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Background The COVID-19 pandemic has seen major shifts in the delivery of health care across the world, including adoption of telemedicine. We present a survey of patient experience with telemedicine for the treatment of breast cancer. Methods A questionnaire designed to assess patient satisfaction with telemedicine was distributed to all patients who underwent surgery at the Providence Breast Centre (PBC) for breast cancer or benign/high-risk lesions with surgery follow-up dates between October 13 and December 31, 2020. Surveys were conducted via phone or at in-person follow-ups. Results A total of 123 of 172 (72%) eligible patients completed the survey; 85% of these patients enjoyed their telemedicine consultation, 93% found there was enough time for dialogue, 66% would choose to have a telemedicine consultation again, 79% would recommend telemedicine at PBC to a friend or family member, and 92% found Zoom© easy to use. When asked whether they prefer a telemedicine initial consultation over an in-person, 28% of patients agreed. When patients are analyzed according to their home address, those more than 10-km away from PBC prefer telemedicine over in-person appointments (37%) more often than those who live less than 10-km away (23%) (p = 0.045). Conclusions Patients report a high level of satisfaction with telemedicine. It may be worthwhile to continue telemedicine beyond the pandemic era, due to its convenience, efficiency, and low-cost while keeping patients, physicians, and office staff safe. It also may be more useful in large geographic areas, such as British Columbia to increase access to care.

We investigated the impact of new systemic therapies approved in Canada for colorectal cancer on the frequency, intensity and duration of oncology clinic and infusion visits over five treatment phases from diagnosis (P1, P3) to treatment (P2, P4) of primary and metastatic disease, respectively, and during the last 6 months of life (P5). In total, 15,157 adult patients with newly diagnosed colorectal cancer and referred between 2000 and 2012 to any cancer clinic in British Columbia, Canada, were included. Frequency, intensity and duration of medical oncology clinic visits (CVs), oncology infusions (OIs) and oncology prescriptions (OPs) were measured by treatment phase. Mean, total and adjusted total duration for CVs increased for P1-5. CVs increased in P1-5, and in P1-4 when adjusted by treatment length. Adjusted and unadjusted OIs decreased in P1 coinciding with the introduction of an oral treatment option, but increased in P2-5. Mean OI duration increased in P1-5, while total and adjusted total decreased in P1 and increased in P2-5. OPs increased in P2-4, but were unchanged in P1 and P5. Multi-fold increases in resources and time required per patient were also observed, which have significant implications for demand projections in cancer care planning and delivery. In conclusion, patients required more visits in almost all treatment phases, visits on average took longer and patients were in treatment for longer periods of time.

Summary General surgery remains a broad and unclearly defined specialty in small and medium-sized communities, where general surgeons perform more subspecialty and non-core procedures than their urban counterparts. It is unclear what specific procedures are being performed or whether today’s residents are being trained to meet community needs. We surveyed the members of the British Columbia (BC) Surgical Society and found that only 3% of BC’s surgeons believe today’s graduates are “definitely prepared” for a broad-based community practice. We also identified several non-core procedures performed more frequently by general surgeons in small and medium-sized communities. General surgery residency is narrowing its focus despite the fact that community general surgeons are maintaining a broad-based practice. To meet the needs of smaller communities, residency programs need to address the discrepancies that exist between the emphasis within the current training structure and the practice of our community surgeons.

Introduction: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established. Methods: We conducted a three arm, single blind, randomised, controlled, multi-site trial comparing accelerated bilateral TBS applied at 80 % or 120 % of the resting motor threshold and left unilateral 10 Hz rTMS. 300 patients with treatment-resistant depression (TRD) were recruited. TBS arms applied 20 bilateral prefrontal TBS sessions over 10 days, while the rTMS arm applied 20 daily sessions of 10 Hz rTMS to the left prefrontal cortex over 4 weeks. Primary outcome was depression treatment response at week 4. Results: The overall treatment response rate was 43.7 % and the remission rate was 28.2 %. There were no significant differences for response (p = 0.180) or remission (p = 0.316) across the three groups. Response rates between accelerated bilateral TBS applied at sub- and supra-threshold intensities were not significantly different (p = 0.319). Linear mixed model analysis showed a significant effect of time (p

Conflicting data persists for use of wound protectors in pancreatoduodenectomy (PD) to prevent surgical site infection (SSI). We aimed to examine, at a multi-institutional level, the effect of wound protectors on superficial or deep SSI following elective open PD.The American College of Surgeons National Surgical Quality Improvement Program pancreatectomy procedure targeted participant use file was queried from 2016 to 2018. Planned open PD procedures were extracted. Univariable, multivariable, and propensity score matched analyses were conducted.11,562 patients undergoing PD were evaluated, 27% of which used wound protectors. Wound protectors decreased superficial or deep SSI risk in all patients (5.7% vs. 9.5%, P 0.001), patients who have (6.6% vs. 12.2%, P 0.001) and who did not have (4.6% vs. 6.5%, P = 0.011) a biliary stent. Propensity score matched analysis confirms such results (OR = 0.56, 95% CI: 0.46-0.69, P 0.001 overall, OR = 0.66, 95% CI: 0.46-0.95, P = 0.03 without biliary stent, OR = 0.57, 95% CI: 0.44-0.73, P 0.001 with biliary stent).Wound protectors reduce risk of superficial or deep SSI in patients undergoing PD, yet only a quarter of PD were associated with their use. This protective effect is seen whether patients have or have not had preoperative biliary stenting.

