Development of patient and catheter specific error thresholds for high dose rate prostate brachytherapy.

BACKGROUND: In-vivo source tracking has been an active topic of research in the field of high-dose rate brachytherapy in recent years to verify accuracy in treatment delivery. Although detection systems for source tracking are being developed, the allowable threshold of treatment error is still unknown and is likely patient-specific due to anatomy and planning variation. PURPOSE: The purpose of this study was to determine patient and catheter-specific shift error thresholds for in-vivo source tracking during high-dose-rate prostate brachytherapy (HDRPBT). METHODS: A module was developed in the previously described graphical processor unit multi-criteria optimization (gMCO) algorithm. The module generates systematic catheter shift errors retrospectively into HDRPBT treatment plans, performed on 50 patients. The catheter shift model iterates through the number of catheters shifted in the plan (from 1 to all catheters), the direction of shift (superior, inferior, medial, lateral, cranial, and caudal), and the magnitude of catheter shift (1-6 mm). For each combination of these parameters, 200 error plans were generated, randomly selecting the catheters in the plan to shift. After shifts were applied, dose volume histogram (DVH) parameters were re-calculated. Catheter shift thresholds were then derived based on plans where DVH parameters were clinically unacceptable (prostate V100 < 95%, urethra D0.1cc > 118%, and rectum Dmax > 80%). Catheter thresholds were also Pearson correlated to catheter robustness values. RESULTS: Patient-specific thresholds varied between 1 to 6 mm for all organs, in all shift directions. Overall, patient-specific thresholds typically decrease with an increasing number of catheters shifted. Anterior and inferior directions were less sensitive than other directions. Pearson's correlation test showed a strong correlation between catheter robustness and catheter thresholds for the rectum and urethra, with correlation values of -0.81 and -0.74, respectively (p < 0.01), but no correlation was found for the prostate. CONCLUSIONS: It was possible to determine thresholds for each patient, with thresholds showing dependence on shift direction, and number of catheters shifted. Not every catheter combination is explorable, however, this study shows the feasibility to determine patient-specific thresholds for clinical application. The correlation of patient-specific thresholds with the equivalent robustness value indicated the need for robustness consideration during plan optimization and treatment planning.

Predictive Factors for Morcellation during Total Laparoscopic Hysterectomy: A Cohort Study.

OBJECTIVES: Our objective was to identify predictors of morcellation during a total laparoscopic hysterectomy (TLH). METHODS: A retrospective cohort study (Canadian Task Force classification II-2) taking place in a university hospital center in Quebec, Canada. Participants were women undergoing a TLH for a benign gynaecologic pathology from January 1, 2017, to January 31, 2019. All women underwent a TLH. If the uterus was too voluminous to be removed vaginally, surgeons favoured in-bag morcellation by laparoscopy. Uterine weight and characteristics were assessed before surgery by ultrasound or magnetic resonance imaging to predict morcellation. RESULTS: A total of 252 women underwent a TLH and the mean age was 46 ± 7 (30-71) years old. The main indications for surgery were abnormal uterine bleeding (77%), chronic pelvic pain (36%) and bulk symptoms (25%). Mean uterine weight was 325 (17-1572) ± 272 grams, with 11/252 (4%) uterus being >1000 grams and 71% of women had at least 1 leiomyoma. Among women with a uterine weight <250 grams, 120 (95%) did not require morcellation. On the opposite, among women with a uterine weight >500 grams, 49 (100%) required morcellation. In addition to the estimated uterine weight (≥250 vs. <250 grams; OR 3.7 [CI 1.8 to 7.7, P < 0.01]), having ≥ 1 leiomyoma (OR 4.1, CI 1.0 to 16.0, P = 0.01) and leiomyoma of ≥5 cm (OR 8.6, CI 4.1 to 17.9, P < 0.01) were other significant predictors morcellation in multivariate logistic regression analysis. CONCLUSIONS: Uterine weight estimated by preoperative imaging as well as the size and number of leiomyomas are useful predictors of the need for morcellation.

