Pre-existing Malignancy Research Articles

Association of Hypothyroidism and Poor Bowel Prep Quality in Initial Screening Colonoscopies

Introduction: Inadequate colonoscopy bowel preparation increases procedural complications. Hypothy-roidism reduces esophageal and gastric motor activity. Investigation to determine if poor prep correlated with incidence of hypothyroidism and/or higher average thyroid stimulat-ing hormone (TSH) levels was undertaken. Methods: Data were collected on 4,200 patients from the Louisville, KY Robley Rex VA Medical Center. Specific exclusion criteria included pro-inflammatory states that are postulated to increase polyposis and pre-existing malignancies. From this group, 328 patients were found to have poor prep and 305 patients with adequate prep were randomly selected to serve as a control group. Average age of patients was 64 and 55 for poor prep and adequate prep, respectively. 306 (94%) and 271 (89%) of poor prep and adequate prep patients were males. I Inadequate bowel prep was defined as “poor” by the performing physician. Patients were hypothyroid if diagnosed and actively being treated. Maximum TSH levels were obtained. Analysis model selection was performed using a stepwise selection process where a model of best fit was produced based on Akaike information criterion (AIC). AIC estimates quality of various models, relative to each other. A Poisson regression was performed, with p-values of <0.05 being deemed statistically significant (Table 1). Figure 1 is a Forest plot of multiple logistic regression using the following variables: African-American race, Male sex, Age, Hypothyroidism, and peak TSH levels.226_A Figure 1. Patient demographics Adequate and poor prep patients with p-values.Results: 40 poor prep and 24 adequate prep patients had a diagnosis of hypothyroidism (p =0.086). The median peak TSH level was 3.1 and 2.2 for poor prep and controls, respectively, which was statistically significant (p<0.001). Multivariate regression demonstrated that TSH levels were a statistically significant factor in bowel prep quality (OR 1.08, CI 1.03-1.15, p-value= 0.010), when controlling for other variables. Conclusion: Patients with poor prep had a higher mean TSH level then controls. A larger number of patients with hypothyroidism had poor prep, but the result was not statistically significant. TSH levels had a statistically significant association with poor prep quality. However, whether or not this is physiologically significant is difficult to determine, and higher powered studies are needed. Patients with abnormal TSH levels, but who are not hypothyroid, may benefit from pre-colonoscopy treatment or intense prep regimens.226_B Figure 2. Forest Plot of multiple logistic regression with corresponding odds ratio, CI, and p-value.

Long-Term Outcome of Mucinous Pancreatic Cystic Lesions in Cancer Survivors or Patients With Extra-Pancreatic Malignancy

Introduction: During surveillance or staging, cancer survivors or patients with extra-pancreatic malignancy may be found to have pancreatic cysts (PCs). Clinical guidelines support decisions based on cyst features without consideration of patient characteristics, including extra-pancreatic cancer-related factors. We evaluated long-term outcomes to assess the behavior of pancreatic cysts in patients with historical or concomitant malignancies. Methods: We retrospectively identified cancer survivors or patients with an extra-pancreatic malignancy who underwent EUS-FNA for suspected PCs from 1/1/2007 to 12/31/2012 and had follow-up details up to 9/1/2017. Comorbidities were classified by Charlson Comorbidity Index (CMI). Cyst high risk features were classified using the 2017 Fukuoka consensus guidelines. Descriptive statistics were used to summarize patient and procedure characteristics and non-parametric tests were used to calculate differences between medians. Results: A total of 113 patients were identified. Median age was 69 (IQR 61-75). Median CMI was 4 (IQR 3-5). By cancer history, 53 (46.9%) were cancer survivors. Most common pre-existing malignancy was breast cancer (N=21, 18.6%). Ten (8.9%) patients had a family history of pancreatic cancer. Cytology identified a mucinous lesion in 73 (64.6%). The median size of mucinous PCs was 21 mm (IQR 14-26) compared to 20 mm (IQR 14.75-25) in other PCs. (p=0.93) Mucinous PCLs were low risk in 55/73 (75.3%) patients and 18/73 (24.7%) had at least one high risk feature on EUS-FNA. In patients with mucinous lesions (n=73), the median follow up after diagnosis was 5 (IQR 4-7) years and 17 (23.3%) patients died of non-pancreatic related causes. Stable lesions were identified in 65 (89%). Six (8.2%) patients were found to have a lesion that increased in size. Ten (13.7%) patients underwent pancreatic resection. On pathology, 7 patients had IPMN with low grade dysplasia, 2 patients high grade dysplasia and one patient had a serous cystadenoma. Conclusion: Over a median follow up of 5 years, two patients (1.8%) were found to have high grade dysplasia and had surgical resection. Patients with extra-pancreatic malignancies are likely at the same risk for malignant degeneration relative to the general population and patients with low risk mucinous lesions could be safely followed. In high-risk patients, comorbidities should be factored in with cyst features for surgical decision-making.

