Loss of H3K27 methylation identifies poor outcomes in adult-onset acute leukemia.

BACKGROUND: Acute leukemia is an epigenetically heterogeneous disease. The intensity of treatment is currently guided by cytogenetic and molecular genetic risk classifications; however these incompletely predict outcomes, requiring additional information for more accurate outcome predictions. We aimed to identify potential prognostic implications of epigenetic modification of histone proteins, with a focus on H3K4 and H3K27 methylation marks in relation to mutations in chromatin, splicing and transcriptional regulators in adult-onset acute lymphoblastic and myeloid leukemia. RESULTS: Histone 3 lysine 4 di- and trimethylation (H3K4me2, H3K4me3) and lysine 27 trimethylation (H3K27me3) mark expression was evaluated in 241 acute myeloid leukemia (AML), 114 B-cell acute lymphoblastic leukemia (B-ALL) and 14T-cell ALL (T-ALL) patient samples at time of diagnosis using reverse phase protein array. Expression levels of the marks were significantly lower in AML than in B and T-ALL in both bone marrow and peripheral blood, as well as compared to normal CD34+ cells. In AML, greater loss of H3K27me3 was associated with increased proliferative potential and shorter overall survival in the whole patient population, as well as in subsets with DNA methylation mutations. To study the prognostic impact of H3K27me3 in the context of cytogenetic aberrations and mutations, multivariate analysis was performed and identified lower H3K27me3 level as an independent unfavorable prognostic factor in all, as well as in TP53 mutated patients. AML with decreased H3K27me3 demonstrated an upregulated anti-apoptotic phenotype. In ALL, the relative quantity of histone methylation expression correlated with response to tyrosine kinase inhibitor in patients who carried the Philadelphia cytogenetic aberration and prior smoking behavior. CONCLUSION: This study shows that proteomic profiling of epigenetic modifications has clinical implications in acute leukemia and supports the idea that epigenetic patterns contribute to a more accurate picture of the leukemic state that complements cytogenetic and molecular genetic subgrouping. A combination of these variables may offer more accurate outcome prediction and we suggest that histone methylation mark measurement at time of diagnosis might be a suitable method to improve patient outcome prediction and subsequent treatment intensity stratification in selected subgroups.

Optimizing VAP scars after childhood cancer treatment: a pilot study.

PURPOSE: Majority of pediatric cancer patients are treated with chemotherapy using Venous Access Ports (VAP). However, after surgical removal of the VAP prominent scars often remain and standard care is lacking. METHODS: Patients (N = 20) who were willing to participate were included prior to surgical removal of their VAP. All patients were off therapy at time of VAP removal. Patients had the option to either choose from Dermatix®, meridian color therapy (MCT), or no additional treatment (NAT). Assessment of scars was done prior to and 3, 6, and 12 months after surgical VAP removal using Patient and Observer Scar Assessment Scales (POSAS) questionnaires. To identify whether Dermatix® or MCT is associated with better scar healing than without additional treatment, Mann-Whitney U tests were used. RESULTS: After 12 months of follow-up, both patients and dermatologists noted VAP scars had healed better after MCT compared to those without treatment (P = 0.010 for both POSAS patient and POSAS observer). No significant differences were observed between VAP scars after Dermatix® use and those with no treatment. CONCLUSIONS: Scar healing after MCT significantly improved, whereas Dermatix® treatment showed no significant differences compared to NAT. To translate this to daily care, a larger prospective study is needed to validate these findings.

IDENTIFYING CANCER SPECIFIC METABOLIC SIGNATURES USING CONSTRAINT-BASED MODELS.

Cancer metabolism differs remarkably from the metabolism of healthy surrounding tissues, and it is extremely heterogeneous across cancer types. While these metabolic differences provide promising avenues for cancer treatments, much work remains to be done in understanding how metabolism is rewired in malignant tissues. To that end, constraint-based models provide a powerful computational tool for the study of metabolism at the genome scale. To generate meaningful predictions, however, these generalized human models must first be tailored for specific cell or tissue sub-types. Here we first present two improved algorithms for (1) the generation of these context-specific metabolic models based on omics data, and (2) Monte-Carlo sampling of the metabolic model ux space. By applying these methods to generate and analyze context-specific metabolic models of diverse solid cancer cell line data, and primary leukemia pediatric patient biopsies, we demonstrate how the methodology presented in this study can generate insights into the rewiring differences across solid tumors and blood cancers.

