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Objectives: To measure the diagnostic accuracy of intraoperative frozen section examination of sentinel lymph nodes (SLN) in vulvar cancer and to describe associated patient outcomes. Methods: This retrospective cohort study included patients with invasive squamous cell carcinoma of the vulva who underwent SLN biopsy with intraoperative frozen section at one cancer centre from Jan 2008 - Feb 2020. Exclusion criteria were tumor size >4cm, multifocal tumor, palpable groin lymph nodes and neoadjuvant therapy. The SLN procedure was performed by injection of the primary vulvar tumor or scar with technetium-99m, ICG and/or blue dye. We compared the intraoperative SLN frozen section diagnosis and the paraffin section report for concordance. Recurrence location was described and recurrence free survival (RFS) was compared using the Kaplan-Meier method. Results: A total of 173 patients (258 groins) met inclusion and exclusion criteria. On frozen section, there were 36/258 positive groins on frozen section and 222 negative groins. On final pathology, there were 39/258 positive groin nodes: 30 macro-metastases, 7 micro-metastases, 2 isolated tumor cells (ITCs). There were 219 negative groins. The sensitivity and specificity for frozen section detecting any metastatic disease compared to final pathology, was 89.7% and 99.5%, respectively. The positive-predictive value (PPV) was 97.2% and the negative-predictive-value (NPV) was 98.2%. There were 4 cases of false negative frozen section where final pathology revealed two cases of ITCs, 1 micro-metastasis and 1 macro-metastasis. A total of 30 patients (17.3%) underwent a full inguinal femoral lymphadenectomy during the same operation due to the frozen section results and avoided a second operation. A total of 2 patients (1.2%) required a second operation for lymphadenectomy due to false negative results on frozen section. Median (range) follow up was 38.0 (1-137.8) months. Median RFS was 14.9 (3.6 to 98.2) months. There were 46 recurrences in the study population, of which 29 were confined to the vulva, 9 groin recurrences and 8 distant recurrences. Among patients with a negative SLN biopsy on both frozen section and final pathology, there were 10 (3.9 %) groin and/or distant recurrences. A total of 6 nodal recurrences were ipsilateral, 1 was contralateral, 2 were bilateral and 1 recurrence was distant. After exclusion of patients with local recurrence only, the RFS at 3 years was 91.6% (95% CI 86.2-97.4%) for patients with negative SLN on frozen section and 64.6% (95% CI 46.5-89.7%) for positive SLN on frozen section. On final pathology, patients with negative SLN had a 3-year RFS of 91.7% (95% CI 86.3-97.4%), macro-metastases 58.4% (95% CI 38.5-87.7%), and micro-metastases/ITCs was 100%. Conclusions: Intraoperative frozen section of SLNs in vulvar cancer is an accurate intraoperative guide to determine if complete inguinal femoral lymphadenectomy should be performed. SLN biopsy reduced the need for a second surgical procedure and does not appear to compromise patient outcomes.

ObjectiveThere has been a contemporary shift in clinical practice towards tailoring treatment in patients with early cervical cancer and low-risk features to non-radical surgery. The objective of this study was to evaluate the oncologic, fertility, and obstetric outcomes after cervical conization and sentinel lymph node (SLN) biopsy in patients with early stage low-risk cervical cancer.MethodsWe conducted a retrospective review in patients with early cervical cancer treated with cervical conization and lymph node assessment between November 2008 and February 2020. Eligibility criteria included patients with a histologic diagnosis of invasive squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage IA1 with positive lymphovascular space invasion (LVSI), stage IA2, or stage IB1 (≤2 cm) with less than two-thirds (ResultsA total of 44 patients were included in the analysis. The median age was 31 years (range 19–61) and 20 patients (45%) were nulliparous. One patient had a 25 mm tumor while the remaining patients had tumors smaller than 20 mm. Eighteen (41%) patients had LVSI. Median follow-up was 44 months (range 6–137). A total of 17 (39%) patients had negative margins on the diagnostic excisional procedure, and none had residual disease on the repeat cone biopsy. Three (6.8%) patients had micrometastases detected in the SLNs and underwent ipsilateral lymphadenectomy; all remaining non-SLN lymph nodes were negative. Six (13.6%) patients required more definitive surgical or adjuvant treatment due to high-risk pathologic features. There were no recurrences documented. Three patients developed cervical stenosis. The live birth rate was 85% and 16 (94%) of 17 patients had live births at term.ConclusionCervical conization with SLN biopsy appears to be a safe treatment option in selected patients with early cervical cancer. Future results of prospective trials may shed definitive light on fertility-sparing options in this group of patients.