A Practical Approach to the Use of Conventional Synthetic, Biologic and Targeted Synthetic Disease Modifying Anti-Rheumatic Drugs for the Treatment of Inflammatory Arthritis in Patients with a History of Malignancy.

Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) have been used in the treatment of inflammatory arthritis (IA) for many years. More recently, biologic (bDMARDs) and targeted synthetic (tsDMARDs) DMARDs have further improved treatment. Due to increased patient longevity and effective oncology treatment, rheumatologists often encounter patients with IA and previous malignancy. The immunosuppressive effect of DMARDs causes concern regarding impaired tumour surveillance with a potential increased risk of malignancy. We reviewed the literature regarding the risk of malignancy in patients on cs-/b-/tsDMARDS and sought to provide practical advice regarding use of these drugs in patients with previous malignancy. Data from randomised controlled trials is limited as patients with pre-existing malignancy are often excluded. Reassuringly, an increasing range of "real world" data from various national b/tsDMARD registries has not provided a convincing signal that these drugs increase tumour recurrence. Nevertheless, awareness of, and adherence to, national screening guidelines for malignancy is important. Given the improvement in quality of life achieved with these novel and well-tolerated therapeutic agents, the benefit/risk profile remains overwhelmingly favourable in most patients.

Infection characteristics and treatment of Staphylococcus aureus bacteraemia at a tertiary children\u2019s hospital

BackgroundStaphylococcus aureus bacteraemia (SAB) causes considerable morbidity and mortality in children. Despite this, its epidemiology and risk factors are poorly understood, with minimal paediatric clinical trial data available to guide clinicians in management. We conducted a pilot study to characterise SAB and validate a severity classification for use in future clinical trials.MethodsPatients with SAB were prospectively identified at Princess Margaret Hospital for Children (Perth, Western Australia) from May 2011 to December 2013. Retrospective data were collected from clinical and laboratory records. Cases were classified based on a priori defined criteria as simple (single or contiguous, peripheral site focus) or complex (multi-site, deep tissue, no focus or sepsis) and tested against risk factors and markers of severity of infection.ResultsThere were 49 cases of SAB (median age 7.7 years), with classification as simple (n = 30, 61%) and complex (n = 19, 39%) respectively. There were no deaths or relapses in our cohort. Only 10% of isolates were methicillin resistant S. aureus (MRSA), and none of these were healthcare-associated. Age, gender, Indigenous status, MRSA and healthcare-associated infections were not predictive of complex infection. Pre-existing malignancy was a risk factor for complex infection (p = 0.02). Complex infections were associated with a higher median maximum C reactive protein (216 mg/L vs 50 mg/L, p = < 0.001), longer median length of stay (42 vs 10 days, p = < 0.001) and longer duration of antibiotic therapy (43 vs 34 days, p = 0.03).DiscussionThis is the first attempt to categorise paediatric SAB as simple versus complex, to guide clinicians in decision making.ConclusionsThere is a wide spectrum of disease severity in paediatric SAB, with maximum CRP, length of stay, and duration of therapy greater in those with complex disease. Distinct cohorts with simple and complex courses which may be a target for future clinical trials have been described.