Background We assessed the cancer upstage rate of Radial Scars (RS), and Complex Sclerosing Lesions (CSL), and risk-stratified lesions based on radiological and pathological features. Methods Characteristics of RS/CSL treated from 2013 to 2018 were examined for features associated with cancer. Results 78 RS/CSL were found on core needle biopsy (CNB) and surgically excised. 9 (11.5%) lesions were upstaged. Upstaged patients were older (66 vs 51, p = 0.033). More upstaged lesions were accompanied by a mass on both mammography (87.5% vs. 30.0%, p = 0.005) and ultrasound (100.0% vs. 62.8%, p = 0.043). 20.5% of lesions biopsied under ultrasound guidance with small needles (14-18G) were upstaged, but no lesions biopsied under stereotactic guidance with large needles (9–12 G) with vacuum assistance were upstaged (p = 0.009). Conclusions Excision of RS/CSL seen on CNB is warranted, especially if the patient is older, the CNB is performed under ultrasound guidance with small needles, or if a mass is present on imaging.

Surgical decisions for ductal carcinoma in situ (DCIS) are based on lesion sizes. This study aims to determine the accuracy of pre-operative imaging in estimating the size of DCIS.This was a retrospective review of clinicopathologic data of patients treated for DCIS with breast conserving surgery (BCS) between 2012 and 2018. Mammographic and sonographic lesion sizes were compared with final pathology sizes.For the 152 lesions visible on mammography, mean size on imaging was significantly smaller when compared to final pathology (2.3 vs. 3.6 cm, p 0.001). The mean difference of 1.3 cm was a significant underestimation with a correlation coefficient of 0.367 (p 0.001). For 48 sonographically visible lesions, the radiologic size was significantly smaller than pathologic size (1.7 vs. 4.1 cm, p 0.001), but the degree of underestimation was not significantly correlated (p = 0.379).DCIS size was significantly underestimated by imaging. This must be taken into consideration during surgical planning.

Pancreatic cystic neoplasms (PCNs) are being incidentally detected at an increased rate due to increased CT and MRI usage. EUS is an emerging tool that can differentiate between benign and malignant features of pancreatic cysts. We hoped to identify the specific cross-sectional imaging findings and patient characteristics that warrant EUS referral.We conducted a retrospective case-control chart review, evaluating patients, who were diagnosed with pancreatic cysts and underwent EUS between January 1, 2010 and December 31, 2017.EUS was found to change management when CT imaging found cyst size4 cm (OR = 4.07, p 0.01), cyst size 3 cm (OR = 3.79, p 0.001) and associated solid component to the cyst (OR = 5.95, p 0.01). Additionally, patient characteristics, including age less than 50 years, male sex and 10-pack year smoking history were significantly associated with EUS change in management.Our findings suggest that EUS referral should be coordinated based on the findings of specific HRFs, with support from high risk patient characteristics, rather than the accumulation of multiple HRFs, as suggested by existing guidelines.

Background : Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression but a standard course can be time-consuming. Of all rTMS protocols, high-frequency rTMS (HF rTMS) is the most studied and applied in clinical settings. Little is known about applying multiple sessions of HF rTMS per day, in so-called accelerated schedules. Methods : We systematically searched electronic records up to September 2019 for studies that applied HF rTMS in accelerated schedules to treat depression to review its efficacy, efficiency and safety. Treatment effect sizes of accelerated rTMS versus standard and sham rTMS were calculated from comparison studies and pooled to derive overall treatment effect. Results : Of 1,361 records screened, 12 met review criteria. Qualitative synthesis suggested accelerated HF rTMS was equally effective as once-daily scheduling in treating depression. It is equivocal if accelerated HF rTMS results in more rapid antidepressant response. Accelerated HF rTMS was well-tolerated. The small number of studies suitable for quantitative analysis led to pooled effect sizes that did not reach statistical significance. Limitations : There was an overall paucity of studies examining the accelerated application of HF rTMS and even fewer studies comparing accelerated HF rTMS with once-daily or sham rTMS. Conclusion : Our review found comparable antidepressant efficacy between accelerated and once-daily HF rTMS. Between group differences in therapeutic effect sizes were not clinically meaningful. More studies investigating accelerated rTMS protocols are needed to validate its utility and guide clinical decision making.

Objective: To examine psychological distress in healthcare workers (HCWs) during the COVID-19 pandemic in April–May 2020. Methods: A cross-sectional survey examining demographic, employment and mental health characteristics of HCWs in a large metropolitan hospital in Australia. Results: HCWs showed significant symptoms of moderate-severe level depression (21%), anxiety (20%) and posttraumatic stress disorder (PTSD; 29%), associated with burnout, prior psychiatric history, profession and resilience. Conclusion: Despite low levels of COVID contact, moderate to high levels of psychological distress were reported. Continued monitoring and support for HCWs’ mental well-being is warranted as the COVID-19 pandemic develops.