AIM Cystoscopic placement of ureteric stents during colorectal surgery (CRS) may aid in the intraoperative identification of the ureters and thus prevent ureteric injury, but may also be associated with prolonged operating time, increased cost and adverse events. No formal recommendations exist regarding the use of ureteric stents prior to CRS. Our aim was to determine the effect of prophylactic ureteric stent insertion on the risk of ureteric injury among adult patients undergoing CRS. METHOD A systematic search using the Ovid platform was completed. The primary outcome was risk of ureteric injury. Secondary outcomes included the risk of acute kidney injury (AKI), urinary tract infection (UTI), sepsis, length of stay (LOS) and mortality. The Paule-Mandel pooling and a random effects model was used to produce odds ratios (ORs) with 95% confidence intervals (CIs) for binary outcomes. Standardized mean differences (MD) were reported for continuous variables. Analyses were completed using R3.5. RESULTS Nine retrospective cohort studies evaluating 98 507 patients were included. The incidence of ureteric injury was 0.6%. Overall, 5.1% of patients underwent ureteric stenting. There was no change in the odds of ureteric injury among stented patients compared with controls (OR 1.30, 95% CI 0.39-4.29, I2 = 25%). Operating time was significantly longer (MD 49.3 min, 95% CI 35.3-63.4, I2 = 96%) in the intervention group. There was no difference in rates of AKI, UTI, sepsis, LOS or mortality between groups. CONCLUSION Given the retrospective nature of the identified studies, the benefit of prophylactic ureteric stenting remains uncertain. Prophylactic ureteric stenting was not associated with increased patient morbidity but did significantly increase operating time.

Study objective: To determine the pre-operative evaluation, surgical management and referral practices in patients with advanced stage endometriosis by Canadian gynaecologists. Design: A survey of obstetricians and gynaecologists. Setting: The survey was initiated and piloted at an academic centre by general gynaecologists and endometriosis specialists. Intervention: Electronically distributed to 733 individuals by the Society of Obstetricians and Gynaecologists of Canada. This included all members, irrespective of subspecialty and practice patterns. Measurement: Responses were collected using a web-based survey tool and analysed using Excel. Results: The response rate was 15.7% (115 respondents). Pre-operatively, 62.2% of respondents perform a transvaginal ultrasound on all of their patients, while magnetic resonance imaging is reserved for patients with physical exam findings suspicious for advanced endometriosis (26.7%) or in whom the surgeons suspect deep infiltrating endometriosis, bowel, bladder or uterosacral disease (54.4%). Most surgeons (81.4%) report encountering advanced disease that they did not suspect pre-operatively Conclusion: Our study identified significant variability in the management of advanced endometriosis in Canada. Understanding these patterns will help us formulate a more universal investigation and management plan, which may improve the identification of patients pre-operatively with advanced stage endometriosis that could benefit from treatment by an endometriosis specialist.

