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To determine long-term kidney outcomes in boys with posterior urethral valve (PUV) undergoing either primary valve ablation or urinary diversion with matched baseline kidney function.After retrospective review of patients managed for PUV at our institution, propensity score matched analysis was conducted using nadir serum creatinine with logistic regression analysis. Nearest neighbor matching was used to allocate boys to primary urinary diversion and primary ablation groups. Primary outcomes included kidney function by creatinine or estimated glomerular filtration rate (eGFR), chronic kidney disease (CKD), and end-stage renal disease (ESRD). Comparative statistics by odds ratio (OR) and hazard ratios (HR) on survival analysis were calculated.A total of 21 boys undergoing primary diversion were matched with 42 boys undergoing ablation using nadir serum creatinine and follow-up time with a median follow-up of 4.8 years. After matching, there was no significant difference in last follow-up kidney function by creatinine (p=0.99) or eGFR (p=0.98). Primary diversion was not associated with increased likelihood of developing CKD stage 3 (OR 1.33; p=0.31) or ESRD (OR 1.88; p=0.35 and HR 1.85; p=0.30) compared to primary ablation.Our propensity matched study suggests that long-term kidney function and kidney outcomes are similar between primary ablation and primary diversion after adjusting for baseline kidney function in boys with PUV.

Background Cellular metabolism is an integral component of cellular adaptation to stress, playing a pivotal role in the resistance of cancer cells to various treatment modalities, including radiotherapy. In response to radiotherapy, cancer cells engage antioxidant and DNA repair mechanisms which mitigate and remove DNA damage, facilitating cancer cell survival. Given the reliance of these resistance mechanisms on amino acid metabolism, we hypothesised that controlling the exogenous availability of the non-essential amino acids serine and glycine would radiosensitise cancer cells. Methods We exposed colorectal, breast and pancreatic cancer cell lines/organoids to radiation in vitro and in vivo in the presence and absence of exogenous serine and glycine. We performed phenotypic assays for DNA damage, cell cycle, ROS levels and cell death, combined with a high-resolution untargeted LCMS metabolomics and RNA-Seq. Results Serine and glycine restriction sensitised a range of cancer cell lines, patient-derived organoids and syngeneic mouse tumour models to radiotherapy. Comprehensive metabolomic and transcriptomic analysis of central carbon metabolism revealed that amino acid restriction impacted not only antioxidant response and nucleotide synthesis but had a marked inhibitory effect on the TCA cycle. Conclusion Dietary restriction of serine and glycine is a viable radio-sensitisation strategy in cancer.

PURPOSE Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than in the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations had significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation followed by consolidative chemotherapy. Overexpression of IGF2 and L1CAM was associated with decreased response to neoadjuvant therapy. RNA-sequencing estimates of immune infiltration identified a subset of microsatellite-stable immune hot tumors with increased response and prolonged disease-free survival.

This study aims to understand perspectives on routine pathological examination of hernia sacs following pediatric inguinal hernia and hydrocele repair among Canadian pediatric urologists, surgeons, and pathologists.All active members of Pediatric Urologists of Canada (PUC), Canadian Association of Pediatric Surgeons (CAPS), and the divisional heads of anatomical pathology at the Canadian children's hospitals (AP) were invited to participate between June 2019 and January 2021 in an anonymous multiple-choice-based questionnaire.The response rates were 71% from PUC (24/34), 20% from CAPS (25/130), and 64% from AP (7/11). The majority of the surgeons (PUC:54%, CAPS:68%) did not routinely send hernia sacs for pathological examination after inguinal hernia repair. Most felt there was a little value in such examination (PUC:96%, CAPS:72%). Among those who submit hernia sacs, the majority did not receive reports that were clinically significant impacting patient management (PUC:82%, CAPS:50%). On the other hand, the pathologists had mixed opinion on the value of examining hernia sacs. Most of them only did gross examination (86%), unless requested by surgeons or concerning features were noted on gross examination. The majority have found clinically meaningful abnormal findings (71%), including vas deferens and portions of the spermatic cord.Currently, there are no evidence-based clinical guidelines on pathological assessment of hernia sacs after pediatric inguinal hernia and hydrocele repair. Instead of making it mandatory, future guidelines should highlight specimens that should be submitted for further investigations (e.g., challenging cases where inadvertent surgical injuries might have occurred). Future studies should also address whether patients who may be at higher risk of having clinically significant pathology can be identified pre- or perioperatively to more efficiently triage specimens that would benefit from pathological examination. Limitation of the study includes low response rate from the CAPS members during the COVID-19 pandemic.While most of the pediatric urologists and surgeons felt there is a little value of pathological examination of hernia sacs following inguinal hernia and hydrocele repair, half of the anatomical pathologists felt there is value. Future studies should aim to establish evidence-based clinical guidelines taking stakeholders perspectives into consideration.

