Feasibility and Perioperative Outcomes of Minimally Invasive Higher Order Myomectomy.

STUDY OBJECTIVE: To investigate perioperative outcomes of minimally invasive higher order myomectomy as defined by removal of 10 or more fibroids. DESIGN: A retrospective cohort study between January 2018 and December 2022. SETTING: A tertiary academic medical center. PATIENTS: Women who underwent minimally invasive myomectomy via laparoscopic or robotic approach. INTERVENTIONS: Surgical intervention in the form of minimally invasive myomectomy. MEASUREMENTS AND MAIN RESULTS: A total of 735 women met inclusion criteria of whom 578 had fewer than 10 fibroids removed, and 157 patients had 10 or more removed (average number of fibroids removed 3.8 vs 14.7, p <.001; specimen's weight 317.4 g vs 371.0 g, p = .07). Body mass index was similar in both groups (p = .66) and patients with higher order myomectomy were more likely to have a history of myomectomy (12.0% vs 26.8%, p <.001). The average estimated blood loss (EBL) was 246 mL vs 470 mL in each group (p <.001). There were no significant differences in packed red blood cell transfusion (1.0% vs 0.6%, p = .65), conversion to laparotomy (0.5% vs 0.6%, p = .86), or complications including visceral injury, wound complication, venous thromboembolism, ileus, or readmission (5.9% vs 4.5%, p = .49). The hospital length of stay was similar in both groups (0.5 days vs 0.5 days, p = .63). On linear regression analysis, after adjusting for specimen's weight, operative time, and history of myomectomy, EBL remained significantly higher in patients with 10 or more fibroids removed (p = .02). CONCLUSION: EBL is increased in higher order myomectomy; however, blood transfusions, conversion to laparotomy, complication rates, and length of hospital stay did not differ compared with patients with fewer than 10 fibroids removed, highlighting the feasibility of minimally invasive higher order myomectomy.

Salpingectomy for ovarian cancer prevention: Video education for the surgeon.

Given the unremitting obstacles to effectively screen for and treat ovarian cancer (OC), prevention is a necessary countermeasure. The recent discovery of the fallopian tube as the origin of the most common and deadly type of OC, high grade serous cancer (HGSC), makes prevention through salpingectomy possible (Madsen et al., 2015). Opportunistic salpingectomy (OS) is the practice of removing the post-reproductive fallopian tubes at the time of other intraperitoneal surgery, or for sterilization in lieu of tubal ligation, to decrease OC risk (Falconer et al., 2015). The safety, effectiveness, and reach of OS as a primary prevention strategy depends on the knowledge mobilization of a standard surgical approach for surgeons (Hanley et al., 2017, Morelli et al., 2013). Resources for accomplishing this knowledge mobilization activity are needed. We therefore aim to create a peer-reviewed, publicly available surgical instructional video that facilitates standardization of the practice of salpingectomy for the purpose of OC prevention. Content creation was generated by a team of surgeon stakeholders, medical illustrators, instructional designers, and health education specialists. Expert gynecologic surgeons were filmed performing salpingectomy in order to build a video library. Accurate illustration and editing of live video footage was executed to support surgeons in visualizing key anatomic landmarks to ensure safe and complete fallopian tube excision. Review of eligibility criteria, fundamentals of preoperative counseling, and strategic and technical points were prioritized. This endeavor is strictly educational, with no commercial benefit. Publicly available, peer-reviewed surgical education tools will help us collaborate to safely and equitably expand OS within and beyond the current scope of surgical practice.

Laparoscopic administration of bupivacaine at the uterosacral ligaments during benign laparoscopic and robotic hysterectomy: a randomized controlled trial.

