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BACKGROUND Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking. METHODS We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points. RESULTS Among 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.3%). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, -1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5%; P=0.048) and beyond 4 weeks (4.7% vs. 11.0%; P=0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.9%; P<0.001). CONCLUSIONS In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.) [ABSTRACT FROM AUTHOR]

BACKGROUND Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking. METHODS We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points. RESULTS Among 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.390). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, -1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5% P = 0.048) and beyond 4 weeks (4.7% vs. 11.0%; P=0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.996; P<0.001). CONCLUSIONS In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.) [ABSTRACT FROM AUTHOR]

Are animals mere things in the eyes of the law? Public discourse suggests so. However, the history of legal discourses about animals reveals another story. For better or for worse, animals have not been considered as mere things in law. It was long recognized that animals possess certain characteristics that are observable in beings, such as agency, sentience, and sociability. Together, agency, sentience, and sociability constitute a cluster of being-like characteristics sketching, through time, a portrait of the animal that is distanced from the image of a mere object of property. To support this conclusion, we ask where the “wild things” are and have been in our legal history. We relocate animals in the history of legal discourses surrounding them in the territory of Quebec, beginning slightly before codification. As many individuals worldwide would like to see their own jurisdiction explicitly recognize that animals are not things but beings, Quebec provides a fruitful case study for international readers on the impact that such a change may have on legal norms and discourses. [ABSTRACT FROM AUTHOR]

Hyperviscosity syndrome (HVS) is an emergent complication of Waldenström macroglobulinemia (WM) characterized by visual, neurologic, and rarely auditory impairment. We report a 69-year-old female with MYD88 and CXCR4-mutant WM who developed HVS resulting in bilateral blindness and deafness associated with neurologic manifestations including confusion, severe generalized weakness, and imbalance. Ophthalmologic evaluation revealed bilateral central retinal vein occlusion (CRVO), diffuse retinal hemorrhages, macular edema, and serous macular detachments (SMD). Magnetic resonance imaging of the brain showed bleeding in the inner ears. Management was challenging as her WM was resistant to systemic therapies including bendamustine + rituximab (BR) and rituximab + bortezomib + dexamethasone (RVD). Bruton's tyrosine kinase inhibitors could not be used initially due to ongoing lower gastrointestinal bleeding. She required five total sessions of plasma exchange and was finally initiated on zanubrutinib, achieving a partial response. She also received intravitreal bevacizumab with rapid resolution of the retinal hemorrhages but with little improvement of the SMD. She had partial restoration of her hearing in the right ear and only slight improvement in her bilateral visual deficits. The management of HVS in frail, elderly patients with therapy-resistant WM can be challenging. In these cases, plasma exchange is required until an effective systemic therapy can be safely instituted. Genomic profiling is important in the management of WM as it can predict treatment resistance and guide therapeutic decisions. [ABSTRACT FROM AUTHOR]

One of the most widely accepted conditioning regimens for hematopoietic stem cell transplantation (HSCT) is BEAM (carmustine, etoposide, cytarabine, melphalan). However, a recent increase in the cost of carmustine has limited its use bringing our institution to replace carmustine with bendamustine. This observational retrospective single-center study aims to report the efficacy and safety of the BeEAM regimen. 55 patients with diffuse large B-cell lymphoma (47%), Hodgkin lymphoma (25%), mantle cell lymphoma (25%), or follicular lymphoma (2%) were included. Progression-free survival (PFS) at 24 months was 75% and overall survival (OS) was 83%. Treatment-related mortality was 4%. The most common adverse effects were febrile neutropenia (98%), mucositis (72%) and colitis (60%). Our study demonstrated excellent efficacy of the BeEAM regimen. However, the toxicity profile of BeEAM significantly varies from one study to another, and guidelines suggesting optimal dose of bendamustine and supportive care are currently lacking. [ABSTRACT FROM AUTHOR]

The article focuses on the threshold for radical hysterectomy in the treatment of low-risk cervical cancer, currently between stages T1a2 and T1b1, and the criteria proposed in the SHAPE trial by Plante et al. that advocate for a simpler hysterectomy approach for tumors up to 2 cm in size combined with limited stromal invasion.

Cervical cancer is the most common gynecologic malignancy and the fourth most common cancer in women worldwide. Over the last two decades, minimally invasive surgery (MIS) emerged as the mainstay in the surgical management of cervical cancer, bringing advantages such as lower operative morbidity and shorter hospital stay compared to open surgery while maintaining comparable oncologic outcomes in numerous retrospective studies. However, in 2018, a prospective phase III randomized controlled trial, "Laparoscopic Approach to Carcinoma of the Cervix (LACC)", unexpectedly reported that MIS was associated with a statistically significant poorer overall survival and disease-free survival compared to open surgery in patients with early-stage cervical cancer. Various hypotheses have been raised by the authors to try to explain these results, but the LACC trial was not powered to answer those questions. In this study, through an exhaustive literature review, we wish to explore some of the potential causes that may explain the poorer oncologic outcomes associated with MIS, including the type of MIS surgery, the size of the lesion, the impact of CO2 pneumoperitoneum, prior conization, the use of uterine manipulator, the use of protective measures, and the effect of surgical expertise/learning curve. [ABSTRACT FROM AUTHOR]

Background: Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers.Methods: In this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed.Findings: Between Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39-62; p<0·0001). In the modified intention-to-treat population (n=176), 545 nodes were identified, of which 513 (94%) were confirmed to be lymph nodes on pathological processing: 229 (92%) of 248 nodes that were both blue and green, all nine nodes that were blue only, and 266 (95%) of 279 nodes that were green only (p=0·30). Nine sentinal lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. 495 (96%) of 513 nodes were identified with the green dye and 238 (46%) with the blue dye (50%, 39-61; p<0·0001).Interpretation: Indocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances.Funding: Novadaq. [ABSTRACT FROM AUTHOR]

