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Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) and both are prevalent in men with testosterone deficiency. Long-term effects of testosterone therapy (TTh) on NAFLD are not well studied. This observational, prospective, cumulative registry study assesses long-term effects of testosterone undecanoate (TU) on hepatic physiology and function in 505 hypogonadal men (T levels ≤350 ng/dL). Three hundred and twenty one men received TU 1000 mg/12 weeks for up to 12 years following an initial 6-week interval (T-group), while 184 who opted against TTh served as controls (C-group). T-group patients exhibited decreased fatty liver index (FLI, calculated according to Mayo Clinic guidelines) (83.6 ± 12.08 to 66.91 ± 19.38), γ-GT (39.31 ± 11.62 to 28.95 ± 7.57 U/L), bilirubin (1.64 ± 4.13 to 1.21 ± 1.89 mg/dL) and triglycerides (252.35 ± 90.99 to 213 ± 65.91 mg/dL) over 12 years. Waist circumference and body mass index were also reduced in the T-group (107.17 ± 9.64 to 100.34 ± 9.03 cm and 31.51 ± 4.32 to 29.03 ± 3.77 kg/m2). There were 25 deaths (7.8%) in the T-group of which 11 (44%) were cardiovascular related. In contrast, 28 patients (15.2%) died in C-group, and all deaths (100%) were attributed to CVD. These data suggest that long-term TTh improves hepatic steatosis and liver function in hypogonadal men. Improvements in liver function may have contributed to reduced CVD-related mortality.

Introduction: There is a paucity of studies examining the prevalence and clinical characteristics of rhabdomyolysis in hospitalized patients with COVID-19 infection. The purpose of this study is to examine the incidence, clinical characteristics, and outcome of hospitalized patients with COVID-19 infection who develop rhabdomyolysis. Methodology: This is a single-center retrospective analysis of all hospitalized patients with COVID-19 admitted between March 8, 2020, and January 11, 2021. All patients with creatinine kinase (CK) levels available during the hospital admission were included. Rhabdomyolysis was defined as an elevation in CK level higher than five times the upper limit of normal (i.e., 1125 U/L). We compared clinical characteristics and outcomes of patients who developed rhabdomyolysis with patients who did not develop rhabdomyolysis. Results: The incidence of rhabdomyolysis in hospitalized patients with COVID-19 infection was 9.2%. There was no significant difference noted in comorbidities and clinical characteristics between the two groups. Moreover, there was no significant difference noted in the presence of severe COVID-19 infection (72.7% vs 54.6%, p = 0.1), mortality (27.3% vs 23.9%, p = 0.72), acute kidney injury (59.1% vs 42.7%, p = 0.14), or need for intensive care unit (ICU) care (72.7% vs 51.4%, p = 0.051). However, a higher percentage of patients in the rhabdomyolysis group required physical rehabilitation after discharge (40.9% vs 19.3%, p = 0.02). Conclusion: The overall incidence of rhabdomyolysis in hospitalized patients with COVID-19 infection was high (9.2%). The presence of rhabdomyolysis was not associated with the increased severity of the disease. Patients with rhabdomyolysis more frequently required physical rehabilitation compared to those without rhabdomyolysis.

Background and aim The hepatitis C virus (HCV) is considered a global health challenge that requires urgent interventions for prevention and control. In this study, we aimed to evaluate the effectiveness of direct-acting antiviral agents (DAAs) for HCV-infected patients in the Kingdom of Saudi Arabia (KSA). Patients and methods In this retrospective cohort study, we ascertained data of patients treated with DAA-based regimens for chronic HCV in the private health-care sector hospitals of KSA between April 2015 and December 2017. Data regarding presence or absence of liver cirrhosis, virus genotype, quantitative HCV RNA test, fibrosis stage, and history of liver disease were included. The primary end point of the study was the overall cure rate, defined as the number of patients achieving sustained viral response (SVR) rate at least 12 weeks following completion of treatment, divided by the total number of patients included in the study. Results A total of 262 patients fulfilled the study inclusion criteria. Adult patients were enrolled, of which 114 (44%) were females and 148 (56%) were males. About 105 of the patients (40%) were cirrhotic and 156 were treatment-naive patients (60%), 84 patients were interferon (INF) experienced, and 22 patients had previously received new DAAs but failed to achieve SVR. The majority of patients received ledipasvir-sofosbuvir±RBV (57%) with SVR rate of approximately 97%. Conclusions Our local real-world data indicate an overall HCV cure rate of 97% following treatment with DDA#x2019;s when prescribed in the private sector. This estimate is acquiescence with previously reported global cure rates.

