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Objective: To evaluate and compare the outcomes of patients with localised renal cell carcinoma (RCC) with and without sarcomatoid features and the impact of this on cancer recurrence and survival., Material and Methods: The Canadian Kidney Cancer information system database was used to identify patients diagnosed with localised RCC between January 2011 and December 2022. Patients with pT1-T3, n Nx-N0N1, M0 stage and documented sarcomatoid status were included. Patients with sarcomatoid RCC were categorised according to the sarcomatoid component percentage (%Sarc). Inverse probability of treatment weighting scores were used to balance the groups. Cox proportional hazards models were used to assess the impact of sarcomatoid status and %Sarc on recurrence-free and overall survival., Results: A total of 6660 patients (201 with and 6459 without sarcomatoid features) with non-metastatic RCC were included. %Sarc data were available in 155 patients, and the median value was 10%. The weighted analysis revealed that the presence of sarcomatoid features was associated with an increased risk of developing metastasis and increased risk of mortality compared to absence of sarcomatoid features. A %Sarc value >10 was associated with an increased risk of developing metastasis and of mortality compared to a %Sarc value ≤10., Conclusions: Patients with a %Sarc >10 have an increased risk of recurrence and mortality. These patients may benefit from a more stringent follow-up and %Sarc could represent an important criterion in the risk assessment for adjuvant therapy., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk., Methods and Analysis: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation., Ethics and Dissemination: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309)., Trial Registration Number: NCT05148715., Competing Interests: Competing interests: CL, FDA, FLam, FLau, F-MC and MC are recipients of research career awards from the Fonds de recherche du Québec-Santé. AFT is the chairholder of the Canada Research Chair in Critical Care Neurology and Trauma. FDA, MW and PC received stipends for their role at Transplant Québec MaS holds research grants from the Canadian Institute of Health Research and the New Frontiers in Research Fund related to organ donation research and received a stipend for his role as the Regional Medical Lead (Donation) from Ontario Health (Trillium Gift of Life Network). MSe, RB, M-HM, MMa, A-JF, BB, AD, EC, SHo, LB, HT, PL, JGB, MKS, KEAB, JZ, SE, GK, AH, SHa, BR, SJWO, DT and MMe declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes., Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively., Results: Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47)., Conclusions: Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objective: To determine the correlation between ultrasound (US), cross-sectional imaging, and pathological renal mass sizes., Methods: Between January 2011 and January 2021, a cohort of patients from 14 academic institutions who had an US and cross-sectional imaging within 8 weeks of each other and within 6 months of surgery were identified. A second cohort of patients with small renal masses (≤4 cm) who had US and cross-sectional imaging within 8 weeks of each other were also examined, regardless of their treatment modality. Correlation coefficients, Bland-Altman plots, and sensitivity tables were generated., Results: A total of 1464 patients were included in the surgical cohort and 1582 patients (1921 imaging pairs) were included in the small renal mass (SRM) cohort. Pearson correlation coefficients between computed tomography (CT)/magnetic resonance imaging (MRI) and pathologic size was 0.93 (P <.0001) and between US and pathological size was 0.90 (P <.0001). The correlation between US and CT/MRI was 0.93 (P <.0001). Bland-Altman plots demonstrated a greater agreement for smaller renal masses. For the SRM cohort when comparing US to CT/MRI, 1441 (75%) SRM measurements were within 0.5 cm and only 149 (7.8%) were greater than 1 cm in difference. Subgroup analysis demonstrated that correlation between US and CT/MRI for SRMs were higher in patients with lower body mass index., Conclusion: There is a strong correlation between US and cross-sectional imaging in 75% of patients at baseline imaging. Our study provides support for utilization of US for active surveillance., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate risk factors associated with urologic injury in women undergoing hysterectomy for benign indication., Methods: A retrospective cohort study for the period of 2011-2018 was conducted using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Women without urologic injury were compared with women with injury. A pre-specified multivariable logistic regression model, controlling for key patient demographic factors and intraoperative variables, was used to assess for surgical factors associated with urologic injury., Results: Among 262 117 women who underwent hysterectomy for benign indication, 1539 (0.6%) sustained urologic injury. On average, patients with urologic injury were younger, had lower body mass index (BMI), and more frequently underwent a transabdominal surgical approach. Patients who underwent total hysterectomy had increased odds of urologic injury than those who underwent subtotal hysterectomy (adjusted OR [aOR] 1.49; 95% confidence interval [CI] 1.21-1.84). Patients with class III obesity had lower odds of injury than patients with normal BMI (aOR 0.64; 95% CI 0.51-0.80). For risk of urologic injury, an interaction was observed between surgical approach and surgical indication. Abdominal compared with laparoscopic approach was associated with urologic injury for women with endometriosis (aOR 2.98; 95% CI 1.99-4.47), pelvic pain (aOR 3.51; 95% CI 1.74-7.08), menstrual disorders (aOR 4.33; 95% CI 1.68-11.1), and fibroids (aOR 2.28; 95% CI 1.72-3.03). Vaginal compared with laparoscopic approach was associated with increased odds of injury for women with menstrual disorders (aOR 7.62; 95% CI 1.37-42.5)., Conclusion: While the risk of urologic injury during hysterectomy for benign indication is low, the risk is dependent on patient disease factors and surgical approach., (Copyright © 2021. Published by Elsevier Inc.)