Objective To evaluate the outcome and the role of adjuvant treatment in the management of patients with endometrial cancer and isolated tumor cells (ITCs) identified by SLN mapping. Methods This single center study identified all patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy and SLN mapping for endometrial cancer between November 2010 and December 2015. Data was prospectively collected. Progression-free survival was analyzed according to the Kaplan-Meier method and compared using the log-rank test. Results A total of 519 patients were included. Overall, 85 patients (16.4%) were found to have SLN metastases of which 43 (51%) were macrometastasis, 11 (13%) micrometastasis (MM) and 31 (36%) ITC. Eleven (35%) of patients with ITCs received adjuvant chemotherapy ± whole pelvic radiation therapy (WPRT), 10 (32%) received WPRT, and 10 (32%) received either no adjuvant treatment or vault brachytherapy (VBT) only. ITC patients received significantly less chemotherapy (p = 0.0001) and WPRT (p = 0.007) compared to patients with macrometastasis. Of note, ITC were not considered node positive in our study. With a median follow-up of 29 months (range: 0–67), the progression free survival (PFS) at 3-years for the ITC patients was 95.5%, similar to node negative (87.6%) and micrometastasis patients (85.5%), but statistically better than patients with macrometastasis (58.5%) (p = 0.0012). Only 1/31 patient with ITC recurred (IB, 7 cm carcinosarcoma) despite adjuvant treatments. None of the ITC patients with endometrioid histology recurred (0/28) and none of the ITC patients who did not receive adjuvant treatment or VBT recurred (0/10). Conclusions Patients with endometrial cancer found to have SLN ITCs have an excellent outcome. The use of adjuvant treatment should be tailored to uterine factors and histology and not solely based on the presence of ITCs. Patients with ITCs and otherwise low-risk uterine disease probably derive little benefit from receiving additional treatments. More studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Objectives: Surgical margin status in women undergoing surgery for early-stage cervical cancer is considered an important prognostic factor. We sought to determine if positive or close surgical margin status (<3mm) is related to the type of surgical approach and associated with worse outcomes. Methods: A national retrospective cohort study of cervical cancer treated with a radical hysterectomy was conducted. Patients with stage IA1 (LVSI positive) to IIIC2 (FIGO 2018) with lesions up to 4cm at ten Canadian institutions from 2007-2019 were included. Surgical approaches for the radical hysterectomy included robotic/laparo- scopic (RLRH), abdominal (ARH), or laparoscopic-assisted vaginal/ vaginal hysterectomy (LVVRH). Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Results: A total of 960 patients met the inclusion criteria. The majority of patients had squamous histology (470, 49%), while 343 (35.7%) had adenocarcinomas and 113 (11.8%) had adenosquamous. Most were stage IB (681, 70.0%) and 183 (19%) were IA. Mode of surgery included: 495 (51.6%) RLRH, 88 (9.2%) LVVRH and 376 (39.2%) ARH. Surgical margins were negative in 819 (85.3%), positive in 15 (1.6%) or close in 103 (10.7%) patients. Factors predictive of close/positive margins included stage, tumor diameter, vaginal involvement, and parametrial extension; the surgical approach was not a predictor of margin status (p=0.38). Close/positive margins were associated with a higher risk of death on univariate analysis (HR: 2.53; 95% CI: 0.78-8.22) for positive margins and 1.83 (95% CI: 1.04-3.24) for close margins, p=0.05), but margin status was not significant for OS or PFS when adjusting for stage, histology, surgical approach, and adjuvant treatment. Overall, 71% of patients with positive margins and 60% of patients with close margins received adjuvant treatment. One patient (6.7%) with positive margins recurred distantly, despite having received adjuvant chemoradiation; 16 patients (15.3%) with close margins recurred (p=0.023), with 73% having received either adjuvant radiation or chemoradiation. The surgical approach was not statistically associated with either OS (p=0.067) or PFS (p=0.06). Conclusions: Positive or close surgical margins were not found to be associated with the use of the minimally invasive surgical (MIS) approach. MIS approach did not appear to negatively impact outcomes. Positive or close surgical margins were not associated with worse outcomes, possibly due to adjuvant treatment. [ABSTRACT FROM AUTHOR]

Objectives Indocyanine green (ICG) with near-infrared (NIR) fluorescence imaging is a new tracer modality used for lymphatic mapping. We report our initial experience with ICG for SLN mapping in cervical and endometrial cancer using a new endoscopic fluorescence imaging system. Methods We reviewed all patients who underwent primary surgery for early-stage endometrial and cervical carcinoma with SLN mapping using fluorescence imaging followed by pelvic lymphadenectomy from February to July 2014. Intracervical injection of ICG at 3 and 9 o'clock was performed in all cases. SLNs were ultrastaged on final pathology. Sensitivity and specificity values were calculated. Results A total of 50 patients were included in the study (42 endometrial and 8 cervical cancers). The median age was 62 (24-88) and median BMI 29 (19-56). The median SLN count was 3.1 (0-7) and median lymph node count was 15 (2-37). The overall and bilateral detection rate was 96% (48/50) and 88% (44/50). Positive SLNs were identified in 22% of patients (11/50), including 8 isolated tumor cells (ITC), 2 micrometastasis and 1 macrometastasis. There was one side-specific false negative case. Sensitivity, specificity and NPV were 93.3%, 100% and 98.7% respectively per side. Paraaortic node dissection was performed in 22% of cases. Two had paraaortic node metastasis both in patients with positive pelvic SLN. There were no allergic reactions to the ICG. Conclusions Based on our pilot experience, NIR fluorescence imaging with ICG is an excellent and safe tracer modality for SLN mapping with a very high overall (96%) and bilateral (88%) detection rate. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To review our first consecutive 125 vaginal radical trachelectomies (VRT) to assess the oncologic, fertility and obstetrical outcomes. Methods: Data from our prospective database was used to identify all VRT planned between October 1991 to March 2010 in patients with early-stage cervical cancer (stages IA, IB and IIA). Chi-square test, Fisher''s exact test and Student t-test were used to compare baseline characteristics and Kaplan–Meier survival curves were constructed and compared with the use of the log-rank test. Results: During the study period, 140 VRT were planned and 125 were performed. The median age of the patients was 31 and 75% were nulliparous. The majority of the lesions were stage IA2 (21%) or IB1 (69%) and 41% were grade 1. In terms of histology, 56% were squamous and 37% were adenocarcinomas. Vascular space invasion was present in 29% of cases, and 88.5% of the lesions measured ≤2cm. The mean follow-up was 93months (range: 4–225months). There were 6 recurrences (4.8%) and 2 deaths (1.6%) following VRT. The actuarial 5-year recurrence-free survival was 95.8% [95% CI: 0.90–0.98], whereas it was 79% [95% CI: 0.49–0.93] in the group where the VRT was abandoned (p=0.001). Higher tumor grade, LVSI and size >2cm appeared to be predictive of the risk of abandoning VRT (p=0.001, p=0.025 and p=0.03 respectively). Tumor size >2cm was statistically significantly associated with a higher risk of recurrence (p=0.001). In terms of obstetrical outcome, 58 women conceived a total of 106 pregnancies. The first and second trimester miscarriage rates were 20% and 3% respectively, and 77 (73%) of the pregnancies reached the third trimester, of which 58 (75%) delivered at term. Overall, 15 (13.5%) patients experienced fertility problems, 40% of which were due to cervical factor. Twelve (80%) were able to conceive, the majority with assisted reproductive technologies. Conclusion: VRT is an oncologically safe procedure in well-selected patients with early-stage disease. Lesion size >2cm appears to be associated with a higher risk of recurrence and a higher risk of abandoning the planned VRT. Fertility and obstetrical outcomes post VRT are excellent. [Copyright &y& Elsevier]