Introduction MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690). Methods A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 [DL1]) or 45 mg BID (dose level 2 [DL2]) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype. Results Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months–NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1–mutated patients, the ORR was 42.8%. Conclusion The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.

Although pericardial effusions are not uncommon in patients with end-stage renal disease, uremic pericardial effusion (UPE) frequently remains unrecognized in the absence of clinical signs and symptoms. We present a case of post-living donor renal transplantation delayed graft function due to asymptomatic undiagnosed chronic nontamponade UPE. The patient developed dramatic intraoperative severe hypotension, electrolyte abnormalities, and atrial fibrillation. Prolonged intraoperative hypotension and allograft hypoperfusion caused mild acute tubular necrosis and postoperative delayed graft function that required 2 weeks to recover. The combination of chronic UPE, even without tamponade, hypotension, and atrial fibrillation could lead to significant hemodynamic instability during renal transplantation. More careful immediate pretransplantation cardiac evaluation and avoidance of intraoperative hypotension could prevent these serious consequences of silent UPE.s.

1034 Background: Anti-HER2 therapy has improved survival in HER2+ MBC. Yet, large patient cohorts with no evidence of disease (NED) with long-term follow up are incompletely described in the literature. We evaluated the clinical characteristics of patients with HER2+ MBC and prolonged response to anti-HER2 therapy, exhibiting NED vs Residual disease (RES). Methods: Patients treated with chemotherapy plus trastuzumab (CT) from 2005-2013, or taxane plus trastuzumab-pertuzumab (TTP), or trastuzumab-emtansine (TDM1) from 2012-2016 for HER2+ MBC at Princess Margaret Cancer Centre in Toronto, Ontario or in Alberta, Canada were included. Duration on anti-HER2 therapy (without switch) was collected. Patients with median duration of response (MDR; months) 2x higher than phase II/III trials for each regimen (CT = 18.2; TTP = 40.4; TDM1 = 25.2) were included to select for prolonged response. Clinical features (ie: stage at diagnosis, survival, etc) and oncologist/radiologist reported best response were collected. Responses were grouped as NED (including sclerotic bone metastases) or RES. Clinical variables were evaluated by Chi-square and survival by Kaplan-Meier (log-rank). Results: 2403 patients (CT = 1830; TTP = 394; TDM1 = 179) were evaluated. After cut-off, 119 patients (5%) were included, with NED in 41% (49/119) and RES in 59% (70/119). More women aged < 50 vs ≥50 (p = 0.015) had NED (61%) than RES (39%). No breast surgery (curative or metastatic) showed higher (p = 0.015) rates of NED (49%) relative to RES (27%). More women having NED (92%) than RES (37%) were still alive (p < 0.0001) at data cut-off, with improved mPFS (years; p < 0.0001) for NED (11.2, 95%CI: 11.2-NR) vs RES (3.0, 2.7-3.6), and mOS (years; p < 0.0001) for NED (NR) vs RES (3.4, 95%CI: 2.8-4.2). Significance persisted with TDM1 patients excluded. Treatment type (p = 0.053) and number of organs with metastases (p = 0.067) were of borderline significance. Conclusions: Patients with NED have improved survival compared to RES. Younger age and avoiding breast surgery correlates with NED. Evaluation of genomic factors influencing NED are planned.