BACKGROUND: Postoperative pain continues to be an undermanaged part of the surgical experience. Multimodal analgesia has been adopted in response to the opioid epidemic, but opioid prescribing practices remain high after minimally invasive hysterectomy. Novel adjuvant opioid-sparing analgesia to optimize acute postoperative pain control is crucial in preventing chronic pain and minimizing opioid usage. OBJECTIVE: This study aimed to determine the effect of direct laparoscopic uterosacral bupivacaine administration on opioid usage and postoperative pain in patients undergoing benign minimally invasive (laparoscopic and robotic) hysterectomy. STUDY DESIGN: This was a single-blinded, triple-arm, randomized controlled trial at an academic medical center between March 15, 2021, and April 8, 2022. The inclusion criteria were patients aged >18 years undergoing benign laparoscopic or robotic hysterectomy. The exclusion criteria were non-English-speaking patients, patients with an allergy to bupivacaine or actively using opioid medications, patients undergoing transversus abdominis plane block, and patients undergoing supracervical hysterectomy or combination cases with other surgical services. Patients were randomized in a 1:1:1 fashion to the following uterosacral administration before colpotomy: no administration, 20 mL of normal saline, or 20 mL of 0.25% bupivacaine. All patients received incisional infiltration with 10 mL of 0.25% bupivacaine. The primary outcome was 24-hour oral morphine equivalent usage (postoperative day 0 and postoperative day 1). The secondary outcomes were total oral morphine equivalent usage in 7 days, last day of oral morphine equivalent usage, numeric pain scores from the universal pain assessment tool, and return of bowel function. Patients reported postoperative pain scores, total opioid consumption, and return of bowel function via Qualtrics surveys. Patient and surgical characteristics and primary and secondary outcomes were compared using chi-square analysis and 1-way analysis of variance. Multiple linear regression was used to identify predictors of opioid use in the first 24 hours after surgery and total opioid use in the 7 days after surgery. RESULTS: Of 518 hysterectomies screened, 410 (79%) were eligible, 215 (52%) agreed to participate, and 180 were ultimately included in the final analysis after accounting for dropout. Most hysterectomies (70%) were performed laparoscopically, and the remainder were performed robotically. Most hysterectomies (94%) were outpatient. Patients randomized to bupivacaine had higher rates of former and current tobacco use, and patients randomized to the no-administration group had higher rates of previous surgery. There was no difference in first 24-hour oral morphine equivalent use among the groups (P=.10). Moreover, there was no difference in numeric pain scores (although a trend toward significance in discharge pain scores in the bupivacaine group), total 7-day oral morphine equivalent use, day of last opioid use, or return of bowel function among the groups (P>.05 for all). The predictors of increased 24-hour opioid usage among all patients included only increased postanesthesia care unit oral morphine equivalent usage. The predictors of 7-day opioid usage among all patients included concurrent tobacco use and mood disorder, history of previous laparoscopy, estimated blood loss of >200 mL, and increased oral morphine equivalent usage in the postanesthesia care unit. CONCLUSION: Laparoscopic uterosacral administration of bupivacaine at the time of minimally invasive hysterectomy did not result in decreased opioid usage or change in numeric pain scores.

Cost drivers for benign hysterectomy within a health care system: Influence of patient, perioperative, and hospital factors.

OBJECTIVE: To identify patient, perioperative, and hospital factors that drive total hospital charges for benign hysterectomy. METHODS: The authors conducted a retrospective cohort study between July 2014 and February 2019 at five academic and community hospitals within an integrated healthcare system in the state of Maryland with a Global Budget Revenue methodology for hospital charges. Predictor variables included patient, perioperative and hospital characteristics. One-way analysis of variance was used to compare charges among approaches. A multiple linear regression model was built to account for the interaction between covariates. RESULTS: A total of 2592 patients underwent hysterectomy via laparoscopic (61%), abdominal (16%), robotic (14%), or vaginal (9%) approaches. Before adjusting for covariates, laparoscopic and vaginal approaches had similar charges ($11 637 and $12 229, respectively), while robotic and open approaches had higher charges ($17 535 and $19 099, respectively). After adjusting, charges for open, laparoscopic, and robotic approaches were higher than the vaginal approach ($692, $712, and $1279, respectively). Each operating room minute resulted in an increased cost of $46. Length of stay >23 h was associated with an increase of $865. Year, uterine size, body mass index, additional procedures, and transfusion influenced charges. CONCLUSION: Perioperative and hospital characteristics significantly influence hospital charges for benign hysterectomy, more so than nonmodifiable patient characteristics. This provides opportunities to reduce healthcare expenditures, such as improving operating room efficiency and reducing length of stay.

