A Novel Treatment for Massive Hemorrhage after Maternal Trauma in Pregnancy.

Background Trauma in pregnancy can lead to life-threatening hemorrhage. Conventional treatments of hemorrhage include medical and surgical management. However, if these measures fail uterine compression is an option to control bleeding. We present a case where this management was employed. Case A patient presented at 36 weeks of gestation with multiple injuries after a motor vehicle collision and experienced disseminated intravascular coagulation (DIC). The use of a Bakri balloon in combination with external compression with Coban, a sterile self-adherent bandage, after delivery temporized her bleeding and allowed her to become stable for further management. Conclusion When other measures fail and a hysterectomy is considered unsafe, the combination of internal and external uterine compression is an option.

Vaginal Mesh Removal Outcomes: Eight Years of Experience at an Academic Hospital.

OBJECTIVES: The purpose of this study is to describe the clinical history leading up to and the outcomes after vaginal mesh removal surgery at an academic hospital. METHODS: A retrospective case series of patients who underwent vaginal mesh removal from 2008 to 2015 was conducted. Demographics, clinical history, physical examination, pre- and postoperative symptoms, and number and type of reoperations were abstracted. RESULTS: Between February 2008 and November 2015, 83 patients underwent vaginal mesh removal surgery at our hospital. The median time interval from initial mesh placement to removal was 58 months (range, 0.4-154 months). The most common preoperative symptoms were vaginal pain (n = 52, 62%), dyspareunia (n = 46, 55%), and pelvic pain (n = 42, 50%). Intraoperative complications were infrequent (n = 3, 4%). Of patients presenting for follow-up within 4 to 6 weeks postoperatively, the most common symptoms were urinary incontinence (n = 15, 28%), vaginal pain (n = 7, 13%), buttock pain (n = 5, 9%), and urinary tract infection (n = 5, 9%). There were no identifiable risk factors to predict which patients would have persistent postoperative symptoms or who would require more than 1 mesh removal surgery. After vaginal mesh removal, 29 patients (35%) required 1 or more reoperations, with 3 being the highest number of reoperations per patient. The total number of reoperations was 43, with a total of 63 individual procedures performed. Forty-four percent (n = 28) of the procedures were graft removals, 40% (n = 25) were pelvic organ prolapse surgeries (only native tissue repairs), and 16% (n = 10) were stress incontinence surgeries. More than 1 procedure was performed in 49% (n = 21) of the reoperations. CONCLUSIONS: Vaginal mesh removal surgery is safe; however, some patients require more than 1 procedure, and the risk factors for reoperations are unclear.

Multispectral fluorescence imaging of human ovarian and fallopian tube tissue for early-stage cancer detection.

With early detection, 5-year survival rates for ovarian cancer exceed 90%, yet no effective early screening method exists. Emerging consensus suggests over 50% of the most lethal form of the disease originates in the fallopian tube. Twenty-eight women undergoing oophorectomy or debulking surgery provided informed consent for the use of surgical discard tissue samples for multispectral fluorescence imaging. Using multiple ultraviolet and visible excitation wavelengths and emissions bands, 12 fluorescence and 6 reflectance images of 47 ovarian and 31 fallopian tube tissue samples were recorded. After imaging, each sample was fixed, sectioned, and stained for pathological evaluation. Univariate logistic regression showed cancerous tissue samples had significantly lower intensity than noncancerous tissue for 17 image types. The predictive power of multiple image types was evaluated using multivariate logistic regression (MLR) and quadratic discriminant analysis (QDA). Two MLR models each using two image types had receiver operating characteristic curves with area under the curve exceeding 0.9. QDA determined 56 image type combinations with perfect resubstituting using as few as five image types. Adaption of the system for future in vivo fallopian tube and ovary endoscopic imaging is possible, which may enable sensitive detection of ovarian cancer with no exogenous contrast agents.