Evaluation of a Standardized Questionnaire for Initial Assessment of Abnormal Uterine Bleeding in Premenopausal Women.

OBJECTIVE: To assess the effect of a standardized questionnaire for premenopausal women with abnormal uterine bleeding (AUB) on clinical information collection and duration of consultation. METHODS: We conducted a before and after study involving 100 premenopausal women undergoing consultation for AUB. During stage 1, 50 consultations were recorded on a consultation sheet with no specific template. During stage 2, 50 women completed a 26-item auto-administered standardized questionnaire before the consultation, which was then reviewed with the consultant and added to the medical record. The duration of consultation was assessed in subgroups of 27 women in each stage. Two independent evaluators assessed the quality and completeness of data collected in the medical records using a score sheet developed by experts. Outcomes from both stages were compared using the t test. RESULTS: The descriptive characteristics were similar in both groups. The mean global scores of the quality and completeness of data collected improved significantly between stages 1 and 2, from 67% ± 12% to 95% ± 5% (P < 0.0001), as did medical background scores (54% ± 29% vs. 85% ± 13%; P < 0.0001) and AUB-related symptoms scores (69% ± 13% vs. 97% ± 5%; P < 0.0001). A mean reduction in duration of consultation of nearly 4 minutes was observed (24.6 ± 4.3 min vs. 20.7 ± 4.8 min; P < 0.0001). CONCLUSION: The AUB-specific standardized questionnaire improves quality and completeness of data collected in medical records and reduces duration of consultation.

Catheters and dose optimization using a modified CVT algorithm and multi-criteria optimization in prostate HDR brachytherapy.

PURPOSE: Currently, in high-dose rate (HDR) brachytherapy planning, the catheter's positions are often selected by the planner, which involves the planner's experience. The catheters are then inserted using a template that helps to guide the catheters. For certain applications, it is of interest to choose the optimal location and number of catheters needed for dose coverage and potential decrease of the treatment's toxicity. Hence, it is of great importance to develop patient-specific algorithms for catheters and dose optimization. METHODS: A modified Centroidal Voronoi tessellation (CVT) algorithm is implemented and merged with a graphics processing unit (GPU)-based multi-criteria optimization algorithm (gMCO). The CVT algorithm optimizes the catheters' positions, and the gMCO algorithm optimizes the dwell times and dwell positions. The CVT algorithm can be used simultaneously for insertion with or without a template. Some improvements to the CVT algorithm are presented such as a new way of considering the area that needs to be covered. One hundred eight previously treated prostates HDR cases using real-time ultrasound are used to evaluate the different optimization procedures. The plan robustness is evaluated using two types of errors: deviations (random) in the insertion and deviation (systematic) in the reconstruction of the catheters. RESULTS: Using gMCO on clinically inserted catheter increases the acceptance rate by 37% for Radiation Therapy Oncology Group (RTOG) criteria. Our results show that all the patients respect RTOG criteria with 11 catheters using CVT+gMCO with a template of 5 mm. The number of catheters needed for all patients to respect RTOG criteria with the freehand technique is 10 catheters using CVT+gMCO. When deviations are introduced, using a template, the acceptance rate goes to 85% with 3 mm deviations using 11 catheters. This decrease is less significant when the number of catheters is higher, decreasing by less than 5% with a 3 mm deviation using 13 catheters or more. In conclusion, it is feasible to decrease the number of catheters needed to treat most patients. CONCLUSIONS: Some cases still need a high number of catheters to reach the plan's criteria. Using gMCO allows an increase in the plan quality, while using CVT reduces the number of catheters. A higher number of catheters equates to plans that are more robust to deviations.