Practice guidelines advocating for regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were published in Ontario in June 2013. Our objectives were to determine whether this policy affected surgical wait times, and whether longer wait time to surgery is a predictor of survival in high grade endometrial cancer patients.This was a population-based retrospective cohort study, which included patients diagnosed with high-grade non-endometrioid endometrial cancer who had a hysterectomy between 2003 and 2017. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between surgical wait time and overall survival (OS).We identified 3518 patients who underwent hysterectomy for high-grade non-endometrioid endometrial cancer. Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 53 days compared to 57 days pre-regionalization (p = 0.0007), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p = 0.0006). Survival was inferior for patients who had surgery within 14 days of diagnosis (HR death 2.7 for 1-7 days, 95% CI 1.61-4.51, and HR death 1.96 for 8-14 days, 95% CI 1.50-2.57), reflective of disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic oncology appointment (HR death 1.19 for 46-60 days, 95% CI 1.04-1.36, and HR death 1.42 for 61-75 days, 95% CI 1.11-1.83).Regionalization of surgery for high-grade endometrial cancer has not had an impact on surgical wait times. Patients who have surgery more than 45 days after surgical consultation have reduced survival.

Lymph node metastasis is the most important prognostic factor in patients with vulvar squamous cell carcinoma (SCC). Previous excision of the vulvar tumor may disrupt lymphatic channels and alter the accuracy of the sentinel lymph node (SLN) biopsy. The purpose of this study was to measure outcomes after SLN biopsy in patients with and without previous excision of the vulvar tumor.Retrospective study of patients at a single institution with primary vulvar cancer, clinically negative nodes, and vulvar tumors 4 cm treated with surgical excision who had SLN biopsy (2008-2015).There were 106 cases of concomitant wide local excision (WLE) and SLN biopsy and 24 additional cases of patients who had previous vulvar surgery and no visible tumor; these patients underwent scar re-excision and SLN biopsy. Median follow-up was 31 months. Patients who had previous tumor excision were more likely to be of younger age (p = 0.0001), have a smaller tumor (p = 0.002), and less depth of invasion (p = 0.02). In the wide local excision of the scar specimen, 11 patients (46%) had no residual disease left, 8 patients (33%) had only vulvar intraepithelial neoplasia (VINIII), 4 patients (17%) had carcinoma in situ with focal invasion and 1 patient (4%) had invasive carcinoma within the second specimen, resected with clear margins. There were no groin recurrences in patients who underwent scar re-excision and who had a negative SLN biopsy.SLN biopsy is feasible and safe in patients who have had previous excision of the vulvar tumor and present with a scar. When a SLN is detected by injecting the remaining scar, this accurately reflects the nodal status and does not negatively impact oncologic outcomes.

Objectives In June 2013, the agency responsible for advancing cancer care in Ontario, Canada, published practice guidelines recommending that gynaecologic oncologists (GOs) at designated centers manage the treatment of patients with high grade endometrial cancers. This study examines the effects of this regionalization of care on patient outcomes. Methods In this retrospective cohort study, patients diagnosed with non-endometrioid high risk endometrial cancer (serous, carcinosarcoma, clear cell, undifferentiated) from 2003–2017 were identified using province-wide administrative databases. Results We identified 3518 patients with high risk endometrial cancer. The case mix as represented by patient comorbidities and disease stage distribution did not differ significantly between the two regionalization periods. There was a significant increase (69% to 85%, p Conclusions The publication of a regionalization policy for the treatment of high risk histology endometrial cancers in Ontario led to an increase in the proportion of surgeries performed by GOs, surgical staging and adjuvant treatment. This also translated into a significant improvement in patient survival.