Guidelines recommend surgical excision of atypical ductal hyperplasia (ADH) due to the concern of undersampling a potential malignancy on core needle biopsy (CNB). The purpose of this study was to determine clinical, radiological and pathological variables associated with ADH upstaging to cancer and to develop a predictive risk calculator capable of identifying women who have a low oncological risk of upstaging. A prospectively collected database from a tertiary breast referral center was analyzed for women diagnosed with ADH on CNB between January 2013 to December 2017 who underwent surgical excision. CNB and surgical pathology reports were examined to determine rate of upstaging. The association between clinical, radiological and pathological variables were evaluated using regression analysis to determine predictors of ADH upstaging to cancer. Significant variables (p ≤ 0.05) identified on univariate analysis were assigned a score of “1” and were included in the ADH upstaging risk calculator. A total of 1986 patients underwent surgery for a high-risk lesion. We identified 318 (16.0%) patients who had ADH identified on their CNB who underwent surgery—of which 290 were included in our study. The upstage rate was 24.8%. Five variables were associated with upstaging and included in our calculator: (1) lesion > 5 mm on ultrasound; (2) lesion > 5 mm on mammogram; (3) one or more “high-risk” lesion(s) on CNB; (4) pathological suspicion for cancer and; (5) incomplete removal of calcifications on CNB. Patients with a score of 0 had a 2% risk of being upstaged to cancer and were deemed low risk with 17.2% of patients falling within this category. Patients with ADH on CNB can be stratified into a low oncological cohort who have a 2% risk of being upstaged to carcinoma. In the future, these select patients may be counselled and potentially offered observation as an alternative to surgery.

Introduction Wide excision margins are traditionally recommended for phyllodes tumours of the breast to reduce recurrence. Recent studies suggest margin status and histopathological features, excluding margin width, influence recurrence. This study evaluated treatment outcomes for phyllodes tumours and examined predictors of recurrence. Methods Clinical and follow-up information for phyllodes tumours patients treated between 2008 and 2017 were obtained from chart review. Tumour subtype and histopathological features were determined from pathology reports. Primary endpoints were recurrence rate and time to recurrence or mortality. Results Among 96 patients, there were 6 local and 1 distant recurrences. Overall recurrence rate was 7.3% and average time-to-recurrence was 13.7 months. Tumour size, margin status, necrosis, and mitoses were associated with recurrence; margin width was not. Two deaths (2.1%) from malignant phyllodes occurred. Conclusions Multiple histopathological features influence phyllodes recurrence. Wide excision and re-excising positive margins for benign tumours was not beneficial.

The diagnosis of acute appendicitis (AA) in pregnancy remains challenging. We investigated which preoperative clinical factors are most predictive of AA in pregnant women.164 pregnant patients undergoing magnetic resonance imaging for suspected AA were retrospectively reviewed. Logistic regression was used to compare those with pathologically confirmed AA and those without.28 patients (17.1%) had pathologically confirmed AA. 42.9% (n = 12) were perforated at the time of operation. Factors associated with AA included history of emesis (p = 0.005), migratory abdominal pain (p = 0.006), rebound tenderness (p = 0.01), elevated white blood cell count (p = 0.003), elevated Alvarado Score (p 0.001), elevated neutrophil count (p = 0.021), and left shift (p = 0.001). As a screening test, a left shift with neutrophils70% provided a sensitivity and negative predictive value of 100.0%.Every patient in our series with AA had a left shift. Neutrophil count and percentage should be considered in the diagnostic evaluation of these patients to better guide resource utilization and treatment.

Immediate breast reconstruction (IBR) following mastectomy remains controversial for locally advanced breast cancer over concerns regarding recurrence and complications which may delay adjuvant therapies. This study aimed to compare the oncologic outcomes and surgical safety of IBR following mastectomy with mastectomy alone (MA) for locally advanced breast cancer. All patients treated at the Providence Breast Center between 2012 and 2017 for biopsy-proven locally advanced breast cancer, AJCC (8th edition) clinical stages (IIB–IIIC), were included. Primary outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Secondary outcomes included recurrence rate, adjuvant therapy use, and reoperation. 267 patients (112 IBR, 155 MA) were included. On average, IBR patients were younger (48.82 years vs 61.42 years, P

Background Enhanced recovery pathways aim to reduce postoperative opioid use and opioid-related complications. These pathways often include epidural analgesia (EA). This study examines postoperative opioid use after elective laparotomy with and without EA. Methods Retrospective chart review of elective laparotomies performed by General Surgery at a tertiary academic center during 2017 was completed. Primary outcome was postoperative opioid usage. Secondary outcomes were time to mobilization, duration of urinary catheterization and postoperative ileus. Results Among 236 patients, 213 (90%) received EA. There was no significant difference in mean total oral morphine equivalent (OME) usage between EA and non-EA groups. Mean OME use on postoperative day three was higher in the EA group (38.0 vs 22.4 mg, p = 0.02). On multivariate analysis, preoperative opioid use was associated with increased postoperative OME consumption (regression coefficient 147.5, p Conclusions In this cohort, epidural analgesia did not reduce postoperative opioid consumption.

Contralateral prophylactic mastectomy (CPM) is not recommended for average-risk women with breast cancer due to lack of evidence for survival benefit, yet recent studies demonstrate increasing CPM rates.We identified patients with breast cancer treated with unilateral mastectomy (UM) with or without CPM. Rates of malignancy in CPM specimens and factors in CPM rates were assessed.From 2013 to 2017, 1353 patients had UM and 355 had CPM. Our institution's occult malignancy detection rate was 5.04%. CPM rates decreased from 31.6% to 17.3% (p 0.001) over 5 years. Compared to patients receiving UM only, patients receiving CPMs had significantly higher reconstruction rates (p 0.001), which did not significantly change over time (p = 0.551) and tended to be younger (p 0.001).Patients having UM have low risk of contralateral malignancy. CPM is associated with younger age and breast reconstruction, suggesting factors to identify for patient and provider education.