Effect of Postoperative Hormonal Suppression on Fertility in Patients With Endometriosis After Conservative Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effect of hormonal suppression on fertility when administered to infertile patients or patient wishing to conceive after surgery for endometriosis. DATA SOURCES: A systematic search of MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov was performed by two independent reviewers from the databases' inception until December 2020. METHODS OF STUDY SELECTION: We included randomized controlled trials comparing any suppressive hormonal therapy to an inactive control (placebo or absence of treatment) after conservative surgery for endometriosis. Studies that did not report fertility outcomes after surgery were excluded. TABULATION, INTEGRATION AND RESULTS: This systematic review and meta-analysis was registered in PROSPERO. Two reviewers extracted data and assessed the risk of bias as well as the strength of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. Relative risks (RRs) were pooled by quantitative random effect meta-analysis. From 3,138 citations, 19 trials (2,028 patients) were included. Overall, no difference was observed between the treatment and the control group for pregnancy (RR 1.15; 95% CI 1.00-1.32) and live births (RR 1.05; 95% CI 0.84-1.32). When pooling all hormonal therapies, the duration of administration of postoperative therapy was identified as a substantial source of heterogeneity between studies (I2 difference=74%) with increased chances of pregnancy compared with control when administered for at least 3 months (RR 1.22; 95% CI 1.04-1.43). Gonadotropin-releasing hormone (GnRH) agonists (14 trials, 1,721 patients) were associated with increased chances of pregnancy compared with placebo or no treatment (RR 1.20; 95% CI 1.03-1.41; I2=25%). Data were limited for other hormonal treatments with no significant difference between groups. Subgroup analyses taking into account the use of fertility treatments (insemination or in vitro fertilization), stages of the disease and risk of bias of included trials did not modify the results. CONCLUSION: Postoperative hormonal suppression should be considered on a case-by-case basis to enhance fertility while balancing this benefit with the risks of delaying conception. If chosen, GnRH agonists would be the treatment of choice, and a duration of at least 3 months should be favored. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021224424.

Artificial Intelligence in Chemistry: Current Trends and Future Directions.

The application of artificial intelligence (AI) to chemistry has grown tremendously in recent years. In this Review, we studied the growth and distribution of AI-related chemistry publications in the last two decades using the CAS Content Collection. The volume of both journal and patent publications have increased dramatically, especially since 2015. Study of the distribution of publications over various chemistry research areas revealed that analytical chemistry and biochemistry are integrating AI to the greatest extent and with the highest growth rates. We also investigated trends in interdisciplinary research and identified frequently occurring combinations of research areas in publications. Furthermore, topic analyses were conducted for journal and patent publications to illustrate emerging associations of AI with certain chemistry research topics. Notable publications in various chemistry disciplines were then evaluated and presented to highlight emerging use cases. Finally, the occurrence of different classes of substances and their roles in AI-related chemistry research were quantified, further detailing the popularity of AI adoption in the life sciences and analytical chemistry. In summary, this Review offers a broad overview of how AI has progressed in various fields of chemistry and aims to provide an understanding of its future directions.

Technicity in Canada: A Nationwide Whole-Population Analysis of Temporal Trends and Variation in Minimally Invasive Hysterectomies.

STUDY OBJECTIVE: The objective of our study was to provide a contemporary description of hysterectomy practice and temporal trends in Canada. DESIGN: A national whole-population retrospective analysis of data from the Canadian Institute for Health Information. SETTING: Canada. PATIENTS: All women who underwent hysterectomy for benign indication from April 1, 2007, to March 31, 2017, in Canada. INTERVENTIONS: Hysterectomy. MEASUREMENTS AND MAIN RESULTS: A total of 369 520 hysterectomies were performed in Canada during the 10-year period, during which the hysterectomy rate decreased from 313 to 243 per 100 000 women. The proportion of abdominal hysterectomies decreased (59.5% to 36.9%), laparoscopic hysterectomies increased (10.8% to 38.6%), and vaginal hysterectomies decreased (29.7% to 24.5%), whereas the national technicity index increased from 40.5% to 63.1% (p <.001, all trends). The median length of stay decreased from 3 (interquartile range 2-4) days to 2 (interquartile range 1-3), and the proportion of patients discharged within 24 hours increased from 2.1% to 7.2%. In year 2016-17, women aged 40 to 49 years had significantly increased risk of abdominal hysterectomy compared with women undergoing hysterectomy in other age categories (p <.001). Comparing women with menstrual bleeding disorders, women undergoing hysterectomy for endometriosis (adjusted relative risk [aRR] 1.36; 95% confidence interval [CI], 1.28-1.44) and myomas (aRR 2.01; 95% CI, 1.94-2.08) were at increased risk of abdominal hysterectomy, whereas women undergoing hysterectomy for pelvic organ prolapse and pelvic pain (aRR 1.47; 95% CI, 1.41-1.53) were at decreased risk. Using Ontario as the comparator, Nova Scotia (aRR 1.35; 95% CI, 1.27-1.43), New Brunswick (aRR 1.25; 95% CI, 1.18-1.32]), Manitoba (aRR 1.35; 95% CI, 1.28-1.43), and Newfoundland and Labrador (aRR 1.18; 95% CI, 1.10-1.27) had significantly higher risks of abdominal hysterectomy. In contrast, Saskatchewan (aRR 0.75; 95% CI, 0.74-0.77) and British Columbia (aRR 0.86; 95% CI, 0.85-0.88) had significantly lower risks, whereas Prince Edward Island, Quebec, and Alberta were not significantly different. CONCLUSION: The proportion of minimally invasive hysterectomies for benign indication has increased significantly in Canada. The declining use of vaginal approaches and the variation among provinces are of concern and necessitate further study.