Background: There is inadequate high-quality evidence on thromboprophylaxis for patients undergoing surgery for abdominopelvic cancer. We surveyed physicians who treat patients with abdominopelvic cancer to determine current thromboprophylaxis practice patterns and to determine where research is needed., Methods: We created an online survey with questions on thromboprophylaxis topics, including type of thromboprophylaxis used, timing of initial thromboprophylaxis dose, use of thromboprophylaxis during chemotherapy, use of extended-duration thromboprophylaxis and areas for future research. The survey questions were reviewed by external content experts to ensure they were appropriate and relevant. Surgeons, thrombosis experts and medical oncologists who manage patients with abdominopelvic cancers at 1 large Canadian academic centre were invited to complete the survey between January and April 2019., Results: Of the 57 physicians invited, 42 (74%) completed the survey, including 27 surgeons (response rate 79%), 9 thrombosis experts (response rate 75%) and 6 medical oncologists (response rate 55%). Most surgeons (22 [82%]) reported using mechanical thromboprophylaxis, whereas only 1 thrombosis expert (11%) recommended mechanical thromboprophylaxis. There was substantial variability in the timing of the initial dose of thromboprophylaxis, with 9/10 urologists (90%) and all 7 general surgeons giving the first dose intraoperatively, and three-quarters of thoracic surgeons (3/4 [75%]), gynecologists (3/4 [75%]) and thrombosis experts (7/9 [78%]) starting thromboprophylaxis after surgery. All medical oncologists believed chemotherapy increases the risk of venous thromboembolism, but 4 (67%) reported that they do not routinely prescribe thromboprophylaxis owing to bleeding concerns. Most respondents (35/38 [92%]) felt there was a need for more research on thromboprophylaxis and indicated willingness to participate in future clinical trials., Conclusion: Variability exists in contemporary thromboprophylaxis practice patterns among physicians treating patients with abdominopelvic cancer. Future research is needed to standardize care and improve outcomes for patients., Competing Interests: Marc Carrier reports grant funding from BristolMyers Squibb, LEO Pharma and Pfizer, and consulting fees from Bayer, Bristol-Myers Squibb, LEO Pharma, Sanofi and Servier, outside the submitted work. Christopher Morash participated in an advisory board run by Sanofi, outside the submitted work. Luke Lavallée reports a quality improvement grant from Sanofi and advisory board participation for AbbVie, Bayer, Sanofi and Ferring, outside the submitted work. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Purpose: Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices., Methods: This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces., Results: Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34-35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces., Conclusion: These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials., Trial Registration: www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