The present randomized controlled split mouth clinical study aimed to investigate the efficacy of Er,Cr:YSGG laser irradiation on pain reduction and healing rate of recurrent aphthous stomatitis. 40 patients with RAS were recruited for this study and RAS ulcerations of each patient were randomly assigned to the control or test group. In the test group, Er,Cr:YSGG laser with non-contact mode was used to irradiate RAS lesions. In the placebo group, RAS lesions were irradiated with the same device without laser emission. Pain was evaluated with visual analog scale (VAS) while a clinician graded healing of RAS (HRAS). In the placebo group at immediate; scores of VAS presented no statistically significance; in the test group, laser application showed significant pain reducing, at 1st day control. In the test group, a significantly healing effect at 1st day control was observed and this effect was maintained throughout the study. In the placebo group, scores of HRAS were statistically significant at controls on 3, 7, 10days. Statistically significant difference between the scores of VAS and HRAS was found for all control days except day 10 according to the intergroup comparisons. Based on these findings, Er,Cr:YSGG laser application at 0.25W without water may be appropriate to reduce pain and also accelerate the healing of RAS.

Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) represent a new treatment paradigm in non-small cell lung cancer. Three phase III trials have demonstrated a survival benefit and improved tolerability of nivolumab and pembrolizumab when compared with standard second-line chemotherapy. Nevertheless, the adverse events associated with PD-1 inhibitors are unique; early recognition and treatment are essential. This review summarizes the required monitoring and appropriate management of immune-related adverse events in lung cancer patients receiving these agents. THE ONCOLOGIST 2017;22:70-80 IMPLICATIONS FOR PRACTICE: : The potential adverse events of immune checkpoint inhibitors differ from conventional chemotherapy and can require a multidisciplinary approach. Continued education is important for all physicians to ensure optimal care for patients.

444 Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have limited treatment options. Management of complex symptoms and psychosocial implications requires an interprofessional approach as prognosis is often measured in months. A multidisciplinary approach has been associated with improvement in clinical outcomes including survival. We aimed to evaluate the impact of an inter-professional approach for PDAC patients at the Wallace McCain Centre for Pancreatic Cancer (WMCPC) at PM on their management and clinical outcomes. Methods: We undertook retrospective review of all patients with PDAC seen at PM two years before (July ‘12 – June ‘14) and two years after (July ‘14 – June ‘16) establishment of the WMCPC. Standard therapies (surgical approach, chemotherapy, radiation therapy) were the same during both time periods. Comparison of overall survival (OS), stage at diagnosis, surgical outcomes, waiting times, and proportion seen by social worker, dietician and clinical nurse specialist (CNS) was explored with descriptive statistic and survival analysis. Results: A total of 993 patients were reviewed; 482 patients pre- and 511 patients post-WMCPC. Age (median 67 yrs), sex (54% men) and stage III/IV (52%) were similar in both groups. There was a trend to improved OS in the post-WMCPC group (9.6 vs. 10.9 m; p = 0.055); multivariable analysis found a significant improvement in OS after adjustment for performance status and stage (p = 0.023; HR 0.84, 95% CI 0.72-0.98). Rate of R0 versus R1/R2 resection for curative surgery (n = 264, 28%) was similar in both groups. Time from referral to first clinic visit significantly decreased from 13.4 to 8.8 days in the post-WMCPC group (p < 0.001) as did time from first clinic appointment to diagnostic biopsy (25.9 vs. 16.9 days, p = 0.022). Patients in the post-WMCPC were more frequently seen by a social worker, dietician or CNS (8% vs. 38%, 9% vs. 35% and 31% vs. 50% respectively, p < 0.001). Conclusions: Establishment of an interprofessional clinic for the treatment of PDAC patients at PM has streamlined diagnosis, aided symptom management and improved overall survival. This has implications for planning care delivery models and proves the value of this intervention.