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada’s single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

Cell-cell interactions influence all aspects of development, homeostasis, and disease. In cancer, interactions between cancer cells and stromal cells play a major role in nearly every step of carcinogenesis. Thus, the ability to record cell-cell interactions would facilitate mechanistic delineation of the role of cancer microenvironment. Here, we describe GFP-based Touching Nexus (G-baToN) which relies upon nanobody-directed fluorescent protein transfer to enable sensitive and specific labeling of cells after cell-cell interactions. G-baToN is a generalizable system that enables physical contact-based labeling between various cell types, including diverse cancer-stromal cell pairs. A suite of orthogonal baToN tools enables reciprocal cell-cell labeling, interaction-dependent cargo transfer, and the identification of higher-order cell-cell interactions across a wide range of cell types. The ability to track physically interacting cells with these simple and sensitive systems will greatly accelerate our understanding of the outputs of cell-cell interactions in cancer as well as across many biological processes.

The aim of this study was to evaluate whether elderly patients undergoing elective hepatectomy experience increased morbidity/mortality and whether these outcomes could be mitigated by minimally invasive hepatectomy (MIH). 15,612 patients from 2014 to 2017 were identified in the Hepatectomy Targeted Procedure Participant Use File of the American College of Surgeons National Surgical Quality Improvement Program. Multivariable logistic regression models were constructed to examine the effect of elderly status (age ≥ 75 years, N = 1769) on outcomes with a subgroup analysis of elderly only patients by open (OH) versus MIH (robotic, laparoscopic, and hybrid, N = 4044). Propensity score matching was conducted comparing the effect of MIH to OH in elderly patients to ensure that results are not the artifact of imbalance in baseline characteristics. Overall, elderly patients had increased risk for 30-day mortality, major morbidity, prolonged length of hospital stay, and discharge to destination other than home. In the elderly subgroup, MIH was associated with decreased major morbidity (OR 0.71, P = 0.031), invasive intervention (OR 0.61, P = 0.032), liver failure (OR 0.15, P = 0.011), bleeding (OR 0.46, P

Introduction: Major depression is a common and debilitating mental disorder that can be difficult to treat. Substantive evidence over the past two decades has established repetitive transcranial magnetic stimulation (rTMS) as an effective antidepressant therapy, although scope exists to improve its efficacy and efficiency. Theta burst stimulation (TBS) is a novel rTMS pattern attracting much research interest as a tool to study neurophysiology and treat neuropsychiatric disorders. Areas covered: This article outlines rTMS' state of development and explores the physiology studies underpinning TBS development and its observable neuronal conditioning and metabolic effects. We present a systematic review of studies that applied TBS to treat depression, followed by commentary on safety and practical considerations. Expert opinion: Much experimental and clinical research have advanced our understanding of the antidepressant effects of TBS, although unanswered questions remain relating to its physiological effects, response variability and optimal parameters for therapeutic purposes. A small number of sham-controlled trials, and one large comparative trial, support the therapeutic efficacy of TBS and demonstrates its non-inferiority relative to traditional rTMS. In this light, TBS can reasonably be offered as an alternative to rTMS in treatment-resistant depression, while ongoing research is likely to inform its therapeutic potential.

Introduction Accelerated or intensive forms of repetitive transcranial magnetic stimulation (rTMS) are increasingly being explored for their potential to produce more efficient and rapid treatment benefits in major depressive disorder (MDD). However, accelerated or intensive protocols using standard forms of rTMS are still quite time-consuming to apply. Theta burst stimulation (TBS) is a novel form of magnetic stimulation with the potential to produce similar anti-depressant effects but in a much abbreviated period of time. The aim of this study was to investigate the comparative efficacy of an intensive TBS protocol compared to standard rTMS treatment. Methods 74 outpatients (36 female, mean age 44.36 ± 12.1 years) with MDD received either intensive TBS (3 intermittent TBS treatments per day for 3 days in week 1, 3 treatments a day for 2 days in week 2, and 3 treatments in 1 day in week 3 and in week 4, or standard rTMS (5 daily sessions per week for 4 weeks). Patients were assessed weekly throughout the treatment course, and at 4 weeks after treatment end. Results There were no significant differences in the degree of reduction in depressive symptoms, the rate of reduction in depressive symptoms, remission or response rates (response rates = 27.8% for intensive group, 26.3% for the standard group, p > 0.05 for all analyses) between the intensive TBS and standard rTMS treatment groups. However, the overall response and remission rates were limited in both groups. There was no difference in rates of side effects, no serious adverse events and no alterations in cognitive performance. Conclusion Intensively applied TBS appears to have similar efficacy to standard rTMS when these were applied as delivered in this study but does not produce more rapid clinical benefits. The overall response rates in both groups in this study were limited, most likely by the total doses provided in both study arms. Clinical trials registration Australian New Zealand Clinical Trials Registry: ACTRN12616000443493.

Background: Theta Burst stimulation (TBS) is a promising alternative to standard repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD). TBS treatment is delivered over a much shorter time than rTMS, enabling more patients to be treated with the same resources. The aim of this preliminary study was to explore the efficacy of an intensive bilateral TBS protocol (BL TBS) compared to a standard rTMS protocol. Methods: Thirty-two outpatients with TRD were randomized to a standard rTMS protocol and 34 outpatients were randomized to a TBS protocol. Treatment was delivered over two week or four weeks. Both treatment groups received twenty treatments in total. Patients were assessed at baseline, week 1, week 2 and week 4. Results: There were no major differences in baseline depression severity between the randomized treatment groups. There was no significant difference in response and remission rates between the two groups. In the standard rTMS group, 40.6% met criteria for response and 25% met criteria for remission. These rates were 20.6% and 25.5% respectively for the TBS group. There was a significant reduction in mean depression scores for both treatment groups (p