Guideline No. 412: Laparoscopic Entry for Gynaecological Surgery.

OBJECTIVE: To evaluate the benefits and risks of laparoscopic surgery and provide clinical direction on entry techniques, technologies, and their associated complications in gynaecological surgery. TARGET POPULATION: All patients, including pregnant women and women with obesity, undergoing laparoscopic surgery for various gynaecological indications. OPTIONS: The laparoscopic entry techniques and technologies reviewed in formulating this guideline included the closed (Veress needle-pneumoperitoneum-trocar) technique, direct trocar insertion, open (Hasson) technique, visual entry systems, and disposable shielded and radially expanding trocars. OUTCOMES: Implementation of this guideline should optimize decision-making in the selection of entry technique for laparoscopic surgery. EVIDENCE: We searched English-language articles from September 2005 to December 2019 in PubMed/MEDLINE, Embase, Science Direct, Scopus, and Cochrane Library using the following MeSH search terms alone or in combination: laparoscopic entry, laparoscopy access, pneumoperitoneum, Veress needle, open (Hasson), direct trocar, visual entry, shielded trocars, radially expanded trocars, and laparoscopic complications. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Canadian Task Force on Preventive Health Care approach (Appendix A). INTENDED AUDIENCE: Surgeons performing laparoscopic gynaecological surgery. SUMMARY STATEMENTS: RECOMMENDATIONS.

Minimally Invasive Hysterectomy Rates in Québec: Trends Over the Last Decade and Predictors of Technicity.

OBJECTIVE: To assess trends and predictors of a high technicity index for hysterectomies performed in the province of Québec. METHODS: We conducted a retrospective study using the ADAM database to determine the annual number hysterectomies performed for a suspected benign condition and the surgical approach used across 81 hospitals in the province of Québec from 2007 to 2017. We calculated the technicity index for each hospital and analyzed trends in surgical approach using the Cochran-Armitage test. We used logistic regression to assess potential predictors of a high technicity index (>70%), including academic centre, urban area, high volume of hysterectomies performed, and greater number of gynaecologists per hospital. RESULTS: Fifty-nine hospitals were eligible for inclusion, representing 96 431 hysterectomies during the study period. Over the decade, the technicity index increased from 43% to 66% (P < 0.001, with a 198% increase in laparoscopic hysterectomies (from 685 to 2039 per year; P < 0.001), a 50% decrease in abdominal hysterectomies (from 5528 to 2790 per year; P < 0.001), and a 8% decrease in vaginal hysterectomies (form 3551 to 3257 per year; P < 0.001). Meanwhile, the total number of hysterectomies per year declined by 17% (P < 0.001). Being an academic centre was the only significant predictor of a high technicity index >70% (68% vs. 38%; OR 7.5; P = 0.047). CONCLUSION: Technicity is increasing in the province of Québec and the majority of hysterectomies are now performed using a minimally invasive approach. This shift has mainly occurred through an increase in the laparoscopic approach and a decrease in the abdominal approach. Academic centres are more likely to have high technicity indexes.

