Search

Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data regarding epidemiology and survival. In this study, we explored clinicopathologic factors and oncologic outcomes of patients with SUC derived from Survival, Epidemiology and End Results (SEER) database, in comparison to conventional UC (CUC).SEER database was searched for patients with invasive (≥T1) SUC or CUC using the topography codes C67.0 to C67.9 for bladder cancer and the morphologic codes 8120/8122 for CUC/SUC respectively. Demographic/clinicopathologic/treatment/survival data were extracted. Disease-specific survival (DSS) was estimated with the Kaplan-Meier method. Chi-squared tests were used for comparative analysis and Cox proportional hazards model for identifying clinical covariates associated with DSS.A total of 569 patients with SUC and 37,740 with CUC were identified. Overall, there was a male predominant population in both cohorts, although a higher proportion of women were noted in the SUC cohort (32 vs. 25%). Patients with SUC had significantly higher incidence of non-bladder confined disease (T3/4, 37% vs. 22%) and nodal invasion (18% vs. 12%) in comparison to those with CUC (all P.05). Median DSS was 16 months (95% CI: 12.4-19.6) in the SUC vs. 82 months (95% CI; 75.9-88.1) in the CUC cohort. Presence of SUC histology was independently associated with shorter DSS in the multivariate analysis, when adjusted for other significant clinicopathologic factors.SUC was associated with advanced stage and shorter DSS compared to CUC. Further studies are needed to better understand biological underpinnings behind its aggressive behavior and the role of novel systemic treatments.

There are substantial unmet needs with regards to adjuvant therapy for muscle-invasive urothelial carcinoma (UC) of the bladder, including patients with persistent disease histologically following neoadjuvant platinum-based therapy and radical resection, as well as patients who are not eligible for or refuse cytotoxic chemotherapy. As such, increased interest has been developed in advancing the use of systemic immunotherapy in the postoperative setting.We begin by examining current uses of systemic immunotherapy in the treatment of advanced UC. We also review emerging neoadjuvant data and describe current adjuvant approaches. We then report and analyze data on adjuvant immunotherapy, including the recent randomized trials on adjuvant nivolumab and atezolizumab, and conclude with a discussion on the available evidence and likely directions of the field.Systemic immunotherapy can serve to enhance postoperative therapies for muscle-invasive bladder UC, as exemplified by the recent approval of nivolumab. Further research will serve to define optimal immunotherapy timing and combinations with other systemic therapies, as well as identify predictive biomarkers to allow effective tailoring of therapy for each patient.

Renal sarcomas are exceedingly rare and lack a prognostic stage classification. We thus aimed to investigate the contemporary clinicopathologic characteristics and outcomes of renal sarcomas at a national level.We utilized the Surveillance, Epidemiology, and End Results database to extract data on patients with renal sarcoma diagnosed between 2004 and 2015. We estimated median, 1-, 3-, and 5-year overall survival (OS) probabilities via Kaplan-Meier curves and used multivariable regression to compare OS between different patient groups.We identified 365 patients; at diagnosis, 104 patients (28.5%) had stage I disease (T1N0M0), 133 patients (36.4%) patients had stage II disease (T2-4N0M0), and 117 patients (32.1%) patients had stage III disease (any T, N1, or M1). Median survival was 105 months (interquartile range [IQR], 29 - not reached) for stage I disease, 46 months (IQR 14-118 months) for stage II disease, 8 months (IQR 3-28 months) for stage III disease, and 32 months (IQR, 8-116 months) for the entire cohort. Patient age (hazard ratio [HR] for death [per year] 1.02, 95% confidence interval [95% CI] 1.00-1.04), stage (II vs. I: HR 1.71, 95% CI 1.00-2.92; III vs. I: HR 4.93, 95% CI 2.68-9.05), grade (grade 3 vs. grade 1: 3.07, 95% CI 1.18-8.00; grade 4 vs. grade 1: HR 3.66, 95% CI 1.41-9.49), and possessing medical insurance (HR 0.40, 95% CI 0.16-0.94) were independently and significantly associated with OS. Performance of nephrectomy also trended towards independently improving OS (HR 0.23, 95% CI 0.05-1.09).A novel staging classification for renal sarcomas into a 3-stage system based on Tumor Node Metastasis (TNM) criteria produces distinct survival curves, although further studies are needed to robustly assess its validity.

The risk of distant metastasis may be estimated using predictive nomograms. The purpose of this study is to develop nomograms that may assess the risk of synchronous metastasis in patients with colon cancer. A retrospective analysis of the Surveillance Epidemiology and End Results database between 2010 and 2014. Logistic regression was performed to identify factors associated with synchronous liver and lung metastasis. Overall, 117,934 patients with colon cancer (59,076 [50.1%] males, mean age 68.3 ± 13.7 years) were included, of which 16,135 (13.7%) had liver metastasis and 4601 (3.9%) had lung metastasis at diagnosis. Age, sex, race, tumor location, tumor grade, CEA levels, perineural invasion, and T and N stage were associated with the presence of liver metastasis. Age, sex, race, tumor location, tumor grade, CEA levels, perineural invasion, T stage, N stage, and presence of liver metastasis were associated with the presence of lung metastasis. These variables were used to construct predictive nomograms. The c-indexes for both predictive models were 0.97. In this study, we constructed predictive nomograms for the presence of synchronous liver and lung metastasis in patients with colon cancer that may be used to quantitatively assess the risk of synchronous metastatic disease.

