Livebirth and utero-placental insufficiency in Papio hamadryas baboons with uterus angiosome perfused by bilateral utero-ovarian microsurgical anastomoses alone.

STUDY QUESTION: Can the baboon uterus support a gestation to livebirth with an angiosome using microsurgically anastomosed utero-ovarian vessels and lacking uterine arteries and veins? SUMMARY ANSWER: Our angiosome model allows healthy livebirth albeit with risk of fetal growth restriction and stillbirth. WHAT IS KNOWN ALREADY: Uterine transplant can provide livebirth in humans, but requires a living donor to undergo a prolonged laparotomy for hysterectomy. In an attempt to avoid the time-consuming dissection of the uterine vein, our group has previously shown maintenance of baboon uterine menstrual function after ligation of the uterine vein and after ligation of both the uterine artery and uterine vein. STUDY DESIGN, SIZE, DURATION: In a 19-month timespan, three baboons underwent laparotomy to surgically alter uterine perfusion, and pregnancy outcomes were monitored after spontaneous mating in a breeding colony. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three nulligravid female Papio hamadryas baboons in a breeding colony underwent laparotomy to ligate uterine arteries and veins along with colpotomy and cervico-vaginal anastomosis. During the same surgery, the utero-ovarian arteries and veins were microsurgically transected and re-anastomosed to themselves. Intraoperative organ perfusion was confirmed with laser angiography. After a recovery period, monitoring of menstrual cycling via menstrual blood flow and sex-skin cycling occurred, as well as uterine viability via sonography and cervical biopsy. Each baboon was released to the breeding colony for spontaneous mating and pregnancies dated by menstrual calendar and compared with early ultrasound. Delivery outcomes were monitored in each including neonate weight and placental pathology. In the event of a stillbirth, the animal was returned to the breeding colony for repeat mating attempts. After achieving a livebirth, the maternal baboon was removed from the study. MAIN RESULTS AND THE ROLE OF CHANCE: Each baboon in the trial underwent successful surgery with all uteri demonstrating viability and return of menstrual function within 10 weeks of surgery. Pregnancies occurred within two menstrual cycles in breeding colony. Baboons one and two initially had vaginal breech stillbirths, both with appearance of placental insufficiency, and one with fetal growth restriction. Baboon three underwent scheduled cesarean delivery resulting in a normally grown livebirth. Baboon one had a subsequent pregnancy resulting in a livebirth via cesarean delivery. LIMITATIONS, REASONS FOR CAUTION: Stillbirth in two of four gestations, and fetal growth restriction in one of four, are the largest concerns in our perfusion model. It remains uncertain whether the stillbirths resulted from placental insufficiency, or birth trauma from breech deliveries. WIDER IMPLICATIONS OF THE FINDINGS: The success of two livebirths warrants further attempts at improving consistency of our proposed uterine angiosome. This may allow living uterine donors to undergo less-invasive and shorter donor hysterectomy procedures. STUDY FUNDING/COMPETING INTEREST(S): The study had no external sponsors, and was supported by the Cleveland Clinic Foundation. Some equipment was loaned without cost to the research team including a laser angiography system courtesy of Novadaq Technologies, Inc. (Missaugua, ON, Canada) and a surgical microscope courtesy of DB Surgical (Coral Springs, FL, USA). B.B., K.A., M.S., K.R., M.M., P.F.E., A.T. and T.F. have no conflicts of interest. M.L.S. and S.Z. report activity as consultants for Medtronic-Covidien, and S.Z. also is a consultant to Applied Medical.

First Report on the Occurrence of Grapevine leafroll-associated virus 5 in Chilean Grapevines.