Morcellation During Total Laparoscopic Hysterectomies: Implications of the Use of a Contained Bag System.

OBJECTIVE: This study sought to report the feasibility and clinical implications of in-bag morcellation for total laparoscopic hysterectomy (TLH). METHODS: Women who required uterine morcellation during TLH from January 2017 to December 2018 (at the Centre Hospitalier Universitaire de Québec - CHUL, Québec, QC) were included. Women with a preoperative suspicion of malignancy were excluded (Canadian Task Force classification II-2). RESULTS: During the 2-year study period, uterine morcellation was required in 42% (106 of 252) of women undergoing TLH. Mean uterine weight of morcellated uterus was 541 ± 291 g, with 11 of 106 uteri weighing >1000 g. In-bag morcellation was attempted in 84 of 106 (79%) and successfully performed in 79 of 84 (94%) women. Failures resulted from inability to insert the specimen into the bag or apparent perforation. Uncontained morcellation was chosen for 22 of 106 (21%) women, most of whom underwent vaginal morcellation of the uterus. Total operative time was 40 minutes longer for the in-bag morcellation group (170 ± 48 vs. 130 ± 43 min; P < 0.001), although this difference can be partly explained by the higher mean uterine size compared with the uncontained morcellation group (580 ± 309 vs. 391 ± 122 g; P = 0.01). In a subgroup analysis of 16 women, the mean times of installation and extraction of the bag were estimated to be 17 ± 9 and 4 ± 3 minutes, respectively. Complications were infrequent (2 of 106) and occurred in the in-bag morcellation group. CONCLUSION: In-bag morcellation is feasible in a high proportion of women undergoing laparoscopic hysterectomy and is associated with an increase in operative time. Larger studies will be required in order to better assess the risk of complications with in-bag morcellation and the potential benefits of this technique, namely, reducing the spread of tissue.

Contained Morcellation of Very Large Uterus.

A 38-year-old woman was referred to our centre for symptomatic leiomyoma. The patient had a large uterus, heavy menstrual bleeding, and compressive symptoms refractory to medical treatments. The patient was then scheduled for total laparoscopic hysterectomy with contained morcellation. After circular colpotomy completion, a strong, folded, 4-L bag with an additional sleeve for the optics was inserted into the abdominal cavity through the vagina. The colored tabs on the edge of the bag mouth served as landmarks during bag deployment. After ensuring optimal positioning, the entire bag was fully deployed, and the specimen was placed inside. Thereafter, the coloured tabs were joined together, and a monofilament drawstring was cinched to close the bag and pulled out through the suprapubic trocar. Next, the small extra sleeve was brought up through the umbilical incision. The bag was then insufflated, and the power morcellator was inserted through the suprapubic incision. After completing the morcellation, the pneumo bag was evacuated, and knots were made in both openings of the bag to avoid spillage. The closed bag was finally removed through the vagina, with final laparoscopic closure of the vaginal vault.

Endometrial ablation or resection versus levonorgestrel intra-uterine system for the treatment of women with heavy menstrual bleeding and a normal uterine cavity: a systematic review with meta-analysis.

