Outcomes of Breast Cancer Patients Treated with Chemotherapy, Biologic Therapy, Endocrine Therapy, or Active Surveillance During the COVID-19 Pandemic.

PURPOSE: Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment. METHODS: Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting. In those diagnosed with SARS-CoV-2 infection, Mann-Whitney test was used to a assess risk factors for severe disease and mortality. RESULTS: Three thousand sixty-two patients met study inclusion criteria with 641 patients tested for SARS-COV-2 by RT-PCR or serology. Overall, 64 patients (2.1%) were diagnosed with SARS-CoV-2 infection by either serology, RT-PCR, or documented clinical diagnosis. Comparing matched patients who received chemotherapy (n = 379) with those who received non-cytotoxic therapies (n = 2343) the incidence of SARS-CoV-2 did not differ between treatment groups (weighted risk; 3.5% CT vs 2.7% E/H, P = .523). Twenty-seven patients (0.9%) expired over follow-up, with 10 deaths attributed to SARS-CoV-2 infection. Chemotherapy was not associated with increased risk for death following SARS-CoV-2 infection (weighted risk; 0.7% CT vs 0.1% E/H, P = .246). Advanced disease (stage IV), age, BMI, and Charlson's Comorbidity Index score were associated with increased mortality following SARS-CoV-2 infection (P ≤ .05). CONCLUSION: BC treatment, including chemotherapy, can be safely administered in the context of enhanced infectious precautions, and should not be withheld particularly when given for curative intent.

Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19.

OBJECTIVE: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), any thrombotic event (19.4% versus 10.2%; adjusted odds ratio, 1.9 [95% CI, 1.4-2.6]; P<0.001), acute kidney injury (42.4% versus 19.0%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), and death (29.9% versus 10.8%; adjusted odds ratio, 2.1 [95% CI, 1.6-2.9]; P<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Utilization rates of enoxaparin and heparin in deep venous thrombosis prophylaxis after education and electronic order change at a single institution: a quality improvement study.

Despite advantages of low molecular weight heparin (LMWH), enoxaparin over heparin (UFH) for venous thromboembolism (VTE), a hospital's prescribing trends analysis showed use of each was about equal. In an attempt to increase LMWH over UFH use, electronic medical record (EMR) changes for medical service patients and education via multidisciplinary grand rounds was provided to all services. This was a unique opportunity to study LMWH and UFH use pre and post interventions at our institution. Citrix Pharmacy data was extracted for 3 months pre and post intervention (August 2016-February 2017). Inclusion criteria were age > 18 and LMWH or UFH VTE prophylaxis. Exclusion criteria were one time or duplicate orders and VTE treatment doses. Primary endpoint was hospital services VTE use with focus on medicine service which had both interventions compared to single intervention among all other services. LMWH use increased from 51 to 57.3% (p < 0.001) and UFH use decreased from 49 to 42.7% (p < 0.001) for all services. For medicine service, LMWH use increased 52.5-59.6% (p < 0.001) and UFH use decreased 47.5-40.4% (p < 0.001). For other services, LMWH use increased 48.8-53.6% (p = 0.005) and UFH use decreased 51.2-46.4% (p = 0.005). EMR changes and prescribers' grand rounds education resulted in 7.1% increase of LMWH use for medicine and 4.8% increase for all other services. The net increase (95% CI) in LMWH use in medicine service is 2.3% (- 1.91%, 6.56%) compared to the other services p = 0.281. Future studies are needed to reassess the effects of continued education and outcome of interventions.

Adherence to thromboprophylaxis guidelines in elderly patients with hospital acquired venous thromboembolism: a case control study.