Grapevine leafroll is one of the most widespread and economically damaging viral diseases of grapevines. At least eight distinct Grapevine leafroll-associated viruses (GLRaVs), all members of the Closteroviridae family, have been associated with this disease (4). GLRaV-5 was recently reported in vineyards from Argentina (2). To determine if GLRaV-5 was present in Chilean grapevines, in addition to the previously reported GLRaV-1, -2, -3, -4, -7, and -9 (1), 45 dormant cane samples from 12 different cultivars were collected from different geographic regions of Chile and screened by reverse transcription-PCR. Two of the forty-five samples (cvs. Sauvignon Blanc and Superior) collected from the III (700 km north of Santiago) and VI (150 km south of Santiago) regions of Chile, respectively, were found to be infected with GLRaV-5 using two different pairs of virus-specific primers. The first pair of primers, LR5-1F: 5'-CCCGTGATACAAGGTAGGACA-3' and LR5-1R: 5'-CAGACTTCACCTCCTGTTAC-3' (3), was used to amplify a 690-bp fragment corresponding to a partial region of the coat protein gene. The sequences obtained from the two positive samples (GenBank Accession Nos. HM214148 and HM214149) shared 97 and 94% of nucleotide identities, respectively, with the corresponding fragment of a reference GLRaV-5 isolate (GenBank Accession No. EU815935). Both samples shared 99% of amino acid identity with the same reference isolate. A second pair of primers, LR5upF: 5'-CTCTGCTTTTCTGCTGGCA-3' and LR5doR: 5'-TATCTTTTATCTCCCGATAAACGAG-3' (4) that amplified a 160-bp fragment of the HSP70h gene was also used. The positive Chilean samples (GenBank Accession Nos. HM214150 and HM214151) shared in both cases 98% nucleotide and 98% amino acid identities with the corresponding fragment of a reference GLRaV-5 isolate (Accession No. AF039552). The two GLRaV-5-positive plants were additionally infected with other viruses previously reported in Chile (1). The cv. Sauvignon Blanc sample was also infected with GLRaV-2, Grapevine fleck virus, and Grapevine rupestris stem pitting-associated virus. The cv. Superior sample was also infected with GLRaV-3, GLRaV-4, and Grapevine virus A. References: (1) E. A. Engel et al. J. Virol. Methods 163:445, 2010. (2) S. Gomez et al. Virus Genes 38:184, 2009. (3) X. Good and J. Monis. Phytopathology 91:274, 2001. (4) V. I. Maliogka et al. J. Virol. Methods 154:41, 2008.

First Detection of Grapevine leafroll-associated virus 4 in Chilean Grapevines.

Grapevine leafroll is one of the most widespread and economically relevant viral diseases of grapevines. At least nine distinct Grapevine leafroll-associated viruses (GLRaVs), all members of the Closteroviridae family, have been associated with this disease in grapevine. Grapevine leafroll-associated virus 4 (GLRaV-4), currently classified as a Closteroviridae member under the Ampelovirus genus, was initially described in California. To determine if GLRaV-4 was present in Chilean grapevines, in addition to the previously reported GLRaV-1, -2, -3, -7, and -9 (1,2), 35 dormant cane samples from 12 different cultivars were collected from different regions of Chile and screened by reverse transcription-PCR. Two of the 35 samples (both cv. Thompson Seedless) collected from the III and VI regions of Chile were found to be infected with GLRaV-4 using two different pairs of GLRaV-4 specific primers. The first pair of primers, HSPV-F: 5'- ACA TTC TCC ACC TTG TGC TTT T -3' and HSPC-R: 5'- CAT ACA AGC GAG TGC AAT TAC -3' (3), was used to amplify a 321-bp fragment corresponding to a partial region of the HSP70h gene. The sequence (GenBank Accession Nos. EU746618 and EU746619) from both positive samples shared 98.4% nucleotide identity and approximately 99% identity with the corresponding fragment of a Californian GLRaV-4 isolate (GenBank Accession No. AF039553). Since there are no commercial antibodies available for GLRaV-4 detection, a second pair of primers, LR4CPINT-F: 5'- GAG AGT GAC AAG CAC CAG GTG C -3' and LR4CPFIN-R: 5'- TCA CCT CCT GTT GCC CA -3' (4), that amplified a 492-bp fragment of the coat protein gene was also used. The sequences of the 492-bp fragment from both Chilean samples (GenBank Accession Nos. EU746620 and EU746621) shared 99.6% nucleotide identity with one another and had 96.5% identity with an Israeli GLRaV-4 isolate (GenBank Accession No. AM176759). To our knowledge, this is the first report of GLRaV-4 in Chile. Further studies will help to establish the effects and incidence of this virus in Chilean grapevines. References: (1) E. Engel et al. Plant Dis. 92:1252, 2008 (2) N. Fiore et al. J. Plant Pathol. 90:125, 2008. (3) F. Osman et al. J. Virol. Methods 141:22, 2007. (4) P. Saldarelli et al. J. Plant Pathol. 88:203, 2006.

Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis, and therapeutic modalities.

