MU variability in CBCT-guided online adaptive radiation therapy.

PURPOSE: CBCT-guided online-adaptive radiotherapy (oART) systems have been made possible by using artificial intelligence and automation to substantially reduce treatment planning time during on-couch adaptive sessions. Evaluating plans generated during an adaptive session presents significant challenges to the clinical team as the planning process gets compressed into a shorter window than offline planning. We identified MU variations up to 30% difference between the adaptive plan and the reference plan in several oART sessions that caused the clinical team to question the accuracy of the oART dose calculation. We investigated the cause of MU variation and the overall accuracy of the dose delivered when MU variations appear unnecessarily large. METHODS: Dosimetric and adaptive plan data from 604 adaptive sessions of 19 patients undergoing CBCT-guided oART were collected. The analysis included total MU per fraction, planning target volume (PTV) and organs at risk (OAR) volumes, changes in PTV-OAR overlap, and DVH curves. Sessions with MU greater than two standard deviations from the mean were reoptimized offline, verified by an independent calculation system, and measured using a detector array. RESULTS: MU variations relative to the reference plan were normally distributed with a mean of -1.0% and a standard deviation of 11.0%. No significant correlation was found between MU variation and anatomic changes. Offline reoptimization did not reliably reproduce either reference or on-couch total MUs, suggesting that stochastic effects within the oART optimizer are likely causing the variations. Independent dose calculation and detector array measurements resulted in acceptable agreement with the planned dose. CONCLUSIONS: MU variations observed between oART plans were not caused by any errors within the oART workflow. Providers should refrain from using MU variability as a way to express their confidence in the treatment planning accuracy. Clinical decisions during on-couch adaptive sessions should rely on validated secondary dose calculations to ensure optimal plan selection.

Commissioning of Mobius3D/FX for patient-specific quality assurance: The CUIMC-NewYork Presbyterian Hospital experience.

PURPOSE: To present the process undertaken by our institute in commissioning Mobius3D (M3D) for patient-specific quality assurance. METHOD: 168 plans were randomly selected to compare dose distribution measured with ArcCheck and dose calculated from M3D, both compared against the treatment planning system (TPS). The gamma criteria for measurement and M3D are 3%/2 mm with 10% and 50% dose thresholds, respectively. The effect of tissue inhomogeneity was investigated on 11 plans by recalculating the dose in M3D on a homogeneous phantom. Tolerance and action limits were established following the AAPM Task Group 218 recommendations. RESULTS: The M3D showed high variability in gamma passing rate compared to the measurement. Twenty-three out of 168 plans had false negative dose comparisons. These plans fall under high tissue inhomogeneity like lung and metal implants, small field targets, and breast plans planned with high energy. One false negative case (0.6%) was observed. A single tolerance limit of 91% and 92% gamma passing rate for the M3D and measurement-based PSQA were established, respectively. Against the expectation, recalculating plans on the homogeneous phantom in M3D did not necessarily increase the gamma passing rate. These plans have a duty cycle >4.2, and the small field sizes combined with differences in slice thickness contributed to observed dose differences in the homogeneous phantom comparisons. CONCLUSION: Following the commissioning, M3D is adopted in our institute. Currently, the gamma criteria used for measurement and M3D are 3%/2 mm, 40% dose threshold, with gamma passing rates of 92% and 95%, respectively. A higher passing rate for M3D is adopted until more data is available. The combined effect of plan modulation, the field sizes, the tissue inhomogeneity, the dose algorithm, and the volume averaging effect from differences in slice thickness can contribute to the differences in dose in M3D and TPS.

A Prospective Study of Bladder Function Following Endometriosis Surgery With Up to Eight years Follow-up.