Background Sarcomatoid renal cell carcinoma (sRCC) constitutes a rare and aggressive subtype of renal cell carcinoma. We aimed to investigate its clinicopathologic characteristics and outcomes at a national level. Patients and Methods We accessed the National Cancer Institute's Surveillance, Epidemiology, and End Results database (2010-2015) and extracted data on patients with sRCC. We estimated median, 1-, 3-, and 5-year disease-specific survival (DSS) probabilities after generation of Kaplan-Meier curves and used multivariable regression to evaluate variables associated with nephrectomy and DSS. Results A total of 879 patients with sRCC were identified; 60.9% patients had stage IV disease at diagnosis, and the median tumor size was 8.3 cm (interquartile range, 5.5-12 cm). The 5-year DSS were 77.7%, 67.8%, 35.4%, and 3.5% for patients with stage I, II, III, and IV disease at diagnosis, respectively; median DSS was 9 months (interquartile range, 4-42 months) for the entire cohort. Older age (hazard ratio [HR] = 1.01; 95% confidence interval [CI], 1.00-1.02), higher tumor stage (stage III vs. I: HR = 3.81; 95% CI, 2.18-6.67; stage IV vs. I: HR = 9.89; 95% CI, 5.80-16.98), and performance of nephrectomy (HR = 0.53; 95% CI, 0.43-0.66) were found to independently affect DSS. Conclusion In the largest sRCC cohort to date, we found that most patients present with metastatic disease, and the prognosis for this disease remains extremely poor. Nephrectomy should be considered in all patients with acceptable surgical risk, including cytoreductive nephrectomy in carefully selected patients with metastatic disease.

6592 Background: Established antineoplastic medication prices are overall increasing, yet the yearly trend and additive cost of such increases relative to overall antineoplastic spending is often unclear. Methods: We accessed the yearly reimbursement files from Medicare Part B for parenteral antineoplastic agents (codes J8501-J9999) for the years 2010-2020 and adjusted all values to 2020 USD to account for inflation. We calculated an initial inflation-adjusted price-per-claim for every medication at the time of medication entry to the database and compared that price with the yearly price-per-claim that Medicare reimbursed. For medications whose price had increased beyond the initial inflation-adjusted price, we multiplied the annual differences with the total annual claims of the medication reimbursed in order to calculate the additional cost accrued by Medicare for every affected year. We only included medications with total annual cost >10 million USD/yr in our analysis. Results: Price increases were noted in 70.9% of already established medications annually (median 74.5%, range 52.17-81.48%). This led to an average additional extra cost of 311 million USD (range 156-492 million USD) annually, for a total of 3.1 billion USD over the 10 years of observation. This extra cost represented 4.6-9.3% of the total Medicare Part B spending for antineoplastic medications annually and this percentage rose yearly by a statistically significant 0.43% (95% CI 0.14%-0.73%, P = 0.01; R2 0.59) in absolute terms (Table). Rituximab (1,003 million USD), trastuzumab (421 million USD), and bevacizumab (326 million USD) accumulated the highest extra costs. Conclusions: The majority of established parenteral antineoplastics are affected by escalating price increases beyond the rate of inflation. Year-by-year, these increases occupy a progressively larger part of overall Medicare Part B spending. Since Medicare does not negotiate medication price nor receives rebates but rather relies on average market prices, these increases likely affect other U.S. markets as well.[Table: see text]

Patients with colorectal cancer are at increased risk of cardiovascular mortality compared to the general population. The purpose of this study is to identify risk factors of cardiovascular mortality in patients with colorectal cancer. A retrospective review of the Surveillance Epidemiology and End Results (SEER) database was performed between 2010 and 2014. Standardized Mortality Ratios (SMRs) for cardiovascular mortality were calculated by comparing the number of expected deaths in the United States according to the National Center for Health Statistics (ICD-10 codes I00-I99) to the number of observed deaths in the database. Logistic regression was used to identify independent risk factors. Overall, 164,719 patients were identified (mean age at diagnosis 67 ± 13.9 years, 52.7% males, 47.3% females), of which 4854 (2.9%) died from cardiovascular disease. The majority of cardiovascular deaths occurred during the first year after diagnosis (2658, 54.8%). SMRs for cardiovascular mortality were 11.7 (95% CI 11.3–12) among all patients, 12.1 (95% CI 11.7–12.6) for male patients and 11.1 (95% CI 10.6–11.6) for female patients, with SMRs being higher for younger patients. Older age, male sex, African–American race, elevated CEA and not undergoing curative surgery were independent risk factors of cardiovascular mortality in patients with colorectal cancer. Patients with colorectal cancer are associated with an increased risk of cardiovascular death, especially during the first year after diagnosis. Older age, male sex, African–American race, elevated CEA and not undergoing curative surgery are independent risk factors of cardiovascular death.

Background The liver is the most common metastatic site in patients with gastrointestinal stromal tumors (GISTs). The purpose of this study is to identify the incidence and predictive factors associated with synchronous liver metastases among patients with GISTs. Methods A retrospective review of the Surveillance Epidemiology and End Results (SEER) database was performed. Results Overall, 2757 patients were identified, of which 276 (10%) had synchronous liver metastases. The two-year survival of patients with synchronous liver metastases was 31.9% overall and 37.1% after undergoing surgery with curative intent. Primary tumor size >5 cm (5–10 cm: OR 2.97, 95% CI: 1.03–8.55, p = 0.044, >10 cm: OR 5.59, 95% CI: 1.95–16.07, p = 0.001), presence of nodal metastases (OR 4.09, 95% CI: 2.01–8.33, p 5/50 HPF (OR 1.58, 95% CI: 1.01–2.47, p = 0.044) were associated with the presence of liver metastases. Conclusions One out of ten patients with GISTs presents with hepatic metastases. Primary tumor size >5 cm, presence of nodal metastases and mitotic count >5/50 HPF are associated with a higher risk of synchronous hepatic metastases.