Using triphasic helical CT to detect focal hepatic lesions in patients with neoplasms.

OBJECTIVE: Our purpose was to determine the value of triphasic helical CT (unenhanced, hepatic arterial, and portal venous phases) in the detection and characterization of focal hepatic lesions due to hepatomas or metastases. MATERIALS AND METHODS: One hundred two patients with known or suspected hepatomas or liver metastases underwent triphasic CT. The number and conspicuity of lesions were evaluated on each phase. RESULTS: Five hundred eighty-four lesions were detected in 102 patients. Patients with hypovascular malignancies had more lesions detected on the portal venous phase with increased conspicuity than on the other phases. Patients with hypervascular malignancies had lesions best detected on the hepatic arterial phase, which revealed small lesions that were not seen on the other phases in seven (21%) of the 33 patients with hypervascular metastases and hepatomas. No lesions were detected on the unenhanced phase that were not seen on the other phases. However, arterial phase images introduced new diagnostic dilemmas because not all lesions seen on the arterial phase alone were caused by hepatomas or metastases, even in patients with known malignancies; several lesions represented benign abnormalities that included focal nodular hyperplasia. CONCLUSION: The unenhanced phase is not routinely necessary for the detection of metastases or hepatomas. Hypovascular malignancies are best evaluated during the portal venous phase. Small lesions due to hypervascular metastases and hepatomas are best evaluated and may be detected only during the hepatic arterial phase, which should be used routinely in these patients. New dilemmas may develop from the increased sensitivity of the hepatic arterial phase for lesions. However, the hepatic arterial phase is of limited value with hypovascular malignancies.

Leiomyoma causing massive ascites, right pleural effusion and respiratory distress. A case report.

BACKGROUND: Pseudo-Meigs' syndrome, or atypical Meigs' syndrome, occurs when a pelvic mass other than an ovarian fibroma is present with hydrothorax and ascites. Leiomyomas rarely cause this condition. CASE: An otherwise healthy 31-year-old woman presented to the emergency department in acute respiratory distress with massive ascites, pleural effusion and a pedunculated leiomyoma. After receiving mechanical ventilation, she underwent myomectomy and recovered fully within four weeks. CONCLUSION: This unique presentation of pseudo-Meigs' syndrome should be included with malignancy in the differential diagnosis of a pelvic mass with ascites.

Using MR imaging to diagnose partial tears of the anterior cruciate ligament: value of axial images.

OBJECTIVE: The purpose of this study was to determine the usefulness of axial MR imaging for diagnosing partial anterior cruciate ligament (ACL) tears and to determine if patients could be categorized as having stable or unstable partial ACL tears on the basis of criteria of axial MR imaging. MATERIALS AND METHODS: We reviewed 238 patients who, over a 2-year period, underwent both MR imaging of the knee and arthroscopic evaluation of the ACL. According to arthroscopic examination, these patients had 143 normal ACLs, 67 complete ACL tears, and 28 partial tears. The 28 partial tears included 20 stable tears (no ACL deficiency) and eight unstable partial tears having ACL deficiency or requiring ACL reconstructive surgery. The axial MR images were retrospectively reviewed by two interpreters who were unaware of the arthroscopic findings, and decisions were reached by consensus. The ACL was classified according to its axial configuration and continuity. RESULTS: By axial MR imaging criteria, we found 109 elliptical ACLs, 45 attenuated ACLs, three ACLs with increased intrasubstance signal intensity, six isolated ACL bundle signs, 19 ACLs that could not be visualized, and 56 cloudlike mass signs. Arthroscopically normal ACLs and stable partial tears were difficult to distinguish reliably on axial MR images. Unstable partial ACL tears could not be distinguished from complete ACL tears. However, using axial MR imaging, our observers were able to segregate stable ACLs (normal ligaments and stable partial tears) from unstable ACLs (unstable partial tears and complete tears) with 100% sensitivity and 96% specificity. CONCLUSION: Axial MR imaging of the ACL may provide important diagnostic information for patients who have ACL injury. On axial MR images, stable ACLs were elliptical, attenuated, or showed as areas of increased intrasubstance signal intensity. At arthroscopy, attenuated ACLs represented normal ACLs (76%) and stable partial tears (24%). On axial MR images, the configurations that indicated unstable ligaments were isolated ACL bundle, nonvisualized ACL, and cloudlike mass.