STUDY OBJECTIVE: To assess long-term urinary function for women having laparoscopic surgery for endometriosis. DESIGN: Institutional Review Board-approved nested cohort study within a larger randomized controlled trial assessing urinary function following any benign laparoscopy for gynecological presentations. SETTING: Two tertiary-level university-affiliated hospitals. PATIENTS: Women with histologically confirmed endometriosis within the randomized controlled trial between April 2012 and November 2019, where baseline urinary function was determined. INTERVENTIONS: Women with histologically confirmed endometriosis were contacted between February and October 2020, and urinary function was re-assessed. MEASUREMENTS AND MAIN RESULTS: Urinary function was assessed using validated questionnaires across the domains of filling, voiding, incontinence, and quality of life determined distant from surgery. Higher scores correlated with a greater severity of symptoms. From 518/711 (72.9%) women with histologically confirmed endometriosis, 289/518 (55.8%) consented to the nested study. At a mean of 50 months (range 12-103 months) post-operatively, 35 participants (12.1%) had sought treatment for bladder symptoms, and 81 participants (28.0%) reported at least one urinary tract infection since their index surgery. There was a significant worsening of symptoms for filling, voiding, incontinence, and quality of life pre-operative to post-operatively (2.27 vs 3.32, 0.93 vs 2.02, 1.06 vs 2.32, 0.83 vs 2.13 respectively, p <.001). There was no statistically significant difference in urinary questionnaire scores in participants with and without uterovesical endometriosis. There was no statistically significant difference in any parameter when comparing any revised American Society of Reproductive Medicine (rASM) stage of endometriosis. Participants who had post-operative urinary retention reported a higher mean voiding score than those who did not (3.24 vs 1.94, p = .017), while participants with post-operative urinary tract infection reported a higher mean frequency score than those who did not (5.17 vs 3.24, p = .016). CONCLUSION: This study suggests a decline in urinary function over time following laparoscopic surgery for endometriosis that is not dependent on the severity or location of the disease.

Vaginal epithelial histology before and after fractional CO2 laser in postmenopausal women: a double-blind, sham-controlled randomized trial.

BACKGROUND: Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO2 laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies. OBJECTIVE: This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies. STUDY DESIGN: This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY). RESULTS: There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166). CONCLUSION: Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO2 laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO2 laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms.

Immediate versus delayed urinary catheter removal following non-hysterectomy benign gynaecological laparoscopy: a randomised trial.

OBJECTIVE: To compare rates of urinary retention and postoperative urinary tract infection between women with immediate versus women with delayed removal of indwelling catheter following benign non-hysterectomy gynaecological laparoscopic surgery. DESIGN: This randomised clinical trial was conducted between February 2012 and December 2019, with follow-up to 6 weeks. SETTING: Two university-affiliated teaching hospitals in Sydney, Australia. POPULATION: Study participants were 693 women aged 18 years or over, undergoing non-hysterectomy laparoscopy for benign gynaecological conditions, excluding pelvic floor or concomitant bowel surgery. METHODS: Three hundred and fifty-five participants were randomised to immediate removal of urinary catheter and 338 participants were randomised to delayed removal of urinary catheter. MAIN OUTCOME MEASURES: The co-primary outcomes were urinary retention and urinary tract infection. Secondary outcomes included hospital readmission, analgesia requirements, duration of hospitalisation and validated bladder function questionnaires. RESULTS: Urinary retention was higher after immediate compared with delayed removal of the urinary catheter (8.2% vs 4.2%, RR 1.8, 95% CI 1.0-3.0, p = 0.04). Although urinary tract infection was 7.2% following delayed removal of the urinary catheter and 4.7% following immediate removal of the urinary catheter, the difference was not statistically significant (RR 0.7, 95% CI 0.3-1.2, p = 0.2). CONCLUSIONS: There is an increased risk of urinary retention with the immediate compared with the delayed removal of the urinary catheter following benign non-hysterectomy gynaecological laparoscopic surgery. The difference in urinary tract infection was not significant. There is 1/12 risk of re-catheterisation after immediate urinary catheter removal. It is important to ensure that patients report normal voiding and emptying prior to discharge, to reduce the need for readmission for the management of urinary retention.

Impact of Adapted Radiotherapy Schedules on Bowel Sparing in Node-Positive Cervical Cancer.