Assessment of the Role of Intraoperative Frozen Section in Guiding Surgical Staging for Endometrial Cancer.

OBJECTIVE: The aim of this study was to assess the role of intraoperative frozen section (FS) in guiding decision making for surgical staging of endometrioid endometrial cancer (EC). METHODS: Medical records were collected retrospectively on 112 patients with endometrioid EC, who underwent total hysterectomy and bilateral salpingo-oophorectomy at the University of Arizona Medical Center from January 1, 2010, to December 31, 2014. Only patients with endometrioid adenocarcinoma, grade 1, less than 50% myometrial invasion, and tumor size less than 2 cm determined by intraoperative FS omitted lymphadenectomy; otherwise, surgical staging was performed with lymph node dissection. The FS results were compared with the permanent paraffin sections (PSs) to assess the diagnostic accuracy. RESULTS: The concordance rate of different variables between FS and PS in EC was 100%, 89.3% (100/112), 97.3% (109/112), and 95.5% (107/112), respectively, with respecting to histological subtype, grade, myometrial invasion, and tumor size. Diagnostic accurate rate of combined risk factors deciding surgical staging at the time of FS was 95.5% (107/112), and the discordance rate of all risk factors considered between FS and PS was 4.5%, resulting 3 cases (2.7%) undertreated and 2 cases (1.8%) overtreated. CONCLUSIONS: Despite nonideal FS evaluation, intraoperative FS diagnosis for EC is highly reliable by providing guidance for the intraoperative decisions of surgical staging at our institution, and such guidelines may be referenced by the institutions with sufficient gynecologic pathology expertise.

Pilot Clinical Evaluation of a Confocal Microlaparoscope for Ovarian Cancer Detection.

OBJECTIVE: The aim of this study is to evaluate the performance of a confocal fluorescence microlaparoscope for in vivo detection of ovarian cancer. METHODS/MATERIALS: Seventy-one patients scheduled for open or laparoscopic oophorectomy were consented for the imaging study. High-resolution confocal microlaparoscopic images of the epithelial surface of the ovary were acquired in vivo or ex vivo after tissue staining using acridine orange. Standard histologic evaluation of extracted tissue samples was performed and used as the gold standard of disease diagnosis. Trained human observers from different specialties viewed the microlaparoscopic images, rating each image on a 6-point scale ranging from "definitely not cancer" to "definitely cancer." Receiver operating characteristic curves were generated using these scores and the gold standard histopathologic diagnosis. Area under the receiver operating characteristic curve (AUC) was calculated as a performance metric. RESULTS: Forty-five of the consented patients were used in the final evaluation study. From these 45 patients, 63 tissue locations or samples were identified and imaged with the confocal microlaparoscope. Twenty of the samples were high-grade cancers, and the remaining 43 samples were normal or noncancerous. Twenty-three of the samples were imaged in vivo, and the remaining 40 samples were imaged ex vivo. The average AUC score and standard error (SE) for detection of cancer in all images were 0.88 and 0.02, respectively. An independent-samples t test was conducted to compare AUC scores for in vivo and ex vivo conditions. No statistically significant difference in the AUC score for in vivo (AUC, 0.850; SE, 0.049) and ex vivo (AUC, 0.888; SE, 0.027) conditions was observed, t(6) = 1.318, P = 0.2355. CONCLUSIONS: Area under the receiver operating characteristic curve scores indicate that high-resolution in vivo images obtained by the confocal laparoscope can distinguish between normal and malignant ovarian surface epithelium. In addition, in vivo performance is similar to that which can be obtained from ex vivo tissue.

Confocal microlaparoscope for imaging the fallopian tube.