Venous thromboembolism (VTE) remains the number one preventable cause of hospital acquired mortality and morbidity. Each year, more than 12 million patients are at risk for VTE. The delivery of appropriate and timely VTE prophylaxis is still suboptimal in many healthcare institutions and can lead to increased readmissions, morbidity, as well as costs. To clarify this issue further, we performed a retrospective case control study at our institution to determine if poor adherence to the VTE prophylaxis guidelines could lead to an increase in VTE events. This was a retrospective case control study conducted at Winthrop-University Hospital from January 2007 to December 2011. Exclusion criteria were age < 18 and concurrent use of anticoagulant agents. Out of 322 cases of hospital acquired VTE or readmission with VTE within 30 days of discharge, 289 cases were selected for final analysis and paired with age and sex matched controls. Patients with a hospital acquired VTE or a readmission for VTE within 30 days of discharge had a significantly reduced rate of VTE prophylaxis when compared to the control group (54.0 vs. 79.2 %, p < 0.0001). The VTE risk assessment rate was also lower in the VTE group (77.2 vs. 85.5 %, p = 0.035). No difference was noted in the time to prophylaxis administration between the two groups (34.8 vs. 33.1 h, p = 0.34). Lastly, sequential compression device (SCD) documentation rate was not different: 68/116 (58.6 %) vs. 44/87 (50.6 %), p = 0.32, between the two arms. Low adherence to the American College of Chest Physician (ACCP) guidelines for VTE prophylaxis correlated with an increase in hospital acquired VTE. The decreased adherence may be linked to a lower VTE risk assessment rate, and other barriers including incorrect identification of contraindications to pharmacologic prophylaxis, and poor documentation of mechanical prophylaxis. There was no difference in SCD documentation rate and timeliness to administration of initial thromboprophylaxis between the two groups. Future studies are needed to reassess adherence and documentation rates after system-wide improvements.

Comparing Length of Stay Between Patients Taking Rivaroxaban and Conventional Anticoagulants for Treatment of Venous Thromboembolism.

BACKGROUND: Recent studies have demonstrated non-inferiority of rivaroxaban when compared to warfarin for the treatment of pulmonary embolism and deep venous thrombosis. Analysis of data from the EINSTEIN trials has demonstrated that patients who received rivaroxaban had a shorter length of stay (LOS) compared to those who received warfarin. However, these trials had strict inclusion and exclusion criteria, and were designed for a different primary outcome. Also, data from these closely monitored clinical trials may not reflect the daily practice of medicine. OBJECTIVES: To clarify this issue further, we performed a retrospective analysis at our institution, comparing the LOS between patients discharged on rivaroxaban and other conventional anticoagulants (warfarin, enoxaparin, and enoxaparin with warfarin). METHODS: This was a retrospective study of consecutive patients admitted to our institution from January 2011 to July 2014 with newly diagnosed venous thromboembolism (VTE). Inclusion criteria were age > 18 years and objective confirmation of VTE. Exclusion criteria included diagnosis of VTE 24 h after admission, contraindication to anticoagulation, treatment with fibrinolytic agents, patients already on anticoagulation, and pregnancy. Out of 1553 consecutive patients diagnosed with VTE, a total of 414 patients met the eligibility criteria. These patients were further subdivided into four groups based on their discharge anticoagulant: rivaroxaban, warfarin, enoxaparin, and warfarin with enoxaparin. RESULTS: Patients discharged on rivaroxaban had a significantly shorter LOS compared with patients discharged on warfarin (3.5 vs. 7.0 days; p < 0.001), but not when compared to those discharged on enoxaparin alone (3.0 days) or enoxaparin with warfarin (4.0 days) (p > 0.05). The hospital incidence of bleeding and the 6-month readmission rates were not different among the different anticoagulants. CONCLUSIONS: In patients admitted with newly diagnosed VTE, those discharged on rivaroxaban had a significantly shorter LOS compared to those discharged on warfarin. In the appropriate subset of patients with VTE, treatment with rivaroxaban may result in significant cost savings for the hospital.

Erdheim-Chester disease: a rare cause of recurrent fever of unknown origin mimicking lymphoma.

We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.

Cancer Antigen 72-4 for the Monitoring of Advanced Tumors of the Gastrointestinal Tract, Lung, Breast and Ovaries.