Objectives Practice guidelines advocating for the regionalization of endometrial cancer surgery to gynecologic oncologists (GO) practicing in designated gynecologic oncology centres were released by Cancer Care Ontario in June 2013. We sought to determine the impact this policy had on contemporary surgical wait times, and whether longer wait time to surgery is a predictor of survival in patients with high risk endometrial cancer. Study Methods This was a retrospective cohort study, which included patients diagnosed with non-endometrioid high-risk endometrial cancer (serous, carcinosarcoma, clear cell, and undifferentiated) between 2003 and 2017. A cut point of January 2014 was chosen to allow 6 months for knowledge translation and define 2 regionalization periods. Results We identified 3518 patients with high risk endometrial cancer. Patients who had surgery with a GO had a median surgical wait time from diagnosis to hysterectomy of 55 days compared to 59 days pre-regionalization (p=0.0002), and from first GO consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p=0.0006). Survival was worst for patients who had surgery within 14 days of diagnosis (HR death 1.94, 95%CI 1.48–2.54), indicating disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient’s first GO appointment (HR death 1.19, 95%CI 1.04–1.36). Conclusion Regionalization of surgery for high risk endometrial cancer has not had a negative impact on surgical wait times. Impact on survival is seen with patients who have surgery more than 45 days after surgical consultation.

ObjectivesMinimally invasive radical hysterectomy is associated with decreased survival in patients with early cervical cancer. The objective of this study was to determine whether the use of an intra-uterine manipulator at the time of laparoscopic or robotic radical hysterectomy is associated with inferior oncologic outcomes.MethodsA retrospective cohort study was carried out of all patients with cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) International Federation of Gynecology and Obstetrics 2009 stages IA1 (with positive lymphovascular space invasion) to IIA who underwent minimally invasive radical hysterectomy at two academic centers between January 2007 and December 2017. Treatment, tumor characteristics, and survival data were retrieved from hospital records.ResultsA total of 224 patients were identified at the two centers; 115 had surgery with the use of an intra-uterine manipulator while 109 did not; 53 were robotic and 171 were laparoscopic. Median age was 44 years (range 38–54) and median body mass index was 25.8 kg/m2 (range 16.6–51.5). Patients in whom an intra-uterine manipulator was not used at the time of minimally invasive radical hysterectomy were more likely to have residual disease at hysterectomy (pConclusionAfter controlling for adverse pathological factors, the use of an intra-uterine manipulator in patients with early cervical cancer who underwent minimally invasive radical hysterectomy was not an independent factor associated with rate of recurrence.

In June 2013, Ontario Health (Cancer Care Ontario), the agency responsible for advancing cancer care in Ontario, Canada, published practice guidelines recommending that gynecologic oncologists at tertiary care centers manage the treatment of patients with high-grade endometrial cancers. This study examines the effects of this regionalization of care on patient outcomes.This study aimed to evaluate the impact of the regionalization of surgery for high-grade endometrial cancer on patient and treatment outcomes.In this retrospective cohort study, patients diagnosed with nonendometrioid high-grade endometrial cancer from 2003 to 2017 were identified using province-wide administrative databases. To allow 6 months for knowledge translation, 2 periods were defined, with January 1, 2014, as the cutoff. Methods for segmented regression were used to test the effect of the guidelines. Multivariable Cox proportional hazards regression was used to evaluate whether regionalization of care had an impact on patient survival.There were 3518 patients with nonendometrioid high-grade endometrial cancer identified. The case mix as represented by patient comorbidities and the disease stage distribution did not differ significantly between the 2 regionalization periods. There was a significant increase (69%-85%; P.001) in the proportion of primary surgeries performed by gynecologic oncologists after regionalization, which was not explained by secular trends. After regionalization, the proportion of patients who had surgical staging (50%-63%; P.001) and the proportion of patients who received adjuvant treatment (65%-71%; P.001) increased significantly. After adjusting for age, stage, and comorbidities, there was a decrease in the hazard of mortality (hazard ratio, 0.85 [95% confidence interval, 0.73-0.99]; P=.04) after regionalization.The publication of a regionalization policy for the treatment of high-grade endometrial cancers in Ontario led to an increase in the proportion of surgeries performed by gynecologic oncologists. This also translated into a significant improvement in patient survival.