PURPOSE: Definitive radiation therapy (RT) for locally advanced node-positive cervical cancer confers significant toxicity to pelvic organs including the small bowel. Gross nodal disease exhibits significant shrinkage during RT, and yet conventional RT does not account for this change. We evaluated the reduction in absorbed bowel dose using various adaptive RT schedules. METHODS AND MATERIALS: We obtained 130 evaluable scans (computed tomography simulation and 25 cone beam computed tomography scans per patient) of 5 patients who had received definitive external beam RT for lymph node positive cervical cancer daily over 5 weeks. Using a single universal volumetric modulated arc therapy plan with predefined optimization priorities, we created adapted RT plans in 4 schedules: Daily, Weekly, Twice, and NoAdapt (mimicking conventional nonadapted RT). The in silico (computer modeled) patients were treated to 45 Gy to primary cervical disease with a simultaneous integrated boost to 55 Gy to involved lymph nodes. We evaluated dose metrics including D2cc, D15cc, and V45 to determine the impact of adapted RT schedules on bowel sparing. Statistical tests included the Student t test, analysis of variance, and the Spearman rank correlation. RESULTS: The quantity of reduced bowel dose was significantly associated with the chosen planning schedule in all evaluated metrics and was proportional to the frequency of adaptive RT with significant moderate-to-strong monotonicity. Both D2cc and D15cc were reduced an average of 2.7 Gy using daily replanning compared with a nonadapted approach. A minimally adapted strategy of only 2 replans also confers a significant dosimetric benefit over a nonadapted approach. Reduced standard deviations of D2cc and V45 bowel doses over the treatment courses were significantly associated with the choice of planning schedule with strong monotonicity. CONCLUSIONS: All adaptive RT schedules evaluated confer significant dosimetric advantages in bowel sparing over a conventional nonadapted technique, with greater sparing seen with more frequent replanning schedules. These findings warrant future trials of adaptive RT for pelvic malignancies.

A review of gynaecological surgical practices for trainees and certified specialists in Australia by volume using MBS and AIHW databases.

BACKGROUND: There is a finite volume of surgery performed annually by trainees and certified specialists alike. The detailed assessment of this surgical substrate is important, since it guides true exposure in gynaecological surgical training and practice after fellowship. AIMS: This study quantifies the volume and profile of major gynaecological surgical procedures performed in Australia within a specified five-year period and discusses the implications for training and practice. MATERIALS AND METHODS: Australian Institute of Health and Welfare data were examined to quantify the total number of major gynaecological procedures performed between 2013 and 2018. Medicare data were analysed to quantify the number of billed procedures. These data were compared with published Australian RANZCOG trainees and operative gynaecologists, to estimate the potential annual average exposure for each procedure. RESULTS: Major open, laparoscopic and vaginal surgeries constitute less than 27% of the 600 000 gynaecological procedures performed annually in Australia. Most major gynaecological surgeries are performed at rates lower than 12 cases per year for both trainees and specialists. Over the study period, laparotomies, vaginal hysterectomies and continence procedures decreased, and operative laparoscopies and laparoscopic hysterectomies increased. CONCLUSIONS: The volume of available major gynaecological procedures in Australia may not allow sufficient exposure for optimal training and practice for all trainees and specialists in operative gynaecology. This shortfall may compromise the ability to obtain and maintain proficiency in some core gynaecological operative procedures.

Dosimetric assessment of patient dose calculation on a deep learning-based synthesized computed tomography image for adaptive radiotherapy.

PURPOSE: Dose computation using cone beam computed tomography (CBCT) images is inaccurate for the purpose of adaptive treatment planning. The main goal of this study is to assess the dosimetric accuracy of synthetic computed tomography (CT)-based calculation for adaptive planning in the upper abdominal region. We hypothesized that deep learning-based synthetically generated CT images will produce comparable results to a deformed CT (CTdef) in terms of dose calculation, while displaying a more accurate representation of the daily anatomy and therefore superior dosimetric accuracy. METHODS: We have implemented a cycle-consistent generative adversarial networks (CycleGANs) architecture to synthesize CT images from the daily acquired CBCT image with minimal error. CBCT and CT images from 17 liver stereotactic body radiation therapy (SBRT) patients were used to train, test, and validate the algorithm. RESULTS: The synthetically generated images showed increased signal-to-noise ratio, contrast resolution, and reduced root mean square error, mean absolute error, noise, and artifact severity. Superior edge matching, sharpness, and preservation of anatomical structures from the CBCT images were observed for the synthetic images when compared to the CTdef registration method. Three verification plans (CBCT, CTdef, and synthetic) were created from the original treatment plan and dose volume histogram (DVH) statistics were calculated. The synthetic-based calculation shows comparatively similar results to the CTdef-based calculation with a maximum mean deviation of 1.5%. CONCLUSIONS: Our findings show that CycleGANs can produce reliable synthetic images for the adaptive delivery framework. Dose calculations can be performed on synthetic images with minimal error. Additionally, enhanced image quality should translate into better daily alignment, increasing treatment delivery accuracy.

Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial.

Importance: Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven. Objective: To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. Design, Setting, and Participants: A double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized. Interventions: Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. Main Outcomes and Measures: The co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). Results: Of 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group. Conclusions and Relevance: Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001403426.