It has been reported that some patients with breast cancer may refuse cancer-directed surgery, but the incidence in the United States is not currently known. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with refusal of recommended breast cancer-directed surgery.A retrospective review of the Surveillance Epidemiology and End Results (SEER) database between 2004 and 2013 was performed. Patients who underwent cancer-directed surgery were compared with patients in whom cancer-directed surgery was refused, even though it was recommended.Of 531,700 patients identified, 3389 (0.64%) refused surgery. An increasing trend was observed from 2004 to 2013 (P = .009). Older age (50-69: odds ratio [OR] 4.96; 95% confidence interval, 1.23-19.96; P = .024, ≥ 70 years: OR 17.27; 95% CI, 4.29-69.54; P .001), ethnicity (P .001), marital status (single: OR 2.28; 95% CI, 1.98-2.62; P .001, separated/divorced/widowed: OR 2.26; 95% CI, 2.01-2.53; P .001), higher stage (II: OR 2.05; 95% CI, 1.83-2.3; P .001, III: OR 2.2; 95% CI, 1.87-2.6; P .001, IV: OR 13.3; 95% CI, 11.67-15.16; P .001), and lack of medical insurance (OR 2.11; 95% CI, 1.59-2.8; P .001) were identified as risk factors associated with refusal of surgery. Survival analysis showed a 2.42 higher risk of mortality in these patients.There has been an increasing rate of patients refusing recommended surgery, which significantly affects survival. Age, ethnicity, marital status, disease stage, and lack of insurance are associated with higher risk of refusal of surgery.

Primary tumor location has been identified as an important prognostic factor among patients with gastrointestinal stromal tumors (GISTs). The purpose of this study is to identify how primary tumor location may affect outcomes after resection for patients with metastatic GISTs. Patients with GISTs and distant metastases at diagnosis were identified in the Surveillance Epidemiology and End Results (SEER) database. Patients that underwent surgery were matched to patients that did not undergo surgery using propensity score matching (PSM) analysis. After PSM, 570 patients were identified (males 334 [58.6%], females 236 [41.4%], age 62 ± 13.9 years). Gastric tumors constituted the majority (325 [57%]), followed by small intestinal (136 [23.9%]), colorectal (19 [3.3%]), and retroperitoneal/peritoneal tumors (23 [4%]). Median follow-up was 25.5 months (95% CI 23–29 months). Undergoing surgery was associated with improved disease-specific survival (DSS) on both univariate (median not reached vs. 51 months, p

Lymph node metastasis is not common among patients with gastrointestinal stromal tumors (GISTs) and its prognostic value is controversial. The purposes of this study are to identify predictors of lymph node metastasis and determine its prognostic associations. A retrospective analysis of the surveillance, epidemiology and end results (SEER) database was performed. Patients with GISTs that underwent surgery and pathologic nodal staging were identified. Logistic regression and Cox regression were performed to identify independent predictors and prognostic factors, respectively. Of 1430 patients (age: 61.5 ± 14.5 years, 52% males), 140 (9.8%) had lymph node metastasis. On multivariable analysis, distant metastasis was the only independent predictor of lymph node metastasis (OR 4.95, 95% CI: 2.43–10.08, p

Nomograms may be used to quantitatively assess the probability of synchronous distant metastasis. The purpose of this study is to develop predictive nomograms for the presence of synchronous distant metastasis in patients with rectal cancer. A retrospective analysis of the Surveillance Epidemiology and End Results database was performed for cases diagnosed between 2010 and 2014. Overall, 46,785 patients with rectal cancer (27,773 [59.4%] males, mean age 63.9 ± 13.7 years) were identified, of which 6192 (13.2%) had liver metastasis, 2767 (5.9%) had lung metastasis, and 601 (1.3%) had bone metastasis. Age, sex, race, tumor location, tumor grade, primary tumor size, CEA levels, perineural invasion, T stage, N stage, and liver and lung metastasis were found to be associated with the presence of synchronous distant metastasis and were included in the predictive models. The c-indexes of these models were 0.99 for liver metastasis, 0.99 for lung metastasis, and 1 for bone metastasis. Predictive nomograms for the presence of synchronous liver, lung, and bone metastasis were developed and may be used to predict the probability of distant disease in rectal cancer patients.

Objective Breast cancer patients are associated with an increased risk for committing suicide. The purpose of this study is to study the trends in the incidence of suicide mortality and identify pertinent risk factors among patients with breast cancer. Methods A retrospective examination of the Surveillance Epidemiology and End Results (SEER) database between years 1973 and 2013 was performed. Results Overall, 474,128 patients were identified of which 773 had committed suicide. There were no significant differences in the incidence of suicide mortality over the last three decades (1984-1993: 0.14%, 1994-2003: 0.16%, 2004-2013: 0.17%, p=0.173). On logistic regression, younger age (