Supplementary Table from KRAS Mutants Upregulate Integrin β4 to Promote Invasion and Metastasis in Colorectal Cancer

KRAS mutation in colorectal cancer is associated with aggressive tumor behavior through increased invasiveness and higher rates of lung metastases, but the biological mechanisms behind these features are not fully understood. In this study, we show that KRAS-mutant colorectal cancer upregulates integrin α6β4 through ERK/MEK signaling. Knocking-out integrin β4 (ITGB4) specifically depleted the expression of integrin α6β4 and this resulted in a reduction in the invasion and migration ability of the cancer cells. We also observed a reduction in the number and area of lung metastatic foci in mice that were injected with ITGB4 knockout KRAS-mutant colorectal cancer cells compared with the mice injected with ITGB4 wild-type KRAS-mutant colorectal cancer cells, while no difference was observed in liver metastases. Inhibiting integrin α6β4 in KRAS-mutant colorectal cancer could be a potential therapeutic target to diminish the KRAS-invasive phenotype and associated pulmonary metastasis rate.Implications:Knocking-out ITGB4, which is overexpressed in KRAS-mutant colorectal cancer and promotes tumor aggressiveness, diminishes local invasiveness and rates of pulmonary metastasis.

Supplementary Figure from KRAS Mutants Upregulate Integrin β4 to Promote Invasion and Metastasis in Colorectal Cancer

KRAS mutation in colorectal cancer is associated with aggressive tumor behavior through increased invasiveness and higher rates of lung metastases, but the biological mechanisms behind these features are not fully understood. In this study, we show that KRAS-mutant colorectal cancer upregulates integrin α6β4 through ERK/MEK signaling. Knocking-out integrin β4 (ITGB4) specifically depleted the expression of integrin α6β4 and this resulted in a reduction in the invasion and migration ability of the cancer cells. We also observed a reduction in the number and area of lung metastatic foci in mice that were injected with ITGB4 knockout KRAS-mutant colorectal cancer cells compared with the mice injected with ITGB4 wild-type KRAS-mutant colorectal cancer cells, while no difference was observed in liver metastases. Inhibiting integrin α6β4 in KRAS-mutant colorectal cancer could be a potential therapeutic target to diminish the KRAS-invasive phenotype and associated pulmonary metastasis rate. Implications: Knocking-out ITGB4, which is overexpressed in KRAS-mutant colorectal cancer and promotes tumor aggressiveness, diminishes local invasiveness and rates of pulmonary metastasis.

To develop a model that predicts whether a child will develop a recurrent obstruction after pyeloplasty, determine their survival risk score, and expected time to re-intervention using machine learning (ML). We reviewed patients undergoing pyeloplasty from 2008 to 2020 at our institution, including all children and adolescents younger than 18 years. We developed a two-stage machine learning model from 34 clinical fields, which included patient characteristics, ultrasound findings, and anatomical variation. We fit and trained with a logistic lasso model for binary cure model and subsequent survival model. Feature importance on the model was determined with post-selection inference. Performance metrics included area under the receiver-operating-characteristic (AUROC), concordance, and leave-one-out cross validation. A total of 543 patients were identified, with a median preoperative and postoperative anteroposterior diameter of 23 and 10 mm, respectively. 39 of 232 patients included in the survival model required re-intervention. The cure and survival models performed well with a leave-one-out cross validation AUROC and concordance of 0.86 and 0.78, respectively. Post-selective inference showed that larger anteroposterior diameter at the second post-op follow-up, and anatomical variation in the form of concurrent anomalies were significant model features predicting negative outcomes. The model can be used at https://sickkidsurology.shinyapps.io/PyeloplastyReOpRisk/ . Our ML-based model performed well in predicting the risk of and time to re-intervention after pyeloplasty. The implementation of this ML-based approach is novel in pediatric urology and will likely help achieve personalized risk stratification for patients undergoing pyeloplasty. Further real-world validation is warranted.

PURPOSE To characterize the relationship between tumor-infiltrating lymphocytes (TIL), tumor mutational burden (TMB), and genetic alterations in microsatellite stable (MSS), microsatellite instability (MSI), or mutant POLE/POLD1 colon cancer. MATERIALS AND METHODS Four hundred ninety-nine resected stage I-III colon tumors treated between 2014 and 2019 were assessed for TIL; somatic mutations, copy number alterations, and structural changes in > 400 oncogenes; and MSI status. RESULTS Of the 499 tumors analyzed, 313 were MSS, 175 were MSI, and 11 had POLE/POLD1 pathogenic mutations. Both the percentage of tumors with a high level of TIL (≥ 4 lymphocytes per high-power field) and the median TMB differed significantly between the three phenotypes: MSS, 4.5% and 6 mutations/Mb; MSI, 68% and 54 mutations/Mb; POLE/POLD1, 82% and 158 mutations/Mb ( P < .05). Within each phenotype, TMB did not vary significantly with TIL level. Among MSI tumors, the median number of frameshift indels was significantly higher in tumors with high levels of TIL (20 v 17; P = .018). In the MSS group, significantly higher proportions of tumors with high levels of TIL had mutations in the transforming growth factor-β (36% v 12%; P = .01), RAS (86% v 54%; P = .02), and Hippo (7% v 1%; P = .046) pathways; in contrast, TP53 alterations were associated with low levels of TIL (74% v 43%; P = .01). CONCLUSION The association between TIL, TMB, and genetic alterations varies significantly between MSI, MSS, and mutant POLE/POLD1 colon tumors. These differences may help explain tumoral immunity and lead to predictors of response to immunotherapy.