Background To determine if an accelerated rTMS protocol results in distinct depressive symptom response trajectories, compared to a standard rTMS protocol. We also sought to validate previous analyses that identified distinct depressive symptom response trajectories with rTMS treatment using an external dataset. Method Data from two recent clinical trials comparing accelerated rTMS protocol delivered to the left dorsolateral prefrontal cortex (DLPFC) with standard once-daily rTMS protocol were used to identify depressive symptom response trajectories. The accelerated protocol in Trial 1 was conventional 10-Hz rTMS, while Trial 2 employed intermittent theta burst stimulation (iTBS). Participants were adult outpatients (18–70 years old) with bipolar or unipolar depression and moderate-severe depression (Montgomery Asberg Depression Rating Scale score >19) who had failed to respond to adequate courses of two different antidepressants. We used group-based trajectory modeling to identify MADRS response trajectories, and regression techniques adjusting for baseline depressive symptom severity to determine the association between treatment protocol and depressive symptom response trajectory. Results Treatment outcomes of 189 participants were analysed. We identified four distinct response trajectories: “nonresponse” (N = 59; 30.7%), “minimal response” (N = 65; 34.1%), “higher symptoms, response” (N = 26; 14.6%), “lower symptoms, response” (N = 39; 20.6%). We failed to find an association between rTMS protocol (accelerated vs standard) with depressive symptom response trajectory even after adjusting for baseline depressive symptom severity. Conclusion The accelerated rTMS protocol in this study did not impact depressive symptom response trajectories. This work provides further confirmatory evidence that there are distinct depressive symptom response trajectories with rTMS delivered to the left DLPFC. Australian new zealand clinical trials registry ACTRN12616000443493 and ACTRN12613000044729.

BACKGROUND Anxiety symptoms are common in major depressive disorder. Whilst therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is well-established, minimal research has investigated rTMS's efficacy in treating anxiety symptoms in depression. METHODS This study investigates the effectiveness of rTMS in treating anxiety symptoms in depression, specifically the relative efficacy of the three rTMS protocols commonly used in clinical practice: left-sided high-frequency, right-sided low-frequency and sequential bilateral rTMS. Antidepressant efficacy of each rTMS protocol is also investigated. Treatment data for 697 patients were pooled from three studies across five sites. Changes in Beck's Anxiety Inventory (BAI) and the Hamilton Depression Rating Scale over 4-week rTMS courses were analysed using latent growth curve modelling. RESULTS All rTMS protocols were effective in treating anxiety symptoms (mean BAI reduction, 8.13 points; p

Bevacizumab may potentiate the risk of venous thromboembolisms (VTEs) in cancer patients, who are already predisposed to pro-thrombotic states. We aimed to characterize the incidence of VTEs in a population-based cohort of metastatic colorectal cancer (mCRC) patients treated with bevacizumab, describe patient and treatment factors associated with VTEs, and examine how VTEs are managed. Patients diagnosed with mCRC from 2006 to 2009 and offered bevacizumab were included. Descriptive statistics were used to describe VTE occurrences and management. Univariate and multivariate regression models were constructed to explore associations between clinical factors and VTEs. We identified 541 mCRC patients: 27 never started bevacizumab and 15 were lost to follow-up. Of the 499 evaluable patients, median age was 61, 59.3 % were men, 88.1 % had ECOG 0/1, and 5.2 % reported previous VTEs. Mean number of bevacizumab doses was 13.3 cycles. After receiving bevacizumab, 81 patients developed 93 cases of VTEs, with 9 patients experiencing >1 event. Individuals who experienced VTEs were more likely to have had pre-existing cardiovascular disease (OR 2.259, p = 0.0245), resection of primary cancer (OR 3.262, p = 0.0269), pre-chemotherapy platelet count ≥350,000/μL (OR 2.295, p = 0.0293), and received >12 bevacizumab cycles (OR 2.172, p = 0.0158). Use of bevacizumab varied after occurrence of VTE where it was discontinued in 34.4 %, continued in 34.4 %, and temporarily held in 1.1 %. VTE risk can be high, especially in patients with specific pre-treatment risk factors as well as in those who received more bevacizumab, suggesting a potential dose-related effect. Management of bevacizumab-related VTEs was variable.

Previously, we reported the synthesis and structure–activity relationship (SAR) study of a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium salts, which had very potent anti-proliferative activities (low μM to nM GI50) against a broad range of cancer cells. These compounds, which can be viewed as cationic anthraquinone analogs (CAAs), are selective against cancer cells over bacteria or fungi as compared to the antibacterial CAAs that have also been reported by our group. Herein, we report a mode of action study of CAAs, which reveals that these compounds trigger apoptosis by generating extensive reactive oxygen species (ROS). The generation of extensive ROS causes oxidative stress, decrease in mitochondrial membrane potential, depletion of glutathione (GSH), and release of caspase-3, which ultimately kills cancer cells by programmed apoptosis. Furthermore, we have also shown that CAAs possess an 8-fold higher activity against the A549 cell line vs. the non-cancerous MRC-5 cell line.

BACKGROUND Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment. METHODS Thirty-seven patients completed a course of at least nine ECT or MST treatments in a randomized double-blind protocol. Assessments of depression severity and cognition were performed before and after treatment. RESULTS No difference in the antidepressant effectiveness between the treatments was seen across any of the clinical outcome measures, although the overall response rates in both groups were quite low. In regards to cognition, following MST there were significant improvements in tests of psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in cognitive performance. Following ECT there was significant improvement in only one of the cognitive inhibition tasks. With respect to the between-group comparisons, the MST group showed a significantly greater improvement on psychomotor speed than ECT. CONCLUSIONS MST showed similar efficacy to right unilateral ECT in patients with treatment-resistant depression without cognitive side effects but in a sample that was only of sufficient size to demonstrate relatively large differences in response between the two groups. Future research should aim to optimize the methods of MST administration and compare its efficacy to ECT in large randomized controlled trials.