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are an increasing cause of resistant infections among patients with malignancy. This study sought to estimate the prevalence of bloodstream infections (BSIs) caused by ESBL-PE in this population and to examine regional and temporal differences. The PubMed and EMBASE databases (to 30 April 2016) were searched to identify studies reporting ESBL-PE BSI rates among patients with malignancies. Of 593 non-duplicate reports, 22 studies providing data on 5650 BSI cases satisfied the inclusion criteria. Among all BSIs the pooled prevalence of ESBL-PE was 11% (95% CI 8–15%) and among Gram-negative BSIs it was 21% (95% CI 16–27%). Among patients with haematological malignancies, the pooled ESBL-PE prevalence was 11% (95% CI 8–15%), whereas no studies providing specific data on patients with solid tumours were identified. Stratifying per geographic region, the pooled prevalence was 7% each in Europe (95% CI 5–11%), the Eastern Mediterranean region (95% CI 4–11%) and South America (95% CI 2–14%), 10% in the Western Pacific region (95% CI 4–19%) and 30% in Southeast Asia (95% CI 18–44%). Importantly, there was a 7.1% annual increase in the ESBL-PE incidence ( P = 0.004). Overall, ca. 1 in 10 BSIs in patients with malignancy is caused by ESBL-PE and in some areas this rate can be as high as 1 in 3 cases. Additionally, the incidence of these resistant infections is rising. These findings should be considered when selecting empirical antimicrobial therapy and should prompt strict adherence to antimicrobial stewardship.

In recent years, a growing amount of research has begun to focus on the oral microbiome due to its links with health and systemic disease. The oral microbiome has numerous advantages that make it particularly useful for clinical studies, including non-invasive collection, temporal stability, and lower complexity relative to other niches, such as the gut. Despite recent discoveries made in this area, it is unknown how the oral microbiome responds to short-term hospitalization. Previous studies have demonstrated that the gut microbiome is extremely sensitive to short-term hospitalization and that these changes are associated with significant morbidity and mortality. Here, we present a comprehensive pipeline for reliable bedside collection, sequencing, and analysis of the human salivary microbiome. We also develop a novel oral-specific mock community for pipeline validation. Using our methodology, we analyzed the salivary microbiomes of patients before and during hospitalization or azithromycin treatment to profile impacts on this community. Our findings indicate that azithromycin alters the diversity and taxonomic composition of the salivary microbiome; however, we also found that short-term hospitalization does not impact the richness or structure of this community, suggesting that the oral cavity may be less susceptible to dysbiosis during short-term hospitalization.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) constitute a global threat and are prevalent in both nosocomial and community settings. These pathogens have been associated with delays in initiation of appropriate antimicrobial therapy and worse clinical outcomes. Patients with solid or hematologic malignancy represent a high-risk population for both colonization and infection with ESBL-PE. Areas covered: A description of the microbiology and epidemiology of the ESBL-PE is presented. Also, we explore studies on ESBL-PE colonization and infection, and examine areas where future research is needed. Expert commentary: ESBL-PE constitute an increasing threat to patients with malignancy. Unfortunately, substantial geographic variations as well as knowledge gaps in certain regions of the world limit our ability to reach conclusions that are valid globally. Furthermore, there is limited evidence regarding the optimal ways to prevent and manage infections caused by ESBL-PE. Research is urgently needed to elucidate these areas and allow the institution of appropriate infection control and antimicrobial stewardship policies and recommendations.

The aim of the present study was to elucidate the clinico-pathological characteristics of female patients with lower genital tract rhabdomyosarcoma (RMS) stratified by age group and investigate their prognosis, using a multi-institutional database. The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database was accessed (1973–2013) and a cohort of females diagnosed with RMS of the lower genital tract (vulva, vagina, cervix) was drawn. Five-year overall survival (OS) rate was estimated following generation of Kaplan–Meier curves and compared with the log-rank test. A total of 144 eligible cases were identified; 51.4 and 48.6% originated from the vagina/vulva and the cervix, respectively. Median patient age was 16 years and distant metastases were rare (ten cases). The majority of tumors were of embryonal histology (75.7%). Non-embryonal RMS was more prevalent in the older patient groups. Tumors originating from the cervix were more common among adolescents and premenopausal women. Rate of LN involvement was 52.9 and 20% for vulvovaginal and cervical tumors (p = 0.02). Five-year OS rate was 68.4%; factors associated with better OS were younger age, absence of distant metastasis, embryonal histology, negative LNs, and performance of surgery. For prepubertal girls and adolescents, radical surgery did not confer a survival benefit compared to local tumor excision. RMS of the lower genital tract primarily affects prepubertal girls and adolescents, who have excellent survival rates; however, outcomes for adults remain poor.

Background Advanced age, history of hospitalization, and antibiotic consumption are associated with the pathogenesis of Clostridium difficile infection (CDI). Long-term care facilities (LTCFs) represent a setting where CDI has been increasingly reported. We aimed to estimate the actual attributable burden of CDI to LTCF stay and determine the characteristics of the disease epidemiology in this setting. Design IRB-approved retrospective cohort study. Setting LTCF and community. Participants One thousand seven hundred and sixty-one patients. Measurements/Results The prevalence of CDI among LTCF residents was 22.4%, whereas the prevalence of CDI among community residents was 6.7% (P < .001). The prevalence of CDI among LTCF residents was significantly higher in both the 18–64 (P < .001) and the ≥65 age groups (P < .010). Measures of hospital exposure and antibiotic consumption between LTCF and community residents prior to CDI diagnosis were non-significant. A strict matching (1:2) between LTCF and community residents adjusting for age, total number of hospital admissions and antibiotic consumption showed that the odds of CDI for an LTCF resident were 6.89 times larger than the odds for a community resident (OR = 6.89, 95%, 4.67–10.17). For an LTCF resident with CDI, the odds of manifesting severe disease were 3.25 times larger than the odds for a community resident with CDI (OR = 3.25, 95%, 1.81–5.86). LTCF residents were more frequently hospitalized (P = .002) required longer hospital stays for their CDI management (P = .03) and had more recurrent CDI cases than community residents (P = .04). Conclusions Our study highlights the increased burden of CDI among LTCF residents independently of age, antibiotic, and hospitalization background. Severe CDI disease and recurrences are more frequent in LTCFs.

