A 10-year restrospective evaluation of ultrasound in pregnant abdominal trauma patients.

The pregnant abdominal trauma patient presents a unique diagnostic challenge. This study aimed to evaluate the accuracy of abdominal sonography for the detection of clinically important injuries in pregnant abdominal trauma patients. A retrospective review was performed of a trauma center database from 2001 to 2011. Medical records were reviewed to determine initial abdominal imaging test results and clinical course. Sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound for detection of traumatic injury were calculated. Of 19,128 patients with suspected abdominal trauma, 385 (2 %) were pregnant. Of these, 372 (97 %) received ultrasound as the initial abdominal imaging test. All 13 pregnant patients who did not receive ultrasound received abdominal CT. Seven pregnant patients underwent both ultrasound and CT. Seven ultrasound examinations were positive, leading to one therapeutic Cesarean section and one laparotomy. One ultrasound was considered false positive (no injury was seen on subsequent CT). There were 365 negative ultrasound examinations. Of these, 364 were true negative (no abdominal injury subsequently found). One ultrasound was considered false negative (a large fetal subchorionic hemorrhage seen on subsequent dedicated obstetrical ultrasound). Sensitivity and positive predictive value were 85.7 %. Specificity and negative predictive value were 99.7 %. Abdominal sonography is an effective and sufficient imaging examination in pregnant abdominal trauma patients. When performed as part of the initial assessment using an abbreviated trauma protocol with brief modifications for pregnancy, ultrasound minimizes diagnostic delay, obviates radiation risk, and provides high sensitivity for injury in the pregnant population.

Complete ultrasonography of trauma in screening blunt abdominal trauma patients is equivalent to computed tomographic scanning while reducing radiation exposure and cost.

BACKGROUND: Liberal use of computed tomography of the abdomen and pelvis (CTAP) in the screening of blunt abdominal trauma (BAT) has heightened concerns for increased radiation exposure and costs. We sought to demonstrate that in a select group of BAT patients, complete ultrasonography of trauma (CUST) is equivalent to routine CTAP but with significantly decreased radiation and costs. METHODS: A retrospective analysis of patients screened for BAT from 2000 to 2011 in a Level 1 trauma center was performed. CUST was available from 8:00 AM to 11:00 PM daily, while CTAP was performed thereafter. Decision to perform CTAP or CUST overnight was made by the attending surgeon based on clinical examination. False negatives (FNs) were described as either a negative CUST or CTAP finding, which later required exploratory laparotomy. Medicare rates and previous data were used for the estimation of cost and radiation exposure. RESULTS: There were 19,128 patients screened for BAT. A total of 12,577 patients (65.8%) initially underwent CUST, and 6,548 (34.2%) underwent CTAP; 11,059 patients (58% of the total BAT patients) avoided a CTAP, yielding an estimated savings of $6.5 million and 188,003 mSv less radiation during the course of the study. Compared with the CTAP group, patients undergoing CUST had lower Injury Severity Score (ISS) (8.1 vs. 9.6), were older (44.7 years vs. 35.2 years), and experienced less traumatic brain injury (61.4% vs. 69.3%) (all with p < 0.002). Mortality was higher in the CUST group (1.8% vs. 1.2%, p = 0.02), but it was insignificant when adjusted for age older than 65 years (1.1% vs. 0.9%, p = 0.23) or head injury (0.6% and 0.3%, p = 0.4). FN CUST and FN CTAP were 0.29% and 0.1%, respectively (p = nonsignificant), with similar mortality (20% vs. 0%, p = 0.44). CONCLUSION: CUST is equivalent to routine CTAP for BAT screening and leads to an average of 42% less radiation exposure and more than $591,000 savings per year. LEVEL OF EVIDENCE: Diagnostic study, level IV; therapeutic/care management study, level IV.

Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

PURPOSE: E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients. EXPERIMENTAL DESIGN: E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented. RESULTS: One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted. CONCLUSIONS: E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.

Epithelioid angiosarcoma of the aorta in a 47-year-old man: a case report and literature review.

Epithelioid angiosarcomas of the aorta are extremely rare neoplasms with only 26 previous reports in the literature. An extremely unusual case is reported of an aortic epithelioid angiosarcoma diagnosed in a 47-year-old man who was being evaluated for his rectal adenocarcinoma. This case prompted a review of literature for aortic intimal neoplasms. No previous reports of a synchronous aortic angiosarcomas and adenocarcinomas of the colorectum have been reported. Even though the occurrence of the aortic intimal neoplasia and rectal cancer in this patient is most likely coincidental, the onset of this disease in a young man without risk factors for either disease probably suggests a genetic basis of his disease.