641 Background: Pancreatic cystic neoplasms (PCNs) are being incidentally detected at an increased rate due to the widespread use of CT and MRI. CT and MRI cannot always differentiate between malignant and benign PCNs. EUS is an emerging tool that provides higher quality descriptions of pancreatic cysts and can be used to differentiate between benign and malignant features. Considering that EUS is a resource dependent tool, we hope to identify the PCN cases in which EUS changes management. Methods: We conducted a retrospective case-control chart review evaluating patients, who were diagnosed with pancreatic cysts and underwent EUS for analysis between January 1, 2010 and December 31, 2017. We determined whether EUS correctly identified high-risk features (HRFs) relative to CT/MRI and whether EUS upstaged or downstaged the CT/MRI diagnosis to change overall patient management. Results: EUS was found to have a high specificity (> 95%) for all high-risk features identified in the AGA and FG guidelines and a low sensitivity ( < 70%) for all high risk features except cyst size > 3cm (82.35%) and mural nodule < 5mm (100%). EUS was found to change management in 29.4% of cases (18.2% upstaged, 11.2% downstaged). EUS screening led to a total of three adenocarcinoma diagnoses, in which two were reported to be invasive. Conclusions: The high specificity of EUS supports its use in the differentiation of high risk PCNs identified on cross-sectional imaging. Its low sensitivity indicates that the reliance on operator experience may be a substantial limitation resulting in inconclusive diagnoses. In conclusion, considering that EUS is successful in changing patient management of PCNs, it should be readily referred when any HRF is identified on cross-sectional imaging.

1546 Background: The US CDC and public health agencies have reported alarming increases in e-cigarette (ecig) use among youth, even as cigarette (cig) use among youth decline. In this study, other risk factors for cig and ecig use are compared. Methods: This study used data from the Health Information National Trends Survey 5 Cycle 1 survey, conducted in 2017. Univariate survey-weighted logistic regression analyzed responses as a nationally representative US population. Results: Inverted trends included being 35 or older (cig: OR=1.22, p

Screening and early diagnosis are the key factors for the reduction of mortality rate and treatment cost of cancer. Therefore, sensitive and selective methods that can reveal the low abundance of cancer biomarkers in a biological sample are always desired. Here, we report the development of a novel electrochemical biosensor for early detection of breast cancer by using bioconjugated self-assembled pH-responsive polymeric micelles. The micelles were loaded with ferrocene molecules as "tracers" to specifically target cell surface-associated epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed, and the resulting sensor was capable of detecting the presence of MUC1 in a sample containing about 10 cells/mL. Such a high sensitivity was achieved by maximizing the loading capacity of ferrocene inside the polymeric micelles. Every single event of binding between the antibody and antigen was represented by the signal of hundreds of thousands of ferrocene molecules that were released from the polymeric micelles. This resulted in a significant increase in the intensity of the ferrocene signal detected by cyclic voltammetry.

LBA3579 Background: Few studies have directly compared health care utilization, costs, and outcomes between geographically similar patients (pts) treated in the U.S.’ multi-payer health system versus Canada’s single-payer system. Using cancer registry and claims data, we assessed systemic therapy (ST) use, cost, and survival for metastatic colorectal cancer (mCRC) pts in Western Washington (WW) and British Columbia (BC). Methods: Pts age ≥ 18 diagnosed with mCRC in 2010 and later were identified from 1) the BC Cancer Agency database and 2) a regional database linking WW SEER to claims from two large commercial insurers. Demographic and treatment characteristics for the two populations were compared using two-sample T tests. ST costs (first-line and lifetime) were expressed as mean per patient per month costs; Canadian costs were expressed in US dollars using the Purchasing Power Parity for Health in 2009. Median survival was reported for both populations. Results: 1622 BC pts and 575 WW pts were included in the analysis. BC pts were more likely to be older (median age 60 vs 66) and male (57% vs 48%, p = < 0.01). A greater proportion of WW versus BC pts received ST (79% vs. 68%, p < 0.01). FOLFIRI plus bevacizumab was the most common first-line regimen in BC (32%) while FOLFOX was the most common first-line regimen in WW (39%). The mean monthly cost of first-line therapy per patient was significantly higher in WW than BC ($12,345 vs $6,195, p = < 0.01), and this was true for all regimens assessed. Mean lifetime monthly ST costs were significantly higher in WW ($7,883 vs $4,830, p = < 0.01). There was no difference in median overall survival between populations among those receiving ST (21.4 months (95% CI 18.0-26.2) in WW and 22.1 months (20.5-23.7) in BC) or among those not receiving ST (5.4 months (2.4-7.7) WW versus 6.3 months (5.2-7.3) BC). Conclusions: Utilization and cost of ST for mCRC was significantly higher for patients in WW compared to BC without differences in overall survival in treated and untreated patients.

10086Background: Patients today have unprecedented access to health and medical information (HMI) from a diverse range of sources. This access helps inform patients, but it may also misinform and a...