211 Background: COMPASS is a prospective study with the primary aim to identify predictive mutational and transcriptional features in advanced PDAC for improved patient stratification and treatment selection. Methods: Patients with advanced PDAC were prospectively recruited prior to first-line combination chemotherapy for whole genome sequencing (WGS) and RNA sequencing (RNASeq). Fresh tumor tissue was acquired by image guided percutaneous core needle biopsy of locally advanced primary or metastatic tumors. Laser capture microdissection was performed for all cases to ensure high-resolution genomic analyses. Primary endpoint was feasibility to report WGS results prior to first disease assessment CT scan at 8 weeks. The main secondary endpoint was discovery of patient subsets with predictive mutational and transcriptional signatures. Results: Of 63 patients who underwent a tumor biopsy between December 2015 and June 2017, WGS and RNASeq were successful in 62 (98%) and 60 (95%), respectively. Genomic results were reported at a median of 35 days (range 19-52 days) from biopsy, meeting the primary feasibility endpoint. Three patients with an ‘unstable’ genomic subtype, including two with a novel ‘duplicator’ phenotype, responded well to m-FOLFIRINOX. Of two cases with the same germline BRCA2 mutation, only the chemotherapy responder had loss of heterozygosity and genomic hallmarks of double stranded break repair deficiency. Approximately 25% of tumors displayed the basal-like RNA expression signature and these were chemotherapy resistant, with tumor shrinkage mainly observed in those with the classical RNA subtype (P = 0.003). Thirty percent of patients had potentially actionable genetic alterations. Conclusions: Prospective comprehensive genomic profiling of advanced PDAC is feasible and our early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes providing the impetus for further studies. Clinical trial information: NCT02750657.

e15715 Background: The standard second line treatment in advanced PDAC pts after m-FFX first line palliative chemotherapy is not clearly defined. G is the standard 2nd line treatment in Canada and GA can only be prescribed for pts with a private fund or private drug plan that covers the cost of Abraxane. More data is needed to establish OS achieved with 2ndline G or GA. Methods: The OS of PDAC pts treated with G or GA after m-FFX palliative chemotherapy given between 01-Dec-2011 and 30-Nov-2015 at the Princess Margaret Cancer Centre (PM), Toronto, Canada were retrospectively reviewed. OS was calculated from date of commencement of 2ndline treatment until death or date of last oncology follow up. Results: Over the 4-year study period, 132 pts were treated with 1st line palliative m-FFX at PM. Of them, at disease progression, 78 (59%) pts received a 2ndline therapy (50 G, 17 GA, 9 clinical trials, and 2 other). The results including demographics, treatment details and survival outcomes of patients treated with G and GA are summarized in the Table 1. Conclusions: Our results do not support single agent G after m-FFX 1st line palliative chemotherapy as median duration of treatment was too short and OS observed with G in this setting is very much limited. The median duration of treatment on GA and OS achieved with GA seem superior but sample size was too small to make a conclusion. [Table: see text]

e15776 Background: Prospective characterization of advanced PDAC using whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) may identify patients (pts) who will benefit from a personalized treatment strategy. The feasibility of this approach has not previously been established in PDAC. Methods: Advanced PDAC pts with ECOG PS 0-1 and accessible metastatic or primary tumors, were recruited. A fresh tumor sample for WGS and WTS was obtained by percutaneous biopsy and a reference whole blood sample for germline DNA analysis collected before starting 1st line palliative chemotherapy. Tumor biospecimens were enriched by laser capture microdissection before genomic analysis. The primary endpoint was feasibility (to report WGS results within 56 days in 40 of the first 50 recruited pts.) with a plan to accrue 200 pts. Results: From Dec 2015 – Jan 2017, 42 pts with advanced PDAC safely underwent tumor biopsy (32 liver, 1 omentum, 1 adrenal, 8 primary tumor). Adequate tumor biospecimens were obtained in all but one pt. The median number of tissue cores was 5 (range 3-6). The median post-enrichment tumor cellularity was 77% (range 37-93). WGS was successful for all samples analyzed. In 41 of 42 pts (97.6%), WGS was feasible and results were reported within 56 days (Median 37 days; range 19 to 52 days) meeting the primary endpoint. Potentially actionable somatic genetic aberrations were found in 12 pts (29%) involving ARID1A (N = 4), PIK3CA (N = 1), PDGFRB (N = 1), ERBB4 (N = 1), ATM (N = 2), CDK4 (N = 1) and CDK6 (N = 2). One pt with a germline BRCA2 mutation and another with somatic DSBR mutation signature achieved partial response with FOLFIRINOX (FFX). WTS results were available for 35 pts (85%). Of those, 19 were evaluable for FFX response. Eight of 9 pts (88%) with ‘classic’ signature and 4 of 10 pts (40%) with ‘basal like’ signature had tumor shrinkage with FFX (P = 0.08). Conclusions: Prospective comprehensive genomic profiling of advanced PDAC is feasible with an acceptable turnaround time. Approximately 30% of advanced PDAC pts have targetable genomic signatures and aberrations. RNA signature may predict FFX response.