Perioperative opioid dispensing and persistent use after benign hysterectomy: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was conducted to (1) assess the quantity and dose of perioperatively dispensed opioids for benign hysterectomy by procedure route and (2) identify the predictors of persistent opioid use after the procedure. DATA SOURCES: PubMed, Web of Science, and Embase were systematically searched from study inception to 25 March 2022. STUDY ELIGIBILITY CRITERIA: Studies reporting data on opioid dispensing among patients undergoing benign hysterectomy were considered eligible. The primary outcome was the dosage of opioids dispensed perioperatively (from 30 preoperative days to 21 postoperative days). The secondary outcome was the predictors of persistent opioid use after benign hysterectomy (from 3 months to 3 years postoperatively). Total opioid dispensing was measured in morphine milligram equivalents units. METHODS: The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. RESULTS: A total of 8 studies presenting data on 377,569 women undergoing benign hysterectomy were included. Of these women, 83% (95% confidence interval, 81-84) were dispensed opioids during the perioperative period. The average amount of perioperatively dispensed opioids was 143.5 morphine milligram equivalents (95% confidence interval, 40-247). Women undergoing vaginal hysterectomy were dispensed a significantly lower amount of opioids than those undergoing laparoscopic or abdominal hysterectomies. The overall rate of persistent opioid use after benign hysterectomy was 5% (95% confidence interval, 2-8). Younger patient age (odds ratio, 1.38; 95% confidence interval, 1.17-1.63), smoking history (odds ratio, 1.87; 95% confidence interval, 1.67-2.10), alcohol use (odds ratio, 3.16; 95% confidence interval, 2.34-4.27), back pain (odds ratio, 1.50; 95% confidence interval, 1.10-2.05), and fibromyalgia (odds ratio, 1.60; 95% confidence interval, 1.39-1.83) were significantly associated with a higher risk of persistent opioid use after benign hysterectomy. However, there was no significant effect of hysterectomy route and operative complexity on persistent opioid use postoperatively. CONCLUSION: Perioperative opioid dispensing was significantly dependent on the route of hysterectomy, with the lowest dispensed morphine milligram equivalents of opioids for vaginal hysterectomy and the highest for abdominal hysterectomy. Nevertheless, hysterectomy route did not significantly predict persistent opioid use postoperatively, whereas younger age, smoking, alcohol use, back pain, and fibromyalgia were significantly associated with persistent opioid use.

Risk Factors for Postoperative Narcotic Use in Benign, Minimally-Invasive Gynecologic Surgery.

Background and Objectives: To evaluate postoperative opioid use after benign minimally-invasive gynecologic surgery and assess the impact of a patient educational intervention regarding proper opioid use/disposal. Methods: Educational pamphlets were provided preoperatively. Patients underwent hysterectomy, myomectomy, or other laparoscopic procedures. Opioid prescriptions were standardized with 25 tablets oxycodone 5mg for hysterectomy/myomectomy, 10 tablets oxycodone 5mg for LSC (oral morphine equivalents were maintained for alternatives). Pill diaries were reviewed and patient surveys completed during postoperative visits. Results: Of 106 consented patients, 65 (61%) completed their pill diaries. Median opioid use was 35 OME for hysterectomy (∼5 oxycodone tablets; IQR 11.25-102.5), 30 OME for myomectomy (∼4 tablets; IQR 15-75), and 18.75 OME for laparoscopy (∼3 tablets; IQR 7.5-48.75). Median last post-operative day (d) of use was 3d for hysterectomy (IQR 2, 8), 4d for myomectomy (IQR 1, 7), and 2d for laparoscopy (IQR 0.5-3.5). One patient (myomectomy) required a refill of 5mg oxycodone. No difference was found between total opioid use and presence of pelvic pain, chronic pain disorders, or psychiatric co-morbidities. Overall satisfaction with pain control (>4 on a 5-point Likert scale) was 91% for hysterectomy, 100% for myomectomy, 83% for laparoscopy. Of the 33 patients who read the pamphlet, 32(97%) felt it increased their awareness. Conclusion: Most patients required <10 oxycodone 5mg tablets, regardless of procedure with excellent patient satisfaction. A patient education pamphlet is a simple method to increase knowledge regarding the opioid epidemic and facilitate proper medication disposal.