Purpose Over the last 6 years, 8 treatments were FDA-approved for patients with distant metastatic cutaneous melanoma on the basis of prolonged overall survival. Several of these treatments are either FDA-approved or in advanced stages of clinical development in the adjuvant setting for patients with high risk for relapse melanoma. The neoadjuvant setting provides even greater opportunities to incorporate these treatments into a more effective multimodality management. While most neoadjuvant strategies involve single modality approach to date, the ability of radiation therapy to synergize with immunotherapies in distant metastatic melanoma should also be considered in the neoadjuvant setting. Methods and results 4 patients with unresectable stage III melanoma were treated with PD-1 inhibitors and concurrently received hypofractionated radiation therapy. This regimen not only rendered their surgery feasible, but also resulted in complete pathologic response in two of these patients without inducing any serious adverse events or surgical complications. Furthermore, we present clinicopathologic and molecular data that may in part explain differences in complete pathologic response among these four subjects. Conclusions In this limited case series, our neoadjuvant combined modality regimen was effective and well tolerated. Concurrent PD-1 blockade with radiation therapy that could readily be applied into daily oncology practice is not limited in particular patient subgroups (e.g. BRAFV600-mutant) and may have a better toxicity profile than concurrent immune checkpoint blockade.

The Aspergillus genus of fungi is associated with a broad range of diseases, from severe invasive infections in immunocompromised hosts, to semi-invasive, to chronic disease. Invasive aspergillosis in particular constitutes the most common fungal infection among hematopoietic stem cell transplant (HSCT) recipients and the second-most common fungal infection among solid organ transplant recipients (1), with associated mortality rates that exceed 50% (1,2). The new IDSA guidelines (3) provide a valuable tool concerning prevention, diagnosis and management of these diseases, building upon the previous version (4), with the incorporation of new clinical data. Thus, they provide a useful, up-to-date scaffold to assist in clinical decision-making.

Cancer patients are vulnerable to infections, including those with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), and most of these infections are associated with colonisation of the gastrointestinal tract. The aim of this study was to estimate the prevalence of gastrointestinal colonisation with ESBL-PE cancer populations and to determine the risk for subsequent bloodstream infection (BSI) with these pathogens. PubMed and EMBASE databases were searched from 1 January 1991 to 1 March 2016 to identify studies regarding ESBL-PE colonisation among patients with malignancies. Ten studies (out of 561 non-duplicate articles) were included, providing data on 2211 patients. The pooled prevalence of ESBL-PE colonisation was 19% [95% confidence interval (CI) 8-32%]. Stratifying per region, the pooled prevalence in Europe was 15% (95% CI 10-21%), whereas in Asia the pooled prevalence was 31% (95% CI 4-69%). In addition, the pooled prevalence was 15% (95% CI 7-24%) among patients with haematological malignancy, whereas no studies were identified that included solely patients with solid tumours. Notably, cancer patients with ESBL-PE colonisation were 12.98 times (95% CI 3.91-43.06) more likely to develop a BSI with ESBL-PE during their hospitalisation compared with non-colonised patients. We found that, overall, one in five patients with cancer is colonised with ESBL-PE and the incidence can be as high as one in three in Asia. This is important because colonisation was associated with an almost 13 times higher risk for developing BSI with ESBL-PE. Screening measures should be evaluated to identify their clinical benefit in patients with malignancy.

The opioid epidemic is an escalating health crisis. We evaluated the impact of opioid prescription rates and socioeconomic determinants on opioid mortality rates, and identified potential differences in prescription patterns by categories of practitioners. We combined the 2013 and 2014 Medicare Part D data and quantified the opioid prescription rate in a county level cross-sectional study with data from 2710 counties, 468,614 unique prescribers and 46,665,037 beneficiaries. We used the CDC WONDER database to obtain opioid-related mortality data. Socioeconomic characteristics for each county were acquired from the US Census Bureau. The average national opioid prescription rate was 3.86 claims per beneficiary that received a prescription for opioids (95% CI 3.86–3.86). At a county level, overall opioid prescription rates (p

Background Mismanagement of asymptomatic patients with positive urine cultures (referred to as asymptomatic bacteriuria [ASB] in the literature) promotes antimicrobial resistance and results in unnecessary antimicrobial-related adverse events and increased health care costs. Methods We conducted a systematic review and meta-analysis of studies that reported on the rate of inappropriate ASB treatment published from 2004 to August 2016. The appropriateness of antimicrobial administration was based on guidelines published by the Infectious Diseases Society of America. Results A total of 2142 nonduplicate articles were identified, and among them 30 fulfilled our inclusion criteria. The pooled prevalence of antimicrobial treatment among 4129 cases who did not require treatment was 45% (95% CI, 39–50). Isolation of gram-negative pathogens (odds ratio [OR], 3.58; 95% CI, 2.12–6.06), pyuria (OR, 2.83; 95% CI, 1.9–4.22), nitrite positivity (OR, 3.83; 95% CI, 2.24–6.54), and female sex (OR, 2.11; 95% CI, 1.46–3.06) increased the odds of receiving treatment. The rates of treatment were higher in studies with ≥100 000 cfu/mL cutoff values compared with Conclusion The mismanagement of ASB remains extremely frequent. Female sex and the overinterpretation of certain laboratory data (positive nitrites, pyuria, isolation of gram-negative bacteria and cultures with higher microbial count) are associated with overtreatment. Even simple stewardship interventions can be particularly effective, and antimicrobial stewardship programs should focus on the challenge of differentiating true urinary tract infection from ASB.

