followed by intraoperative hyperthermic cisplatin and postoperative intraperitoneal paclitaxel and fluorouracil. Fourteen months after the conclusion of her therapy, she spontaneously conceived, resulting in an uneventful term pregnancy and spontaneous vaginal delivery. Conclusion. Fertility may be preserved in select patients after radical cytoreduction and hyperthermic intraperitoneal chemotherapy.

Tumor cells from 7 freshly isolated human ovarian tumors and 2 continuous human ovarian cancer cell lines were analyzed for their surface expression of MHC class-1, class 11 and ICAM-1 surface antigens before and after exposure to gamma-irradiation and/or the cytokines TNF-alpha plus IFN-gamma. All 7 fresh tumors expressed high levels of MHC class 1 and 1CAM-1 antigens, and levels were markedly up-regulated after exposure to TNF-alpha plus IFN-gamma Similarly, class-11 antigens were either induced (3 out of 7 tumors) or significantly up-regulated by TNF-alpha plus IFN-gamma. Exposure to high doses of gamma-irradiation also increased the expression of MHC class-1 and ICAM-1 antigens, albeit to a modest degree. MHC class 1 and ICAM-1 antigens expression was much lower on continuous human ovarian cell lines than on the fresh tumors. Exposure of these cells to TNF-alpha plus IFN-gamma markedly up-regulated antigen expression to levels comparable to those expressed on the freshly isolated tumors. With the established ovarian cell lines, removal of cytokines caused a rapid down-regulation of antigen expression to basal levels within 6 days, while in the fresh tumors a low level of up-regulation was still present at this time. In contrast, exposure to cytokines followed by high-dose gamma-irradiation resulted in a highly significant and long-lasting expression of each surface antigen which was either up-regulated or induced by the cytokines. These data indicated that the combination of these modalities may be beneficial in generating optimal antigen expression for use of tumor cells in vaccine studies.

The density-dependent purification of islets from several species of mammalian pancreata is improved by prior storage of the dispersed, collagenase-digested pancreas in suitable storage solutions, such as University of Wisconsin (UW) solution. The optimal composition of such solutions, however, is not fully established, although previous investigations have suggested separately that cellular impermeants and colloids are important components. To investigate this issue further, dispersed tissues from 7 porcine and 7 human pancreata were stored in UW or in solutions containing the impermeants lactobionate and raffinose, with either no added colloid or in the presence of the colloids hydroxyethyl starch, dextran 40, dextran 250, or Ficoll 400; hydroxyethyl starch-containing solutions in which the principal cation was sodium, rather than potassium, were also studied. Subsequent purification of islets on continuous linear density gradients of BSA was then assessed by insulin/amylase assay of gradient fractions. Islet purity was slightly reduced using solutions containing impermeants but lacking a colloid, compared with using UW. In the combined presence of impermeants and a colloid, however, islet purity was similar to that obtained with UW, and for porcine pancreata, solutions containing Ficoll 400 or dextran 40 were slightly superior to UW. Purity was not, however, influenced by the sodium to potassium ratio of storage media. In conclusion, impermeants and colloids are both essential components of solutions used to preserve pancreatic tissue before islet purification, findings which may be relevant when designing media for use during other phases of islet isolation, e.g., during collagenase digestion/density gradient purification.

Background. Incontinent urinary diversions are frequently performed in gynecologic oncology. The incontinent urinary diversions generally utilize a short segment of distal ileum or colon as a conduit. Conduit complications such as anastomosis leaks and strictures may be related to the technique utilized for inserting and securing the ureters and the degree of postimplant manipulation. Technique. We describe a technique using a metal Yankaur suction device placed through the conduit's matured stoma to facilitate the mucosa-to-mucosa anastomosis of the ureters. This procedure allows for tension-free ureteral anastomoses, the isolation of the ideal conduit length, optimal stomal maturation, and reduced manipulation of the conduit after the ureteral anastomoses. Conclusion. This modification provides an elegant, yet simple and expedient, method of ureteral anastomosis to the incontinent urinary conduit.

While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand.Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed.525 participants completed the informed consent survey (Heng County, China¼255, Xinjiang, China¼229, Chiang Mai, Thailand¼41). Mean age was 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6e10 yrs vs 0e5 yrs: OR¼0.27, p¼0.03; more than 11 yrs vs 0e5 yrs: OR¼0.18, p¼0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR¼0.07; p¼0.01), not minding (OR¼0.26; p¼0.03), being bored (OR¼0.25; p¼0.01) and not finding the questions easy (OR¼0.10; p¼0.01).Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent.clinicaltrials.gov number NCT00270257.

article i nfo 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 (b50, ≥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%,pb0.01),non-localized tumors(31.8% vs 24.5%, p=0.02),andpoorly differentiated tumors (20.5% vs 15.0%, pb0.01). Among women 50 years and older, similar significant racial disparitieswereobserved.However,nosignificantracialdifferenceswereobservedamongyoungpatients.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.