Optimizing Perioperative Venous Thromboembolism Chemoprophylaxis on a Gynecologic Oncology Service.

BACKGROUND: Perioperative venous thromboembolism (VTE) is a significant cause of morbidity and mortality after gynecologic cancer surgery. Here we report a quality improvement intervention to increase perioperative VTE chemoprophylaxis compliance. STUDY DESIGN: All operations performed by a gynecologic oncologist at a tertiary urban university medical center admitted to the hospital for at least one midnight were included. Using a pre/post design with a washout period, we sought to increase perioperative VTE chemoprophylaxis compliance from 22% in the historical control (HC) cohort to 90% in the quality improvement (QI) cohort. The perioperative VTE chemoprophylaxis process was standardized by addressing four domains: preoperative VTE chemoprophylaxis, surgical time-out, postoperative VTE chemoprophylaxis, and intervention education and compliance tracking. Pearson's chi-square test was used to compare HC vs QI cohort compliance. RESULTS: There were 130 surgical cases in the HC cohort and 131 in the QI cohort. Forty-two percent underwent laparotomy, and 57% had cancer at the time of operation. VTE chemoprophylaxis compliance improved from 22% in the HC cohort to 82% in the QI cohort (p < 0.001). Preoperative VTE chemoprophylaxis compliance improved from 76% in the HC cohort to 94% in the QI cohort (p < 0.001), and postoperative VTE chemoprophylaxis compliance improved from 27% to 87% (p < 0.001). Thirty-day postoperative VTE occurred in three patients (2%) in the HC cohort and none in the QI cohort (p = 0.08). CONCLUSIONS: A low-cost and low-technology QI initiative intervention improved perioperative compliance with VTE chemoprophylaxis.

Modifiable risk factors associated with long-term survival in women with serous ovarian cancer: a National Cancer Database study.

OBJECTIVE: To identify patient, clinical and hospital factors associated with long-term survival (≥10 years) in women with serous ovarian cancer. METHODS: This National Cancer Database cohort study included women with stage II-IV serous ovarian cancer. Multivariate logistic regression models were used to examine the association of long-term survival with patient (race, insurance, location, household income, education, distance traveled), clinical (age, comorbidities, stage, grade, primary treatment) and hospital factors (region, institution, hospital volume ≥20). RESULTS: Of the 4640 women identified, 12% (n=561) experienced long-term survival. Median overall survival was 41 months (95% CI 39 to 42). The odds of long-term survival were lower for women with public or no insurance (adjusted OR 0.71, 95% CI 0.55 to 0.92), age ≥75 years (0.33, 0.22 to 0.50), any comorbidities (0.70, 0.54 to 0.92), higher stage (stage III: 0.31, 0.25 to 0.41; stage IV: 0.16, 0.12 to 0.22), and moderately/poorly differentiated, undifferentiated, or tumors of unknown grade (moderately/poorly differentiated: 0.30, 0.20 to 0.47; undifferentiated: 0.28, 0.17 to 0.47; unknown: 0.30, 0.18 to 0.50). The odds of long-term survival among women who were publicly insured were lower with neoadjuvant chemotherapy (0.13, 0.04 to 0.044) and higher with optimal cytoreduction (2.24, 1.49 to 3.36). Among women who were privately insured, the odds of long-term survival were higher with optimal cytoreduction (1.99, 1.46 to 2.70) and unaffected by neoadjuvant chemotherapy. CONCLUSIONS: While immutable clinical factors such as age, stage, and grade are associated with long-term survival in women with serous ovarian cancer, modifiable factors, such as insurance type, optimal cytoreductive status, and neoadjuvant chemotherapy provide an opportunity for targeted improvement in care with potential to affect long-term patient outcomes.