Isolated proximal greater saphenous vein thrombosis and the risk of propagation to deep vein thrombosis and pulmonary embolism

ObjectivesGreater saphenous vein (GSV) thrombosis is concerning due to its close proximity to the deep femoral vein. This study sought to identify the risk of propagation to deep vein thrombosis (DVT) or pulmonary embolism (PE) among patients with isolated proximal GSV superficial thrombosis and describe provider practice patterns related to treatment.Materials and methodsThis is an Institutional Review Board-approved retrospective multi-center study. Patients presented to one of three possible emergency departments in a large health system. About 21,716 patients were queried through the electronic medical record. Ninety-five patients or 0.4% of study subjects met inclusion criteria of isolated proximal GSV thrombosis. Forty-five patients were excluded, leaving a final data set of 40 patients. Investigators recorded radiology impressions, patient demographics, past medical history, DVT/PE risk factors, and treatment plans. Propagation of GSV thrombosis to DVT/PE was also noted. Follow-up methods included chart review, primary care physician follow-up, and direct, scripted patient follow-up phone calls. Descriptive statistics were applied to study subjects using SAS for Windows, version 9.3.ResultsThree patients (7.5%) had progression of GSV thrombosis to DVT/PE. Twenty percent of patients without malignancy were treated with anticoagulation compared to 14% of those with preexisting malignancy upon initial diagnosis of isolated GSV thrombosis. Forty-five percent of patients were prescribed some type of supportive therapy to aid in the treatment of GSV thrombosis.ConclusionIsolated proximal GSV thrombosis, while uncommon, may frequently progress to DVT or PE. Our work suggests clinicians should consider anticoagulation for isolated GSV thrombosis.

Outcomes of Heart Transplant Recipients With Preexisting Malignancies

BackgroundEnsuring careful selection of heart transplant recipients with pretransplant malignancies (PTM) has been suggested in several retrospective studies. However, cancer survival rates continue to increase and we still lack outcomes data on PTM patients who have undergone heart transplantation (HT) within the Asian region. Herein we report pretransplant characteristics and outcomes among PTM patients with HT. MethodsA total of 354 patients underwent HT from January 2004 to January 2016. Eight of these patients had a history malignancy that was being treated before transplantation. Posttransplant outcomes and clinical characteristics were collected and possible prognostic factors analyzed. ResultsThe median age of the patients with a preexisting malignancy was 60 years. The PTM group included 5 males and 3 females, with a median duration of follow-up of 43 months. In this group there were 2 patients with lymphoma after chemotherapy, 1 with colon cancer postoperatively, and 1 was on chemotherapy. In the other 4 patients, nasopharyngeal cancer, thyroid cancer, breast cancer, and endometrial cancer were identified, and each had undergone treatment. Only 1 premalignancy patient, with nasopharyngeal cancer, had disease recurrence. The 5-year overall survival of these patients was 50.0 ± 17.7%, but 5-year survival for those without PTM was 68.7 ± 2.0%. ConclusionPTM was 2.3% in our cohort. PTM is associated with an increased risk of all-cause mortality. Thus, our findings suggest careful consideration when selecting PTM patients for HT.

Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis.

The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy following sepsis.

Factors Influencing Prostate Specific Antigen Testing in the United States

IntroductionGiven the ongoing controversies regarding its benefit, prostate specific antigen based prostate cancer screening should be offered with patient preferences in mind. Understanding subsets of men who may or may not choose prostate specific antigen screening and their associated characteristics may allow more efficient care and may identify subsets of patients for whom additional counseling is warranted. MethodsWe analyzed male participants from the 2001 to 2010 cycles of the NHANES (National Health and Nutrition Examination Survey) who were 40 years old or older, and without a history of prostate cancer, recent prostate manipulation or hormone therapy use (8,133). All men were given an opportunity to undergo or refuse prostate specific antigen testing after a standardized explanation about prostate cancer screening from a physician. Univariable and multivariable logistic regressions were conducted after adjusting for survey weights to identify independent sociodemographic and clinical predictors for opting out of prostate specific antigen testing. ResultsA total of 7,732 men met the inclusion criteria. Overall 95.64% of the study cohort elected to undergo prostate specific antigen testing. The odds of declining prostate specific antigen testing were significantly higher in men 80 years old or older (OR 1.78, p=0.008), black men (OR 3.23, p <0.001), divorced/separated men (OR 1.66, p=0.002) and men with a preexisting nonprostate malignancy (OR 1.65, p=0.012). ConclusionsIn the setting of the NHANES program, between 2001 and 2010 the majority of men who were offered prostate cancer screening underwent prostate specific antigen testing. Black men, a subgroup subject to more aggressive prostate cancer, were more likely to refuse prostate specific antigen testing.