Background Conditional survival (CS) analysis represents a novel method that may provide more clinically relevant perspectives to cancer management compared to conventional survival analysis. The purpose of this study was to evaluate conditional survival for patients with intraductal papillary mucinous neoplasms (IPMNs) undergoing curative resection. Methods A retrospective search of the Surveillance Epidemiology and End Results (SEER) database was performed. Three-year conditional survival (i.e. probability that a patient will survive an additional 3 years if they have already survived x years) was calculated using the formula 3-CS(x)=OS(x+3)/OS(x), where OS represents overall survival. Results Overall, 1303 patients were identified, with mean age of 65.2 ± 12.2 years. 3-CS at 1, 3 and 5 years after diagnosis was 35.8%, 47.5% and 44.7%. Patients with stage III/IV disease demonstrated small differences in 3-CS at 1–3 years after diagnosis compared to patients with stage I/II disease (I/II: 35.1%–46.9%, III/IV: 22.1%–42.3%, d range 0.09–0.28), while their 3-CS was superior at 4–5 years after diagnosis (I/II: 41.5%–45.7%, III/IV: 57.9%–64.7%, d range 0.24–0.47). Differences in 3-CS based on tumor grade displayed a different pattern, with small differences at 1–3 years after diagnosis (well-differentiated (WD)/moderately-differentiated (MD): 34.6%–50%, poorly-differentiated (PD)/undifferentiated (UD): 23.2%–40%, d range 0.18–0.24), before becoming prominent at 4–5 years after diagnosis (WD/MD: 50%–51.7%, PD/UD: 24.1%–30%, d range 0.4–0.55). Conclusions Conditional survival for patients with IPMNs undergoing resection improves over time, especially for patients with high-risk features. This information may be used to provide individualized approaches to surveillance and treatment.

The objectives of this study were to estimate the colonisation rate by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) among residents of long-term care facilities (LTCFs) and to identify pertinent risk factors. A systematic search of PubMed and EMBASE databases for studies published up to May 2016 that provided raw data for gastrointestinal colonisation by ESBL-PE among LTCF residents was performed. Twenty-three studies reporting data on 9775 screened subjects met the inclusion criteria. The pooled prevalence of ESBL-PE among LTCF residents was 18% [95% confidence interval (CI) 12–24%]. Risk factors for colonisation included recent antibiotic use (within 6 months) [odds ratio (OR) = 2.06, 95% CI 1.78–2.38], previous hospitalisation (within 2.5 years) (OR = 1.50, 95% CI 1.04–2.15), history of invasive procedures (within 2 years) (OR = 2.79, 95% CI 1.66–4.70), previous ESBL-PE colonisation or infection (OR = 6.77, 95% CI 1.33–34.62), history of urinary tract infection (OR = 2.66, 95% CI 1.76–4.01) and urinary catheter use (OR = 2.55, 95% CI 1.29–5.04). In conclusion, almost one in five LTCF residents is colonised with ESBL-PE, and colonised residents are more likely to have a history of recent antibiotic use or healthcare facility utilisation. Strict adherence to antimicrobial stewardship in LTCFs is needed to address these high resistance rates.

e16085 Background: Patients with renal cell carcinoma (RCC) often harbor risk factors for cardiovascular disease and may receive anti-VEGF agents, which are associated with cardiovascular toxicity. However, the risk for cardiovascular mortality in this patient population is currently unknown. Methods: Utilizing the SEER database, we identified patients with RCC diagnosed between 2007 (approval of sunitinib) and 2015 and selected patients aged ≥ 45 years. We calculated standardized mortality ratios (SMRs) for cardiovascular mortality (ICD-10 codes I00-I99) by comparing the number of observed deaths in the database to the number of expected deaths in age-matched groups of the US general population drawn from the CDC WONDER database. Multivariable Cox regression was used to identify risk factors for cardiovascular mortality in patients with RCC. Results: We identified 36,576 patients with RCC, of which 33,748 (92.3%) were ≥ 45 years old and among these, 1650 (4.9%) died of cardiovascular diseases. The SMR for cardiovascular mortality was 2.85 (95% CI 2.72-2.99) for all patients, 2.78 (95% CI 2.62-2.95) for males and 2.86 (95% CI 2.64-3.10) for females. Among the various age groups, the SMR was 4.75 (95% CI 3.82-5.84) for patients aged 45-54 years, 3.35 (95% CI 2.93-3.83) for patients aged 55-64 years, 2.75 (95% CI 2.49-3.04) for patients aged 65-74 years, 2.25 (95% CI 2.07-2.45) for patients aged 75-84 years, and 1.47 (95% CI 1.33-1.61) for patients aged > 85 years. In multivariate analysis, advancing age (HR 1.06, 95% CI 1.06-1.07), male sex (HR 1.18, 95% CI 1.05-1.33), black race (HR 1.48, 95% CI 1.27-1.73), stage IV disease (HR 1.21, 95% CI 1.01-1.45), and performance of surgery directed to the primary tumor (HR 0.33, 95% CI 0.29-0.38) were independently associated with cardiovascular mortality. Conclusions: Patients with RCC possess an almost 3-fold greater risk for cardiovascular mortality than the general population and this risk is even more pronounced in middle-aged patients. Aggressive management of modifiable cardiovascular risk factors in this patient population is thus warranted.