Objectives To assess the cost-effectiveness of using maintenance hormonal therapy in patients with low grade serous ovarian cancer (LGSC). Methods A simulated decision analysis with a Markov decision model over a lifetime horizon was performed using the base case of a 47-year old patient with stage IIIC, LGSC following first-line treatment with primary cytoreductive surgery and adjuvant chemotherapy. Two treatment strategies were analyzed - maintenance daily letrozole until disease progression and routine observation. The analysis was from the perspective of the healthcare payer. Direct medical costs were estimated using public data sources and previous literature and were reported in adjusted 2018 Canadian dollars. The model estimated lifetime cost, quality-adjusted life years (QALY), life years (LY), median overall survival (OS), and number of recurrences with each strategy. Cost-effectiveness was compared using an incremental cost-effectiveness ratio (ICER). A strategy was considered cost-effective when the ICER was less than the willingness to pay (WTP) threshold of $50,000 CAD per QALY. Deterministic sensitivity analysis was performed to assess the impact of changing key clinical and cost variables. Results Maintenance letrozole was the preferred strategy with an associated lifetime cost of $69,985 CAD ($52,620 USD) and an observed improvement of 0.91 QALYs and 1.55 LYs. The ICER for letrozole maintenance therapy was an additional $11,037 CAD ($8298 USD) per QALY. The modeled median OS was 150 months with maintenance letrozole and 126 months in the observation strategy. The maintenance letrozole strategy resulted in 34% and 17% fewer first recurrences at 5-year and 10-year follow-up, respectively. Conclusion Maintenance letrozole is a cost-effective treatment strategy in patients with advanced LGSC resulting in clinically-relevant improvement in QALYs, LYs, and fewer disease recurrences.

Objectives The primary objective of this study is to determine if early administration of intraperitoneal (IP) chemotherapy and intra-operative insertion of an IP port are associated with increased complications in patients who undergo a bowel resection procedure as part of primary cytoreductive surgery for ovarian cancer. Methods This was a multi-centre retrospective cohort study, at 2 high volume cancer centers. For our primary outcomes, univariate logistic regression was completed to assess the impact of timing of IP chemotherapy administration and IP port insertion on perioperative complications. Kaplan Meier survival curves were compared using the Log-Rank test. Results We identified 131 patients treated with IP chemotherapy after bowel resection during primary cytoreduction for advanced ovarian cancer; 75 patients started IP treatment at the first adjuvant chemotherapy, while 56 patients received intravenous (IV) chemotherapy and later transitioned to IP chemotherapy. The majority of patients had stage III/IV disease (87%) and high-grade serous histology (91.6%). Compared to patients who received their first cycle of chemotherapy IV, patients who started with IP chemotherapy were not at increased risk of intra-abdominal infections (8% vs 16% (p = 0.15)), IP port related complications (20% vs 19.6% (p = 0.96)), or anastomotic leak (2.7% vs 3.6% (p = 0.8)). There was a non-statistically significant trend for increased rates of anastomotic leak (5.6% vs 3.3% (p = 0.62)), intra-abdominal infection (16.7% vs 6.7% (p = 0.17)) and IP port related complications (24.1% vs 13.3% (p = 0.21)) in patients who had intra-operative IP port insertion compared to delayed post-operative port insertion. Conclusions Administration of IP chemotherapy in the first post-operative cycle after bowel resection is not associated with increased post-operative complications in women with advanced ovarian carcinoma undergoing primary cytoreductive surgery. Intra-operative IP port insertion may be associated with a small increase in major complications in this population.