Abstract: Objective. : The significance of negative sentinel lymph nodes (SLN) is important in the staging and treatment of melanoma and a few other cancers, but is controversial in uterine cervix carcinoma. Our study was aimed at correlating the SLN status in cervical carcinoma with non-sentinel lymph nodes (non-SLN), in a uniform and well controlled population. Methods. : This study includes 36 patients with stage I and IIA cervical carcinoma and bilaterally negative SLN on final pathology. SLN were identified using blue dye and radioisotopic techniques. Frozen section examination was performed for all SLN; the rest of the tissue was formalin fixed and paraffin embedded. The protocol used for SLN was also applied for non-SLN. For each block, six 4-μm thick sections were cut at 40 μm intervals and stained with H&E; an additional section taken between the 3rd and 4th levels was imunostained using AE1/AE3 cytokeratin. Results. : The mean age for the study population was 39 years (range 25–76); the number of SLN ranged from 2 to 6 (mean 2.7) and the non-SLN from 8 to 49 (mean 23) per case. No metastasis was found in any SLN and non-SLN by step sections and IHC. Conclusion. : Our study demonstrates that bilaterally negative SLN on final pathology accurately predict the absence of metastases in non-SLN in cervical carcinoma. If confirmed by larger trials, these results may influence the clinical management of early cervical cancer. [Copyright &y& Elsevier]

Abstract: Background. : We present 3 young women with bulky stage IB1 cervical cancer treated with neoadjuvant chemotherapy followed by laparoscopic pelvic node dissection and vaginal radical trachelectomy. Cases. : In the last year, we have treated 3 young women with large cervical lesions who wished to preserve fertility with induction chemotherapy followed by fertility-sparing surgery. They all had lesions measuring 3 to 4 cm and felt to be too big to safely undergo a radical trachelectomy. Three cycles of platinum-based combination chemotherapy were given and were well tolerated. The 3 patients had a significant clinical response to chemotherapy. A complete pathological response was confirmed by the absence of residual invasive cancer in the three trachelectomy specimens. There has been no recurrence so far and no pregnancy yet. Conclusion. : Neoadjuvant chemotherapy followed by a fertility-sparing surgery may become a valuable option for young women with bulky stage IB1 cervical cancer who wish to preserve their fertility potential. [Copyright &y& Elsevier]

Abstract: Objective.: To report the obstetrical results following vaginal radical trachelectomy (VRT), a fertility-preserving surgery in the treatment of early-stage cervical cancer. Methods.: Retrospective review of our first 72 patients treated by a laparoscopic pelvic lymphadenectomy followed by a VRT from October 1991 to October 2003 with regards to their reproductive function. Results.: Patients'' median age was 32 years old (21–42) and 53 (74%) were nulligravida. A total of 50 pregnancies occurred in 31 women. The majority (66%) had only one pregnancy, 19% had 2 pregnancies and 16% had 3 pregnancies or more. The rate of first trimester miscarriage was 16%, the rate of second trimester miscarriage was (4%) and 2 women (4%) elected to have pregnancy termination. A total of 36 pregnancies (72%) reached the third trimester. Of those, 3 (8%) ended prematurely at &#60;32 weeks gestation, 5 (14%) delivered between 32 and 36 weeks and 28 (78%) delivered at term (>37 weeks). One newborn died of neonatal sepsis from E. coli infection and one died from cardiac malformation (trisomy-18). Seven patients (10%) had infertility problems: 3 from ovulatory causes of which 2 successfully conceived with IVF, one from endometriosis and low sperm count and 3 from probable cervical cause of which one conceived with IUI. One patient had a twin pregnancy following IVF and elected to have embryo reduction and subsequently delivered at 37 weeks. Conclusion.: Based on our experience, the obstetrical results following VRT for early-stage cervical cancer are very encouraging. The majority of women can anticipate to conceive spontaneously and deliver near term. [Copyright &y& Elsevier]

Objectives: This study aimed to identify hospital resources by region, determine human Resources by type of service and region, and describe how services generally operate in child psychiatry within the province of Quebec. Methods: Data collection took place from May to October 2001. We sent a semistructured questionnaire to all child psychiatry service heads. We collected b m resource data and produced organizational charts based on the regions obtained. Thew charts were forwarded to each of the participating services for validation. We grouped Quebec's 18 social health regions into 3 categories: central (4 regions with 606 370 youths), adjoining (4 regions with 589 750 youths), and peripheral (10 regions with 368 635 youths). Results: The response rate was 100?. We identified 35 child psychiatry services: 13 in the central regions, 9 in the adjoining regions, and 13 in the central regions. Overall, we identified 177 short-stay beds, 476 places in day or evening hospitals, and 113 places in day or evening centres. Most of these resources were located in the central regions. Quebec had 138.2 full-time equivalent (FTE) child psychiatrists (69.8% in the c e m l regions) and 706 FTE professionals. At March 31, 2001, 4285 youths were waiting for services. Conclusions: We observed a shortage of child psychiatrists and professionals, regardless of the norm used Adjoining and peripheral regions should have access to a minimal range of human and hospital resources in child psychiatry. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify hospital resources by region, determine human resources by type of service and region, and describe how services generally operate in child psychiatry within the province of Quebec.Methods: Data collection took place from May to October 2001. We sent a semistructured questionnaire to all child psychiatry service heads. We collected human resource data and produced organizational charts based on the responses obtained. These charts were forwarded to each of the participating services for validation. We grouped Quebec's 18 social health regions into 3 categories: central (4 regions with 606 370 youths), adjoining (4 regions with 589 750 youths), and peripheral (10 regions with 368 635 youths).Results: The response rate was 100%. We identified 35 child psychiatry services: 13 in the central regions, 9 in the adjoining regions, and 13 in the peripheral regions. Overall, we identified 177 short-stay beds, 476 places in day or evening hospitals, and 113 places in day or evening centres. Most of these resources were located in the central regions. Quebec had 138.2 full-time equivalent (FTE) child psychiatrists (69.8% in the central regions) and 706 FTE professionals. At March 31, 2001, 4285 youths were waiting for services.Conclusions: We observed a shortage of child psychiatrists and professionals, regardless of the norm used. Adjoining and peripheral regions should have access to a minimal range of human and hospital resources in child psychiatry. [ABSTRACT FROM AUTHOR]