BACKGROUND AND OBJECTIVES: Watch-and-wait is variably adopted by surgeons and the impact of this on outcomes is unknown. We compare the disease-free survival and organ preservation rates of locally advanced rectal cancer patients treated by expert colorectal surgeons at a comprehensive cancer center. METHODS: This study included retrospective data on patients diagnosed with stage II/III rectal adenocarcinoma from January 2013 to June 2017 who initiated neoadjuvant therapy (either with chemoradiation, chemotherapy, or a combination of both) and were treated by an expert colorectal surgeon. RESULTS: 444 locally advanced rectal cancer patients managed by 5 surgeons were included. Tumor distance from the anal verge, type of neoadjuvant therapy, and organ preservation rates varied by treating surgeon. There was no difference in disease-free survival after stratifying by the treating surgeon (p=0.2). On multivariable analysis, neither the type of neoadjuvant therapy nor the treating surgeon was associated with disease-free survival. CONCLUSIONS: While neoadjuvant therapy type and organ preservation rates varied among surgeons, there were no meaningful differences in disease-free survival. These data suggest that amongst expert colorectal surgeons, differing thresholds for selecting patients for watch-and-wait do not affect survival.

ImportanceThe risk of recurrence in patients with locally advanced rectal cancer has historically been determined after surgery, relying on pathologic variables. A growing number of patients are being treated without surgery, and their risk of recurrence needs to be calculated differently.ObjectiveTo develop a dynamic calculator for estimating the probability of recurrence-free survival (RFS) in patients with rectal cancer who undergo total neoadjuvant therapy (TNT) (induction systemic chemotherapy and chemoradiotherapy) and either surgery or watch-and-wait management.Design, Setting, and ParticipantsThis cohort study included patients who presented with stage II or III rectal cancer between June 1, 2009, and March 1, 2015, at a comprehensive cancer center. Conditional modeling was incorporated into a previously validated clinical calculator to allow the probability of RFS to be updated based on whether the patient remained in watch-and-wait management or underwent delayed surgery. Data were analyzed from November 2021 to March 2022.ExposureTNT followed by immediate surgery or watch-and-wait management with the possibility of delayed surgery.Main Outcomes and MeasuresRFS, concordance index, calibration curves.ResultsOf the 302 patients in the cohort, 204 (68%) underwent surgery within 3 months from TNT completion (median [range] age, 51 [22-82] years; 78 [38%] women), 54 (18%) underwent surgery more than 3 months from TNT completion (ie, delayed surgery; median [range] age, 62 [31-87] years; 30 [56%] female), and 44 (14%) remained in watch-and-wait management as of April 21, 2021 (median [range] age, 58 [32-89] years; 16 [36%] women). Among patients who initially opted for watch-and-wait management, migration to surgery due to regrowth or patient choice occurred mostly within the first year following completion of TNT, and RFS did not differ significantly whether surgery was performed 3.0 to 5.9 months (73%; 95% CI, 52%-92%) vs 6.0 to 11.9 months (71%; 95% CI, 51%-99%) vs more than 12.0 months (70%; 95% CI, 49%-100%) from TNT completion (P = .70). RFS for patients in the watch-and-wait cohort at 12 months from completion of TNT more closely resembled patients who had undergone surgery and had a pathologic complete response than the watch-and-wait cohort at 3 months from completion of TNT. Accordingly, model performance improved over time, and the concordance index increased from 0.62 (95% CI, 0.53-0.71) at 3 months after TNT to 0.66 (95% CI, 0-0.75) at 12 months.Conclusions and RelevanceIn this cohort study of patients with rectal cancer, the clinical calculator reliably estimated the likelihood of RFS for patients who underwent surgery immediately after TNT, patients who underwent delayed surgery after entering watch-and-wait management, and patients who remained in watch-and-wait management. Delayed surgery following attempted watch-and-wait did not appear to compromise oncologic outcomes. The risk calculator provided conditional survival estimates at any time during surveillance and could help physicians counsel patients with rectal cancer about the consequences of alternative treatment pathways and thereby support informed decisions that incorporate patients’ preferences.