6519 Background: Antineoplastic medication prices are overall increasing yet this phenomenon is not limited to new medications but can also be observed in already established medications. Methods: We accessed the yearly payment files from Medicare Part B for injectable antineoplastic agents (codes J8501-J9999) for the years 2010-2017 and all costs were adjusted to 2017 USD to adjust for inflation. We then calculated the price-per-dose for every medication and compared that price with the price-per-dose that the medication would have if its initial price was only affected by inflation. We subsequently multiplied the difference with the total doses of the medication administered in order to calculate the additional cost accrued by Medicare from medications whose price had increased more than the inflation rates. Only medications with total annual payments >10 million USD/yr were included in the analysis. Notably, Medicare provides reimbursement based on average U.S. market prices. Results: Price increases were noted on average in 64.5% of already established medications (median 69.6%, range 45.4-74.1%), leading to an average additional extra cost of 243 million USD per year (range 140-330 million USD), for a total of 1.7 billion USD over the 7 years of observation. Rituximab (539 million USD), trastuzumab (221 million USD), and bevacizumab (178 million USD) accrued the highest extra costs. This extra cost represented 4.6-8.9% of the annual total Medicare Part B spending for antineoplastic medications (Table). Conclusions: The majority of already established injectable chemotherapeutics demonstrate price increases that lead to substantial additional financial cost to Medicare and likely other U.S. markets as well. Price increases of Medicare Part B antineoplastic medications with cost >10 million USD/yr. [Table: see text]

Background Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development. Methods We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or β-lactam/β-lactamase inhibitors (BL/BLIs). Results Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83–1.37; I2 = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25–1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491–2.095; I2 = 62.5%; P = .046), compared with the use of empiric carbapenems. Conclusions These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.

Background Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting. Methods We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016. Results Thirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035–1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038–2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089–2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004–1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009). Conclusions Cefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

Background Vancomycin-resistant enterococci (VRE) cause severe infections among patients with malignancy, and these infections are usually preceded by gastrointestinal colonization. Methods We searched the PubMed and EMBASE databases (up to May 26, 2016) to identify studies that reported data on VRE gastrointestinal colonization among patients with solid or hematologic malignancy. Results Thirty-four studies, reporting data on 8391 patients with malignancy, were included in our analysis. The pooled prevalence of VRE colonization in this population was 20% (95% confidence interval [CI], 14%–26%). Among patients with hematologic malignancy, 24% (95% CI, 16%–34%) were colonized with VRE, whereas no studies reported data solely on patients with solid malignancy. Patients with acute leukemia were at higher risk for VRE colonization (risk ratio [RR] = 1.95; 95% CI, 1.17–3.26). Vancomycin use or hospitalization within 3 months were associated with increased colonization risk (RR = 1.92, 95% CI = 1.06–3.45 and RR = 4.68, 95% CI = 1.66–13.21, respectively). Among the different geographic regions, VRE colonization rate was 21% in North America (95% CI, 13%–31%), 20% in Europe (95% CI, 9%–34%), 23% in Asia (95% CI, 13%–38%), and 4% in Oceania (95% CI, 2%–6%). More importantly, colonized patients were 24.15 (95% CI, 10.27–56.79) times more likely to develop a bloodstream infection due to VRE than noncolonized patients. Conclusions A substantial VRE colonization burden exists among patients with malignancy, and colonization greatly increases the risk for subsequent VRE bloodstream infection. Adherence to antimicrobial stewardship is needed, and a re-evaluation of the use of vancomycin as empiric therapy in this patient population may be warranted.

Background Urinary tract infections (UTIs) are the most common infectious complications among renal transplant recipients (RTR). UTIs caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) have been associated with inferior clinical outcomes and increased financial burden. Methods We performed a systematic review and meta-analysis by searching through the PubMed and EMBASE databases (to May 20, 2016) and identifying studies that reported data on the number of RTR who developed an ESBL-PE UTI. Results Our analysis included seven studies, out of 357 non-duplicate articles, that provided data on 2824 patients. Among them, 10% (95% confidence interval [CI] 4%-17%) developed an ESBL-PE UTI over their follow-up periods. The proportion of RTR affected by an ESBL-PE UTI was 2% in North America (95% CI 1%-3%), 5% in Europe (95% CI 4%-6%), 17% in South America (95% CI 10%-27%), and 33% in Asia (95% CI 27%-41%). In addition, patients affected with an ESBL-PE UTI were 2.75-times (95% CI 1.97-3.83) more likely to suffer a recurrent UTI. Conclusions Based on a limited number of studies, one in 10 RTR will develop a UTI caused by an ESBL-PE, and these patients face an almost 3 times greater risk of recurrence. A more rigorous monitoring of RTR, both during and after resolution of their infection, should be evaluated in order to reduce the incidence and the clinical impact of these resistant infections.

Medication shortages are frequent and have clinical and financial ramifications; however, their effect on drug prices remains unknown. To examine price progression of medications affected by a shortage. We collected prices of medications covered under Medicare Part B, reflective of general market prices, and data on clinically relevant shortages for the period 2005–16. We used linear mixed-effects models to examine the price growth of affected medications. Shortage medications demonstrated a quarterly price growth of −0.5 % (95 % confidence interval [CI] −1.6, 0.6) in the period preceding a shortage, 4.3 % (95 % CI 3.6, 4.5) during a shortage, and 4.1 % (95 % CI 2.6, 5.5) in the post-shortage period. Medications not affected by a shortage had a quarterly price growth of 0.2 % (95 % CI −0.3, 0.6). Medication shortages are associated with price increases, and these increases are likely reactive to the low profitability of the affected medications and thus, proactive collaboration between the US Food and Drug Administration and industry can serve to identify low-profit drugs and evaluate measures to ensure continued production.