Objective. To review the oncological results and complication rate of our first consecutive 72 completed cases of vaginal radical trachelectomies (VRT).Methods. From October 1991 to October 2003, we have planned 82 VRT in patients with early-stage cervical cancer (stages IA, IB, and IIA). The VRT was preceded by a complete laparoscopic pelvic node dissection and laparoscopic parametrectomy.Results. The planned procedure was successfully completed in 72 cases and was abandoned in 10 cases (12%) because of either positive nodes discovered at the time of surgery (4), positive endocervical margins (5) or extensive tubal adhesions (1). The median age of the remaining 72 patients was 31 and most (75%) were nulliparous. The majority of the lesions were stage IA2 (32%) or IB1 (60%) and 54% were grade 1. In terms of histology, 58% were squamous and 42% were adenocarcinomas. Vascular space invasion was present in 20% of cases, and 90% of the lesions measured ≤2 cm. An average of 32 lymph nodes has been removed laparoscopically. The mean follow-up is 60 months (6–156). The intraoperative complication rate was low (6%) and the postoperative morbidity was also low mainly involving bladder hypotonia (16%) and vulvar edema (12%). There were no bladder or ureteral injuries. The average hospital stay was 3 days. Excluding one patient with a small cell neuroendocrine tumor who rapidly recurred and died, there were two recurrences (2.8%) and one death (1.4%). The actuarial recurrence-free survival is 95%. Tumor size >2 cm was statistically significantly associated with a higher risk of recurrence (P = 0.03). The recurrence-free survival of the nine patients who did not have the planned VRT because of more advanced disease was statistically significantly less (P = 0.003).Conclusion. VRT is an oncologically safe procedure in well-selected patients with early-stage disease. Lesion size >2 cm appears to be associated with a higher risk of recurrence. The morbidity of the procedure is low and it allows fertility preservation. [Copyright &y& Elsevier]

Explores the strategy in family shuffling to evolve biphenyl dioxygenases. Detection of catechol metabolites from chlobiphenyls; BphA variants with extended potency to degrade polychlorinated biphenyls; Replacement of a short segment of LB400 BphA.

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy. [ABSTRACT FROM AUTHOR]

Although minimally invasive hysterectomy (MIS-H) has been associated with worse survival compared to abdominal hysterectomy (AH) for cervical cancer, only 8% of patients in the LACC trial had microinvasive disease (Stage IA1/IA2). We sought to determine differences in outcome among patients undergoing MIS-H, AH or combined vaginal-laparoscopic hysterectomy (CVLH) for microinvasive cervical cancer. A retrospective cohort study of all patients undergoing hysterectomy (radical and non radical) for FIGO 2018, microinvasive cervical cancer across 10 Canadian centers between 2007 and 2019 was performed. Recurrence free survival (RFS) was estimated using Kaplan Meier Survival analysis. Chi-square and log-rank tests were used to compare outcomes. 423 patients with microinvasive cervical cancer were included; 259 (61.2%) Stage IA1 (22/8.5% with LVSI) and 164(38.8%) IA2. The median age was 44 years (range 24–81). The most frequent histology was squamous (59.4%). Surgical approach was: 50.1% MIS-H (robotic or laparoscopic), 35.0% AH and 14.9% CVLH. Overall, 70.9% underwent radical hysterectomy and 76.5% had pelvic lymph node assessment. There were 16 recurrences (MIS-H:4, AH:9, CVLH: 3). No significant difference in 5-year RFS was found (96.7% MIS-H, 93.7% AH, 90.0% CVLH, p = 0.34). In a sub-analysis of patients with IA1 LVSI+/IA2(n = 186), survival results were similar. Further, there was no significant difference in peri-operative complications (p = 0.19). Patients undergoing MIS-H had a shorter median length of stay(0 days vs 3 (AH) vs. 1.5 (CVLH), p < 0.001), but had more ER visits (16.0% vs 3.6% (AH), 3.5% (CVLH), p = 0.036). In this cohort, including only patients with microinvasive cervical cancer, no difference in recurrence was found by surgical approach. This may be due to the low rate of recurrence making differences hard to detect or due to a true lack of difference. Hence, this patient population may benefit from MIS without compromising oncologic outcomes. • There was no difference in RFS by surgical approach (MIS/open/CVLH) in patients with Stage IA1/IA2 cervical cancer. • This suggests that for microinvasive cervical cancer, MIS is safe and feasible. • Similar results were found in patients with Stage IAI LVSI+/IA2. • There were no differences in peri-operative complications between surgical groups. • Patients undergoing MIS had a shorter median length of stay but more ER visits. [ABSTRACT FROM AUTHOR]

A randomized non-inferiority trial showed worse survival in women with early-stage cervical cancer treated with radical hysterectomy by minimally invasive approach compared to laparotomy; the impact of surgical approach on survival following radical trachelectomy is unknown. To examine oncologic outcomes in women with early-stage cervical cancer who underwent robotic or vaginal radical trachelectomy at Canadian cancer centers with the highest volumes of radical trachelectomy procedures. Retrospective multi-centre cohort analysis which includes patients who had surgery between 2006 and 2019. Women with International FIGO 2009 stage IA-IB cervical cancer who underwent radical trachelectomy and lymph node assessment were grouped by surgical approach (vaginal versus robotic surgery). A total of 197 patients were included from 4 regional referral centres. 56 women underwent robotic radical trachelectomy and 141 underwent vaginal radical trachelectomy. All patients had lymph node assessment by a minimally invasive technique. Median age was 32 years, median tumor size was 12 mm, and median depth of invasion was 5 mm. Recurrence-free survival was 97% in both groups at a median follow-up of 57 months. On multivariable analysis, after adjusting for previously chosen confounders (high risk pathologic criteria, tumor size, and LVSI) there was no statistically significant difference in PFS between the 2 groups (HR 2.1, 95%CI 0.3–7.1, p = 0.5). Tumor size larger than 2 cm (HR 9.4, 95%CI 2.8–26, p = 0.003) was the only variable predictive of recurrence. Survival outcomes were excellent in both cohorts of patients undergoing robotic vs. vaginal radical trachelectomy. The surgical approach was not significantly associated with risk of recurrence after adjusting for clinically important confounders. • In carefully selected patients, RRT and VRT are associated with excellent oncologic outcomes. • Tumor size >2 cm is a strong predictor of recurrence. • Further research is necessary to define the role of non-radical fertility sparing surgery in early cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS; their proliferation, activation, and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. Methods: Here, we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system; the knockout (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knockout at 3 months old, before plaque formation, and evaluated both 6- and 8-month-old groups of mice. Results: Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate-control groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology are associated with a decrease in plaque volume in the cortex and hippocampus area. A compensating system seems to take place following the knockout, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain. Conclusions: Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD. [ABSTRACT FROM AUTHOR]