Mismatch repair deficient colon cancer is heterogeneous. Differentiating inherited constitutional variants from somatic genetic alterations and gene silencing is important for surveillance and genetic counseling.Determine the extent to which the underlying mechanism of loss of mismatch repair influences molecular and clinicopathologic features of microsatellite instability-high colon cancer.Retrospective analysis.Comprehensive cancer center.Patients with microsatellite instability-high colon cancer of stage I, II, or III.Curative surgical resection.Hypermethylation of the MLH1 promoter, biallelic inactivation, constitutional pathogenic variant, and loss of specific mismatch repair proteins.Of the 157 identified tumors with complete genetic analysis, 66% had hypermethylation of the MLH1 promoter, 18% had constitutional pathogenic variant (Lynch syndrome), 11% had biallelic somatic MMR gene pathogenic variants, and 6% had unexplained high microsatellite instability. The distribution of mismatch repair loss was as follows: MLH1 and PMS2 co-loss, 79% of the tumors; MSH2 and MSH6 co-loss, 10%; MSH6 alone, 3%; PMS2 alone, 2%; other combinations, 2%; no loss, 2%. Tumor mutational burden was lowest in MLH1- and PMS2-deficient tumors. MSH6-deficient tumors had the lowest levels of tumor-infiltrating lymphocytes, lowest MSIsensor scores, and fewest frameshift deletions. Patients with MLH1 promoter hypermethylation were significantly more likely to be older and female and to have right-colon lesions than patients with biallelic inactivation. Mutation was the most prevalent second hit in tumors with biallelic inactivation and tumors of patients with Lynch syndrome.Potential selection or referral bias, missing data for some patients, and relatively small sizes of some subgroups.Clinical characteristics of mismatch repair deficient colon cancer vary with the etiology of microsatellite instability, and its molecular characteristics vary with the affected mismatch repair protein. See Video Abstract at http://links.lww.com/DCR/B984.

Interfaces govern thermal transport in a variety of nanostructured systems such as FinFETs, interconnects, and vias. Thermal boundary resistances, however, critically depend on the choice of materials, nanomanufacturing processes and conditions, and the planarity of interfaces. In this work, we study the interfacial thermal transport between a nonreactive metal (Pt) and a dielectric by engineering two differing bonding characters: (i) the mechanical adhesion/van der Waals bonding offered by the physical vapor deposition (PVD) and (ii) the chemical bonding generated by plasma-enhanced atomic layer deposition (PEALD). We introduce 40-cycle (∼2 nm thick), nearly continuous PEALD Pt films between 98 nm PVD Pt and dielectric materials (8.0 nm TiO2/Si and 11.0 nm Al2O3/Si) treated with either O2 or O2 + H2 plasma to modulate their bonding strengths. By correlating the treatments through thermal transport measurements using time-domain thermoreflectance (TDTR), we find that the thermal boundary resistances are consistently reduced with the same increased treatment complexity that has been demonstrated in the literature to enhance mechanical adhesion. For samples on TiO2 (Al2O3), reductions in thermal resistance are at least 4% (10%) compared to those with no PEALD Pt at all, but could be as large as 34% (42%) given measurement uncertainties that could be improved with thinner nucleation layers. We suspect the O2 plasma generates stronger covalent bonds to the substrate, while the H2 plasma strips the PEALD Pt of contaminants such as carbon that gives rise to a less thermally resistive heat conduction pathway.

The optimal follow-up duration and frequency following hypospadias repair is unclear within the pediatric urology community. This analysis aims to delineate the time to various complications following primary hypospadias repairs. A retrospective review of a single-surgeon hypospadias database over 2001–2017 was performed. The primary outcome of the study was determining the significant factors leading to complications over time. As a secondary outcome, subgroup analysis was performed to determine whether there was a significant difference in time to detecting voiding-related complications (fistula, stricture/stenosis, and diverticulum) based on age. Eight hundred and thirty-two patients were identified. The complication rates for distal, midshaft, and proximal hypospadias were 17.9% (112/625), 36.7% (40/109), and 55.1% (49/89), respectively (p 30° (p 30° are likely to occur within 2 years of surgery. Surgeons may consider more frequent follow-up within the first 2 years of surgery to detect these complications.

Mesoporous metals are used in applications requiring high specific surface area and fast mass transport in an electrically conductive network and are primarily produced via dealloying. However, dea...

A barrier to the widespread adoption of watch-and-wait management for locally advanced rectal cancer is the inaccuracy and variability of identifying tumor response endoscopically in patients who have completed total neoadjuvant therapy (chemoradiotherapy and systemic chemotherapy).