Obesity has escalated worldwide and in Canada. Many chronic conditions, including type 2 diabetes, are directly correlated with obesity, and although the benefits and effectiveness of bariatric surgery have been proven in terms of sustained weight loss and improving comorbidities, the procedure is underaccessed and underutilized in Canada. We explored the complex landscape of bariatric surgery in Canada, reviewing the current state and focusing on the volume of procedures nationwide and at the provincial level, the type of surgical procedures performed, their outcomes and their associated complications. Barriers and challenges curbing access to bariatric surgery are also explored. Approximately 8,583 publicly funded bariatric surgeries were performed in 9 of 10 provinces in 2015/2016; Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding and biliopancreatic diversion with or without duodenal switch are the most common procedures performed, and coverage varies among provinces and territories. Dedicated bariatric programs have been created and, in some instances, provincial networks have also emerged. Weight loss, resolution of comorbidities and rates of complications in Canada are similar to those found in the literature. The increase in the number of bariatric procedures performed over time has still not met the current demand. The rise in obesity rates, the speed and regional variations in the development and standardization of processes, adequate patient selection, funding and prioritization and gaps in knowledge and attitudes about the merits of bariatric surgery of patients, health providers and policy makers create considerable waiting times and are some of the barriers to better access to bariatric surgery., (Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Purpose: Older age (> 60) has been considered a relative contraindication for bariatric surgery due to increased complication risk. This study examined the risks and benefits of bariatric surgery for patients older than 60 years in Canadian population., Methods: This was a retrospective cohort study of the Ontario Bariatric Registry: a database recording peri-operative and post-operative outcomes of publicly funded bariatric surgeries across the province. Patients who completed 1 year follow-up, who underwent laparoscopic gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between January 2010 and May 2013, were divided into older (> 60) and younger (> 60) cohorts, and outcomes were compared., Results: Between January 2010 and May 2013, 3166 registry patients underwent LRYGB or LSG and completed 1-year follow-up. Of these, 204 (6.5%) were older than 60 years, with 175 (85.8%) undergoing LRYGB and 29 (14.2%) LSG. Demographics were similar, except for a higher number of males in the older group (59 (28.9%) versus 452 (15.3%) (p < 0.001)). No significant difference in complication rate was noted (15% for younger cohort versus 13.8% (p = 0.889)). The average percentage of excess weight loss was significantly higher in the younger population (60.72% versus 56.25% (p < 0.05)) overall, however not significantly in the LSG group. Reduction in medication use post-surgery for management of co-morbidities was significantly higher in the older patients (- 0.91 versus - 2.03 (p < 0.001))., Conclusion: The older cohort who underwent LRYGB or LSG was at no greater risk for intra-operative and post-operative complications and showed greater reduction in medication use post-surgery when compared to the younger cohort.

Objective: To examine the feasibility and preliminary impact of a home-based obesity prevention intervention among Canadian families., Methods: Families with children 1.5-5 years of age were randomized to one of three groups: (1) four home visits (HV) with a health educator, emails, and mailed incentives (4HV; n = 17); (2) two HV, emails, and mailed incentives (2HV; n = 14); or (3) general health advice through emails (control; n = 13). Parents randomized to the 2HV and 4HV groups completed post-intervention satisfaction surveys. At baseline and post-intervention, parents reported frequency of family meals and their children's fruit, vegetable, and sugar-sweetened beverage (SSB) intake. We assessed the children's physical activity, sedentary behaviour, and sleep using accelerometers and their % fat mass using bioelectrical impedance analysis. Differences in outcomes at post-intervention, controlling for baseline, were examined using generalized estimating equations., Results: Of the 44 families enrolled, 42 (96%) had 6-month outcome data. Satisfaction with the intervention was high; 80% were "very satisfied" and 20% were "satisfied." At post-intervention, children randomized to the 4HV and 2HV groups had significantly higher fruit intake and children randomized to the 2HV group had significantly lower percentage of fat mass, as compared to the control. No significant intervention effect was found for frequency of family meals, the children's vegetable or SSB intake, physical activity, sedentary behaviour, or sleep., Conclusions: Our results suggest that the delivery of a home-based intervention is feasible among Canadian families and may lead to improved diet and weight outcomes among children. A full-scale trial is needed to test the effectiveness of this home-based intervention., Clinical Trials Registration Number: NCT02223234.