Modelling the Development of Precancerous Polyps: Utility of Social History, Comorbidities, FOBT/FIT Testing, and NSAID Use

Introduction: Studies have attempted to ascertain the risk factors (RF) for developing colorectal cancer (CRC), but few have attempted to elucidate the causes of precancerous (PC) polyposis. Early detection of PC polyps is essential to prevent progression to CRC. Evaluation of RF such as family history (FH), tobacco and alcohol abuse, and glycemic control may be useful in determining which patients may be more likely to have PC polyps. Methods: Data were collected on 4200 patients at the Robley Rex VAMC in Louisville, Ky. 2758 were excluded based on exclusion criteria: diagnosis of IBD and pre-existing malignancies, birth prior to 1948, poor bowel preparation, and lack of pathologic/histologic data from first colonoscopy. Of the 1442 patients included in the study, a subset had: FOBT or FIT testing, positive family history of CRC, positive smoking history, COPD, history of NSAID use, and hemoglobin A1c within 6 months of colonoscopy. A Poisson regression was used for analysis of relative risk (RR). P<0.05, was deemed statistically significant. Results: Delaying colonoscopy had a RR of 1.03 (P<0.001) per year and males had an increased RR of 1.32 (P=0.011) when compared to females. Family history of CRC (first degree relative) had a RR of 1.179 (P=0.016). Hemoglobin A1c >6.5% had a RR of 1.147 (P=0.031). A positive FOBT/FIT also demonstrated an increase in RR of 1.677 (P<0.001). Current smokers had a RR of 1.215 (P=0.003) when compared to those who never smoked. Patients with COPD had a RR of 1.348 (P<0.001). NSAID users had a decreased RR of 0.688 (P<0.001), if NSAIDs were used within 6 months preceding initial colonoscopy. Conclusion: Development of PC polyps is multifactorial. Increased risk occurs in those with a positive family history, smoking, history of COPD and suboptimal glycemic control. Results indicate that positive FOBT and FIT are also associated with an increased relative risk for PC polyps. This may illustrate a greater ability of these testing modalities to detect PC polyps. Interestingly, the use of NSAIDs appears to have a protective effect, thereby decreasing the RR. The major limitation of this study is the primarily male VA population. In the future, utilization of the factors identified in this study may allow for further risk stratification, resulting in specific target years for initial screening colonoscopies.Table: Table. Model for precancerous colonic polyp risk

Intraorbital tumor as the first and sole manifestation of breast cancer

Orbital metastasis is an unusual occurrence and it is rarely the leading manifestation of systemic malignancy. Breast carcinoma accounts for the majority of metastatic lesions to the eye. We report the case of a 56-year-old woman presenting with ophthalmic symptoms and no history of pre-existing malignancy. A left intraorbital mass was observed on magnetic resonance imaging examination and further investigations revealed a left breast carcinoma as the primary tumor. When confronted with similar findings, ophthalmologists should include orbital metastasis in the differential diagnosis. A thorough clinical assessment is also mandatory.

Case Report: Renal Cell Carcinoma of First Kidney Allograft in Transplanted Recipient for Second Time

The uses of immunosuppressive therapy to preserve the new allograft function can significantly increases the incidence of malignancies in transplanted recipients compared with that of general population. The ability to identify and prevent solid organ tumours in the transplant patients, particularly early stages carcinomas depends on regular screening examinations and strict adherence to prophylactic measures. Screening of the patient and donor prior to transplant can help to detect any underlying pre-existing malignancy. Identification of tumor in renal allograft are usually accidental following ultrasonography, CT scan or MRI imaging, so special attention is essential during any imaging examination of renal allograft to detect an early probable tumours. We hereby, present a case record of 51 years old male who had his first kidney transplant in 1987 on the right side from living unrelated donor; he had approached ESRD in 2006 and underwent his second renal transplantation in June 2006 on the left side from living unrelated donor. Though he had stable kidney function, he started to have intermittent haematuria with lump at right lower loin. Allograft sonography had revealed a big mass in the first right transplanted kidney. CT scan with contrast demonstrated a large lobulated enhancing mass arising from the iliac fossa of first transplanted kidney with local, right common iliac vein metastasis and lungs metastasis. Due to above finding patient underwent right allograft nephrectomy.