Ureteroarterial fistulas (UAF) are a rare but potentially life-threatening complication of intra-abdominal malignancy, typically occurring after vascular or pelvic surgery. Patients with a history of radical pelvic surgery, chronic indwelling ureteral stents, and prior pelvic radiation appear to be at increased risk. The predisposing risk factors suggest that gynecological oncologists are the likely specialty to face this problem and should be familiar with the clinical presentation and etiology of UAF. We present two such cases to illustrate these salient points of clinical diagnosis and management.

Optical coherence tomography as a diagnostic aid to visual inspection and colposcopy for preinvasive and invasive cancer of the uterine cervix.

The purpose of this study was to determine the sensitivity and specificity of optical coherence tomography (OCT) under two well-defined clinical settings. First, as an aid to cervical cancer screening, using visual inspection with acetic acid (VIA) in low-resource settings, and the second, as an adjunct to the traditional management of abnormal cervical cytology with colposcopy and biopsy. Patients referred for colposcopy with > or = atypical squamous cells of undetermined significance were accrued for the study. Each subject underwent VIA and colposcopy. OCT was performed in all VIA- and colposcopy-positive areas and at the squamocolumnar junction in all four quadrants. The sensitivity of VIA for > or = cervical intraepithelial neoplasia 2 was 76% (95% CI 58-88). When OCT was applied to VIA as a secondary screen, the specificity improved from 34% (95% CI 27-41) to 61% (95% CI 60-74). With liberal diagnostic criteria for the majority of the colposcopy examinations, OCT showed an even greater relative improvement in specificity. OCT proved to be a fair diagnostic modality (receiver operating characteristic curve 0.73) adjunctive to VIA and colposcopy. On the basis of the above findings, we believe that this technology could potentially show greatest utility in the management of cervical dysplasia in low-resource settings where a single episode of care is most desirable.

Primary gynecological neoplasms and clinical outcomes in patients diagnosed with breast carcinoma.

The purpose of this study was to quantify and describe nonmammary neoplasms (n-MN), particularly gynecological neoplasms, in a patient population previously diagnosed with breast cancer. Data were collected prospectively in our institutional review board-approved registry for patients diagnosed with infiltrating breast cancer or ductal carcinoma in situ. Patients who developed a second, n-MN were identified; neoplastic site, time to development after breast cancer, and clinical outcomes were recorded. FIGO stage was recorded for patients who developed a gynecological neoplasm. Synchronous bilateral breast cancer was defined as a second, contralateral diagnosis made within 12 months of the first and, similarly, synchronous n-MN were defined as those identified within 1 year of a breast cancer diagnosis. Outcome curves were generated using the method of Kaplan and Meier, and compared using the log-rank test. Of 4126 patients diagnosed with breast cancer, 3% developed a n-MN, the majority of which were nongynecological and asynchronous to the initial breast cancer diagnosis. Three percent of patients diagnosed with breast cancer were diagnosed with a second, n-MN. Among patients who developed a n-MN, most developed a nongynecological cancer more than 1 year after the initial breast cancer diagnosis, and their outcomes were significantly worse than those patients who did not develop a n-MN.

Breast papillomas: current management with a focus on a new diagnostic and therapeutic modality.

Breast papilloma is a term that describes an intraductal papillary configuration of the mammary epithelium on macroscopic or microscopic examination. It includes solitary intraductal papillomas, multiple papillomas, papillomatosis, and juvenile papillomatosis (JP).Recent advances in mammary ductoscopy (MD) have raised new possibilities in the diagnosis and treatment of breast papillomas. This technique represents an important diagnostic adjunct in patients with pathological nipple discharge (PND) by allowing direct visualisation and biopsy of intraductal lesions and guiding duct excision surgery. Treatment of breast papillomas often entails surgical duct excision for symptomatic relief and histopathological examination. Recently, more conservative approach has been adapted. MD-assisted microdochectomy should be considered the procedure of choice for a papilloma-related single duct discharge. Furthermore, there is increasing evidence that MD has the potential to reduce the number of duct excision procedures and minimise the extent of surgical resection. Imaging-guided vacuum-assisted core biopsy can be diagnostic and therapeutic for papillomas seen on mammography and/or ultrasound. Patients with multiple papillomas do have an increased risk of developing cancer and should be kept under annual review with regular mammography (preferably digital mammography) if treated conservatively. Magnetic resonance (MR) can be also used in surveillance in view of its high sensitivity. Because the risk is small, long term and affects both breasts, long-term follow-up is more appropriate than prophylactic mastectomy. Patients who prove to have solitary duct papilloma have insufficient increase in the risk of subsequent malignancy to justify routine follow-up.