Options for the treatment of well-differentiated neuroendocrine tumors (NETs) are limited. We evaluated the efficacy of capecitabine and temozolomide combination in patients from Jordan.A retrospective review was conducted of 21 patients with metastatic well-differentiated NETs who failed somatostatin analogues and chemotherapy. Patients received capecitabine and temozolomide regimen every 28 days, and evaluation was done every 2 cycles.Twelve patients (57%) achieved partial response, and 5 (23%) achieved stable disease. Median progression-free survival was 16.5 months (range, 14.8-18 months). Of the 7 carcinoid tumors, 2 had partial response, and 2 had stable disease. There were no grade 4 toxicities or treatment-related deaths.Capecitabine and temozolomide regimen is an effective and well-tolerated salvage option for well-differentiated NETs.

© 2009 Mayo Foundation for Medical Education and Research An 83-year-old woman with Alzheimer dementia presented to the emergency department with abdominal distention. Her husband provided the history. After having constipation for 1 week, she developed a progressively distended abdomen in the course of 2 days, with anorexia but no vomiting, melena, or hematochezia. She had no history of fever, rigors, dyspnea, or weight loss. Her medical history was remarkable for hypertension, coronary artery disease, and impaired fasting blood glucose levels. Despite the recent symptoms, she had no history of gastroenterologic symptoms, cancer, abdominal surgeries, or colon screening studies. She lived with her husband in the community and was dependent on him for her activities of daily living except for ambulation with a walker and feeding herself. She was a nonsmoker and nondrinker. Her medications were 60 mg/d of isosorbide mononitrate, 325 mg/d of aspirin, 2.5 mg/d of amlodipine, 20 mg/d of atorvastatin, and a combination of 37.5 mg/d of triamterene and 25 mg/d of hydrochlorothiazide. On examination, the patient appeared to be in mild distress with abdominal distention. Her vital signs were as follows: temperature, 36.6oC; blood pressure, 154/89 mm Hg; regular pulse, 84 beats/min; respiration rate, 20 breaths/ min; and oxygen saturation, 94% while breathing room air. Abdominal examination revealed marked distention with diminished bowel sounds and moderate discomfort with deep palpation of the left lower quadrant, but no peritoneal irritation signs, Murphy sign, McBurney point tenderness, abdominal bruit, ascites, hepatosplenomegaly, or palpable mass. Rectal examination revealed no stool in the vault and no obvious mass. The patient had normal levels of hemoglobin, white blood cells, platelets, chloride, bicarbonate, creatinine, blood urea nitrogen, troponin, and lipase, as well as a prothrombin time within the normal range. She had a serum sodium of 126 mEq/L (reference ranges provided parenthetically) (135-145 mEq/L), a potassium level of 2.5 mmol/L (3.6-4.8 mmol/L), and a blood glucose level of 198 mg/ dL (70-100 mg/dL). Urinalysis was positive for trace occult blood and 1+ protein. Abdominal plain radiography showed prominent gaseous dilatation of the transverse colon and redundant sigmoid colon without distinct signs of obstruction or free air.