Background Metastatic resection (MR) of liver-limited disease is an effective therapy for selected patients with metastatic colorectal cancer (mCRC). Despite limited data, this approach has been expanded to include MR of other sites, such as the lung, locoregional, and other distant disease (ODD). We performed a population-based study of patients with mCRC who had undergone MR and compared survival between MR of the liver and MR of other sites. Methods Patients with mCRC who were referred to the British Columbia Cancer Agency between 1995 and 2010 were reviewed. Patients were included if they had an R0 MR with a negative margin and no residual disease. The site of MR was classified according to collaborative staging criteria as liver, lung, locoregional, or ODD. Median overall survival (mOS) was assessed with Kaplan–Meier methods and compared using the log-rank test. A Cox proportional-hazards model was used to compare mOS, while adjusting for known prognostic factors. Results A total of 2082 patients with mCRC were identified, of whom 257 underwent R0 MR. Sites of MR included liver (65%), lung (16%), locoregional (5%), and ODD (14%). The mOS of liver, lung, locoregional, and ODD were 48.0, 42.8, 37.2, and 26.2 months, respectively ( P = .087). On multivariate analysis, only MR of ODD had a significantly different survival estimate than MR of the liver (hazard ratio, 1.78; 95% confidence interval, 1.13-2.80; P = .012). Conclusions Patients with limited lung and locoregional disease seem to have a comparable survival advantage from MR as patients with liver-limited metastases.

There has been a sharp reduction in complications associated with tibial pilon fractures with the introduction of the two-step approach to treatment. However, there has yet to be any real reevaluation of the standard anterior approach used to expose and reduce these fractures. Now, with the ability to obtain computed tomographic (CT) scans after initial reduction, the fracture pattern of the tibia can be seen more clearly, suggesting that perhaps other surgical approaches may be better suited to visualize, reduce, and stabilize these injuries. At our institution, a two-incision approach using standard medial and lateral incisions, when appropriate to the fracture pattern, was found to allow improved visualization of the tibial articular surface and talus, ease of fixation placement with the new plate designs, and a low complication rate regarding soft-tissue issues when compared with published methods.

6552 Background: Substantial advances in therapy of CRC pts occurred between 2000 and 2012 contributing to a significant increase in overall survival. The objective of this study is to quantify the change in treatment (tx) intensity as measured by clinic and tx visits at a network of medical and radiation oncology clinics. Methods: Electronic scheduling records of stage I-IV CRC patients referred between 2000-2012 to the six oncology centers comprising the British Columbia Cancer Agency were reviewed and stratified by tx phases: I and II (adjuvant first 6 months, continued), III and IV (palliative first 6 months, continued), and V (last 6 months of life). Clinic Visit Intensity (CVI), Chemo Tx Intensity (CTI), number of chemo agents and number of cycles (CC), Radiotherapy (Rx) courses (RC) and fractions (RF) were measured, and trends by referral year were modelled using zero inflated negative binomial regression. Mean duration of visit for chemo tx (CHD) and clinic visits (CVD) were modelled using linear regression. Sex, age at diagnosis, stage, income, and community size were included in models if terms were significant. Results: 15,157 pts were included across 10 cohorts. CTI and CC increased significantly in tx phases II-V with later year of referral, while phase I results were stable or decreased, likely due to the substitution of oral for intravenous regimens. Rx increased only in advanced phases. Mean duration of scheduled time showed significant increases. Conclusions: CRC pts referred in 2012 vs 2000 receive significantly greater intensity and duration of care in tx phases II-V. Results have significant implications for resource allocation and the patient experience. [Table: see text]

153 Background: Informed consent forms (ICFs) should provide prospective subjects with an opportunity to balance the risks and benefits of study participation. However, there are growing concerns about the quality of ICFs. Optional ICFs are also increasingly used as the number of companion studies and biomarker evaluations requiring additional tests become more frequent. We examined trends in the content and format of main and optional ICFs. Methods: ICFs from clinical trials at a tertiary cancer center in British Columbia from 2000 to 2015 were reviewed. We focused on breast or gastrointestinal (GI) cancer studies. Readability was evaluated with the Flesch Reading Ease Score (FRES) and Flesch Kincaid Grade Level (FKGL) where a higher FRES (maximum 100) and a lower FKGL (maximum 12) indicated easier readability. We applied t-tests and linear regressions to examine variations among clinical trials and changes over time. Results: We identified 133 main ICFs of which 70% had optional ICFs and where 57% and 43% were breast and GI cancer studies. Phase III trials (44%), industry funded investigations (70%), and studies involving palliative therapies (72%) were most common. Trials from recent years were more likely to have optional ICFs than those from earlier years (p < 0.001). The median length and median word count in main and optional ICFs were 16 and 6 pages and 6183 and 1862 words, respectively. These changed significantly over time whereby main ICFs increased approximately by 1 page and 364 words per year over the 15 year period (p < 0.001). Industry funded trials also had longer ICFs (p = 0.006). Study methods, risks, and confidentiality occupied 29%, 20%, and 11% of the content on ICFs, respectively. Sections pertaining to eligibility (p < 0.001) and screening procedures (p = 0.007) also increased with time, particularly for industry funded studies (p = 0.006). In terms of readability, optional ICFs were generally more difficult to read than main ICFs (FRES 48.3 vs 50.0, p = 0.024; FKGL 11.8 vs 11.1, p < 0.001), especially in recent years (p < 0.001). Conclusions: This is one of the first analyses to include optional ICFs. Length of ICFs is increasing and readability is discordant with the average reading level of potential trial participants.