Bariatric surgery in the field of gynecological oncology.

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

The Martius flap neovagina revisited.

The Martius bulbocavernosus flap has been used frequently in the repair of various vaginal fistulas. It can also be a useful source for the construction of a neovagina if used in the appropriate patient. We present a case of a patient who underwent a total pelvic exenteration for recurrent cervical cancer. For her neovagina, a novel variation of the Martius flap was constructed. In carefully selected patients, this can be a useful option for neovagina reconstruction.

Diagnostic efficacy of optical coherence tomography in the management of preinvasive and invasive cancer of uterine cervix and vulva.

The purpose of this study was to understand the capabilities and utility of optical coherence tomography (OCT) in characterizing tissue in patients with precancer and cancer of the uterine cervix and vulva. OCT is an optical technique that uses low-coherence interferometer to develop a two-dimensional image of optical scattering from internal tissue microstructure. This study was designed to develop diagnostic criteria. Women undergoing colposcopic evaluation secondary to an abnormal Papanicolaou smear or visualized grossly abnormal vulvar lesion comprised the study population. Under colposcopic visualization, the OCT device was applied to normal regions in all patients and abnormal areas when present, and images were captured. Each subject then underwent multiple directed biopsies. Images were then reviewed and compared with matched histology. A total of 50 women were recruited for the study. Of the 50 patients evaluated, 18 had cervical intraepithelial neoplasia (CIN) II,III, 14 had CIN I, 13 had metaplasia/inflammation, two had invasive squamous cell carcinoma of the cervix, and three had a diagnosis of Paget's disease of the vulva. Analysis of the OCT images showed a repetitive pattern that represented normal squamous epithelium of the cervix in 100% of the normal biopsies. Images of the 18 patients with histologically proven CIN II,III showed an unstructured homogeneous highly backscattering region with fast attenuation of the signal in 16 (89%) of the patients. OCT is a new approach for the early identification of cervix and vulvar malignancies. Using information inherent to the returning photon signals from tissue, early morphological and light-scattering changes can be detected during tumorigenesis. It has the potential to be a true optical biopsy. If diagnostically comparable to a biopsy, then clearly the ability of OCT to provide a point of service diagnosis would serve a significant advantage.

Three-dimensional power Doppler ultrasound improves the diagnostic accuracy for ovarian cancer prediction.

OBJECTIVE: The goal of this study was to determine if three-dimensional power Doppler ultrasound improves the specificity for ovarian cancer detection as compared with two-dimensional ultrasound. METHODS: Seventy-one women with a known complex pelvic mass were referred for a preoperative ultrasound evaluation with both two-dimensional and three-dimensional gray-scale ultrasonography. The 3D studies were performed with the Kretz Voluson 530D using a mechanized transvaginal probe. Surface rendering and power Doppler imaging were performed by the same gynecologic sonologist, and reassigned to one of four echo patterns: cystic, multicystic, complex, or solid. Sonographic criteria used for diagnosing ovarian cancer were based on a system that included morphological characteristics, histological prediction, and power Doppler imaging. RESULTS: Seventy-one women underwent surgical exploration: 14 (19.7%) had ovarian cancer (2 FIGO stage I, 2 stage II, 7 stage III, and 3 metastatic colon) and 2 had uterine cancer. Two-dimensional gray-scale ultrasound identified 40 masses as suspicious for cancer, including all 14 malignancies, yielding a sensitivity, specificity, and positive predictive value of 100, 54, and 35%, respectively. However, evaluation with 3D power Doppler identified only 28 cases as suspicious (including all 14 cancers), resulting in a sensitivity, specificity, and positive predictive value of 100, 75, and 50%, respectively. CONCLUSIONS: Three-dimensional power Doppler imaging better defines the morphological and vascular characteristics of ovarian lesions. All malignancies were correctly identified by both 2D and 3D imaging; however, the specificity significantly improved with the addition of 3D power Doppler. This improved diagnostic accuracy may promote improved patient care by separating complex benign masses from ovarian cancer, therefore facilitating appropriate physician referral.