Background: Muramyl dipeptide (MDP) is a component derived from minimal peptidoglycan motif from bacteria, and it is a ligand for the NOD2 receptor. Peripheral administration of MDP converts Ly6Chigh into Ly6Clow monocytes. Previously, we have shown that Ly6Clow monocytes play crucial roles in the pathology of a mouse model of Alzheimer's disease (AD). However, medications with mild immunomodulatory effects that solely target specific monocyte subsets, without triggering microglial activation, are rare.Methods: Three months old APPswe/PS1 transgenic male mice and age-matched C57BL/6 J mice were used for high frequency (2 times/week) over 6 months and low frequency (once a week) over 3 months of intraperitoneally MDP (10 mg/kg) administrations. Flow cytometry analysis of monocyte subsets in blood, and behavioral and postmortem analyses were performed.Results: Memory tests showed mild to a strong improvement in memory function, increased expression levels of postsynaptic density protein 95 (PSD95), and low-density lipoprotein receptor-related protein 1 (LRP1), which are involved in synaptic plasticity and amyloid-beta (Aβ) elimination, respectively. In addition, we found monocyte chemoattractant protein-1(MCP-1) levels significantly increased, whereas intercellular adhesion molecule-1(ICAM-1) significantly decreased, and microglial marker (Iba1) did not change in the treatment group compared to the control. In parallel, we discovered elevated cyclooxygenase-2 (COX2) expression levels in the treated group, which might be a positive factor for synaptic activity.Conclusions: Our results demonstrate that MDP is beneficial in both the early phase and, to some extent, later phases of the pathology in the mouse model of AD. These data open the way for potential MDP-based medications for AD. [ABSTRACT FROM AUTHOR]

Stroke is the second cause of mortality worldwide and occurs following the interruption of cerebral blood circulation by cerebral vessel burst or subsequent to a local thrombus formation. Ischemic lesion triggers an important inflammatory response, characterized by massive infiltration of leukocytes, activation of glial cells and neurovascular reorganization. Chemokines and their receptors, such as CCR2 and CX3CR1, play an important role in leukocyte recruitment in the damaged area. Mice genetically depleted for the two receptors CCR2 and CX3CR1 underwent focal cerebral ischemia, based on the topical application of ferric chloride to truncate the distal middle cerebral artery. The infarct, limited only to the cortical area, remained stable in WT mice, while it is reduced overtime in the transgenic mice. Moreover, we did not observe any significant changes in the level of the inflammatory response in the infarcted areas while immune cell infiltration and neurovascularization are modulated according to genotype. Our results show that the genetic deletion of both CCR2 and CX3CR1 receptors has neuroprotective effects in response to a cerebral permanent ischemia. This study underlines a key role of CCR2- and CX3CR1-expressing immune cells in the neuropathology associated with ischemic injuries. [ABSTRACT FROM AUTHOR]

Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. 956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%). Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases. • In patients with Stage Ia1-Ib2 cervical cancer, there was no association between surgical approach and margin status. • Close margins (<3 mm) had double the risk of death than negative margins, but not significant when adjusted for confounders. • In the total cohort, minimally invasive radical hysterectomy was associated to worse overall survival. • Therefore surgical margin status may not be the driver of worse survival in minimally invasive radical hysterectomy. [ABSTRACT FROM AUTHOR]

Obesity has risen to affect >25% of the Canadian population. Perioperative challenges with increased morbidity are encountered. We evaluated the outcome of robotic-assisted surgery for endometrial cancer (EC) in obese patients. We retrospectively reviewed all robotic surgeries performed for EC in women with BMI ≥40 kg/m2, from 2012 to 2020 in our center. Patients were divided into 2 groups (class III: 40-49 kg/m2, class IV: ≥50 kg/m2). Complications and outcome were compared. 185 patients were included: 139 class III and 46 class IV. The main histology was endometrioid adenocarcinoma (70,5% of class III and 58,1% of class IV (p = 0,138)). The mean blood loss, overall sentinel node detection and median length of stay were similar in both groups. Six class III (4,3%) and 3 class IV (6,5%) patients required conversion to laparotomy due to poor surgical field exposure (p = 0,692). The rate of intraoperative complications was similar between the 2 groups (1.4% in class III vs none in class IV, p = 1). There were 10 class III (7,2%) and 10 class IV (21,7%) post-operative complications (p = 0.011), but most were grade 2 (3,6% in class III vs 13% in class IV, p = 0.029)). Grade 3 and 4 postoperative complications were low (2.7%) and not statistically different between the 2 groups. Readmission rate was low in both groups (4 in each group, p = 1.07). Recurrence occurred in 5,8% of class III and 4,3% of class IV patients (p = 1). Robotic-assisted surgery for EC in class III and class IV obese patients is a safe and feasible procedure, with low complication rate, similar oncologic outcome, conversion rate, blood loss, readmission rate and length of hospital stay. • Robotic surgery in endometrial cancer is a safe procedure in the class III and class IV obese patients. • We found low rates of major intra and postoperative complications, conversion rate and blood loss. • Oncological outcome seems favorable with a low recurrence rate. [ABSTRACT FROM AUTHOR]

Background. Endometrial cancer is the fourth most prevalent cancer in Canadian women. Radiotherapy (RT) is frequently recommended as an adjuvant treatment. There is a high prevalence (>80%) of urinary incontinence (UI) after RT. It is plausible that UI is associated, at least in part, with alterations of the pelvic-floor muscles (PFM). Objective. The aim of this exploratory study was to compare the PFM functional properties of women reporting UI after hysterectomy and RT for endometrial cancer with those of women with a history of hysterectomy but without UI. Design. A descriptive cross-sectional study was conducted. Eleven women were recruited for the affected group, and 18 were recruited for the comparison group. Methods. Urogenital and bowel functions were assessed using International Consultation on Incontinence Questionnaires, and PFM properties were evaluated using a Montreal dynamometer. Nonparametric tests were used for comparison of personal characteristics, functional status, and muscle properties. A correspondence analysis detailed the association between UI severity and PFM properties. Results. Maximal opening of dynamometer branches, maximal vaginal length, PFM maximum force and rate of force development in a strength test, and number of rapid contractions during a speed test were reduced in the affected group. No significant difference was found for the endurance test. The severity of UI was found to correspond to the rate of force development and the number of rapid contractions in a speed test, endurance, age, and vaginal length. Limitations. The results are limited to the population studied. The small sample size limited the strength of the conclusions. Conclusions. Some evidence of alterations in PFM properties were found in women with UI after hysterectomy and RT for endometrial cancer. These alterations appeared to be associated with UI, suggesting a possible role for rehabilitation. [ABSTRACT FROM AUTHOR]

Purpose In Canada, recommendations for clinical management of hereditary breast and ovarian cancer among individuals carrying a deleterious BRCA1 or BRCA2 mutation have been available since 2007. Eight years later, very little is known about the uptake of screening and risk-reduction measures in this population. Because Canada's public health care system falls under provincial jurisdictions, using provincial health care administrative databases appears a valuable option to assess management of BRCA1/2 mutation carriers. The objective was to explore the usefulness of public health insurance administrative databases in British Columbia, Ontario, and Quebec to assess management after BRCA1/2 genetic testing. Methods Official public health insurance documents were considered potentially useful if they had specific procedure codes, and pertained to procedures performed in the public and private health care systems. Results All 3 administrative databases have specific procedures codes for mammography and breast ultrasounds. Only Quebec and Ontario have a specific procedure code for breast magnetic resonance imaging. It is impossible to assess, on an individual basis, the frequency of others screening exams, with the exception of CA-125 testing in British Columbia. Screenings done in private practice are excluded from the administrative databases unless covered by special agreements for reimbursement, such as all breast imaging exams in Ontario and mammograms in British Columbia and Quebec. There are no specific procedure codes for risk-reduction surgeries for breast and ovarian cancer. Conclusion Population-based assessment of breast and ovarian cancer risk management strategies other than mammographic screening, using only administrative data, is currently challenging in the 3 Canadian provinces studied. [ABSTRACT FROM AUTHOR]