Kinetic analysis of dominant intraprostatic lesion of prostate cancer using quantitative dynamic [18F]DCFPyL-PET: comparison to [18F]fluorocholine-PET.

PURPOSE: Identification of the dominant intraprostatic lesion(s) (DILs) can facilitate diagnosis and treatment by targeting biologically significant intra-prostatic foci. A PSMA ligand, [18F]DCFPyL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid), is better than choline-based [18F]FCH (fluorocholine) in detecting and localizing DIL because of higher tumour contrast, particularly when imaging is delayed to 1 h post-injection. The goal of this study was to investigate whether the different imaging performance of [18F]FCH and [18F]DCFPyL can be explained by their kinetic behaviour in prostate cancer (PCa) and to evaluate whether DIL can be accurately detected and localized using a short duration dynamic positron emission tomography (PET). METHODS: 19 and 23 PCa patients were evaluated with dynamic [18F]DCFPyL and [18F]FCH PET, respectively. The dynamic imaging protocol with each tracer had a total imaging time of 22 min and consisted of multiple frames with acquisition times from 10 to 180 s. Tumour and benign tissue regions identified by sextant biopsy were compared using standardized uptake value (SUV) and tracer kinetic parameters from kinetic analysis of time-activity curves. RESULTS: For [18F]DCFPyL, logistic regression identified Ki and k4 as the optimal model to discriminate tumour from benign tissue (84.2% sensitivity and 94.7% specificity), while only SUV was predictive for [18F]FCH (82.6% sensitivity and 87.0% specificity). The higher k3 (binding) of [18F]FCH than [18F]DCFPyL explains why [18F]FCH SUV can differentiate tumour from benign tissue within minutes of injection. Superior [18F]DCFPyL tumour contrast was due to the higher k4/k3 (more rapid washout) in benign tissue compared to tumour tissue. CONCLUSIONS: DIL was detected with good sensitivity and specificity using 22-min dynamic [18F]DCFPyL PET and avoids the need for delayed post-injection imaging timepoints. The dissimilar in vivo kinetic behaviour of [18F]DCFPyL and [18F]FCH could explain their different SUV images. Clinical Trial Registration NCT04009174 (ClinicalTrials.gov).

The Efficacy of Vaginal Laser and Other Energy-based Treatments on Genital Symptoms in Postmenopausal Women: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review examined energy-based treatments of the vagina for postmenopausal vaginal symptoms. DATA SOURCES: We performed a systematic review from April 2017 (the end date of our previous review) to April 2020, searching Medline, Embase, and Scopus. METHODS OF STUDY SELECTION: The inclusion criteria were all randomized studies, prospective studies with >10 cases, and retrospective studies with >20 cases published in English or French that assessed change in postmenopausal vaginal symptoms and/or sexual function in women after energy-based vaginal treatments. Meta-analyses were performed on randomized data. TABULATION, INTEGRATION, AND RESULTS: Of the 989 results retrieved, 3 randomized studies, 16 prospective studies, and 7 retrospective studies were included in the review, representing data from 2678 participants. Pooled data from 3 randomized controlled trials show no difference between vaginal laser and topical hormonal treatments for change in vaginal symptoms (-0.14, 95% confidence interval -1.07 to 0.80) or sexual function scores (2.22, 95% confidence interval -0.56 to 5.00). Furthermore, no difference among vaginal laser, topical hormone, and lubricant was demonstrated in sexual function (p = .577). As in our previous review, non-randomized data support energy-based treatments in improving vaginal symptoms, sexual function, and clinician-reported outcomes. No severe adverse events were reported in the included studies. Significant heterogeneity of data arising from differing measures and reported outcomes continues to be an issue, with data remaining low quality, with high risk of bias, and no double-blind or placebo-controlled randomized trials yet reported, although 1 has now completed recruitment. CONCLUSION: There are 3 randomized trials comparing energy-based systems with hormonal treatment, with no clinical difference in these 2 approaches. Although prospective data continue to show promising outcomes, without strong evidence from well-powered, double-blind placebo-controlled trials to determine the efficacy of treatment compared with placebo, the use of energy-based treatments should continue to be undertaken in research studies only, with high-quality studies essentially free from bias (International Prospective Register of Systematic Review registration number: 178346).

Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography.