Pattern of serum immunoreactivity against breast cancer cell lysates may predict severity of disease in breast cancer patients.

Humoral tumor-specific immunity has been investigated as a potential tool to identify tumor-associated antigens and evaluate cancer diagnosis and prognosis. Using SDS-PAGE and western blotting techniques we investigated the humoral immune response against tumor cell antigens in 36 breast cancer patients, 17 node-positive (NP) and 19 node-negative (NN). As a source of antigens, we prepared protein lysates from four breast cancer cell lines (AU565, BT474, MCF-7 and MDA-MB-231) which in vitro exhibit different features of invasion, estrogen receptor/progesterone receptor status and HER2/neu expression thereby potentially representing mild to aggressive forms of clinical disease. A higher number of immunocomplexes Ag-Ab were formed when serum from NN patients was immunoreacted against lysates from AU565 and MCF-7 in comparison to serum from NP patients (P < 0.01). BT474 cells were not a good antigenic source. MDA-MB-231 cells could not significantly discriminate between NN and NP patients since both groups showed higher amounts of reactivity against the lysate. However, comparative analysis of protein preparations purified from MCF-7 and MDA-MB-231 cells and immunodetected concomitantly with the same serum samples showed that serum from patients with cancers with worse prognosis (stage, nodality, HER2/neu and hormonal status) reacted more intensely to proteins purified from the relatively more invasive cell line MDA-MB-231 compared to MCF-7. These findings suggest that the study of serum antibody reactivity to antigens purified from breast cancer cell lines with different invasive properties should be further investigated for its potential in providing beneficial prognostic information in breast cancer.

Assessing serum cytokine profiles in breast cancer patients receiving a HER2/neu vaccine using Luminex technology.

We used the Luminex assay to compare serum cytokine profiles of breast cancer patients (BCa) to healthy controls, node-positive (NP) patients to node-negative (NN), and pre- and post-vaccination serum of BCa vaccinated with a HER2/neu E75 peptide vaccine. Sera from 36 pre- and post-vaccination BCa, (12 NP and 24 NN) and 13 healthy, female donors, were evaluated using Luminex technology. Levels of 22 cytokines consisting of interleukin (IL)-1alpha, -1beta, -2, -4, -5, -6, -7, -8, -10, -12, -13, -15, -17, IFN-gamma, G-CSF, GM-CSF, TNF-alpha, IP-10, MIP-1alpha, RANTES, eotaxin and monocyte chemotactic protein-1 (MCP-1) were assessed. Six of 22 cytokines showed significant differences between BCa and healthy controls. MCP-1, eotaxin, RANTES and GM-CSF levels were significantly elevated in BCa (P<0.009) and IL-1alpha and IL-4 levels were significantly decreased in BCa (P<0.015). Cytokine levels were generally elevated in NN patients compared to NP patients with the exception of eotaxin and IL-13, which were increased in NP patients. Three cytokines, IL-6, MIP-1alpha and G-CSF reached statistical significance (P<0.05). In 34 vaccinated BCa, MCP-1, eotaxin and IL-13 were significantly elevated post-vaccination with MCP-1 demonstrating the most significant response (median, 145.8-217.0 pg/ml, P=0.003). Using a multiplex assay we found significant differences in cytokine levels in sera of BCa compared to healthy controls, in NN compared to NP patients, and in vaccinated patients. Our results support an extended analysis of serum cytokine profiles for the potential development of predictive panels in diagnosis, staging and monitoring cancer vaccine trials.

Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine.