Castleman disease presenting as a pelvic mass.

BACKGROUND: To our knowledge, giant lymph node hyperplasia (Castleman disease) may present as a pelvic mass on magnetic resonance imaging (MRI). CASE: A postmenopausal woman with rapidly enlarging leiomyoma uteri was found to have a suspicious left adnexal mass mimicking an ovarian neoplasm on preoperative MRI. At laparotomy, the suspected uterus and normal ovaries were extirpated. In addition, a firm, 4 x 8-cm solid mass within the sigmoid colon mesentery was found and resected. The final histologic diagnosis was Castleman disease. CONCLUSION: Entities such as Castleman disease should be considered when assessing a pelvic mass. Characterization of the origin of pelvic masses can often be difficult, despite sophisticated diagnostic imaging studies such as MRI.

MR imaging of the posterior cruciate ligament: normal, abnormal, and associated injury patterns.

The posterior cruciate ligament (PCL) of the knee has received little attention in the radiology literature, but its importance in knee stability has come under close scrutiny in recent years. Unrepaired injury of the PCL can lead to chronic instability and early joint degeneration. Three major mechanisms of trauma that involves the PCL are posterior displacement of the tibia in a flexed knee, hyperextension, and rotation combined with an adduction or abduction force. The spectrum of PCL injuries includes partial tear or intrasubstance injury, complete ligamentous rupture, and avulsion of the PCL insertion site on the posterior tibia. Associated injuries include injury of other ligaments, meniscal tear, bone injury, and joint effusion. PCL rupture is easily identified with magnetic resonance (MR) imaging by using simple signal intensity and structural characteristics. Because clinical and arthroscopic assessment of the PCL can be difficult, MR imaging can be valuable for evaluating the acutely injured knee when operative repair of the PCL is being considered.

CT diagnosis of acute appendicitis: imaging findings.

Acute appendicitis, at times, is a difficult clinical diagnosis. CT can play a valuable role in selected patients with suspected appendicitis; the CT diagnosis of acute appendicitis has high positive and negative predictive values, 96% and 95%, respectively [1]. In this essay, we review the normal CT anatomy of the appendix and the right lower quadrant and illustrate the CT signs of appendicitis and important differential diagnostic entities. The CT appearance of complications of acute appendicitis is also presented, as are issues concerning examination technique and patient preparation.

MR imaging appearance of the extensor mechanism of the knee: functional anatomy and injury patterns.

Trauma to the extensor mechanism of the knee, a common clinical problem, can be accurately evaluated with magnetic resonance (MR) imaging. The extensor mechanism consists of the quadriceps muscle and tendon, patella, patellar tendon, and patellar retinacula. Injuries of these structures can be classified into partial and complete tears. Acute injuries are associated with edema, hemorrhage, and fluid collections; chronic injuries often demonstrate redundancy, atrophy, and retraction of the affected structures. MR imaging is useful in differentiating partial and complete tears and in evaluating tissue edema and hemorrhage. It also allows detection of unsuspected nondisplaced patellar fractures and chronic conditions due to repetitive trauma. Transient dislocation of the patella is an often clinically unsuspected entity for which MR imaging can serve an important diagnostic role. A detailed understanding of the functional and anatomic relationships of the extensor mechanism can greatly assist in interpretation of MR images of the traumatized knee.

Semiautomatic evaluation of left ventricular diastolic function with cine magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Cine magnetic resonance (MR) imaging is a relatively new technique that can be used to study cardiac function with high spatial and temporal resolution. However, detailed functional analysis of the entire cardiac cycle with cine MR imaging is time consuming and labor intensive. We analyzed diastolic function using a semiautomatic routine that reduces the time necessary for analysis. METHODS: Twenty subjects (10 normal control subjects and 10 patients with isolated diastolic dysfunction) were examined. Short-axis cine MR images were obtained at 32 phases of the cardiac cycle. A semiautomatic boundary-finding routine was used to determine left ventricular (LV) volumes at each phase. Volume-versus-time and first-derivative curves were created from these data. Several parameters derived from the MR imaging curves were used to characterize diastole. RESULTS: Two parameters--the ratio of early peak filling rate to late peak filling rate and the percentage of filling during early diastole--perfectly distinguished subjects with LV diastolic dysfunction from the normal control subjects. The semiautomatic analysis method substantially reduced the time necessary for analyzing the MR imaging data, compared with manual analysis. CONCLUSION: Cine MR imaging, especially with time-saving techniques such as our service automatic analysis method, has promise as a research and clinical tool in evaluating LV diastolic function.