Single-Center Experience with Romiplostim for Management of Chemotherapy-Induced Thrombocytopenia (CIT)

Background: Chemotherapy-induced thrombocytopenia (CIT) is a frequent complication in cancer patients receiving myelosuppressive chemotherapy. Current management is limited to platelet transfusions, chemotherapy dose reductions, and delays in treatment. Romiplostim is a thrombopoeitin receptor agonist that increases platelet production by stimulating the maturation of megakaryocytes. It is currently approved for the treatment of idiopathic thrombocytopenic purpura (ITP). Literature describing its efficacy and safety in cancer patients undergoing chemotherapy is limited. The optimal dose and schedule of romiplostim in this setting is also unclear. Here we describe our single-center experience with the use of romiplostim for the management of CIT.Methods: This retrospective case series describes 32 patients who received romiplostim for the management of CIT at DFCI/BWH Cancer Center from August 2008 to April 2016. Patient characteristics collected include age, gender, cancer diagnosis, and chemotherapy. Romiplostim dose adjustments were made per clinican discretion. Four patients received only one dose; these patients were only included in adverse event outcomes analysis. Efficacy outcome measures (N=28 patients) included average dose, average time between doses, achievement of platelet count ≥ 100 x109/L, and completion of at least 2 subsequent chemotherapy cycles without dose-limiting toxicity or delays. Romiplostim-associated adverse events were assessed for safety.Results: Median age was 54 years and 59% of patients had gastrointestinal malignancies. The most commonly-implicated chemotherapeutic agents were platinum-based. Platelet counts improved in all 28 patients included in the efficacy population allowing all 28 patients to receive additional chemotherapy. Median baseline platelets were 68 x 109/L. Twenty-six patients achieved a platelet count of ≥ 100 x 109/L. Twenty-five patients were able to receive ≥ 2 subsequent cycles of chemotherapy without delays or dose reductions for thrombocytopenia. The median duration of treatment was 131.5 days (IQR 66.5,255.5). Dose and timing of romiplostim administration varied greatly at the discretion of the treating physician. Overall, romiplostim administration was avoided on days of chemotherapy adminitration although 2 patients did have romiplostim administered on the same day. The median average dose was 2.4 mcg/kg (IQR 2, 5.4) and the median average time between doses was 2.1 weeks (IQR 1.0-2.8).In the safety analysis, 4 patients developed venous thromboembolism. Our rate of thrombotic events 12.5% (0.035-0.29, 95% CI) was high, but may be consistent with the general rate of thrombosis in the oncology population (Timp et al., 2013). All patients who experienced thrombotic adverse events had underlying malignancies that were associated with high risk for thrombosis (3 pancreatic cancer, 1 astrocytoma). Of note, 1 patient was diagnosed with AML in the setting of romiplostim treatment. However, rising leukocyte counts prior to adminstration may have indicated a pre-existing hematologic malignancy. This case highlights safety concerns regarding romiplostim and the risk of aggravating underlying hematologic cancers.Conclusions: In our retrospective case series, romiplostim showed efficacy in improving platelet counts in patients with CIT allowing for the resumption of chemotherapy. The rate of thrombosis was high, but may be consistent with that reported in the literature. Further studies are required to understand the optimal dose, timing strategies, and safety of romiplostim in the setting of CIT and to develop strategies to mitigate adverse reactions. DisclosuresNo relevant conflicts of interest to declare.

Clinical outcome in lung cancer with a second malignancy: The time sequence matters.