IntroductionAs sentinel lymph node biopsy is evolving to an accepted standard of care, clinicians are being faced with more frequent cases of small volume nodal metastatic disease. The objective of this study is to describe the management and to measure the effect on recurrence rates of nodal micrometastasis and isolated tumor cells in patients with early stage cervical cancer at two high-volume centers.MethodsWe conducted a review of prospectively collected patients with surgically treated cervical cancer who were found to have micrometastasis or isolated tumor cells on ultrastaging of the sentinel lymph node. Our practice is to follow patients for ≥5 years post-operatively either at our center or another cancer center closer to home.ResultsNineteen patients with small volume nodal disease were identified between 2006 and 2018. Median follow-up was 62 months. Ten (53%) had nodal micrometastatic disease, while nine (47%) had isolated tumor cells detected in the sentinel lymph node. Seven patients (37%) underwent completion pelvic lymphadenectomy and four of them also had para-aortic lymphadenectomy; there were no positive non-sentinel lymph nodes. The majority (74%) received adjuvant treatment, mostly driven by tumor factors. We observed two recurrences. Recurrence-free survival was comparable with historical cohorts of node negative patients, and adjuvant treatment did not seem to impact the recurrence rate (p=0.5).ConclusionGiven the uncertainties around the prognostic significance of small volume nodal disease in cervical cancer, a large proportion of patients receive adjuvant treatment. We found no positive non-sentinel lymph nodes, suggesting that pelvic lymphadenectomy or para-aortic lymphadenectomy may not be of benefit in patients diagnosed with small volume nodal metastases. Recurrence-free survival in this group did not seem to be affected. However, given the small numbers of patients and lack of level 1 evidence, decisions should be individualized in accordance with patient preferences and tumor factors.

Objectives: Practice guidelines advocating for the regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were released by Cancer Care Ontario in June 2013. We sought to determine the impact this policy had on contemporary surgical wait times. Moreover, a discussion about the impact of delays in treatment has never been more timely than in the context of the current COVID19 pandemic, which has burdened health care systems around the world. Our primary objective was to establish whether longer wait time to surgery is a predictor of survival in patients with high grade endometrial cancer. Methods: This was a retrospective cohort study, which included patients diagnosed with non-endometrioid high-grade endometrial cancer (serous, carcinosarcoma, clear cell, and undifferentiated) between 2003 and 2017. A total of 2 regionalization periods were defined, before and after January 2014 to allow 6 months for knowledge translation after guideline publication. Patients were identified in population-based administrative provincial data sources. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between wait time and overall survival, as measured from time of surgery. Results: We identified 3518 patients with high grade endometrial cancer. Median wait time between diagnosis and surgery for the entire cohort did not significantly change with regionalization of care (50 vs 52 days, p=0.14). Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 55 days compared to 59 days pre-regionalization (p=0.0002), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p=0.0006). Survival was worst for patients who had surgery within 14 days of diagnosis (HR death 2.7, 95% CI 1.61-4.51 for 1-7 days and HR death 1.96, 95% CI 1.5-2.57 for 8-14 days), indicating disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic-oncology appointment (HR death 1.19, 95% CI 1.04-1.36 for 46-60 days and HR death 1.42, 95% CI 1.11-1.82). Download : Download high-res image (109KB) Download : Download full-size image Conclusions: Regionalization of surgery for high grade endometrial cancer has not had a negative impact on surgical wait times. Impact on survival is seen with patients who have surgery more than 45 days after surgical consultation.

Background Although sentinel lymph node (SLN) biopsy has been routinely used in the treatment of invasive squamous cell carcinoma (SCC), questions still remain regarding the management of patients with positive nodes, as well as its use in patients with larger tumors. Methods Retrospective study of all patients at a single institution with primary vulvar cancer who had SLN biopsy (2008–2015). Patient and tumor characteristics were collected from hospital records. For patients with positive SLN and for those with tumors ≥40 mm, recurrence rates and location were specifically recorded. Results SLN biopsy was successful in 159 patients (245 groins). Median follow-up was 31 months. 120 patients (187 groins) had a negative SLN without an inguinofemoral lymph node dissection (IFL); there were 6 ipsilateral groin recurrences (5%). 7 patients had micrometastasis (≤2 mm) in the SLN and were treated by radiotherapy. There were no recurrences in the irradiated groins. 19 patients with a positive unilateral SLN had bilateral IFL. One (5.3%) had a positive node in the contralateral groin. 9 patients with positive unilateral SLN had subsequent ipsilateral IFL; there were no groin recurrences in the contralateral groin. 20 patients had tumor size ≥40 mm. 11 patients had a negative SLN biopsy, and thus no IFL; of these patients, 1 had an isolated groin recurrence (9%). Conclusion These data suggest it is reasonable to omit a full groin dissection for micrometastatic disease in the SLN, and to perform a unilateral groin dissection in patients with unilateral SLN metastasis. SLN alone in larger tumors may have a higher groin recurrence rate.