BACKGROUND: Endometrial ablation/resection and the levonorgestrel intra-uterine system (LNG-IUS) are well-established treatment options for heavy menstrual bleeding to avoid more invasive alternatives, such as hysterectomy. OBJECTIVE: The aim was to compare the efficacy and safety of endometrial ablation or resection with the LNG-IUS in the treatment of premenopausal women with heavy menstrual bleeding and to investigate sources of heterogeneity between studies. SEARCH METHODS: We searched the databases MEDLINE, EMBASE, CENTRAL, Web of Science, Biosis and Google Scholar as well as citations and reference lists published up to August 2019. Two authors independently screened 3701 citations for eligibility. We included randomized controlled trials published in any language, comparing endometrial ablation or resection to the LNG-IUS in the treatment of premenopausal women with heavy menstrual bleeding and a normal uterine cavity. OUTCOMES: Thirteen studies (N = 884) were eligible. Two independent authors extracted data and assessed the quality of included studies. Random effect models were used to compare the modalities and evaluate sources of heterogeneity. No significant differences were observed between endometrial ablation/resection and the LNG-IUS in terms of subsequent hysterectomy (primary outcome, risk ratio (RR) = 1.13, 95% CI 0.60 to 2.11, P = 0.71, I2 = 14%, 12 studies, 726 women), satisfaction, quality of life, amenorrhea and treatment failure. However, side effects were less common in women treated with endometrial ablation/resection compared to the LNG-IUS (RR = 0.52, 95% CI 0.37 to 0.71, P < 0.001, I2 = 0%, 10 studies, 580 women). Three complications were reported in the endometrial ablation/resection group and none in the LNG-IUS group (P = 0.25). Mean age of the studied populations was identified as a significant source of heterogeneity between studies in subgroup analysis (P = 0.01). In fact, endometrial ablation/resection was associated with a higher risk of subsequent hysterectomy compared to the LNG-IUS in younger populations (mean age ≤ 42 years old, RR = 5.26, 95% CI 1.21 to 22.91, P = 0.03, I2 = 0%, 3 studies, 189 women). On the contrary, subsequent hysterectomy seemed to be less likely with endometrial ablation/resection compared to the LNG-IUS in older populations (mean age > 42 years old), although the reduction did not reach statistical significance (RR = 0.51, 95% CI 0.21 to 1.24, P = 0.14, I2 = 0%, 5 studies, 297 women). Finally, sensitivity analysis taking into account the risk of bias of included studies and type of surgical devices (first and second generation) did not modify the results. Most of the included studies reported outcomes at up to 3 years, and the relative performance of endometrial ablation/resection and LNG-IUS remains unknown in the longer term. WIDER IMPLICATIONS: Endometrial ablation/resection and the LNG-IUS are two excellent treatment options for heavy menstrual bleeding, although women treated with the LNG-IUS are at higher risk of experiencing side effects compared to endometrial ablation/resection. Otherwise, younger women seem to present a lower risk of eventually requiring hysterectomy when treated with the LNG-IUS compared to endometrial ablation/resection.

Intermittent systemic hypoxic-hyperoxic training for myocardial protection in patients undergoing coronary artery bypass surgery: first results from a single-centre, randomised controlled trial.

Background: Although remote ischaemic preconditioning (RIP) provides protection against myocardial ischaemia and reperfusion injury during cardiac surgery, it is not widely used. Systemic intermittent hypoxic-hyperoxic training (IHHT) may be a suitable alternative. Methods: This is a prospective, single-centre, randomised controlled trial. 127 patients with ischaemic heart disease and indication for coronary artery bypass graft (CABG) surgery from the Cardiology Clinic IM Sechenov First Moscow State Medical University were randomly assigned to IHHT, IHHT-control or RIP. Primary endpoint was serum concentration of troponin I and lactate 2 and 24 hours after surgery. Results: Median value for troponin I 24 hours after surgery was 1.068 (0.388-1.397) ng/mL in the IHHT group and was significantly lower compared with IHHT-controls with 1.980 (1.068-3.239) ng/mL (p=0.012) and to the RIP group with 1.762 (1.288-2.186) ng/mL (p=0.029), while there was no significant difference between RIP and the IHHT-control. Serum lactate after surgery was 1.74 (1.23-2.04) mmol/L in the IHHT group and was also significantly lower compared with IHHT-controls with 2.10 (1.80-2.29) mmol/L (p=0.045) and RIP with 2.12 (1.91-2.33) mmol/L (p=0.032). No significant complications or serious adverse events were observed during IHHT. Intraoperative and early postoperative complications did not differ significantly between groups. Conclusions: The results of this first trial using IHHT for myocardial protection against perioperative ischaemic myocardial injury in patients undergoing CABG surgery are promising and further larger trials should be done with adequate power to detect clinical rather than surrogate marker benefits.