Recent evidence suggests that ovarian cancer can originate in the fallopian tube. Unlike many other cancers, poor access to the ovary and fallopian tubes has limited the ability to study the progression of this deadly disease and to diagnosis it during the early stage when it is most amenable to therapy. A rigid confocal microlaparoscope system designed to image the epithelial surface of the ovary in vivo was previously reported. A new confocal microlaparoscope with an articulating distal tip has been developed to enable in vivo access to human fallopian tubes. The new microlaparoscope is compatible with 5-mm trocars and includes a 2.2-mm-diameter articulating distal tip consisting of a bare fiber bundle and an automated dye delivery system for fluorescence confocal imaging. This small articulating device should enable the confocal microlaparoscope to image early stage ovarian cancer arising inside the fallopian tube. Ex vivo images of animal tissue and human fallopian tube using the new articulating device are presented along with in vivo imaging results using the rigid confocal microlaparoscope system.

IMP3 as a cytoplasmic biomarker for early serous tubal carcinogenesis.

BACKGROUND: Serous tubal intraepithelial carcinoma (STIC) and the p53 signature in tubal mucosa have been supported to be precursor lesions in high-grade serous carcinoma (HGSC) of the fallopian tube, ovary, and peritoneum. It remains critical to find biomarkers for precursor lesions in order to detect HGSCs efficiently. IMP3 is an oncoprotein that has been explored in human malignancies. No studies have specifically addressed the expression of IMP3 in precursor or early lesions of HGSC. The main purposes of this study are to evaluate if IMP3 plays any role in the process of pelvic serous carcinogenesis by examining its expression in HGSC precursor lesions, to examine the relationship between IMP3 and p53 in those precursor lesions, and to check if IMP3 can be used as a biomarker for early diagnosis. METHODS: Immunohistochemistry for IMP3 and p53 was performed and evaluated in 48 HGSCs with STIC, 62 HGSCs without STIC, and 60 benign cases as negative controls. Sections of fallopian tubes with or without STIC , as well as cancers within the ovaries, were studied. IMP3 signature was defined as strong IMP3 cytoplasmic staining in 10 or more consecutive benign-looking tubal epithelial cells. The relationship between IMP3 and p53 overexpression was examined. RESULTS: In the 48 HGSC patients with STIC, IMP3 was positive in 46% of STIC lesions and had a similar positive rate in the invasive components of HGSC. IMP3 was also expressed in normal appearing tubal epithelia (IMP3 signature) in 15 (31%) of 48 HGSC cases with STIC and 10 (16%) of 62 cases without STIC. In contrast, no single IMP3 signature was found in the benign control group. Concordant expression of IMP3 and p53 signatures in the STIC group was found in up to one-third of the cases. There were also five (10%) STIC cases with positive IMP3 and negative p53. CONCLUSIONS: We conclude that IMP3 may be involved in the process and progression of pelvic HGSC and may serve as a complimentary biomarker in diagnosing STIC.

Simultaneous multiplane imaging of human ovarian cancer by volume holographic imaging.

Ovarian cancer is the most deadly gynecologic cancer, a fact which is attributable to poor early detection and survival once the disease has reached advanced stages. Intraoperative laparoscopic volume holographic imaging has the potential to provide simultaneous visualization of surface and subsurface structures in ovarian tissues for improved assessment of developing ovarian cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume holographic imaging system (VHIS) to characterize the microarchitecture of 78 normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube, uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73 undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo-oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully imaged with the VHIS in both reflectance- and fluorescence-modes revealing morphological features which can be used to distinguish between normal, benign abnormalities, and cancerous tissues. We present the development and successful application of VHIS for imaging human ovarian tissue. Comparison of VHIS images with corresponding histopathology allowed for qualitatively distinguishing microstructural features unique to the studied tissue type and disease state. These results motivate the development of a laparoscopic VHIS for evaluating the surface and subsurface morphological alterations in ovarian cancer pathogenesis.

Wide-field spectral imaging of human ovary autofluorescence and oncologic diagnosis via previously collected probe data.