Introduction: Bariatric surgery has been shown to lead to significant improvement in glucose homeostasis, resulting in greater rates of type 2 diabetes mellitus (T2DM) remission. While there is substantial evidence of the benefits of bariatric/metabolic surgery in obese diabetic patients on oral therapy (O-T2D), more evidence is necessary in the case of insulin-treated type 2 diabetes (I-T2D) patients and the selection of surgical procedure., Methods: Analysis of the Ontario Bariatric Registry data was performed, comparing outcomes of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on insulin-treated versus non-insulin-treated T2DM patients. We compared weight loss, medication use and remission rates during a 3-year follow up., Results: A total of 3668 diabetic Bariatric Registry patients underwent surgery from Jan 2010 to Feb 2017, across 7 Bariatric Centers of Excellence in Ontario. Of these 2872 were O-T2D and 1187 were I-T2D. Weight loss was similar between the two groups at 3 years; with mean %WL of 30.1% for the insulin group vs. 28.3% non-insulin (p = 0.0673). At 3 years, 11.3% of the non-insulin and 59.6% of the insulin-dependent group were using anti-diabetic medication (p < 0.0001). Among insulin-dependent patients, RYGB showed greater reduction in insulin use with 26.5 and 40% compared to SG at 3 years. O-T2D patients experienced more complete diabetes remission, with 66.5 vs. 18.5% (p < 0.0001) at 3 years. Complete remission for I-T2D patients was higher in the RYGB group than SG (p < 0.0001) at years 1 and 2 (8.5 vs. 5.4% and 24.4 vs. 21.1%). The same trend was found regardless of insulin use; complete remission higher for RYGB at 1 and 2 years [50.7 vs. 39.8% (p < 0.0001), and 54.6 vs. 49.1% (p < 0.0001)]., Conclusion: While both RYGB and SG procedures provide effective treatment for I-T2D patients in terms of weight loss and diabetes, incidence of complete remission for insulin-dependent patients is higher with RYGB in earlier years.

Background: The Ontario Bariatric Network implemented an online referral system to completely replace a fax-based system in 2015. Strategies such as electronic information transfer have been suggested to improve the bariatric referral process but few studies exist demonstrating their efficacy. Therefore, the purpose of this study was to determine the impact on referral rates to bariatric surgery after converting to an online referral system from a fax-based system., Methods: All referrals from 2011 to 2015 were included in the study. The main outcomes included the total number of referrals and whether a practitioner increased referrals after the implementation of the online referral system. A hierarchical logistic regression model was used for the final analysis. Predictors of interest included physician and neighbourhood level factors RESULTS: Referrals more than doubled overall and increased significantly across all health regions. Compared to practitioners in their first five years, all other experience groups were approximately 50% less likely to increase referrals. Compared to those within 50 km of a bariatric facility, practitioners 50-99 km (OR 0.76 95% CI 0.58-0.98 p = 0.04) and 100-199 km (OR 0.73 95% CI 0.55-0.96 p = 0.03) away were both significantly less likely to increase referrals., Conclusion: This study found that referrals increased significantly after implementing an online referral system. Furthermore, physicians in their first five years of practice as well as those practicing closer to bariatric centers were more likely to increase referrals. Our findings demonstrate that an online referral system may aid in increasing referrals to bariatric surgery.