BACKGROUND: In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High-performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma; however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers-[18F]FAZA and [18F]FEPPA, for imaging hypoxia and inflammation, respectively. RESULTS: Radioactivity as low as 17 Bq in 2 µL of pig's plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n = 8) in the autoradiographic image. Significant intersubject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [18F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5-min post injection, while for [18F]FAZA, significant metabolites did not appear until 50-min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32-400% parameter error can result without radio-metabolites correction. CONCLUSION: TLC coupled with autoradiography is a good alternative to high-performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 µL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies.

The Impact of Limbal Mesenchymal Stromal Cells on Healing of Acute Ocular Surface Wounds Is Improved by Pre-cultivation and Implantation in the Presence of Limbal Epithelial Cells.

While limbal epithelial cells are used for treating ocular surface wounds, the therapeutic potential of mesenchymal cells cultivated from the limbal stroma (LMSC) is less clear. We have therefore examined the effects of LMSC when applied to acute ocular surface wounds. LMSC derived from male rabbits (RLMSC) were applied to the ocular surface of female rabbits immediately following removal of the corneal and limbal epithelium. Human amniotic membrane (HAM) was used as the vehicle for implanting the RLMSC. The effects of RLMSC were examined when applied alone (n = 3) and in conjunction with a stratified culture of human limbal epithelial cells (HLE) grown on the opposing surface of the HAM (n = 3). Outcomes were monitored over 3 months in comparison with animals receiving no treatment (n = 3) or treatment with HLE alone on HAM (n = 3). Animals treated with RLMSC (n = 6) displayed faster re-epithelialization (∼90% versus 70% healing after 12 weeks), with best results being observed when RLMSC were pre-cultivated and implanted in the presence of HLE (p < 0.01; 90% healing by 7 weeks). While all animals displayed conjunctival cells on the corneal surface (by presence of goblet cells and/or keratin 13 expression) and corneal neovascularization, evidence of corneal epithelial regeneration was observed in animals that received RLMSC in the presence of HLE (by staining for keratin 3 and the absence of goblet cells). Conversely, corneal neovascularization was significantly greater when RLMSC were applied in the absence of HLE (<0.05; 90% of cornea compared with 20-30% in other cohorts). Nevertheless, neither human nuclear antigen nor rabbit Y chromosome were detected within the regenerated epithelium. Our results demonstrate that while cultured LMSC encourage corneal re-epithelialization, healing is improved by the pre-cultivation and implantation of these mesenchymal cells in the presence of limbal epithelial cells.

Cesarean Scar Pregnancies: A Systematic Review of Treatment Options.

The objective of this systematic review was to assess the efficacy and safety of treatment options of cesarean scar pregnancies (CSPs). We searched MEDLINE, Embase, and the Cochrane Library from inception to June 2016 as well as reference lists. We included English publications reporting treatment outcomes of at least 10 cases of CSPs. Two authors screened for eligibility, extracted data, and assessed the quality of the included studies. Treatment was considered successful if no subsequent intervention was required after the index treatment. Of the 1257 citations identified, 63 studies were eligible. The overall success rate of systemic methotrexate (MTX) and/or local injection of MTX or potassium chloride was 62%. Dilation and curettage (D&C) was associated with a 28% risk of hemorrhage that dropped to 4% when combined with uterine artery embolization (UAE). Hysteroscopic resection of CSP was unsuccessful in 12% of cases, and inadequate human chorionic gonadotropin decay was the primary indication for additional intervention. Laparoscopic, vaginal, and open excision and repair of the defect were associated with a high success rate (≥96%) and a low risk of hemorrhage (≤4%). Expectant management resulted in a 57% live birth rate, but 63% of women required hysterectomy because of placental implantation abnormalities or second trimester uterine rupture. Most studies were of low methodologic quality, and given the heterogeneity between the studies and groups, statistical comparison of treatment options was deemed inappropriate. In conclusion, the decision to allow the progression of CSPs exposes women to a high risk of life-threatening hemorrhage and hysterectomy. Medical treatment options alone are often insufficient. D&C is a reasonable option in well-selected women or when combined with UAE. The potential benefits of excision and repair of scar defect on further pregnancy outcomes need to be further assessed.

Imaging for Polyps and Leiomyomas in Women With Abnormal Uterine Bleeding: A Systematic Review.