Recent data support the predictive implications of molecular subtype assignment in endometrial cancer (EC). Our objective was to retrospectively assess clinical outcomes according to adjuvant treatment received within EC molecular subtypes. Clinical outcomes (disease-specific and progression-free survival DSS/PFS) of EC patients from a single institution and population-based cohorts that had undergone molecular classification were assessed with respect to adjuvant therapy received and 2016 ESMO risk group. 2472 ECs were assessed; 184 (7.4%) POLE mut, 638 (25.8%) MMRd, 1223 (49.5%) NSMP and 427 (17.3%) p53abn. N = 774 (34.6%) of the cohort were ESMO 2016 high risk and 109 (4.8%) were advanced or metastatic. In patients with MMRd EC, assessed across and within stage, there was no observed benefit in DSS or PFS with the addition of chemotherapy +/− radiation compared to radiation alone in ESMO high risk (p = 0.694) or ESMO high, advanced, metastatic risk groups combined (p = 0.852). In patients with p53abn EC, adjuvant chemotherapy given with radiation was associated with significantly longer DSS compared to radiation alone in ESMO high risk (p = 0.007) and ESMO high, advanced and metastatic risk groups combined (p = 0.015), even when restricted to stage I disease (p < 0.001) and when compared in serous vs. non-serous histotypes (p = 0.009). Adjuvant chemotherapy is associated with more favorable outcomes for patients with p53abn EC, including stage I disease and non-serous histotypes, but does not appear to add benefit within MMRd ECs for any stage of disease, consistent with PORTEC-3 molecular subanalysis. Prospective trials, assessing treatment efficacy within molecular subtype are needed, however these 'real-world' data should be considered when discussing adjuvant treatment with patients. • Greater precision is needed in making adjuvant treatment decisions for chemotherapy (chemo) and radiation (RT) in endometrial cancer (EC). • Retrospective data from 2500 ECs assessed the associations of chemo and RT on clinical outcomes within molecular subtype. • Adjuvant chemo and RT was associated with longer DSS for patients with p53abn EC, including stage I and non-serous ECs. • Chemo was not associated with improved outcomes in MMRd EC patients, even in stage III disease. • Molecular subtype should be considered when making adjuvant therapy decisions in EC. [ABSTRACT FROM AUTHOR]

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan–Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Abstract: The vaginal radical trachelectomy has emerged as a valuable fertility-preserving treatment option for young women with early-stage disease. Cancer-related infertility is associated with feelings of depression, grief, stress, and sexual dysfunction. Data have shown that the overall oncological outcome is safe and that the obstetrical outcome is promising. In this article, we analyze the data on the vaginal radical trachelectomy published over the last 10years in the context of what we have learned, what issues remain unclear, and what the future holds. [Copyright &y& Elsevier]

The role of lymph node assessment/dissection (LND) in endometrial cancer (EC) has been debated for decades, with significant practice variation between centers. Molecular classification of EC provides prognostic information and can be accurately performed on preoperative endometrial biopsies. We assessed the association between molecular subtype and lymph node metastases (LNM) in order to determine if this tool could be used to stratify surgical decision making. All EC patients undergoing primary staging surgery with planned complete pelvic +/− para-aortic LND from a single institution in the 2015 calendar year were identified, with clinicopathological and outcome data assessed in the context of retrospectively assigned molecular classification. 172 patients were included. Molecular classification of the total cohort showed 21 POLE mut (12.2%), 47 MMRd (27.3%), 74 NSMP (43.1%), and 30 p53abn (17.4%) ECs. Complete pelvic +/− para-aortic LND was performed in 171 of 172 patients, and LNM were found in 31/171 (18.1%). This included macrometastases (19/31), micrometastases (5/31), and isolated tumour cells (ITCs) (7/31). LNM were pelvic only in 83.9%, and pelvic plus para-aortic in 16.1%. There were no isolated para-aortic LNM. Molecular subtype was significantly associated with LNM (p = 0.004). There was a strong association between the presence of LNM and p53abn EC (nodal involvement in 44.8% of cases), with LNM detected in 14.2% of POLE mut, 14.9% of MMRd, and 10.8% of NSMP EC. On multivariate analysis, molecular subtype and preoperative CA 125 > 25 were significantly associated with LNM (p = 0.021 and p = 0.022 respectively) but preoperative grade and histotype were not (p = 0.24). EC molecular subtype is significantly associated with the presence of LNM. As molecular classification can be obtained on preoperative diagnostic specimens, this information can be used to guide surgical treatment planning and may reduce the cost and morbidity of unnecessary lymph node staging in EC care. • Molecular classification in EC was significantly associated with lymph node metastases (LNM). • Molecular subtype was a stronger predictor of LNM compared to preoperative grade and histotype on multivariate analysis. • Nearly half of patients with p53abn EC (44.8%) had lymph node metastases. • Molecular classification can be obtained on preoperative biopsies and can be used to guide surgical decision making. • Outcomes in patients with ITCs were equivalent to node negative patients. [ABSTRACT FROM AUTHOR]

Abstract: In attempt to discover novel aberrantly hypermethylated genes with putative tumor suppressor function in epithelial ovarian cancer (EOC), we applied expression profiling following pharmacologic inhibition of DNA methylation in EOC cell lines. Among the genes identified, one of particular interest wаs DOK1, or downstream of tyrosine kinase 1, previously recognized as a candidate tumor suppressor gene (TSG) for leukemia and other human malignancies. Using bisulfite sequencing, we determined that a 5′-non-coding DNA region (located at nt −1158 to −850, upstream of the DOK1 translation start codon) was extensively hypermethylated in primary serous EOC tumors compared with normal ovarian specimens; however, this hypermethylation was not associated with DOK1 suppression. On the contrary, DOK1 was found to be strongly overexpressed in serous EOC tumors as compared to normal tissue and importantly, DOK1 overexpression significantly correlated with improved progression-free survival (PFS) values of serous EOC patients. Ectopic modulation of DOK1 expression in EOC cells and consecutive functional analyses pointed toward association of DOK1 expression with increased EOC cell migration and proliferation, and better sensitivity to cisplatin treatment. Gene expression profiling and consecutive network and pathway analyses were also confirmative for DOK1 association with EOC cell migration and proliferation. These analyses were also indicative for DOK1 protective role in EOC tumorigenesis, linked to DOK1-mediated induction of some tumor suppressor factors and its suppression of pro-metastasis genes. Taken together, our findings are suggestive for a possible tumor suppressor role of DOK1 in EOC; however its implication in enhanced EOC cell migration and proliferation restrain us to conclude that DOK1 represents a true TSG in EOC. Further studies are needed to more completely elucidate the functional implications of DOK1 and other members of the DOK gene family in ovarian tumorigenesis. [Copyright &y& Elsevier]