Background: The use of natural health products in prostate cancer (PrCa) is high despite a lack of evidence with respect to safety and efficacy. Fish-derived omega-3 fatty acids possess anti-inflammatory effects and preclinical data suggest a protective effect on PrCa incidence and progression; however, human studies have yielded conflicting results., Methods: A search of OVID MEDLINE, Pre-MEDLINE, Embase, and the Allied and Complementary Medicine Database (AMED) was completed for human interventional or observational data assessing the safety and efficacy of fish-derived omega-3 fatty acids in the incidence and progression of PrCa., Results: Of 1776 citations screened, 54 publications reporting on 44 studies were included for review and analysis: 4 reports of 3 randomized controlled trials, 1 nonrandomized clinical trial, 20 reports of 14 cohort studies, 26 reports of 23 case-control studies, and 3 case-cohort studies. The interventional studies using fish oil supplements in patients with PrCa showed no impact on prostate-specific antigen levels; however, 2 studies showed a decrease in inflammatory or other cancer markers. A small number of mild adverse events were reported and interactions with other interventions were not assessed. Cohort and case-control studies assessing the relationship between dietary fish intake and the risk of PrCa were equivocal. Cohort studies assessing the risk of PrCa mortality suggested an association between higher intake of fish and decreased risk of prostate cancer-related death., Conclusions: Current evidence is insufficient to suggest a relationship between fish-derived omega-3 fatty acid and risk of PrCa. An association between higher omega-3 intake and decreased PrCa mortality may be present but more research is needed. More intervention trials or observational studies with precisely measured exposure are needed to assess the impact of fish oil supplements and dietary fish-derived omega-3 fatty acid intake on safety, PrCa incidence, treatment, and progression.

The purpose of this study was to determine whether there has been an improvement in short- and long-term clinical outcomes since 2010, when the Ontario Bariatric Network led a province-wide initiative to establish a standardized system of care for bariatric patients. The system includes nine bariatric centers, a centralized referral system, and a research registry. Standardization of procedures has progressed yearly, including guidelines for preoperative assessment and perioperative care., Methods and Procedures: Analysis of the OBN registry data was performed by fiscal year between April 2010 and March 2015. Three-month overall postoperative complication rates and 30 day postoperative mortality were calculated. The mean percentage of weight loss at 1, 2, and 3 years postoperative, and regression of obesity-related diseases were calculated. The analysis of continuous and nominal data was performed using ANOVA, Chi-square, and McNemar's testing. A multiple logistic regression analysis was performed for factors affecting postoperative complication rate., Results: Eight thousand and forty-three patients were included in the bariatric registry between April 2010 and March 2015. Thirty-day mortality was rare (<0.075 %) and showed no significant difference between years. Three-month overall postoperative complication rates significantly decreased with standardization (p < 0.001), as did intra-operative complication rates (p < -0.001). Regression analysis demonstrated increasing standardization to be a predictor of 3 month complication rate OR of 0.59 (95 %CI 0.41-0.85, p = 0.00385). The mean percentage of weight loss at 1, 2, and 3 years postoperative showed stability at 33.2 % (9.0 SD), 34.1 % (10.1 SD), and 32.7 % (10.1 SD), respectively. Sustained regression in obesity-related comorbidities was demonstrated at 1, 2, and 3 years postoperative., Conclusion: Evidence indicates the implementation of a standardized system of bariatric care has contributed to improvements in complication rates and supported prolonged weight loss and regression of obesity-related diseases in patients undergoing bariatric surgery in Ontario.

Background: A sub-study of the Ontario Bariatric Registry was conducted to evaluate the impact of bariatric surgery on mobility, health-related quality of life (HRQoL), healthcare resource utilization (HRU), and employment status., Methods: The 1-year change in mobility following bariatric surgery was evaluated using the mobility domain of the EuroQOL-5D-5L (EQ-5D-5L), which was self-administered at baseline and 1 year after bariatric surgery along with questions on HRU. Another questionnaire was used to document employment status at time of surgery and 1 year later., Results: The population included 304 individuals (mean age = 46 years; 85 % female). At baseline, 68 % of participants had some problems in walking compared to 14 % at 1 year following surgery (p < 0.001). The EQ-5D-5L health utility score increased from 0.73 to 0.90 (p < 0.001). The number of hospitalizations increased significantly before and after surgery (p = 0.021). Of the 304 study participants, 138 completed the questionnaire and responses indicated that more individuals reported a change in their employment status within 1 year following surgery (26 %) compared to 1 year prior to the surgery (9 %) (p < 0.001)., Conclusions: Within the limitations of this study, there is a suggestion that bariatric surgery has a major impact on mobility and HRQoL. More research is warranted to understand the benefits, costs, and cost-effectiveness of bariatric surgery in Canada.