There are several databases across the world that collect pediatric KT data. We compare the hospitalization outcomes for pediatric KT recipients from a large Canadian transplant center (SickKids database; The Hospital for Sick Children Kidney Transplantation Institutional Database), United States (NAPRTCS), and Europe (CERTAIN registry).An institutional retrospective review of KT was performed between 2000 and 2015. Baseline characteristics, duration of initial hospitalization/readmission at 1-5 and 6- to 11-month posttransplant, and 1-year graft survival data were collected. Corresponding data from the NAPRTCS 2014 Annual Transplant Report and CERTAIN registry were compared.Posttransplant, patients from NAPRTCS had the shortest duration of hospitalization within the first month (10.4 days, SE 0.2), followed by SickKids (20.3 days, SE 0.7) and CERTAIN (25.5 days, SE 0.7). For both living and deceased donor populations, patients from SickKids were most likely to be hospitalized at 1- to 5-month posttransplant (82.4% [89/108]; 72.1% [98/136]), followed by Europe (52.1% [198/380]; 61.6% [501/813]) and United States (45.4% [2379/5241]; 51.4% [2517/4896]). Patients from Europe were most likely to be hospitalized at 6- to 12-month posttransplant (42.1% [160/380]; 51.7% [420/813]), followed by SickKids (35.2% [38/108]; 37.5% [51/136]) and United States (28.3% [1387/4901]; 31.6% [1411/4465]). Across all databases, the most commonly addressed issues during readmissions were infectious complications.The differences observed in this investigation may reflect the local reimbursement models, resources for outpatient management, and practice variations across a large Canadian transplant center, United States, and European countries.

This study assesses whether post-operative check-in phone calls (POPC) performed within 48 h of outpatient pediatric urological surgeries by a non-medical professional (NMP) would increase patient/family satisfaction and minimize extraneous resource use by increasing email/telephone communication, while reducing emergency department (ED) visits within 30 days of that procedure. Families of patients undergoing ambulatory pediatric urology surgeries were enrolled over 8 weeks. Group 1 did not receive POPC. Group 2 received a POPC within 48 h of their operation by a NMP. Both groups received a phone-call survey 2 weeks after surgery to assess families’ perioperative satisfaction. In total, 74 families were enrolled (Group 1 = 44, Group 2 = 31). The response rates to phone surveys for Groups 1 and 2 were 59.1% and 77.4%, respectively. POPC did not improve perioperative satisfaction, nor did it significantly promote the use of nursing email/telephone communication (19.2% vs. 4.2%, p = 0.128) or reduce ED visits (15.4% vs. 0.0%, p = 0.111). However, all families in Group 2 thought POPC was timed appropriately and 79.1% perceived it to be helpful in reducing post-operative anxiety. POPC by a NMP within 48 h of surgery may not affect perioperative satisfaction of families of patients undergoing same-day pediatric urology surgery but may have an impact in reducing post-operative anxiety.

Lipid peroxidation is generally accepted to increase during ageing. We focused on stable lipid peroxidation end products, lipophilic fluorescent pigments (LFP). Their role in ageing in animal/human model has thoroughly been investigated. Changes in characteristics and quantity of LFP during tobacco leaf ageing were studied. We evaluated effect of altered ageing rate on LFP characteristics and accumulation. We employed plants with modulated cytokinins (CK) levels as they are plant hormones controlling development and ageing. Tobacco transgenic plants with senescence-induced CK up-regulation (SAG-ipt plants) displayed rejuvenation of senescent leaves. Slowed ageing was achieved in plants with constitutively down-regulated CK (CKX plants). Both 3D and synchronous fluorescence spectra of LFP indicate more marked differences of fluorophores´ compositions between two different control tobacco cultivars than between control and its transgenic plant. Major fluorophore amount increased with leaf age in both control and CKX plants, in SAG-ipt tobacco its quantity declined in the oldest leaves. The postponed leaf ageing in CKX plants resulted in a diminution of LFP. Higher LFP level in SAG-ipt plants compared with their control leaves of the same age was observed. LFP composition as well as relative abundance of individual LFP might be characteristic for each tobacco cultivar and depend on leaf age.

Background The clinical and economical value of routine submission of hernia sacs for pathological examination and scheduled clinic follow-ups after inguinal hernia and hydrocele repair has been questioned. Herein, we assessed the institutional variability in these routine practices. Methods We retrospectively reviewed patients who underwent unilateral or bilateral inguinal hernia and/or hydrocele repair, open or laparoscopically, at our institution from 2015 to 2018. Results 1181 patients were included (1074 inguinal hernias and 157 hydroceles). Of 531 specimens obtained from 446 (38%) patients, 515 (97%) were normal. 16 (3%) abnormal pathological findings included 7 with mesothelial hyperplasia, 5 with nonfunctional genital ductal remnants, 3 with ectopic adrenal cortical tissues, and 1 epidydimal structure which was not recognized at the time of surgery. 418 (35%) patients had scheduled clinic follow-ups 65 (IQR 46–94) days postoperatively. 44 (4%) patients with unexpected postoperative Emergency Department visits within 30 days of surgery were identified. Only one patient required inpatient treatment, and the rest did not require intervention or admission. The total direct cost of analyzing specimens during the study period was $30,798 CAD ($10,266/year). The average cost to detect a potentially significant finding was $1924.88/specimen and $2053.20/patient. Conclusions Routine pathological examination of hernia sacs and scheduled clinic follow-ups were associated with significant costs and predominantly nonsignificant findings. They should therefore be reserved for patients with a high clinical suspicion of injuries/abnormalities or risk factors for potential complications. Level of Evidence This is a level III evidence study.