The aim of the study was to determine the clinical outcome of lung cancer patients with a secondary malignancy according to the time sequence between the lung cancer and the secondary malignancy.Retrospective review of all lung cancer patients with any secondary cancer treated from June 2004 to July 2012. The survival of patients with a secondary malignancy was compared to those patients without a secondary malignancy. According to the time sequence between the lung cancer and the secondary malignancy, patients were divided into 4 groups. Group I: lung cancer without any other malignancy, Group II: lung cancer with a secondary malignancy at follow-up, Group III: lung cancer with a pre-existing malignancy, Group IV: synchronous malignancies (diagnosis interval between lung cancer and a secondary malignancy of less than 3 months).Patients with any secondary cancer in their history or at follow up included 157 patients (9.5%). Collectively; the median survival was significantly better for patients with a secondary malignancy, 19.09 months, compared to those without a secondary malignancy, 9.53 months, P < 0.001, HR 0.66 (95% CI 0.55 – 0.79). However, the survival differed significantly according to the time sequence between the lung cancer and the secondary malignancy. The median survival was 47.9 months for group II patients, 12.19 months for group III, 17.51 months for group IV, and 9.53 months for group I; P = 0.001. In Cox proportional hazard analysis, the risk of dying decreased by 68% in group II patients compared to group I patients, HR 0.32 (95% CI 0.21–0.5), P < 0.001. Although the risk of dying for group III and IV decreased by 19% and 16% respectively compared to group I patients, it did not reach statistical significance.Nowadays, secondary malignancy in lung cancer patients is a frequent finding. Better survival was observed for patient with secondary malignancy following lung cancer.

Abstract PR107

Background & Objectives: Lactate elevation is strongly associated with morbidity and mortality in critically ill medical and surgical patients. Patients with oncohaematological (OH) malignancies are at a very high risk of developing severe infectious complications that need immediate recognition and prompt treatment. It is difficult to apply classical SIRS criteria for OH patients due to preexisting malignancy, chemotherapy and insufficiency of immune response [1]. Our aim was to evaluate the prognostic value of consecutive lactate measurements as an additive indicator of transfer of high risk OH patients to Intensive Care Unit (ICU). Materials & Methods: A retrospective study was conducted in Vilnius University Hospital Santariskiu Clinics during 1-year period from September 1, 2014 until August 31, 2015. During this period 88 patients were transferred from General Haematology Unit and Bone Marrow Transplantation Unit to ICU. A control group were patients treated during the same period of time in the same units but who did not require transfer to ICU. Data of lactate measurements on the day of transfer and up to 7 previous days were obtained with vital signs (heart beat, respiration rate, temperature, white blood cell count) from medical records. Study group was divided into survivors and non-survivors. Statistical Package for the Social Sciences (SPSS) was used for statistical analysis, using percentages to describe qualitative variables and means or medians to describe quantitative variables. Results: Overall analysis included 80 patients in study group and 190 patients in control group. ICU mortality in study group was 46,25% (43 patients survived). Transferred patients had significantly higher lactate level on transfer day compared to control group (2,13 (0,62-17,78) vs. 1,57 (0,54-13,26), p=0,001). A day prior transfer lactate was measured in survivors group for 41,9% patients and in non-survivors for 43,2% of patients. Lactate level obtained in ICU after transfer was significantly higher in non-survivors group (2,5 (0,4-14,6) vs. 1,4 (0,4-7,6), p=0,014). Non survivors group had significantly higher heart rate (116±26 vs. 105±22, p=0,04) and respiratory rate (25 (14–44) vs. 30 (20–43), p=0,013). Conclusion: A simple and inexpensive consecutive lactate level measurements can have additive value to vital signs monitoring identifying early deterioration of OH patients. Careful and frequent evaluation of OH patients and their dynamics is essential to identify those who will need more intensive treatment.

Serial cerebrospinal fluid examinations to diagnose hematological malignancy causing neurological disease.