Introduction: Stereotactic ablative body radiotherapy (SABR) is currently under study regarding its clinical application in management of patients with kidney tumors. CyberKnife can accurately deliver ablative tumor radiation doses while preserving kidney function. We report Canada's first use of CyberKnife SABR system in treating primary kidney tumors., Materials and Methods: Between January 2011 and February 2012, we treated three patients with renal tumors using CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient had a recurrent tumor after two previous radiofrequency ablation treatments. Platinum seed fiducials were used for real time tumor tracking. Magnetic resonance imaging registration was used for tumor delineation in all cases. The patients were followed with regular renal scans and renal function tests., Results: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy in 3 fractions was delivered. The post treatment follow up times were 15 months, 13 months and 12 months. Local control was obtained in all three patients. No acute or chronic toxicity was reported. Kidney functions remained unaffected after treatment., Conclusion: CyberKnife is technically feasible for treatment of medically inoperable renal tumors or tumors in a solitary kidney.

Objectives: To evaluate the efficacy and toxic effects of intensive chemoradiotherapy as a primary modality for organ preservation in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and to define the patterns of treatment failure associated with this therapy., Design: Retrospective review., Setting: Tertiary care referral center., Patients: A total of 127 consecutive patients with advanced SCCHN treated with primary concurrent chemoradiotherapy., Main Outcome Measures: Efficacy data included the rates of tumor response to therapy, organ preservation, disease recurrence, overall and disease-specific survival, and patterns of treatment failure. Toxic effect data included the rate and grade of treatment-related complications and the rate of unscheduled hospital admissions for managing treatment-related toxic effects., Results: Ninety-six patients (76%) were men and 31 (24%) were women. Average age at diagnosis was 62 years (range, 37-85 years). The primary tumor site was the oropharynx in 58 patients (46%), the larynx in 36 (28%), the hypopharynx in 20 (16%), the oral cavity in 10 (8%), and another site in 3 (2%). Most patients (91%) had stage III or IV disease. Average follow-up was 36 months. Primary chemoradiotherapy achieved complete response at the primary tumor site in 109 patients (86%). Patients with partial response, stable or progressive disease, or recurrence at the primary site underwent salvage surgery. Overall, at mean follow-up of 3 years, local disease control was achieved in 113 patients (89%), and organ preservation was possible in 102 patients (80%). Two thirds of all patients (n = 83) had clinical N+ disease. Complete clinical response to chemoradiotherapy in the neck was achieved in 57 of these patients (69%). However, complete response to chemoradiotherapy was 93%, 62%, and 47% for N1, N2, and N3 disease, respectively (P <.001). Patients achieving less than complete clinical response underwent salvage neck dissection. Overall, at an average follow-up of 36 months, regional disease control was achieved in 76 (92%) of the 83 patients with neck metastasis. Despite this high locoregional control rate, distant metastasis occurred in 18 patients (14%), was the most common site of disease recurrence (53%), and accounted for almost 40% of all treatment failures. Severe (grade 3 or 4) mucositis and neutropenia occurred in 33% and 25% of patients, respectively. Two patients (2%) died of treatment-related toxic effects. At 3-year mean follow-up, disease-specific and overall survival were 72% and 57%, respectively. Most deaths were due to distant metastasis, comorbidity, and second primary tumors., Conclusions: High rates of locoregional disease control and organ preservation are achievable with primary chemoradiotherapy in patients with advanced SCCHN, but they are associated with severe treatment-related toxic effects. Despite this effective local and regional disease control, improved survival is hampered by the relatively high incidence of distant metastasis, second primary tumors, and comorbidity.