Malignant and borderline ovarian tumors of epithelial origin are rarely encountered among prepubertal girls and adolescents. The aim of this population-based study was to elucidate their clinicopathological characteristics and prognosis using a multi-institutional tumor registry.The National Cancer Institute's Surveillance, Epidemiology, and End Results database was accessed and a cohort of females aged=19years old, diagnosed between 1988 and 2013 with a borderline ovarian tumor (BOT) or a malignant epithelial ovarian carcinoma (EOC) was accessed. Observed survival (OS) was assessed using the Kaplan-Meier method. Comparisons were made using the log-rank test.A total of 114 cases diagnosed with BOT between 1988 and 2000 were identified; 61/114 (53.5%) and 51/114 (44.8%) of BOT were of serous or mucinous histology respectively. Ten-year OS for those with BOT was 97.3%. A total of 140 cases of EOC were identified. Median age was 17 years and the most common histological subtypes were mucinous 79/140 (56.4%) and serous 29/140 (20.7%) adenocarcinoma. Most had stage I disease 92/131 (70.2%) and fertility-sparing surgery was commonly performed. Five-year OS for those with stage I disease was 93.6% compared to 48.3% for cases with exta-ovarian tumor spread (p0.001).BOT and EOC are exceedingly rare in the pediatric and adolescent population. In this age group EOC consists mostly of low-grade mucinous and serous tumors confined to the ovary. OS survival for those with stage I disease is excellent.

The objective of this study was to estimate the rate and significance of colonisation with vancomycin-resistant enterococci (VRE) among hospitalised children. The PubMed and EMBASE databases were systematically searched (last accessed on 29 May 2016) to identify studies evaluating VRE colonisation of the gastrointestinal tract of hospitalised children in non-outbreak periods. Of 945 non-duplicate citations, 19 studies enrolling 20 234 children were included. The overall and paediatric intensive care unit (PICU) rate of VRE colonisation were both 5% [95% confidence interval (CI) 3–8% overall and 95% CI 2–9% in the PICU] but was 23% in haematology/oncology units (95% CI 18–29%). Studies that were exclusively performed in haematology/oncology units reported significantly higher rates compared with all other studies in the univariate and multivariate analyses ( P = 0.001). Previous vancomycin [risk ratio (RR) = 4.34, 95% CI 2.77–6.82] or ceftazidime (RR = 4.15, 95% CI 2.69–6.40) use was a risk factor for VRE colonisation. Importantly, VRE colonisation increased the risk of subsequent VRE infection (RR = 8.75, 95% CI 3.19–23.97). In conclusion, a high rate of VRE colonisation was found among hospitalised children in institutions that performed targeted screening. Importantly, colonised children were almost 9 times more likely to develop subsequent VRE infection. Judicious use of specific antibiotics along with intensification of infection control measures should be considered in high-prevalence institutions. Also, the high incidence of VRE colonisation among children with haematological/oncological diseases identifies a high-risk population.

Summary Objectives We aimed to evaluate the prevalence of paediatric urinary tract infections (UTIs) caused by extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), identify predisposing factors and examine their effect on the length of hospital stay (LOS). Methods For this systematic review and meta-analysis, we searched the PubMed and EMBASE databases for studies that provide data on the rate of ESBL-PE among paediatric UTIs. Results Out of 1828 non-duplicate citations, 16 studies reporting a total of 7374 cases of UTI were included. The prevalence of ESBL-PE was 14% [(95%CI 8, 21)]. Vesicoureteral reflux (VUR) [OR = 2.79, (95%CI 1.39, 5.58)], history of UTI [OR = 2.89 (95%CI 1.78, 4.68)] and recent antibiotic use [OR = 3.92, (95%CI 1.76, 8.7)] were identified as risk factors. The LOS was significantly longer among children infected with ESBL-PE, compared to those infected with other uropathogens. [SMD = 0.88, (95%CI 0.40, 1.35)]. Conclusions In the paediatric population, 1 out of 7 UTIs are caused by ESBL-PE. Patients with VUR, previous UTI or recent antibiotic use constitute a high risk group and these pathogens are associated with increased LOS. The significant incidence of ESBL-PE in this population should be taken into consideration in the development of empiric treatment protocols and antibiotic stewardship programmes, especially in high-prevalence areas.

Background Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) may cause severe infections, often preceded by ESBL-E gastrointestinal (GI) colonization. Methods We conducted a review of the literature, investigating the prevalence of ESBL-E GI colonization in solid organ transplant (SOT) patients and the risk for subsequent ESBL-E infection. We searched the PubMed and EMBASE databases (to April 1, 2016) looking for studies that contained data on ESBL-E colonization among transplant patients. Results Out of 341 non-duplicate citations, 4 studies reporting data on 1089 patients fulfilled our inclusion criteria. Among them, the pooled prevalence for ESBL-E colonization was 18% (95% confidence interval [CI] 5%-36%). Stratifying by transplant type, we identified an ESBL-E colonization rate of 17% (95% CI 3%-39%) among liver transplant recipients and 24% (single report) among kidney transplant recipients. Conclusions Among SOT patients, approximately 1 in 5 patients is colonized with ESBL-E, although this finding may be skewed by reporting bias from centers with high ESBL-E prevalence. ESBL-E screening in SOT patients should be considered and evaluated in future studies. This article is protected by copyright. All rights reserved.