BACKGROUND: Cancer antigen CA72-4 is a tumor marker found to be elevated in a variety of human adenocarcinomas. Using the DRG TM-CA72-4, we quantified the elevation of CA72-4 compared to current United States Food And Drug Administration-approved tumor markers in various cancer types. MATERIALS AND METHODS: We conducted a prospective, single-center study enrolling 96 patients between March 2013 and August 2016 with different locally advanced, unresectable or metastatic cancer known to express CA72-4. Quantification of CA72-4 was performed according to the manufacturer's instructions using the DRG TM-CA72-4 enzyme-linked immunosorbent assay kit and the positivity rates were calculated. RESULTS: CA72-4 expression varied with tumoral site of origin, with the highest positivity rates found in pancreatic and ovarian malignancies. Correlation with clinical activity was also noted in some patients. CONCLUSION: CA72-4 may have a potential role as an adjunct to conventional biomarkers in disease monitoring of pancreatic, ovarian and colorectal carcinomas.

A combined modality approach to recurrent cardiac sarcoma resulting in a prolonged remission: a case report.

We report a case of cardiac fibrosarcoma that was treated with cardiac tumor resection, chemotherapy, cardiac explantation, tumor repeat resection, and autotransplantation followed by external beam irradiation. The patient was able to achieve clinical remission and remained disease free > 2 years after the initial diagnosis. This case report demonstrates that a sustained remission from cardiac sarcoma is possible with an aggressive combined modality approach.

An effective in vitro antitumor response against human pancreatic carcinoma with paclitaxel and daunorubicin by induction of both necrosis and apoptosis.

The highly metastatic human pancreatic cell line L3.6 was used to study mechanisms for antitumor activity with various chemotherapeutic drug combinations. The most effective drugs were daunorubicin (IC50 0.4 microM), doxorubicin (IC50 22 microM), paclitaxel (IC50 5.3 microM) and 5-fluorouracil (IC50 5.4 microM). The most effective drug combination was equitoxic concentrations of paclitaxel and daunorubicin. Kinetic analysis demonstrated that both paclitaxel and daunorubicin had to be added simultaneously for maximum cytotoxicity. Daunorubicin treatment alone demonstrated ROS (reactive oxygen species) induction and cellular morphological changes more consistent with chemical damage in a total of 93% of the cells and apoptotic changes in 20% of the cell population. The apoptosis induced by daunorubicin does not appear to be caspase-dependent, as demonstrated by the lack of conversion of the procaspases 8 and 3. Within 24 h of treatment with paclitaxel, Bcl-2 formed a doublet at 26 kilodaltons and the expression was abrogated with daunorubicin and the combination of the two drugs as determined by Western blots. These data suggest that the human pancreatic cell line L3.6 is more effectively killed following treatment with chemotherapeutic agents that cause death through at least two pathways, a caspase-dependent and caspase-independent apoptosis and necrosis.

Sex hormone receptors in breast cancer.

The dependency of certain breast cancers on estrogen is undeniably one of the most important observations in oncology. Since this early observation, there has been a tremendous effort to define the precise roles of the estrogen receptor (ER) in the pathogenesis of breast cancer. Estrogen signaling pathways can also be exploited as effective targets for cancer treatment. Both ligand-dependent and ligand-independent receptor activation pathways have been successfully blocked by hormonal therapies including selective ER modulators such as tamoxifen, by blocking and accelerating the degradation of ER (fulvestrant), and by depleting tissue levels of estrogen (aromatase inhibitors). Because of the immense prognostic and predictive value of the ER and PR receptor, accurately defining hormone dependency is also of paramount importance. Despite this avalanche of discovery and development resulting in improved outcome for the patient, resistance to these therapies, both intrinsic and acquired, is well known. Uncovering the various mechanisms of resistance has deepened scientific understanding of posttranslational modifications of these receptors, as well as their cross talk with other receptor families such as the HER-2/neu receptor. The recent discovery that orphan estrogen-related receptors may also play an important role in breast cancer is just starting to be appreciated. A clear understanding of the historical perspective and the intricacies of ER structure and function is required to improve current therapeutic strategies for breast cancer.

Coronary Calcium Scanning in Patients after Adjuvant Radiation for Early Breast Cancer and Ductal Carcinoma In situ.