Identifying overexpressed genes in tumours is a critical step for tumour diagnosis, prognosis, and treatment. Using differential display polymerase chain reaction, sequence analysis, and gene Blast searches, we discovered that human prostaglandin F synthase (hPGFS) was upregulated in squamous cell carcinoma of the head and neck (SCCHN). Northern blot analysis indicated that up to a 16-fold increase in the level of hPGFS expression was detected in 40.5% (15 out of 37) of SCCHN primary tumours. The increased expression of hPGFS in SCCHN was primarily detected in SCC of larynx and hypopharynx (59%, P<0.05). Using the same primary tissue samples, increased levels of epidermal growth factor receptor (EGFR) expression were detected in only 32% of tumour tissues, suggesting hPGFS may have the potential to become a drug target or molecular marker for SCCHN. To determine if the increased level of hPGFS expression came from tumour cells, we determined the level of hPGFS expression in SCCHN tumour cell lines. A high level of hPGFS expression was detected in four out of five tumour SCCHN cell lines. To determine if upregulation of hPGFS is SCCHN-specific, hPGFS expression was analysed in 59 tumour cell lines derived from different types of tumours. The expression of hPGFS was increased from two- to 500-fold in a large portion of cell lines derived from lung (five out of nine), colon (five out of seven) as well as head and neck cancer (four out of five). These data link hPGFS expression to tumours located in the respiratory and digestive organs.

Purpose: Lingual thyroid has a reported incidence between 1:10 and 1:100,000. When symptomatic, patients may present with dysphagia, choking, and/or dyspnea. Current surgical treatment options range from tumor extirpation or transposition to excision and reimplantation. Tracheotomies are often performed postoperatively for reliable airway control. Iodine 131 (131I) has not been a popular modality of treatment for lingual thyroid because of theoretical fears of increased airway obstruction from thyroiditis. We believe that these fears were not substantiated, and that symptomatic patients needed a reliable, nonsurgical treatment option. Therefore, our goal was to further investigate the use of 131I for the treatment of symptomatic lingual thyroid., Patients and Methods: A 6-year retrospective chart review was performed. From 1994 to 2000, 2 patients with symptomatic lingual thyroid presented to the Arkansas Cancer Research Center Head and Neck Oncology clinic, University of Arkansas for Medical Sciences, Little Rock, AR. Patients underwent pretreatment computed tomography, and iodine 123 scans. They then received 1 oral dose of 131I. Doses ranged from 30 to 85 mCi. Patients were then followed daily for signs of airway compromise., Results: Complete resolution of symptoms was seen 2 months after treatment. Patients did not complain of any increased airway compromise during treatment initiation. Patients remain symptom-free and are maintained on thyroid hormone replacement., Conclusions: Iodine 131 ablation of lingual thyroid is a safe and effective treatment in symptomatic patients and should be included in the algorithm when formulating a treatment plan.

Accurate prediction of human tumor response to radiation therapy and concomitant chemoradiation would be an important tool to assist the physician in making recommendations for tumor treatment. Most of the studies that define the molecular markers for prediction of radiation response are based on the observation of gene expression using immunostaining, Northern blot, or Western blot analysis of a single or several genes. The results vary among different studies, and some results are contradictory. However, the studies agree that the change in expression of the tumor-related gene affects the radiation response. In this study, we explored a novel approach to predict the radiation response of human tumor using Atlas human cancer 1.2 cDNA array to analyze the expression profile of 1187 tumor-related genes in radiation-resistant and radiation-sensitive tissues. Sixty tumor-related genes were selected as predictors of radiation response of squamous cell carcinoma of the head and neck. Using the expression intensity of these 60 tumor-related genes, in combination with cluster analysis, we successfully predicted the radiation identity of two tumor samples.