Posterior cruciate ligament injury: MR imaging diagnosis and patterns of injury.

PURPOSE: To illustrate the variety of posterior cruciate ligament (PCL) injuries and assess the type and frequency of associated knee injuries. MATERIALS AND METHODS: In a retrospective review of 1,950 magnetic resonance (MR) examinations of the knee, 47 patients with MR imaging findings of PCL injury were identified. In 24 patients, the findings on MR images were correlated with athroscopic findings (n = 14) or findings at physical examination (n = 10). Patterns of associated injuries were described and tabulated. RESULTS: Twenty-one patients (45%) had complete PCL tears; 22 patients (47%), partial tears; and four patients (9%), bone avulsion. Associated injuries were seen in 34 patients (72%). Patterns of injuries differed from those seen in anterior cruciate ligament injury and correlated with the mechanism of trauma. CONCLUSION: MR imaging proved accurate in assessment of the PCL in patients with clinical correlation and demonstrated patterns of associated injury that may affect management strategy.

Appendices epiploicae of the colon: radiologic and pathologic features.

Appendices epiploicae are adipose structures protruding from the serosal surface of the colon. They can be seen with abdominal radiography and cross-sectional imaging if the colonic wall is surrounded by intraperitoneal contrast material, ascites, or blood. Normal appendices epiploicae appear as lobulated masses of pericolic fat, usually 2-5 cm long and 1-2 cm thick. Their enlargement, deformity, or altered radiopacity may result from various pathologic processes that can originate locally or extend from adjacent viscera. In a series of 22 cases, appendices epiploicae were affected by spontaneous torsion and hemorrhagic infarct, calcification due to aseptic fat necrosis, primary or secondary inflammation, enlargement by lipomas or metastases, and incarceration in hernias. Disorders of appendices epiploicae are often manifested by nonspecific clinical signs and symptoms (eg, torsion is often mistaken for appendicitis or diverticulitis). These entities should be included in the differential diagnosis of any unexplained abdominal pain or pericolic lesions in adults.

Platelet-interactive products of Streptococcus sanguis protoplasts.

To isolate a more native, platelet-interactive macromolecule (class II antigen) of Streptococcus sanguis, cultured protoplasts were used as a source. Protoplasts were optimally prepared from fresh washed cells by digestion with 80 U of mutanolysin per ml for 75 min at 37 degrees C while osmotically stabilized in 26% (wt/vol) raffinose. Osmotically stabilized forms were surrounded by a 9-nm bilaminar membrane, as shown by transmission electron microscopy. Protoplasts were cultured in chemically defined synthetic medium and osmotically stabilized by ammonium chloride. Spent culture media were harvested daily for 7 days. Each day, soluble proteins were isolated from media, preincubated with platelet-rich plasma, and tested for inhibition of platelet aggregation induced by S. sanguis cells. Products released from S. sanguis protoplasts and reactive with an anti-class II antigen immunoaffinity matrix were able to inhibit S. sanguis-induced platelet aggregation. As resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, anti-class II-reactive protoplast products included silver-stained bands of 67, 79, 115, 216, and 248 kDa. The 115-kDa protein fraction was isolated by gel filtration and ion-exchange chromatography. This form of the class II antigen contained N-formylmethionine at its amino terminus. Rhamnose constituted 18.2% of the total residual dry weight and nearly half of its carbohydrate content. Diester phosphorus constituted 1% of this fraction. After trypsinization of the protoplast products from either preparation, a 65-kDa protein fragment was recovered. This protoplast protein fragment and the S. sanguis cell-derived 65-kDa class II antigen, previously implicated in the induction of platelet aggregation, were shown to be functionally and immunologically identical.

MR imaging in hydatid disease of the liver.

We describe the appearance on MR of hydatid disease of the liver in 2 patients. The lesions were well demonstrated using spin-echo pulse sequences, and could be easily seen with either T1 or T2 weighting; however, maximum information was obtained using both. In these 2 cases, a thin, low signal boundary was noted around the cysts; this finding may prove useful in differential diagnosis.