Summary Background Genitourinary injuries in athletes engaging in high-impact sports such as football and rugby may have catastrophic consequences, especially in individuals with pre-existing urologic concerns, such as a solitary kidney. Objective To summarize the current literature on football-related or rugby-related genitourinary organ injuries in both adult and pediatric populations in an effort to risk stratify the likelihood of these injuries. Methods An independent systematic literature search for records reporting football-related or rugby-related injuries was conducted by a certified librarian and reviewer in March 2019. The search electronic databases included Medline, EMBASE, Scopus, and Web of Science. All studies reporting football-related or rugby-related genitourinary injuries were included. Results Twenty-two records (11 research studies, 11 case reports) were identified. In the pediatric population, the reported football-related kidney injuries were 0.1–0.7% of all football-related injuries, 0.07–0.5% of all sports-related injuries, and 1.5–37.5% of all sports-related genitourinary injuries, with incidence ranging from 0.00000084 to 0.0000092 injuries per exposure (five studies). Pediatric football-related testicular injuries were reported to be 0.11% of all football injuries, 0–0.07% of all sports-related injuries, and 0–37.5% of all sports-related genitourinary injuries; injury per exposure was 0.0000092 (four studies). In adults, there was no proportion of genitourinary injuries that could be determined, and football-related kidney injury incidence was 0.000012 injuries per exposure (one study). No adult literature investigated testicular injuries. Eleven case reports were additionally identified. Review of the case reports suggests that patients with previously existing urologic abnormalities such as ureteropelvic junction obstruction may predispose an individual to kidney injuries. Conclusion There is little to suggest that those engaged in football or rugby have a significant risk of genitourinary injury; therefore, future guidelines should reflect this.

The learning curves for minimally invasive pyeloplasty techniques have been described in the past. However, the learning curve in achieving competency in open pyeloplasty has not been described. Hence, we aim to evaluate a single surgeon series of open pyeloplasty technique using the cumulative sum (CUSUM) methodology.We retrospectively reviewed all open pyeloplasties performed by a single surgeon (AJL) between January 2008 and March 2020. Collected variables included: sex, age at surgery, operative time, hospital stay, pre-operative ultrasound, pre-operative nuclear scans, pre-operative anteroposterior diameter, associated anomalies, laterality (left or right), type of stent, pre-operative split renal function, and duration of follow-up. A CUSUM analysis was used: the highest peak, plateau and downward trends for complications (defined as Clavien-Dindo classification ≥ 3b) were identified on the plot and set as the transition points between five phases (learning, competency, proficiency, case-mix, and mastery).Based on the CUSUM analysis, the index surgeon reached the competency phase after performing their 13th open pyeloplasty and became proficient after the 70th case. In the case-mix phase (104th-126th cases), where the surgeon may be performing more complex cases while increasing trainee involvement, there was a slight increase in complication rates. After the 126th case, the surgeon entered the mastery phase, where there was consistent decreasing trend in complications.Surgeons performing open pyeloplasty in children following completion of their surgical training will continue to learn through their early cases until achieving competency. Technical competency may be reached after the 13th case. In this report, we looked at the number of cases to become proficient in open pyeloplasty procedure in children. A surgeon may achieve technical proficiency in the procedure after their 13th case.

We describe a mouse model of rectal cancer (RC) involving rapid tumor organoid engraftment via orthotopic transplantation in an immunocompetent setting. This approach uses simple mechanical disruption to allow engraftment, avoiding the use of dextran sulfate sodium. The resulting RC tumors invaded from the mucosal surface and metastasized to distant organs. Histologically, the tumors closely resemble human RC and mirror remodeling of the tumor microenvironment in response to radiation. This murine RC model thus recapitulates key aspects of human RC pathogenesis and presents an accessible approach for more physiologically accurate, preclinical efficacy studies.

We describe a new mouse model of rectal cancer (RC) involving rapid tumor organoid engraftment via orthotopic transplantation; the resulting RC tumors invaded inward from the mucosal surface and metastasized to distant organs. Histologically the tumors closely resemble human RC and mirror remodeling of the tumor microenvirnoment (TME) in response to radiation. This murine RC model thus recapitulates the pathogenesis of human RC, thereby fulfilling the need for a physiologically accurate model for preclinical efficacy studies.