Gene therapy with IL-12 has been shown to elicit potent systemic antitumor response in a variety of tumors. Although direct intratumoral injection is the most commonly used delivery route for gene therapy of solid tumors, the skeletal muscle has been shown to be an ideal tissue for gene delivery to produce systemic gene expression. We have previously demonstrated that electroporation delivery of a reporter gene to muscle enhances the transfection efficiency and the level of gene expression by two to three logs. We report here that intramuscular (i.m.) injection of as little as 10 microg of the IL-12 DNA plasmid followed by electroporation prevents squamous cell carcinoma (SCCVII) tumor establishment in up to 40% of experimental animals and reduces the volume of established tumors by 75% compared to controls (P<.05). By comparison, there was no difference in tumor growth observed between IL-12 injection alone and injection of empty vector with or without electroporation. The induction of antitumor activity by i.m. electroporation delivery of the IL-12 gene is associated with an increase in IL-12 expression in muscle and serum. The level of IL-12 expression in muscle and serum was 1500 pg/tibialias muscle and 170 pg/mL serum, respectively, at day 6, after the gene was delivered by electroporation. In contrast, the level of IL-12 when the gene was injected without electroporation was hardly detectable after subtracting the background level of IL-12 detected in naïve mice. The high level of IL-12 expression led to a 170-fold induction of IFN-gamma expression in serum at day 6 after i.m. electroporation delivery of IL-12 DNA plasmid, which was equal to 1450 pg/mL in the serum. The induction of antitumor activity by i.m. electroporation delivery of the IL-12 gene also correlates with increased CD8+ T-cell population in peripheral blood but not in spleen. Our findings suggest that i.m. delivery of IL-12 gene using electroporation is an effective method of inducing a systemic antitumor response against SCC.

Although electroporation has been shown in recent years to be a powerful method for delivering genes to muscle, no gene therapy via electro-injection has been studied for the treatment of tumors. In an immunocompetent tumor-bearing murine model, we have found that delivery of a low dose of reporter gene DNA (10 microg) to muscle via electroporation under specific pulse conditions (two 25-ms pulses of 375 V/cm) increased the level of gene expression by two logs of magnitude. Moreover, administration of 10 microg of interferon (IFN)-alpha DNA plasmid using these parameters once a week for 3 weeks increased the survival time and reduced squamous cell carcinoma (SCC) growth at a distant site in the C3H/HeJ-immunocompetent mouse. IFN-alpha gene therapy delivered to muscle using electroporation demonstrated statistically significant (P < 0.05) therapeutic efficacy for treating SCC located at a distant site, compared with interleukin (IL)-2 or endostatin gene, also delivered by electro-injection. The increased therapeutic efficacy was associated with a high level and extended duration of IFN-alpha expression in muscle and serum. We also discovered that the high level of IFN-alpha expression correlated with increased expression levels of the antiangiogenic genes IP-10 and Mig in local tumor tissue, which may have led to the reduction of blood vessels observed at the local tumor site. Delivery of increasing doses (10-100 microg) of IFN-alpha plasmid DNA by injection alone did not increase antitumor activity, whereas electroporation delivery of increasing doses (10-40 microg) of IFN-alpha plasmid DNA did increase the survival time. Our data clearly demonstrate the potential utility of electroporation for delivery of gene therapy to muscle for the treatment of residual or disseminated tumors.

Metabolic activation, DNA adducts, and H-ras mutations were examined in human laryngeal tissue (n = 16) from both smoker and non/ex-smoker patients with laryngeal cancer. DNA adducts detected by 32P-postlabelling were evident only in smokers (n = 13); in fact, smoking cessation for as little as 10 months resulted in no DNA adducts detected (n = 3). Total DNA adduct levels in these samples were significantly correlated with levels of cytochromes P-4502C and 1A1 in laryngeal microsomes. Moreover, the P-4501A1 levels represent the highest yet found in human tissues. In contrast, laryngeal microsomes did not have detectable P-4501A2 activity, while laryngeal cytosols showed appreciable N-acetyltransferase activity for p-aminobenzoic acid (NAT1) but not sulfamethazine (NAT2). DNA was extracted from laryngeal specimens and amplified by PCR. Nylon filter dot or slot blots were hybridized with 32P-labelled probes for codons 12, 13, and 61 of the H-ras gene. Sixty percent of specimens demonstrated mutations in either codon 12, 13, or 61; a single common and specific mutation was a Gln-->Glu transversion in codon 61. This mutation appeared in 5 laryngeal specimens, all from smokers. These results implicate cigarette smoke components, bioactivated by CYP1A1 and/or CYP2C, in DNA adduct formation. These results also demonstrate a probable smoking-related H-ras Gln-->Glu transversion in codon 61.