To determine the diagnostic utility of serial cerebrospinal fluid (CSF) examinations for hematological malignancy causing neurological disease. All CSF cytology reports at Mayo Clinic Rochester from 2005 to 2014 (n=20,018) were reviewed. Study inclusion criteria were: repeated CSF examinations within 1year in patients without known hematological malignancy performed to determine if hematological malignancy was the cause of neurological disease. Exclusion criteria were: preexisting hematological malignancy; >1year between CSF examinations, serial CSF examinations for infection, tumor surveillance or intrathecal therapies, and for assessment or treatment of CSF dynamics (e.g. idiopathic intracranial hypertension, CSF shunt or persistent CSF leak). The initial study population included patients undergoing three or more serial CSF examinations; subsequently those undergoing two serial CSF examinations were investigated. A total of 613 patients met the study criteria with 477 having two CSF examinations and 136 having three or greater CSF examinations. Of those with three or greater serial CSF examinations none were found to have hematological malignancy exclusively on the third or subsequent CSF examinations. Of those with two CSF examinations 0.4% (2/477) were found to have hematological malignancy (large B cell lymphomas) exclusively on the second CSF. Ten patients (1.6%) had suspicious hematological abnormalities on initial CSF examinations confirmed on subsequent CSF examinations. Serial CSF examinations are of low yield to diagnose hematological malignancy as a cause of neurological disease but may confirm atypical features observed in an initial CSF examination.

The Shreveport Myeloma Experience: Survival, Risk Factors and Other Malignancies in the Age of Stem Cell Transplantation

Background: The overall prognosis of multiple myeloma has improved significantly over the last 15 years. We wondered whether the overall improvement would also be seen in unselected patients in an academic center in Northwest Louisiana with a high proportion of minority patients, and if second malignant neoplasms are relevant for our patients. Materials and Methods: Between 1998 and 2009, 215 patients were treated for multiple myeloma at our center and had complete follow-up until May 2013. Results: The mean survival of patients with multiple myeloma increased from 3.25 to 5.34 years, which is comparable to patients treated at larger centers. No prognostic difference was observed in the subgroups of myeloma patients. Among 215 patients followed for the development of secondary cancers, 16 already had a preexisting or concomitant malignancy (7.4%) and 10 developed secondary cancers. Our data indicate a significant background of histologically unrelated cancers and a cumulative incidence of new cancers of about 20% after 10 years of follow-up. Based on SEER data, preexisting or secondary cancers were not statistically increased in our population. Conclusions: The use of autologous transplantation and the introduction of new agents resulted in a significant improvement in the prognosis of multiple myeloma. Other cancers are not statistically increased before or after multiple myeloma is diagnosed and are not prognostically relevant.

Enhancing Dendritic Cell-based Immunotherapy with IL-2/Monoclonal Antibody Complexes for Control of Established Tumors.

U.S. Food and Drug Administration-approved high-dose IL-2 therapy and dendritic cell (DC) immunization offer time-tested treatments for malignancy, but with defined issues of short in vivo t1/2, toxicity, and modest clinical benefit. Complexes of IL-2 with specific mAbs (IL-2c) exhibit improved stability in vivo with reduced toxicity and are capable of stimulating NK cell and memory phenotype CD8 T cell proliferation. In this study, we demonstrate that IL-2c treatment in tumor-bearing mice can enhance NK cell and tumor-specific CD8 T cell numbers. Importantly, DC immunization coupled with stabilized IL-2c infusion drastically improves the tumor-specific effector CD8 T cell response. DC + IL-2c treatment enhances number, 41BB and GITR expression, granzyme B production, CTL/regulatory T cell ratio, and per-cell killing capacity of CD8 T cells without increasing inhibitory molecule expression. Notably, IL-2c treatment of anti-CD3-stimulated human CD8 T cells resulted in higher number and granzyme B production, supporting the translational potential of this immunotherapy strategy for human malignancy. DC + IL-2c treatment enhances both endogenous NK cell and tumor Ag-specific CD8 T cell immunity to provide a marked reduction in tumor burden in multiple models of pre-existing malignancy in B6 and BALB/c mice. Depletion studies reveal contributions from both tumor-specific CD8 T cells and NK cells in control of tumor burden after DC + IL-2c treatment. Together, these data suggest that combination therapy with DC and IL-2c may be a potent treatment for malignancy.

The Risks for Ovarian, Endometrial, Breast, Colorectal, and Other Cancers in Women With Newly Diagnosed Endometriosis or Adenomyosis: A Population-Based Study.