The survival benefit for single-agent anti&ndash, epidermal growth factor receptor (egfr) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan. The study enrolled patients with KRAS wt mcrc previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab&ndash, irinotecan before April 1, 2011, at the BC Cancer Agency (bcca). Patients were excluded if they had received anti-egfr agents in earlier lines of therapy. Data were prospectively collected, except for performance status (ps), which was determined by chart review. Information about systemic therapy was extracted from the bcca Pharmacy Database. Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab&ndash, irinotecan. Compared with patients treated with cetuximab&ndash, irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ecog) ps of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab&ndash, irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28, p = 0.34). An ecog ps of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37, p < 0.01). Single-agent panitumumab and cetuximab&ndash, irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mcrc.

Low enrolment rates in clinical trials present a barrier to the development of novel cancer therapies. Currently, only 3% of patients with cancer participate, and many studies fail to achieve necessary enrolment. The objective of this study was to evaluate whether a screening intervention to identify potentially eligible patients (PEPs) would increase accrual rates.Over a 4-month intervention period, PEPs for 21 phase II-IV breast, gastrointestinal, genitourinary, gynecology, and lung cancer trials were identified by a screening coordinator. This individual reviewed the electronic medical records of patients attending outpatient clinics and flagged PEPs for 10 medical oncologists at the BC Cancer Agency. Patients who were already documented to be trial eligible by physicians were not flagged. Oncologists were surveyed regarding the helpfulness and accuracy of the intervention.During the intervention period, 73 patients were enrolled, compared with 61 patients enrolled in the 4 months prior and 51 patients in the 4 months after. A total of 2,098 charts were reviewed, and 120 PEPs were identified during the intervention period, resulting in 19 PEPs who enrolled and four PEPs who declined a clinical trial. Relative accrual rates adjusted for oncologist appointments were 0.85 (P = .15) before and 0.70 (P.005) after, relative to the intervention period. Oncologist-returned surveys indicated that 67% of flags were helpful, and 70% were accurate.In this study, manually screening patient records increased enrolment to specific clinical trials. A screening intervention process, involving a dedicated screening coordinator, should be considered to improve clinical trial accrual.

e21624Background: New targeted therapies and immuno-oncology agents in advanced melanoma have resulted in an unprecedented number of survivors. Because side effects can impact their long-term quali...

6529Background: In 2016, there will be an estimated 134,490 new cases of colorectal cancer (CRC) in the US alone. Treatments for CRC include radiotherapy, and chemotherapy; options for which have i...

e13047Background: Electronic cigarettes (e-cigs) are a novel nicotine delivery system introduced in 2003 as a harm-reducing substitute for conventional cigarettes. E-cigs have been described by exp...

6551 Background: Studies indicate that racial minorities are underrepresented in clinical trials. The outcomes of these minority groups following study enrollment are less clear. Our aims were to c...

Aim: Significant changes in surgical and systemic management of mCRC have occurred since 1995. The impact of exposure to All 3 Agents (5-Fluorouracil, Irinotecan, Oxaliplatin), All 4 (plus Bevacizumab) or All 5 (plus EGFR inhibitors [i]) and ROM is not well described. The objective of this study is to characterize the 15-year changes in surgical and systemic therapy and to measure associations between these treatments advances and outcomes. Methods: All patients with relapsed or mCRC referred to the BC Cancer Agency diagnosed in 1995-96, 2000, 2003-04, 2006 and 2009-10 were included. Outcomes and systemic therapy data were prospectively collected. Information on ROM of liver, lung, ovarian, peritoneal and other sites was retrospectively abstracted. Cox regression analysis was conducted to examine associations between treatment variables and Overall Survival (OS), while accounting for era of diagnosis. Results: Variable p-value 1Year Hazard Ratio 95% CI ROM vs no ROM 0.32 0.25 0.36 All 3 Agents vs. None 0.33 0.25 0.39 All 4 or 5 Agents vs.None 0.21 0.18 0.25 Only 1-2 Agents vs. None 0.68 0.62 0.74 A total of 3731 eligible patients were included with a median age of 68 years which did not differ between eras (p = .13). In 2009-10, 24% of treated patients underwent ROM, 42% received All 3 Agents, 54% received Bevacizumab and 18% received anti-EGFR agents. Patients who were only able to receive 1-2 agents had a median OS of 1.18 years (95% CI 1.09-1.25), those treated with All 3 Agents survived 1.93 years (95% CI 1.77-2.11) and those with All 4 or 5 Agents survived 2.49 years (95% CI 2.30-2.66). Median OS of ROM patients was 3.65 years (95% CI 3.25-3.95). Regression analysis demonstrated the independent prognostic effect of systemic therapy and ROM. Conclusions: The introduction of 4 and 5 active agents in mCRC is associated with a measurable improvement OS with an incremental effect related to an increasing number of agents received. ROM is associated with prolonged survival, independent of systemic therapy. Effects are independent of era of diagnosis. Disclosure: All authors have declared no conflicts of interest.

9584 Background: The risk of infertility and sexual dysfunction from cancer therapy is inadequately discussed at the time of cancer diagnosis (Wang et al, ASCO 2013) even though these issues can cause significant distress. Our aims were to survey young cancer patients to 1) ascertain their expectations of physicians in addressing these concerns and 2) characterize how patients’ expectations modify the likelihood of having discussions about reproductive and sexual health. Methods: Patients aged 20 to 39 diagnosed with solid tumors from 2006 - 2008, evaluated at any 1 of 5 regional cancer centers in British Columbia and alive at >/= 2 years after diagnosis were surveyed to determine their views about oncologists’ and PCPs’ responsibilities for reproductive and sexual health. Survey responses were paired with tumor and treatment characteristics from patients’ medical records. Using logistic regression, we explored for associations between expectations and whether or not patient-physician conversations had oc...