Predictors of Minimally Invasive Myomectomy in the National Inpatient Sample Database, 2010-2014.

BACKGROUND AND OBJECTIVES: This study aims to characterize the utilization of minimally invasive myomectomy in the United States and to identify the patient and hospital factors associated with surgical approach to myomectomy. METHODS: This is a cross-sectional study using the National Inpatient Sample database. We extracted women aged 18-50 years who underwent open and minimally invasive (laparoscopic and robotic) myomectomy (MIM) from January 1, 2010-December 31, 2014. Descriptive statistics were obtained for patient and hospital characteristics. We then performed multivariable logistic regression to examine the association of patient (age, race, insurance status, median household income) and hospital (bed size, teaching status, for-profit status, census region, cases volume) characteristics with the likelihood of undergoing MIM. RESULTS: Of 114,850 myomectomy cases, 8,330 (7%) underwent MIM and 106,520 (93%) were open. Over time, the proportion of MIM remained very low and slightly decreased from 8.2% in 2010 to 6.1% in 2014 (p-for-trend: 0.001). Most hospitals performed few MIM per year, with 50% performing five or less, and 25% performing three or fewer per year. African American, Hispanic, and women of other races were less likely to undergo MIM compared to Caucasian women (adjusted odds ration [OR] 0.57, 95% confidence interval [CI] 0.50-0.64; 0.71, 95% CI 0.60-0.83; 0.62, 95% CI 0.52-0.74, respectively). Women in the West (adjusted odds ratio (aOR) 1.23, 95% CI 1.04-1.46) and Midwest (aOR 1.27, 95% CI 1.07-1.52) had higher odds of undergoing MIM. CONCLUSION: MIM appears to be an underutilized modality, accounting for less than10% of myomectomies. This underutilization disproportionally affects minority women.

Systematic Review of Intraoperative Assessment Tools in Minimally Invasive Gynecologic Surgery.

OBJECTIVE: To collect, summarize, and evaluate the currently available intraoperative rating tools used in abdominal minimally invasive gynecologic surgery (MIGS). DATA SOURCES: Medline, Embase, and Scopus databases from January 1, 2000, to May 12, 2020. METHODS OF STUDY SELECTION: A systematic search strategy was designed and executed. Published studies evaluating an assessment tool in abdominal MIGS cases were included. Studies focused on simulation, reviews, and abstracts without a published manuscript were excluded. Risk of bias and methodological quality were assessed for each study. TABULATION, INTEGRATION, AND RESULTS: Disparate study methods prevented quantitative synthesis of the data. Ten studies were included in the analysis. The tools were grouped into global (n = 4) and procedure-specific assessments (n = 6). Most studies evaluated small numbers of surgeons and lacked a comparison group to evaluate the effectiveness of the tool. All studies demonstrated content validity and at least 1 dimension of reliability, and 2 have external validity. The intraoperative procedure-specific tools have been more thoroughly evaluated than the global scales. CONCLUSION: Procedure-specific intraoperative assessment tools for MIGS cases are more thoroughly evaluated than global tools; however, poor-quality studies and borderline reliability limit their use. Well-designed, controlled studies evaluating the effectiveness of intraoperative assessment tools in MIGS are needed.

Predictors of Overnight Admission After Laparoscopic Myomectomy in a High-Volume Minimally Invasive Gynecologic Surgery Setting.