The thermomechanical motion imposes the fundamental noise limit in room-temperature resonant sensors and oscillators. Due to the inherently low sensitivity of capacitive transduction in microelectromechanical (MEM) resonators, its effects are often masked by noise in the subsequent amplifier and measurement stages. In this work, we demonstrate a capacitive transduction scheme for measuring kHz-MHz frequency MEM resonators across 1 $\mu \text{m}$ capacitive gaps with 99.8% thermomechanical-noise-limited resolution. We delineate the transimpedance gain and noise of our custom off-chip differential transimpedance amplifier setup. The thermomechanical noise spectrum can provide estimates of the resonant frequency, quality factor, and electromechanical transduction factor comparable to the commonly used driven response, without the downsides of capacitive feedthrough or nonlinearity. [2019-0115]

Peritoneal dialysis (PD) is an option for ultrafiltration for patients with end-stage renal disease. Once placed, PD catheters may malfunction often due to omental wrapping. Omental procedures such as omentectomy and omentopexy may reduce this risk. This investigation aims to perform a systematic review and meta-analysis of the literature on the role of omental procedures on PD catheter insertions.Following protocol registration on PROSPERO (CRD42020218950), a systematic review was performed in accordance with the Cochrane Collaboration. A literature search was performed in February 2021 across Medline, EMBASE, Scopus, and Cochrane Library. Records with patients who underwent PD catheter insertion with and without omental manipulation were included. The records underwent screening, full-text review, and data extraction. Study qualities were assessed using RoBINS-I and RoB2. Effect estimates were extracted as risk ratios and corresponding 95% confidence intervals (CI) were pooled using inverse variance method with random-effect model.Of 510 records identified, 15 studies were included in the meta-analysis (1 RCT, 2 prospective, 12 retrospective). With omental procedures, there was decreased the likelihood of failure requiring removal of PD catheter (RR 0.47, 95% CI 0.38, 0.58) and PD catheter obstruction (RR 0.23, 95% CI 0.14, 0.39); there was no difference in likelihood of catheter malposition or migration (RR 0.87, 95% CI 0.23, 3.29) or peritonitis (RR 0.74, 95% CI 0.40, 1.35).Based on the current low to moderate quality of evidence, omental manipulation at the time of PD catheter insertion confers benefits of decreased obstruction and failure requiring removal.

Introduction: We performed a systematic review and meta-analysis of the current literature to assess the efficacy and safety of tranexamic acid (TXA) in the management of postoperative bleeding aft...

To develop a model that predicts whether a child will develop a recurrent obstruction after pyeloplasty, determine their survival risk score, and expected time to re-intervention using machine learning (ML).We reviewed patients undergoing pyeloplasty from 2008 to 2020 at our institution, including all children and adolescents younger than 18 years. We developed a two-stage machine learning model from 34 clinical fields, which included patient characteristics, ultrasound findings, and anatomical variation. We fit and trained with a logistic lasso model for binary cure model and subsequent survival model. Feature importance on the model was determined with post-selection inference. Performance metrics included area under the receiver-operating-characteristic (AUROC), concordance, and leave-one-out cross validation.A total of 543 patients were identified, with a median preoperative and postoperative anteroposterior diameter of 23 and 10 mm, respectively. 39 of 232 patients included in the survival model required re-intervention. The cure and survival models performed well with a leave-one-out cross validation AUROC and concordance of 0.86 and 0.78, respectively. Post-selective inference showed that larger anteroposterior diameter at the second post-op follow-up, and anatomical variation in the form of concurrent anomalies were significant model features predicting negative outcomes. The model can be used at https://sickkidsurology.shinyapps.io/PyeloplastyReOpRisk/ .Our ML-based model performed well in predicting the risk of and time to re-intervention after pyeloplasty. The implementation of this ML-based approach is novel in pediatric urology and will likely help achieve personalized risk stratification for patients undergoing pyeloplasty. Further real-world validation is warranted.

Background Total neoadjuvant therapy (TNT) improves tumor response in locally advanced rectal cancer (LARC) patients compared to neoadjuvant chemoradiotherapy alone. The effect of TNT on patient survival has not been fully investigated. Materials and Methods This was a retrospective case series of patients with LARC at a comprehensive cancer center. Three hundred and eleven patients received chemoradiotherapy (chemoRT) as the sole neoadjuvant treatment and planned adjuvant chemotherapy, and 313 received TNT (induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy in the neoadjuvant setting). These patients then underwent total mesorectal excision or were entered in a watch-and-wait protocol. The proportion of patients with complete response (CR) after neoadjuvant therapy (defined as pathological CR or clinical CR sustained for 2 years) was compared by the χ2 test. Disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival were assessed by Kaplan-Meier analysis and log-rank test. Cox regression models were used to further evaluate DFS. Results The rate of CR was 20% for chemoRT and 27% for TNT (P=.05). DFS, local recurrence-free survival, metastasis-free survival, and overall survival were no different. Disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12). Conclusions Although TNT does not prolong survival than neoadjuvant chemoradiotherapy plus intended postoperative chemotherapy, the higher response rate associated with TNT may create opportunities to preserve the rectum in more patients with LARC.