OBJECTIVE: To evaluate the accuracy of saline infusion sonohysterography in comparison with transvaginal ultrasonography for diagnosing polyps and submucosal leiomyomas in women with abnormal uterine bleeding. DATA SOURCES: We searched the databases MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov as well as citations and reference lists to the end of November 2015. METHODS OF STUDY SELECTION: Two authors screened 5,347 citations for eligibility. We included randomized controlled trials or prospective cohort studies published in English, assessing the accuracy of saline infusion sonohysterography and transvaginal ultrasonography for diagnosing polyps and submucosal leiomyomas in women with abnormal uterine bleeding. We considered studies using histopathologic specimens obtained at either hysteroscopy or hysterectomy as criterion standard. TABULATION, INTEGRATION, AND RESULTS: Twenty-five studies were eligible. Two authors extracted data and assessed the quality of included studies. Bivariate random-effects models were used to compare the different tests and evaluate sources of heterogeneity. Saline infusion sonohysterography was superior to transvaginal ultrasonography with pooled sensitivity and specificity of 0.92 and 0.89 compared with 0.64 and 0.90, respectively (P<.001). Transvaginal ultrasound sensitivity for diagnosing polyps was particularly low (0.51). Saline infusion sonohysterography was also compared with hysteroscopy in seven studies and had similar sensitivity but inferior specificity (0.93 and 0.83 compared with 0.95 and 0.90, respectively, P=.007). All three procedures were well-tolerated by women. Saline infusion sonohysterography was successfully completed in 95% of women. Technical variations such as the use of balloon catheters were not found to affect diagnostic accuracy. CONCLUSION: Transvaginal ultrasonography lacks sensitivity to be used alone to exclude the presence of polyps and leiomyomas in women with abnormal uterine bleeding. Although less specific than hysteroscopy, saline infusion sonohysterography offers a similar detection rate and permits concomitant visualization of the ovaries and myometrium. Cost, convenience, and tolerability of different imaging techniques require further evaluation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO, CRD42016034005.

Concise reviews: can mesenchymal stromal cells differentiate into corneal cells? A systematic review of published data.

The majority of stem cell therapies for corneal repair are based upon the use of progenitor cells isolated from corneal tissue, but a growing body of literature suggests a role for mesenchymal stromal cells (MSC) isolated from noncorneal tissues. While the mechanism of MSC action seems likely to involve their immuno-modulatory properties, claims have emerged of MSC transdifferentiation into corneal cells. Substantial differences in methodology and experimental outcomes, however, have prompted us to perform a systematic review of the published data. Key questions used in our analysis included: the choice of markers used to assess corneal cell phenotype, the techniques used to detect these markers, adequate reporting of controls, and tracking of MSC when studied in vivo. Our search of the literature revealed 28 papers published since 2006, with half appearing since 2012. MSC cultures established from bone marrow and adipose tissue have been best studied (22 papers). Critically, only 11 studies used appropriate markers of corneal cell phenotype, along with necessary controls. Ten out of these eleven papers, however, contained positive evidence of corneal cell marker expression by MSC. The clearest evidence is observed with respect to expression of markers for corneal stromal cells by MSC. In comparison, the evidence for MSC conversion into either corneal epithelial cells or corneal endothelial cells is often inconsistent or inconclusive. Our analysis clarifies this emerging body of literature and provides guidance for future studies of MSC differentiation within the cornea as well as other tissues.

Late-onset persistent Descemet's membrane detachment following uncomplicated clear corneal incision cataract surgery.

We report the case of a 76-year-old man who developed a late-onset Descemet's membrane detachment (DMD) 5 months after uncomplicated cataract surgery. Despite two air tamponade procedures that initially appeared successful, the DMD continued to return. After careful examination it was found that a surgical entry wound may have been scarred open (fish-mouthing), which continually promoted Descemet's membrane to detach. Excision of the abnormal scar led to an almost complete resolution of the DMD. To our knowledge, this is the first report of a pathological (fish-mouthing) entry wound causing a persistent, late DMD. We discuss the reasons why the management of late DMDs requires careful consideration.

Integrating information from disparate sources: the Walter Reed National Surgical Quality Improvement Program Data Transfer Project.

The Walter Reed National Surgical Quality Improvement Program Data Transfer web module integrates with medical and surgical information systems, and leverages outside standards, such as the National Library of Medicine's RxNorm, to process surgical and risk assessment data. Key components of the project included a needs assessment with nurse reviewers and a data analysis for federated (standards were locally controlled) data sources. The resulting interface streamlines nurse reviewer workflow by integrating related tasks and data.