With no sufficient screening test for ovarian cancer, a method to evaluate the ovarian disease state quickly and nondestructively is needed. The authors have applied a wide-field spectral imager to freshly resected ovaries of 30 human patients in a study believed to be the first of its magnitude. Endogenous fluorescence was excited with 365-nm light and imaged in eight emission bands collectively covering the 400- to 640-nm range. Linear discriminant analysis was used to classify all image pixels and generate diagnostic maps of the ovaries. Training the classifier with previously collected single-point autofluorescence measurements of a spectroscopic probe enabled this novel classification. The process by which probe-collected spectra were transformed for comparison with imager spectra is described. Sensitivity of 100% and specificity of 51% were obtained in classifying normal and cancerous ovaries using autofluorescence data alone. Specificity increased to 69% when autofluorescence data were divided by green reflectance data to correct for spatial variation in tissue absorption properties. Benign neoplasm ovaries were also found to classify as nonmalignant using the same algorithm. Although applied ex vivo, the method described here appears useful for quick assessment of cancer presence in the human ovary.

Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

PURPOSE: This phase I trial evaluated intraperitoneal (i.p.) pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer. EXPERIMENTAL DESIGN: Dose escalation of day 1 i.p. pemetrexed accrued three patients to each of five dose levels (60-1,000 mg/m(2)), along with day 2 i.p. cisplatin (75 mg/m(2)) and day 8 i.p. paclitaxel (60 mg/m(2)). The goals were to determine maximum tolerated dose (MTD), 18-month progression-free survival (PFS), and pharmacokinetics of i.p. pemetrexed. RESULTS: Cycles, given every 21 days, had an 80% 6-cycle completion rate. There was minimal grade III toxicity in the first 4 dose levels and remarkably an almost complete absence of peripheral neuropathy and alopecia. At the highest dose level, two of three patients experienced ≥ grade III and dose-limiting toxicity (DLT; hematologic, infection, gastrointestinal). There was a pharmacokinetic advantage for i.p. pemetrexed with an intraperitoneal:plasma area under the concentration-time curve ratio of 13-fold. Neither analysis of pharmacokinetic nor homocysteine levels explains the unexpected severity of toxicity in those two patients. On the basis of plasma C(24h) levels, the 42 cycles at ≥ 500 mg/m(2) i.p. pemetrexed without DLT, the MTD appears to be 500 mg/m(2). Median PFS is 30.1 months; 18-month PFS is 78.6% (median follow-up 22.4 months). CONCLUSIONS: This i.p.-only regimen in front-line ovarian cancer is feasible with PFS in line with recent literature. We suggest phase II trials of this regimen in this population with i.p. pemetrexed at 500 mg/m(2). The favorable toxicity profile at doses <1,000 mg/m(2), which needs to be confirmed, appears to compare well with standard combination i.v./i.p. platinum/taxane chemotherapy in this disease.

Overexpression of tumor vascular endothelial growth factor A may portend an increased likelihood of progression in a phase II trial of bevacizumab and erlotinib in resistant ovarian cancer.

PURPOSE: This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer; exploratory biomarker analyses, including that of tumor vascular endothelial growth factor A (VEGF-A), were also done. EXPERIMENTAL DESIGN: Forty heavily pretreated patients received erlotinib (150 mg/d orally) and bevacizumab (10 mg/kg i.v.) every 2 weeks until disease progression. Primary end points were objective response rate and response duration; secondary end points included progression-free survival (PFS), toxicity, and correlations between angiogenic protein levels, toxicity, and efficacy. RESULTS: Grade 3 toxicities included skin rash (n = 6), diarrhea (n = 5), fatigue (n = 4), and hypertension (n = 3). Grade 4 toxicities were myocardial infarction (n = 1) and nasal septal perforation (n = 1). Only one grade 3 fistula and one grade 2 bowel perforation were observed. Nine (23.1%) of 39 evaluable patients had a response (median duration, 36.1+ weeks; one complete response), and 10 (25.6%) patients achieved stable disease, for a disease control rate of 49%. Median PFS was 4 months, and 6-month PFS was 30.8%. Biomarker analyses identified an association between tumor cell VEGF-A expression and progression (P = 0.03); for every 100-unit increase in the VEGF-A score, there was a 3.7-fold increase in the odds of progression (95% confidence interval, 1.1-16.6). CONCLUSIONS: Bevacizumab plus erlotinib in heavily pretreated ovarian cancer patients was clinically active and well tolerated. Erlotinib did not seem to contribute to efficacy. Our study raises the intriguing possibility that high levels of tumor cell VEGF-A, capable of both autocrine and paracrine interactions, are associated with resistance to bevacizumab, emphasizing the complexity of the tumor microenvironment.