Introduction Traumatic diaphragm rupture injury repairs are predominately performed through thoracotomy, laparotomy, or a combination of the two approaches. While open surgery is often necessary to follow the fundamentals of damage-control operations in unstable or polytrauma patients, minimally invasive surgery may be an alternative for those with a low injury burden to reduce the postoperative morbidities associated with open operations. Case Description We describe the first case of a right-sided diaphragm rupture from blunt trauma that was repaired by a robotic transthoracic approach in the index admission. Conclusion Minimally invasive repair of an acute traumatic diaphragm rupture is feasible in selected trauma patients.

To determine if late gadolinium MRI enhancement of colorectal liver metastases (CRCLM) is associated with overall survival among nonsurgical patients. This retrospective study was approved by the institutional research ethics board. Late gadolinium enhancement was measured using target tumour enhancement (TTE) in all nonsurgical patients with CRCLM who received a 10-min delayed phase gadobutrol-enhanced liver MRI between March 1, 2006, and August 31, 2014. A total of 122 patients met inclusion/exclusion criteria. Patients were dichotomized into strong and weak TTE. Kaplan-Meier and Cox regression statistics were used to determine whether TTE was associated with overall survival. Noncontributory potential confounding variables (age, sex, number and size of metastases, carcinoembryonic (CEA) level, and presence of extrahepatic disease) were excluded from the final Cox regression model using the backward Wald elimination. Subgroup Kaplan-Meier survival analyses were performed on patients who were chemotherapy-naive and chemotherapy-treated at the time of MRI. Strong TTE had increased survival compared with those with weak TTE on Kaplan-Meier analysis (2-year survival: 69.8% vs. 43.5%, p = 0.002). Among 96 patients where data was available for multivariable analysis, weak TTE was associated with death (adjusted hazard ratio 0.25, 95% CI 0.11–0.59, p = 0.002), after adjusting for CEA level. Other potential confounders were noncontributory. Subgroup analyses demonstrated that strong TTE had increased survival compared with those with weak TTE in both the chemotherapy-naive (p = 0.047) and chemotherapy-treated (p = 0.008) groups. Strong late gadolinium MRI enhancement of CRCLM is associated with overall survival among nonsurgical patients. • MRI enhancement of colorectal liver metastases is associated with overall survival in nonsurgical patients. • MRI enhancement of colorectal liver metastases is associated with overall survival in both chemotherapy-naive and chemotherapy-treated subgroups.

Summary Introduction Voiding cystourethrogram (VCUG) with fluoroscopy remains the gold standard for detection and evaluation of vesicoureteral reflux (VUR) among children. However, the ionizing radiation exposure remains a concern for this diagnostic modality. Recent studies have proposed using contrast-enhanced ultrasound as an alternative option for VUR screening and follow-up in children. The aim of the study was to review the literature of comparative studies that assessed the diagnostic accuracy of contrast-enhanced ultrasound compared with VCUG. Methodology A systematic literature search was performed on electronic medical literature databases in July 2017. Literature identification, screening, and assessment of eligibility were performed by five reviewers with a pediatric radiologist. Literature was summarized for the study population, contrast used, and ultrasound mode as well as the timing of comparative reference study being performed. The studies were clustered according to the kind of contrast used. Reported diagnostic accuracy was extracted from individual studies and summarized across the included studies using descriptive statistics of median and interquartile range (IQR). Result A total of 45 comparative studies were identified as eligible for the summary of the literature. Two generations of ultrasound contrast were identified in the available studies (first generation, Levovist and second generation, SonoVue). For the ultrasound studies using the first-generation contrast, the median sensitivity, regardless of the ultrasound mode, was 90.25 (IQR 83.25–97), and the median specificity was 93 (IQR 91.3–95.25). Among studies using the second-generation contrast, the median sensitivity was 86.26 (IQR 81.13–97), and the median specificity was 90.99 (IQR 84–98). No serious adverse events were reported in any of the studies. Conclusion Overall, this review highlights the application of contrast-enhanced ultrasound for its advantage of no exposure to ionizing radiation and diagnostic accuracy relatively comparable to VCUG in the evaluation of VUR. In addition to the functional evaluation of the VUR, it also provides an anatomic evaluation of the kidneys and bladder with ultrasound imaging. However, one should also note that this alternate procedure is highly operator dependent where diagnostic accuracy is excellent when the expertise is available.