STUDY OBJECTIVE: Our primary goal was to uncover preoperative and intraoperative risk factors that prevented same-day discharge (SDD) after myomectomy in a setting where SDD was the standard of care. Uncovered predictors would serve to enhance patient counseling and medical optimization before surgery. DESIGN: Single-center retrospective cohort study. SETTING: Urban university hospital center, by fellowship-trained minimally invasive gynecologic surgeons. PATIENTS: A total of 315 consecutive patients undergoing minimally invasive myomectomy between March 2012 and May 2018. INTERVENTION: Minimally invasive myomectomy. MEASUREMENTS AND MAIN RESULTS: Preoperative and intraoperative characteristics were collected for analysis as predictors of SDD vs overnight admission. Comparisons of demographic, clinical, imaging, and operative characteristics were made using appropriate statistical methods for normally distributed, skewed, and categorical variables. Length of stay was analyzed as a categorical variable, SDD vs overnight admission. A logistic regression model was used to evaluate SDD vs any overnight stay. Out of the 315 patients undergoing laparoscopic myomectomy, 208 (66.03%) were discharged on the same day, and 107 (33.96%) were admitted for at least 1 day after surgery. The patients were more likely to be admitted overnight if they were of Asian ethnicity (p = .01), or if they had a lower preoperative Hct (36.15 vs 37.57; p < .003). An increase in any myoma characteristic metric was associated with overnight stay after surgery; these included mean myoma weight (512.0 g vs 310.1 g; p < .001), estimated size of the largest myoma on imaging (9.01 cm vs 7.77 cm; p < .001), and number of myomas removed (6.59 vs 5.57; p = .021). Other statistically significant differences between the overnight admission and SDD groups were mean estimated blood loss (599.4 mL vs 221.9 mL; p < .001), operative time (224.4 minutes vs 140.9 minutes; p < .001), and surgery end time (15:02 hours vs 12:43 hours; p < .001). Intraoperative complications associated with overnight admission were estimated blood loss >1 L (p < .001) and any intraoperative transfusion (p < .001). The adjusted logistic regression model identified an increase in operative time (by 60 minutes) and later surgery end time (by 60 minutes) as predictors of an overnight stay, whereas an 5% increase in preoperative hematocrit was associated with a 34% decrease in odds for an overnight stay. CONCLUSION: Perioperative factors, such as preoperative hematocrit, and myoma characteristics, as well as intraoperative factors, such as prolonged operative time and surgery end-time, are independent predictors of overnight hospital admission after minimally invasive myomectomy. Our present data can be used to provide better patient counseling before surgery.

Rates of regression of cervical dysplasia between initial biopsy and excisional procedure in routine clinical practice.

PURPOSE: To determine rates and factors associated with regression of cervical intraepithelial neoplasia (CIN) 2 + between colposcopic biopsy and therapeutic excisional procedure in standard practice. METHODS: A retrospective chart review was performed for women undergoing a cervical excisional procedure for CIN 2 + at clinics at three academic institutions over a 3-year period. Cytology, histology, patient age and time-to-excision were analyzed to determine factors influencing rates of regression. RESULTS: Of 356 women undergoing excision for CIN 2 + on colposcopic biopsy, 91 (25.3%) of final pathology diagnoses displayed clinically significant regression. Age and time-to-excision were not associated with regression, but referral cytology and severity of initial biopsy histology were, with ASC-H (aOR 0.1, CI 0.03, 0.8) and CIN 3/AIS (aOR 0.4, CI 0.2, 0.7) being less likely to regress than less severe lesions. CONCLUSIONS: Disease severity by referral cytology or diagnostic biopsy, as opposed to age or length of time-to-excision, is likely the most relevant factor in determination of regression for cervical intraepithelial neoplasia in women undergoing excisional treatment for biopsy-confirmed CIN2 +.

Effects of Cancer Genetic Panel Testing on at-Risk Individuals.