Abstract: Large cell neuroendocrine carcinoma of the ovary is a rare recently established entity. Few cases have been reported in the literature, and they are usually associated with another type of surface epithelial tumor. The association of a large cell neuroendocrine carcinoma with a surface epithelial tumor and a teratoma is even rarer, with only two cases previously described. We report the cases of two patients in their fifties who presented with a growing abdominal mass and died of metastatic disease within less than a year. Histological assessment revealed large cell neuroendocrine carcinoma admixed with mucinous adenocarcinoma and teratoma. Different hypotheses regarding the origin of large cell neuroendocrine carcinoma of the ovary are discussed. The immunohistochemical pattern of staining for cytokeratin 7 and cytokeratin 20 suggests that the composite epithelial tumors originated from the pre-existing teratoma. [Copyright &y& Elsevier]

Introduction and hypothesis: There is a high prevalence of urinary incontinence among endometrial cancer survivors. They are also known to present with pelvic floor muscle alterations. Evidence on the effects of conservative interventions for the management of UI is scarce. This study aims at verifying the effects of an in-home rehabilitation program, including the use of a mobile technology, to reduce UI severity in endometrial cancer survivors. Methods: This study used a single-case experimental design with replications. Primary outcome for UI severity was the pad test, and secondary outcomes were the ICIQ-UI SF questionnaire and 3-day bladder diary. Pelvic floor muscle function was assessed using 2D-transperineal ultrasound and intravaginal dynamometry. Adherence was documented using mobile technology and an exercise log. Visual and non-parametric analyses of longitudinal data were conducted. Results: Results show a reduction in UI severity for 87.5% of participants, with a significant relative treatment effect of moderate size (RTE: 0.30). Significant small relative treatment effects were found for the quick contraction and endurance dynamometric tests. Conclusion: This study provides new evidence that endometrial cancer survivors can improve the severity of their UI following an in-home rehabilitation program, including the use of a mobile technology. This mode of delivery has the potential to address a gap in access to pelvic floor physiotherapy services for survivors of EC living in rural and remote communities. [ABSTRACT FROM AUTHOR]

Minimally invasive surgery (MIS) is a standard surgical approach for comprehensive surgical staging in women with endometrial cancer. As rates and complexity of MIS are steadily increasing, it is important to identify potential risk factors which may be associated with this approach. This study evaluates the impact of local factors on the risk of disease recurrence. A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) who underwent MIS between 2012 and 2016 at eight Canadian centers. Data was collected from medical records. The 75th percentile was calculated for estimated uterine volume and weight. All recurrences were categorized into two groups; intra-abdominal vs. extra-abdominal. To search for significant covariates associated with recurrence-free survival a Cox proportional hazard model was performed. A total of 758 patients were included in the study. Intra-uterine manipulator was used in 497 (35.8%) of patients. Vaginal lacerations were documented in 9.1%. Median follow-up was 30.5 months (interquartile range 20–47). There were 157 who had disease recurrence (20.71%), including 92 (12.14%) intra-abdominal and 60 (7.92%) extra-abdominal only recurrences. In univariate analysis myometrial invasion, LVI, stage, uterine volume and weight > 75th percentile and chemotherapy were associated with increased risk of intra-abdominal recurrence. In multivariable analysis only stage, and specimen weight > 75th percentile (OR 2.207, CI 1.123–4.337) remained significant. Uterine volume, and weight were not associated with increased risk of extra-abdominal recurrences. For patients diagnosed with HGEC undergoing MIS, extracting a large uterus is associated with a significantly increased risk for intra-abdominal recurrence. • Extracting a large uterus at MIS for high-grade endometrial cancer is associated with increased risk of recurrence. • We observed increased risk for intra-abdominal recurrence but not for extra-abdominal recurrences. • The pattern of recurrences raises concern of tumor spillage when extracting a large uterus. • The use of intra-uterine manipulator is associated with increased risk of single-site abdominal recurrence. [ABSTRACT FROM AUTHOR]

Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) specifically target homologous recombination deficiency (HRD) cells and display good therapeutic effect in women with advanced-stage BRCA1/2-mutated breast and epithelial ovarian cancer (EOC). However, about 50% of high grade serous ovarian cancers (HGSOC) present with HRD due to epigenetic BRCA1 inactivation, as well as genetic/epigenetic inactivation(s) of other HR genes, a feature known as "BRCAness". Therefore, there is a potential for extending the use of PARPis to these patients if HR status can be identified.Methods: We have developed a 3D (spheroid) functional assay to assess the sensitivity of two PARPis (niraparib and olaparib) in ascites-derived primary cell cultures (AsPCs) from HGSOC patients. A method for AsPCs preparation was established based on a matrix (agarose), allowing for easy isolation and successive propagation of monolayer and 3D AsPCs. Based on this method, we performed cytotoxicity assays on 42 AsPCs grown both as monolayers and spheroids.Results: The response to PARPis treatment in monolayer AsPCs, was significantly higher, compared to 3D AsPCs, as 88% and 52% of the monolayer AsPCs displayed sensitivity to niraparib and olaparib respectively, while 66% of the 3D AsPCs were sensitive to niraparib and 38% to olaparib, the latter being more consistent with previous estimates of HRD (40%-60%) in EOC. Moreover, niraparib displayed a significantly stronger cytotoxic effect in both in 3D and monolayer AsPCs, which was confirmed by consecutive analyses of the HR pathway activity (γH2AX foci formation) in PARPis-sensitive and resistant AsPCs. Global gene expression comparison of 6 PARPi-resistant and 6 PARPi-sensitive 3D AsPCs was indicative for the predominant downregulation of numerous genes and networks with previously demonstrated roles in EOC chemoresistance, suggesting that the PARPis-sensitive AsPCs could display enhanced sensitivity to other chemotherapeutic drugs, commonly applied in cancer management. Microarray data validation identified 24 potential gene biomarkers associated with PARPis sensitivity. The differential expression of 7 selected biomarkers was consecutively confirmed by immunohistochemistry in matched EOC tumor samples.Conclusion: The application of this assay and the potential biomarkers with possible predictive significance to PARPis therapy of EOC patients now need testing in the setting of a clinical trial. [ABSTRACT FROM AUTHOR]