Recent studies report a link between endometriosis and ovarian cancer (OC). Using a population-based cohort study to confirm the association between endometriosis and cancer is desirable. We thus examined the magnitude of the risks of OC, endometrial cancer (EC), breast cancer, colorectal cancer (CRC), and other cancers in women with newly diagnosed endometriosis or adenomyosis (internal endometriosis). Women older than 20 years with claims data between 2003 and 2005 were identified from the Longitudinal Health Insurance Dataset containing 1 million individuals randomly sampled from the National Health Insurance Research Database. Those with preexisting malignancies, hysterectomy, or oophorectomy were excluded. The endometriosis cohort (n = 2266, including 768 cases of pure adenomyosis) and comparison cohort (n = 9064), formed by 1:4 matching, were followed up until incidence cancer, dropout, or December 31, 2008. Outcome measures included cancer incidence and adjusted hazard ratio by Cox model adjusted for age group, comorbidities, and endometriosis medication use. With 9842 person-years of follow-up in endometriosis cohort and 36,274 person-years of follow-up in comparison cohort, there were increased risks of all cancers (adjusted hazard ratio, 1.8; 95% confidence interval, 1.4-2.4), OC (4.56, 1.72-12.11), and EC (4.05, 1.20-13.66). The ovarian endometriosis group was associated with increased risk of subsequent OC (4.37, 1.07-17.83). The adenomyosis group was strongly associated with both OC (5.50, 1.95-15.50) and EC (5.13, 1.36-19.40). Increased risk of subsequent CRC was observed in women with adenomyosis with coexistent endometriosis at other sites (13.04, 2.21-77.04). However, no statistically significant increased risk of breast or other cancers was observed. Having limitations such as lacking of parity information which may affect the magnitude of risk estimates, this study demonstrates that ovarian endometriosis has a 4-fold increased risk of OC. Adenomyosis may associate with a 4- to 5-fold increased risk of OC and EC, and unexpectedly, a 13-fold increased risk of CRC.

Ideal cardiovascular health behaviors and factors prevent the development of hypertension in prehypertensive subjects

Background: Seven ideal health metrics were defined by AHA to monitor cardiovascular health. This study aimed to investigate the impact of ideal cardiovascular health behaviors and factors on the development of hypertension in prehypertensive subjects. Methods: Thirty-two thousand eight-hundred and eighty-seven participants with prehypertension were included in the study after excluding for preexisting stroke, myocardial infarction or malignancy. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals [CI] for the development of hypertension. Results: During a follow-up of 52.2 months, 15 500 prehypertensive participants developed hypertension. The cumulative incidence of hypertension decreased with the number of ideal health metrics increased. It was 78.61%, 71.08%, 63.15%, 56.07% and 61.62% in prehypertensive individuals carrying ≤1, 2, 3, 4 and ≥5 ideal health behaviors or factors, respectively. After adjustment for age, gender, family history of hypertension, alcohol consumption, resting heart rate, plasma triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein, the risk ratios of incident hypertension in the subjects who carried 2, 3, 4, and ≥5 ideal health metrics were 0.833 (95%CI: 0.789–0.880), 0.710 (95%CI: 0.672–0.749), 0.604 (95%CI: 0.568–0.642), and 0.581 (95%CI: 0.524–0.643), respectively, in comparison to those with ≤1 ideal health metric. A similar trend was also observed in male and female populations. Poor health metrics, including body mass index, diet (salt intake), physical activity, total cholesterol, and smoking, were predictors for the development of hypertension in prehypertensive individuals. Conclusion: Ideal cardiovascular health behaviors and factors are protective factors to prevent the progression from prehypertension to hypertension.

Mammalian target of rapamycin inhibition after solid organ transplantation: can it, and does it, reduce cancer risk?

The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been increasingly used as immunosuppressants for recipients of solid organ transplants. Over the years, potential advantages unique to this class of immunosuppressants have been recognized, including chemoprevention by virtue of their antiproliferative effects. Prevention of malignancy after transplant through mTOR inhibitor-based immunosuppression may have a specific practical application in transplant recipients with preexisting malignancy including hepatocellular carcinoma or cholangiocarcinoma. This review will reveal how the biochemistry of the mTOR pathway, as it pertains to chemoprevention, can support a clinical role for mTOR inhibitors in the prevention of malignancies, recurrent or de novo, after solid organ transplantation in selected patients.