OBJECTIVE: To evaluate the role of screening patients at increased risk for hereditary cancer syndromes with an extended panel of cancer predisposition genes to identify actionable genetic mutations. METHODS: A retrospective chart review was conducted of all patients presenting to a multidisciplinary cancer program for genetic counseling and testing from January 2015 to December 2016. Individuals presenting to the program were identified as at-risk by a personal or family history of cancer, by their health care provider, or by self-referral. All participants met current National Comprehensive Cancer Network criteria for genetic risk evaluation for hereditary cancer. The results of testing and its implications for management, based on National Comprehensive Cancer Network guidelines, were recorded. RESULTS: Of 670 at-risk patients who underwent genetic testing, 66 (9.9%) had BRCA-limited testing; of these, 26 of 670 (3.9%) had a deleterious or likely pathogenic mutation. Expanded panel testing was done for 560 of the 670 patients (83.4%), and abnormal results were found in 65 of 670 (9.7%); non-BRCA mutations (predominantly CHEK2) were found in 49 of the 65 (75%). Abnormal genetic testing was associated with increased surveillance in 96% of those with deleterious mutations, whereas negative testing for a known familial mutation in 45 patients was associated with a downgrade of their risk and reduction of subsequent surveillance and management. CONCLUSION: Guideline-based management is frequently altered by genetic testing, including panel testing, in patients at risk for cancer. We recommend that obstetrics and gynecology providers routinely refer at-risk patients for genetic counseling and testing when clinically appropriate.

Choriocarcinoma with brain, lung and vaginal metastases successfully treated without brain radiation or intrathecal chemotherapy: A case report.

•There is no consensus on optimal treatment for GTN and brain metastases.•Brain metastasis treated with craniotomy and intravenous, EMA-CO chemotherapy•Intravenous high-dose methotrexate may be adequate to treat brain metastases.

Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer.

BACKGROUND: The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling and delays tumor growth in murine prostate cancer xenograft models. We conducted a noncomparative, randomized, phase II study evaluating the antitumor efficacy of two doses of oral itraconazole in men with metastatic prostate cancer. PATIENTS AND METHODS: We randomly assigned 46 men with chemotherapy-naïve metastatic castration-resistant prostate cancer (CRPC) to receive low-dose (200 mg/day) or high-dose (600 mg/day) itraconazole until disease progression or unacceptable toxicity. The primary endpoint was the prostate-specific antigen (PSA) progression-free survival (PPFS) rate at 24 weeks; a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints included the progression-free survival (PFS) rate and PSA response rate (Prostate Cancer Working Group criteria). Exploratory outcomes included circulating tumor cell (CTC) enumeration, serum androgen measurements, as well as pharmacokinetic and pharmacodynamic analyses. RESULTS: The high-dose arm enrolled to completion (n = 29), but the low-dose arm closed early (n = 17) because of a prespecified futility rule. The PPFS rates at 24 weeks were 11.8% in the low-dose arm and 48.0% in the high-dose arm. The median PFS times were 11.9 weeks and 35.9 weeks, respectively. PSA response rates were 0% and 14.3%, respectively. In addition, itraconazole had favorable effects on CTC counts, and it suppressed Hedgehog signaling in skin biopsy samples. Itraconazole did not reduce serum testosterone or dehydroepiandrostenedione sulfate levels. Common toxicities included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia, hypertension, and edema. CONCLUSION: High-dose itraconazole (600 mg/day) has modest antitumor activity in men with metastatic CRPC that is not mediated by testosterone suppression.

Probabilistic evaluation of three-dimensional reconstructions from X-ray images spanning a limited angle.

An important part of computed tomography is the calculation of a three-dimensional reconstruction of an object from series of X-ray images. Unfortunately, some applications do not provide sufficient X-ray images. Then, the reconstructed objects no longer truly represent the original. Inside of the volumes, the accuracy seems to vary unpredictably. In this paper, we introduce a novel method to evaluate any reconstruction, voxel by voxel. The evaluation is based on a sophisticated probabilistic handling of the measured X-rays, as well as the inclusion of a priori knowledge about the materials that the object receiving the X-ray examination consists of. For each voxel, the proposed method outputs a numerical value that represents the probability of existence of a predefined material at the position of the voxel while doing X-ray. Such a probabilistic quality measure was lacking so far. In our experiment, false reconstructed areas get detected by their low probability. In exact reconstructed areas, a high probability predominates. Receiver Operating Characteristics not only confirm the reliability of our quality measure but also demonstrate that existing methods are less suitable for evaluating a reconstruction.