BACKGROUND AND OBJECTIVE: Radiation therapy (RT) is part of standard adjuvant treatment for breast cancer. Earlier studies demonstrated increased cardiac morbidity and mortality from this. Coronary Calcium scanning utilizing Multidetector Computed Tomography (MDCT) can detect early atherosclerosis in coronary arteries by identifying the amount of calcifications. In our study we employed these tools to detect occult atherosclerosis at least 5 years following breast RT. METHODS: We evaluated 20 asymptomatic patients, <60 years old, treated with RT at least 5 years prior to enrollment. Nine received RT to the left and 11 to the right chest wall. The median interval between RT and calcium scan was 8 years. All patients were treated with external beam RT using tangential technique. All patients underwent MDCT to compute volumetric and Agatston calcium scores of the coronary arteries and the aorta. RESULTS: Eleven patients had RT to the right chest wall, and eight had a calcium score of 0, while two had minimally elevated scores and one patient had a significantly elevated score. Meanwhile nine patients had RT to the left chest wall, and seven had a calcium score of 0. None had significantly elevated scores. In the aorta, 11 of 20 patients had a score of 0, while 8 of 20 had minimally elevated scores. CONCLUSION: In contrast to studies demonstrating increased cardiovascular morbidity, our pilot study did not detect significant occult atherosclerosis using MDCT of the coronaries and aorta of patients assessed five or more years following radiation for treatment of breast cancer.

Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer.

Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention.

Is pylorospasm a cause of delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy?

BACKGROUND: Delayed gastric emptying (DGE) occurs in 14% to 61% of patients after pylorus-preserving pancreaticoduodenectomy, but its pathogenesis is unclear. We hypothesized that DGE may be due to pylorospasm secondary to vagal injuries at operation and may be preventable by the addition of pyloromyotomy. METHODS: Patients operated on consecutively between April 2000 and August 2003 were studied. Pyloromyotomy was of the Fredet-Ramstedt type combined with antroplasty. DGE-free recovery was defined as tolerance of a diet for three successive days by postoperative day 8. The symptom of nausea was used as a basis for nasogastric tube removal and diet resumption. A gastric emptying test (GET) with solid food was obtained. Patients with difficulty swallowing were fed via a feeding tube. RESULTS: There were 47 patients. Two patients were excluded because of death (n = 1) and ileus with pancreatic fistula (n = 1). Diagnoses were pancreatic cancer (n = 23), chronic pancreatitis (n = 11), ampullary cancer (n = 5), mucinous cystic neoplasm (n = 5), and duodenal villous adenoma (n = 3). Median times to nasogastric tube removal, start of liquid diet, and start of solid diet were postoperative days 2, 3, and 5, respectively. Two patients had tube feedings. Preoperative GET was abnormal in 51%, and postoperative GET was abnormal in 37%. The average length of stay was 9.5 days (median, 7 days). DGE occurred in only one patient (2.2%). There were no late complications during a 6-month follow-up. CONCLUSIONS: The addition of pyloromyotomy to pylorus-preserving pancreaticoduodenectomy is effective in preventing DGE. Results are supportive of the hypothesis that DGE may be caused by operative injuries of the vagus innervating the pyloric region.

First Isolation of West Nile virus from a patient with encephalitis in the United States.

West Nile virus (WNV) was isolated from a patient who developed encephalitis while undergoing treatment with CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine [Oncovin], predisone) and rituximab for a non-Hodgkin B-cell lymphoma. Both standard reverse transcription-polymerase chain reaction (RT-PCR) and Taqman RT-PCR established the diagnosis of WNV infection from cerebrospinal fluid (CSF). Several whole blood samples and one serum sample underwent further testing. CSF and serum samples were negative for WNV antibody; however, all samples were positive by both RT-PCR assays. Infectious virus was recovered from a blood sample, and its identity was confirmed by using a WNV-specific immunofluorescence assay. The complete WNV genomes determined from CSF and from the virus isolate adapted from cell culture were the same. The results represent the first complete WNV genome sequence obtained directly from human CSF and the first time that infectious WNV has been recovered from a patient with encephalitis in North America.