We are conducting clinical trials of the E75 peptide as a vaccine in breast cancer (BrCa) patients. We assessed T cell subpopulations in BrCa patients before and after E75 vaccination and compared them to healthy controls. We obtained 17 samples of blood from ten healthy individuals and samples from 22 BrCa patients prior to vaccination. We also obtained pre- and post-vaccination samples of blood from seven BrCa patients who received the E75/GM-CSF vaccine. CD4, CD8, CD45RA, CD45RO, and CCR7 antibodies were used to analyze the CD4+ and CD8+ T cells by four-color flow cytometry. Compared to healthy individuals, BrCa patients have significantly more memory and less naïve T cells and more effector-memory CD8+ and less effector CD4+ T cells. Phenotypic differences in defined circulating CD4+ and CD8+ T cell subpopulations suggest remnants of an active immune response to tumor distinguished by a predominant memory T cell response and by untapped recruitment of naïve helper and cytotoxic T cells. E75 vaccination induced recruitment of both CD4+ and CD8+ naïve T cells while memory response remained stable. Additionally, vaccination induced global activation of all T cells, with specific enhancement of effector CD4+ T cells. E75 vaccination causes activation of both memory and naïve CD4+ and CD8+ T cells, while recruiting additional naïve CD4+ and CD8+ T cells to the overall immune response.

Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients.

PURPOSE: We studied serum monocyte chemotactic protein-1 (MCP-1) levels in breast cancer patients in relationship to their clinicopathologic variables and immune response to a /neu E75 vaccine. EXPERIMENTAL DESIGN: We measured MCP-1 levels in 32 /neu(+) breast cancer patients before and after vaccination with a /neu E75 peptide + granulocyte macrophage colony-stimulating factor vaccine. Clinical prognostic variables were collected. Vaccine-specific immunologic responses were monitored. RESULTS: Serum MCP-1 levels >250 pg/mL (MCP-high) correlated with favorable prognostic variables. MCP-high patients compared with MCP-low (<250 pg/mL) patients showed statistically significant later onset of disease, earlier stage of disease, fewer nodal metastasis, and less chemotherapy. MCP-high patients had increased levels of preexisting immunity when compared with MCP-low patients (69% versus 21%; P = 0.02). However, MCP-low patients showed higher inducible levels of MCP-1 compared with MCP-high patients (median increase, 41% versus 0%; P = 0.001) after vaccination. Moreover, MCP-low patients with >50% increase in MCP-1 levels (response-high) had worse clinical prognostic variables compared with patients with <50% increase (response-low). Response-high patients had statistically significant more poorly differentiated tumors, later stage of disease, and higher percentage of large tumors. Patients with >30% postvaccination MCP-1 increase also showed significant increases in E75-specific CD8(+) T-cells (0.05% versus 0.38%; P = 0.03) in response to vaccination. CONCLUSIONS: High serum MCP-1 levels in breast cancer patients correlate with favorable prognostic variables and increased preexisting /neu immunity. E75 vaccination induces the largest MCP-1 response in patients with unfavorable clinicopathologic variables. Therefore, low serum MCP-1 levels may identify patients with worse prognosis and those most likely to benefit from this vaccination.

Phase I clinical trial of a HER-2/neu peptide (E75) vaccine for the prevention of prostate-specific antigen recurrence in high-risk prostate cancer patients.

PURPOSE: The E75 peptide is an immunogenic peptide from the HER-2/neu protein that is substantially expressed in prostate cancer. We are conducting a clinical trial of an E75/granulocyte macrophage colony-stimulating factor vaccine to prevent post-prostatectomy prostate-specific antigen (PSA) recurrences in high-risk prostate cancer (HRPC) patients. EXPERIMENTAL DESIGN: Prostate cancer patients at high risk for recurrence were prospectively evaluated and identified by the validated Center for Prostate Disease Research (CPDR)/CaPSURE high-risk equation. From these high-risk equation patients, 27 HER-2/neu-expressing prostate cancer patients were enrolled. HLA-A2+ patients (n = 17) were vaccinated, whereas HLA-A2- patients (n = 10) were followed as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence were measured. RESULTS: This vaccine is safe with only minor toxicities observed. Additionally, the vaccine is immunogenic with all patients showing both in vivo and in vitro phenotypic and functional immune responses, although variable. HLA-A2+ patients were found to have larger tumors, higher postoperative Gleason scores, and more high-risk CPDR scores than HLA-A2- patients. Despite these differences, disease-free survival was not different between the vaccinated HLA-A2+ patients and the HLA-A2- controls at a median follow up of 23 months. Three of the four vaccinated patients that recurred had rising PSAs at the initiation of the trial. Ex vivo phenotypic assays were predictive of recurrences and correlated in general with functional assays. CONCLUSIONS: The E75 vaccine strategy is safe and effective in eliciting an immune response against the HER-2/neu protein in HRPC patients and may be useful as a preventive strategy against disease recurrence. Vaccination in response to a rising PSA may be too late.