High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36–4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33–2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52–0.96). GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed. • Endometrial biopsies accurately predict high grade cancer in 80% of cases. • Endometrial biopsies are more accurate when reported by a gynecologic pathologist. • Discrepancy in endometrial biopsy interpretation impacts clinical management. • Surgical staging should not be based solely on preoperative endometrial biopsy. [ABSTRACT FROM AUTHOR]

Clinical utility of new biomarkers often requires the identification of their optimal threshold. This external validation study was conducted to assess the performance of the preoperative plasma tumor markers HE4 and CA125 optimal cut-offs to predict cancer mortality in women with epithelial ovarian cancer (EOC). Participating women had upfront debulking surgery in the University Hospital of Quebec City (Canada) between 1998 and 2013. A total of 136 women participated in the training cohort (cohort 1) and 177 in the validation cohort (cohort 2). Preoperative plasma HE4 and CA125 levels were measured by Elecsys. Optimal thresholds were identified in the cohort 1 using time-dependent receiver operating characteristic (ROC) curves. Multivariate Cox models were used to validate the biomarkers using their optimal cut-offs in the cohort 2. The likelihood ratio (LR) test was done to test whether the biomarkers added prognostic information beyond that provided by standard prognostic factors. The Areas Under the Curves (AUC) for HE4 and CA125 were respectively 64.2 (95% CI: 54.7–73.6) and 63.1 (95%CI: 53.6–72.6). The optimal thresholds were 277 pmol/L for HE4 and 282 U/ml for CA125. Preoperative plasma HE4 (≥277 pmol/L) was significantly associated with EOC mortality (adjusted hazard ratio (aHR): 1.90; 95% CI:1.09–3.29). The prognostic effect of HE4 was strongest in the subgroup of women with serous ovarian cancer (aHR: 2.42; 95% CI: 1.25–4.68). Using a multivariate model including all standard prognostic factors, this association was maintained (aHR: 2.21; 95% CI: 1.15–4.23). In addition, preoperative plasma HE4 added prediction for death over the standard prognostic markers in women with serous tumors (p-value for LR-test: 0.01). Preoperative CA125 was not associated with cancer mortality, both in women with EOC and in those with serous tumors. Preoperative HE4 is a promising prognostic biomarker in EOC, especially in serous tumor. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Purpose: The objective of this study was to compare three widely used interbody fusion approaches in regard to their ability to correct sagittal balance, including pelvic parameters. Overview of Literature: Restoration of sagittal balance in lumbar spine surgery is associated with better postoperative outcomes. Various interbody fusion techniques can help to correct sagittal balance, with no clear consensus on which technique offers the best correction. Methods: The charts and imaging of patients who have undergone surgery through either open transforaminal lumbar interbody fusion (TLIF), minimally invasive TLIF (MIS TLIF), or oblique lumbar interbody fusion (OLIF) were retrospectively reviewed. The following sagittal balance parameters were measured pre- and postoperatively: segmental lordosis, lumbar lordosis, disk height, pelvic tilt, and pelvic incidence. Data on postoperative complications were gathered. Results: Only OLIF managed to significantly improve segmental lordosis (4.4°, p <0.001) and lumbar lordosis (4.8°, p approaches significantly augmented disk height, with OLIF having the greatest effect (3.7°, p <0.001). No approaches were shown to significantly correct pelvic tilt. Pelvic incidence remained unchanged in all approaches. Open TLIF was the only approach with a higher rate of postoperative complications (33%, p =0.009). Conclusions: The OLIF approach might offer greater correction of sagittal balance over open and MIS TLIF, mainly in regard to segmental lordosis, lumbar lordosis, and disk height. MIS TLIF, although offering more limited access than open TLIF, was not inferior to open TLIF in regard to sagittal balance correction. A higher rate of complications was shown for open TLIF than the other approaches, possibly due to its more invasive nature. [ABSTRACT FROM AUTHOR]

Background: The expression of high temperature requirement factor A1 (Htra1) has been reported to be decreased in ovarian carcinoma, but its prognostic effect remains undetermined. Methods: We evaluated the impact of HtrA1 downregulation in tumoral tissues on cancer progression and death in women with serous ovarian carcinoma. HtrA1 staining was performed on tissue microarrays (TMA) comprised of tumor samples from a cohort of 106 women who were diagnosed with primary high-grade serous ovarian carcinoma and receiving standard treatment at the Québec University Hospital between 1993 and 2006. HtrA1 expression was assessed visually (percentage of positive nuclei) and by digital image analysis (percentage of positive area). Cox regression multivariate models included standard prognostic factors and were used to estimate adjusted hazard ratios (aHR) for progression or death in the cohort. Results: By visual analysis, a low percentage of HtrA1-positive nuclei (< 10% vs ≥10%) tend to be associated with a lower risk of progression (aHR = 0.71; 95% Confidence interval (CI) = 0.46–1.09; P = 0.11) and mortality (aHR = 0.65; 95% CI = 0.41–1.04; P = 0.07). Low nuclear HtrA1 expression assessed by digital image analysis (< median % vs ≥ median %) showed a significant association with lower risk of progression (aHR = 0.62; 95% CI = 0.40–0.95; p = 0.03) and death (aHR = 0.60; 95% CI = 0.38–0.95; p = 0.03). Conclusion: Altogether, our results demonstrate that nuclear downregulation of HtrA1 is associated with a better prognosis in women with high grade serous ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Objective To determine the validity of sentinel lymph node (SLN) biopsy with ICG in endometrial cancer and to evaluate the factors associated with poor mapping or false negative. Methods We reviewed all patients who underwent primary surgery for endometrial carcinoma with SLN mapping using ICG followed by pelvic lymphadenectomy from February 2014 to December 2015. SLNs were ultrastaged on final pathology. Patients' demographics, surgical approach and histopathological factors were prospectively collected. Detection rate, sensitivity and negative predictive value (NPV) were calculated and univariate analysis was performed to evaluate factors associated with failed bilateral detection of SLNs. Results A total of 119 patients were included. The overall and bilateral detection rates were 93% and 74%. Sensitivity and NPV were 100% in patients with bilateral detection; 95% and 99% respectively in cases with at least unilateral detection. Advanced FIGO stage (III or IV) was the only factor related to failed bilateral detection ( p  = 0.01). In 14 hemi-pelvis, the specimen labelled as SLN did not contain nodal tissue on final pathology (only lymphatic channels), which represented 37% of the “failed detection” cases. One false negative occurred in a patient with an ipsilateral clinically suspicious enlarged lymph node. Conclusion ICG is an excellent tracer for SLN mapping in endometrial cancer. Advanced FIGO stage correlated with failed bilateral detection ( p  = 0.01). Suspicious lymph nodes should be removed regardless of the mapping. Care should be taken to ensure that SLN specimen actually contains nodal tissue and not only swollen lymphatic channels, as this represents a significant cause of failed SLN mapping. [ABSTRACT FROM AUTHOR]