Understanding healthcare providers' preferences, values, and beliefs around AVF eligibility is important to explain variability in practice. We conducted a survey of international surgeons, using hypothetical patient scenarios, to assess resources used, variables, perceived barriers, and absolute contraindications to access creation. A total of 134 surgeons completed the survey. Venous duplex ultrasound mapping (VDUM) was offered to all patients by 90% of US, 68% Canadian, and 63% European respondents. VDUM altered clinical decision less than 25% of the time for 33% American, 48% Canadian, and 85% European surgeons. Increased comorbidities and previous failed access were deterrents to AVF creation as was vessel size. Second choice access was the AV graft in the US and Europe and the catheter in Canada. Absolute contraindications to AVF creation included patient life expectancy

Understanding healthcare providers' preferences, values, and beliefs around AVF eligibility is important to explain variability in practice. We conducted a survey of international surgeons, using hypothetical patient scenarios, to assess resources used, variables, perceived barriers, and absolute contraindications to access creation. A total of 134 surgeons completed the survey. Venous duplex ultrasound mapping (VDUM) was offered to all patients by 90% of US, 68% Canadian, and 63% European respondents. VDUM altered clinical decision less than 25% of the time for 33% American, 48% Canadian, and 85% European surgeons. Increased comorbidities and previous failed access were deterrents to AVF creation as was vessel size. Second choice access was the AV graft in the US and Europe and the catheter in Canada. Absolute contraindications to AVF creation included patient life expectancy1 year, left ventricular ejection fraction (LVEF)15%, and a history of dementia, while 42% surgeons reported no absolute contraindications. Perceived barriers included patient preferences, long wait times for surgery, and late referral to a Nephrologist. Significant variability exists in the surgical preoperative assessment of patients, and the eligibility criteria used for fistula creation. Understanding surgeons' preferences can aid in establishing standardization for VA access eligibility, including surgical assessment.

BackgroundHuman embryonic stem cells (hESC) should enable novel insights into early human development and provide a renewable source of cells for regenerative medicine. However, because the three-dimensional hESC aggregates [embryoid bodies (hEB)] typically employed to reveal hESC developmental potential are heterogeneous and exhibit disorganized differentiation, progress in hESC technology development has been hindered.Methodology/principal findingsUsing a centrifugal forced-aggregation strategy in combination with a novel centrifugal-extraction approach as a foundation, we demonstrated that hESC input composition and inductive environment could be manipulated to form large numbers of well-defined aggregates exhibiting multi-lineage differentiation and substantially improved self-organization from single-cell suspensions. These aggregates exhibited coordinated bi-domain structures including contiguous regions of extraembryonic endoderm- and epiblast-like tissue. A silicon wafer-based microfabrication technology was used to generate surfaces that permit the production of hundreds to thousands of hEB per cm(2).Conclusions/significanceThe mechanisms of early human embryogenesis are poorly understood. We report an ultra high throughput (UHTP) approach for generating spatially and temporally synchronised hEB. Aggregates generated in this manner exhibited aspects of peri-implantation tissue-level morphogenesis. These results should advance fundamental studies into early human developmental processes, enable high-throughput screening strategies to identify conditions that specify hESC-derived cells and tissues, and accelerate the pre-clinical evaluation of hESC-derived cells.