Clinical research device for ovarian cancer detection by optical spectroscopy in the ultraviolet C-visible.

Early detection of ovarian cancer could greatly increase the likelihood of successful treatment. However, present detection techniques are not very effective, and symptoms are more commonly seen in later stage disease. Amino acids, structural proteins, and enzymatic cofactors have endogenous optical properties influenced by precancerous changes and tumor growth. We present the technical details of an optical spectroscopy system used to quantify these properties. A fiber optic probe excites the surface epithelium (origin of 90% of cases) over 270 to 580 nm and collects fluorescence and reflectance at 300 to 800 nm with four or greater orders of magnitude instrument to background suppression. Up to four sites per ovary are investigated on patients giving consent to oophorectomy and the system's in vivo optical evaluation. Data acquisition is completed within 20 s per site. We illustrate design, selection, and development of the components used in the system. Concerns relating to clinical use, performance, calibration, and quality control are addressed. In the future, spectroscopic data will be compared with histological biopsies from the corresponding tissue sites. If proven effective, this technique can be useful in screening women at high risk of developing ovarian cancer to determine whether oophorectomy is necessary.

In vivo imaging of ovarian tissue using a novel confocal microlaparoscope.

OBJECTIVE: The objective of the study was to develop a clinical confocal microlaparoscope for imaging ovary epithelium in vivo with the long-term objective of diagnosing cancer in vivo. STUDY DESIGN: A confocal microlaparoscope was developed and used to image the ovaries of 21 patients in vivo using fluorescein sodium and acridine orange as the fluorescent contrast agents. RESULTS: The device was tested in vivo and demonstrated to be safe and function as designed. Real-time cellular visualization of ovary epithelium was demonstrated. CONCLUSION: The confocal microlaparoscope represents a new type of in vivo imaging device. With its ability to image cellular details in real time, it has the potential to aid in the early diagnosis of cancer. Initially the device may be used to locate unusual regions for guided biopsies. In the long term, the device may be able to supplant traditional biopsies and allow the surgeon to identify early-stage ovarian cancer.

Clinical confocal microlaparoscope for real-time in vivo optical biopsies.

Successful treatment of cancer is highly dependent on the stage at which it is diagnosed. Early diagnosis, when the disease is still localized at its origin, results in very high cure rates-even for cancers that typically have poor prognosis. Biopsies are often used for diagnosis of disease. However, because biopsies are destructive, only a limited number can be taken. This leads to reduced sensitivity for detection due to sampling error. A real-time fluorescence confocal microlaparoscope has been developed that provides instant in vivo cellular images, comparable to those provided by histology, through a nondestructive procedure. The device includes an integrated contrast agent delivery mechanism and a computerized depth scan system. The instrument uses a fiber bundle to relay the image plane of a slit-scan confocal microlaparoscope into tissue. It has a 3-mum lateral resolution and a 25-mum axial resolution. Initial in vivo clinical testing using the device to image human ovaries has been done in 21 patients. Results indicate that the device can successfully image organs in vivo without complications. Results with excised tissue demonstrate that the instrument can resolve sufficient cellular detail to visualize the cellular changes associated with the onset of cancer.

Laparoscopic optical coherence tomography imaging of human ovarian cancer.

OBJECTIVES: Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10-20 microm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo. METHODS: A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue. RESULTS: Thirty ovaries in 17 primarily peri- or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma. CONCLUSIONS: We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and an imaging modality for further evaluation of ovarian cancer pathogenesis.

Complete resolution of Paget disease of the vulva with imiquimod cream.

Extra mammary Paget disease (EMPD) is a neoplastic disease of apocrine gland bearing skin. Surgical excision is the standard of care for EMPD; however, it is accompanied by recurrence in more than 60% of the patients. Recently, imiquimod cream has been reported to induce complete responses in primary or recurrent EMPD. We report on 2 women with vulva EMPD who achieved biopsy-confirmed resolution of their disease after topical application of imiquimod 5% cream.

Learning and teaching advanced laparoscopic procedures: do alternating trainees impair a laparoscopic surgeon's learning curve?

STUDY OBJECTIVE: In this study we investigated whether teaching advanced laparoscopic procedures like laparoscopic-assisted surgical staging (LASS) for endometrial cancer negatively affects the learning curve of the attending surgeon. DESIGN: Retrospective study (Canadian Task Force classification II-3.) SETTING: Department of Obstetrics and Gynecology, University of Arizona, Tucson. PATIENTS: One hundred twenty-four patients undergoing LASS for endometrial cancer at our institution from 1992 through 2004 were included for analysis. INTERVENTIONS: Cases were classified into 3 groups. Group A comprised the initial learning phase where 2 attending gynecologic oncologists used other faculty as assistants (first 30 cases). Groups B and C comprised procedures after the learning phase involving attendings (n = 27, group B) or obstetrics and gynecology residents (n = 67, group C) as trainees. Groups were compared with respect to general outcome parameters and disease-free survival. MEASUREMENTS AND MAIN RESULTS: Patients within all groups were comparable with respect to age and height or body mass index. In the subgroup analysis, a decrease in blood loss and length of stay occurred mainly during the group B series. Pelvic lymph node yield reached oncologic standards during the initial learning curve (median 12-13) and remained stable during both teaching phases. Intraoperative and postoperative complications occurred in 2.4% and 13.7% of cases, respectively. Ninety percent of intraoperative and 64% of postoperative complications occurred within the first half of the series and were not correlated with type of assistance. Survival data were obtainable in 65% of cases with a median follow-up of 3.6 years. Disease free-survival was 92.5% in stage I disease and without significant difference among the groups. CONCLUSION: After gaining proficiency in the procedure, more or less surgically experienced trainees can be actively included without hampering the progress of the attending's learning curve.

A3. Vaginal intraepithelial neoplasia (VAIN).

VAIN is much rarer than the equivalent dysplastic changes found in the cervix but may accompany cervical intraepithelial neoplasia. VAIN is also HPV in-duced and may be an extension of a cervical lesion or a satellite lesion. VAIN lesions are usually asymptomatic and detected by cytologic screening. Lesions can be ex-cised, vaporized or treated locally with medical therapies. The incidence of vaginal cancer is very rare.

CHAPTER 4 Clinical manifestations of HPV infection Section A: Benign manifestations of HPV infection: A1. Anogenital condylomas.

The clinical manifestation of infection with HPV is determined by multi-ple factors which include the type of HPV, the type of skin infected, the status of host immunity and smoking. The incubation period for HPV is 3 weeks to 8 months. While there is no specific anti-HPV therapy, local topical therapy, excision, cautery and laser vaporization have all been used with a range of success rates.

A2. Vulval intraepithelial neoplasia (VIN).

VIN 3 is most likely a cancer precursor and is induced by infection with high-risk types of HPV. VIN 3 lesions may be asymptomatic or present with itching and/or burning or the appearance of a vulval lesion (often raised and hyperpig-mented), which may be unifocal or multifocal. All vulval lesions should be biopsied to confirm the diagnosis. Treatment options include laser vaporization, excision or cautery. Long term follow up is essential.