Dariusz Borys

Congenital Diaphragmatic Hernia and Chromosomal Anomalies: Autopsy Study

In a 10-year review of autopsy records from Lutheran General Hospital (1992–2002), 13 cases of congenital diaphragmatic hernia (CDH) were found. The fetuses ranged between 21 and 35 wk of gestation. Four were born alive and five were diagnosed prenatally. The defect was left-sided in 11 cases. Cytogenetic study revealed five cases with normal karyotype and three cases with complex karyotypes. In five cases, no karyotype was performed. The three complex karyotypes were: 46,XX,del(8)(p23.1), 47,XX,+i(12)(p10)[6]/46XX[14] (Pallister-Killian syndrome), and 47,XY,+der(22)t(11:22)(q23.3:q11.2). The unbalanced translocation of chromosomes 11 and 22 in congenital diaphragmatic hernia has not been previously described. Three fetuses had heart abnormalities, including one which was associated with the 8p deletion. The other two had no karyotype study. Neither in this study, nor in the literature, is there a consistent or prevailing association between a specific chromosomal anomaly and CDH. The embryologic closure of the diaphragmatic leaflets may be mediated by a nonstructural chromosomal defect, more than one gene, and/or may be related to abnormalities not currently detectable.

Predicting Survival for Well-Differentiated Liposarcoma: The Importance of Tumor Location

BACKGROUND Although well-differentiated liposarcoma (WD Lipo) is a low grade neoplasm with a negligible risk of metastatic disease, it can be locally aggressive. We hypothesized that survival for WD Lipo varies significantly based on tumor location. METHODS We identified 1266 patients with WD Lipo in the Surveillance, Epidemiology, and End Results database from 1988-2004. After excluding patients diagnosed by autopsy only, those lacking histologic confirmation, those lacking data on tumor location, and those with metastatic disease or unknown staging information, we arrived at a final study cohort of 1130 patients. Clinical, pathologic, and treatment variables were analyzed for their association with overall survival (OS) and disease-specific survival (DSS) using Kaplan-Meier analysis and Cox proportional hazards multivariate models. RESULTS Mean age was 61 y (± 14.6), 72.2% were white, and 60.4% were male. Eighty-one percent of patients were treated with surgical therapy alone, 4.6% were treated with radiotherapy (RT) alone, and 12.9% were treated with both surgery and RT. Extremity location was most common (41.6%), followed by trunk (29%), retroperitoneal/intra-abdominal (RIA, 21.6%), thorax (4.2%), and head/neck (3.6%). With a median follow-up of 45 mo, median OS was 115 mo (95% confidence interval [CI] 92-138 mo) for RIA tumors compared to not reached for other tumor locations (P = 0.002). On multivariate analysis, increasing age and RIA location both predicted worse OS and DSS while tumor size, race, sex, receipt of RT, and Surveillance, Epidemiology, and End Results (SEER) stage did not. Tumor size became a significant predictor of worse DSS, but not OS, only when site, SEER stage, and extent of resection were removed from the multivariate model. Non-RIA locations, including extremity, experienced statistically similar OS, but 5-y DSS for trunk location was intermediate [92.3%, (95% CI 88.5%-96.1%) compared with 98.0% (95% CI, 96.2%-99.8%) for extremity and 86.6 (95% CI 81.1%-92.1%) for RIA, P < 0.001]. CONCLUSIONS Among patients with WD Lipo, RIA location is associated with significantly worse outcomes independent of tumor size. Future studies should focus on the anatomic and biologic reasons for these differences.

Interaction of Histologic Subtype and Histologic Grade in Predicting Survival for Soft-Tissue Sarcomas

BACKGROUND Histologic grade is considered the paramount prognostic factor in predicting survival for soft-tissue sarcomas (STS). Increasing data suggest that histologic type substantially impacts STS behavior. STUDY DESIGN The Surveillance, Epidemiology, and End Results program was used to identify 17,364 cases of STS diagnosed between 1988 and 2004. Using death from STS as 1 of the outcomes variables, histologic types were grouped into 3 categories: favorable (survival >or= 20% above the mean), neutral (survival within 20% of the mean), and unfavorable (survival >or= 20% below the mean). The effect of histology on survival was analyzed stratified by tumor grade. Five-year survival was calculated using Kaplan-Meier analysis. RESULTS Among 73 histologic types, malignant fibrous histiocytoma (24.1%); leiomyosarcoma, not otherwise specified (14.8%); sarcoma, not otherwise specified (12.8%); and myxoid liposarcoma (5.9%) were the most prevalent. Grade distribution was as follows: low, 12.6%; intermediate, 14.9%; high, 37.1%; and unknown, 35.4%. Risk of death from STS increased with increasing grade: 8.0% for low, 25.9% for intermediate, and 38.3% for high. Among low-grade tumors, risk of death from STS ranged from 4.3% for favorable types to 15.3% for unfavorable types. Among intermediate-grade tumors, risk of death from STS ranged from 6.0% for favorable types to 45.4% for unfavorable types. Among high-grade tumors, risk of death from STS ranged from 24.3% for favorable types to 58.9% for unfavorable types. CONCLUSIONS Within categories of STS grade, there are substantial differences in survival, depending on histologic type. Histologic type is an important predictor of biologic behavior in STS.

Lack of survival benefit following adjuvant radiation in patients with retroperitoneal sarcoma: A SEER analysis

BACKGROUND The benefit of radiation therapy (RT) among patients with retroperitoneal sarcoma (RPS) is controversial. We performed a retrospective analysis of the effect of RT on survival among RPS patients using a nationwide cancer registry. METHODS Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, we identified 2308 cases of RPS from 1988 to 2004. We excluded 773 cases for age < 18, identification by autopsy only, absence of histologic confirmation, presence of metastatic disease, or lack of surgical intervention. Overall survival (OS) and disease-specific survival (DSS) were estimated using the Kaplan-Meier method. Multivariate analysis was performed using a Cox proportional hazards model, adjusting for significant covariables. RESULTS Among 1535 patients who met entry criteria, RT was administered to 373 patients (24.3%). The majority of RT (n = 300, 80.4%) was administered postoperatively. Median OS was 60 and 60 mo, respectively, for patients receiving and not receiving RT (P = 0.59). Median DSS was 86 and 117 mo, respectively, for patients receiving and not receiving RT (P = 0.84). On multivariate analysis, younger age, female gender, low and intermediate histologic grade, liposarcoma histology, tumor size 5-10 cm, and completeness of resection all independently predicted better OS and DSS, while RT did not (HR for OS with RT 0.92, 95% CI 0.78-1.09 and HR for DSS with RT 0.96, 95% CI 0.78-1.17). On subgroup analysis by histology, patients with malignant fibrous histiocytoma (MFH) receiving RT demonstrated statistically improved OS (P = 0.002) and DSS (P = 0.01), respectively. CONCLUSIONS With the possible exception of MFH, postoperative RT offers no survival benefit in RPS. Further studies are necessary to determine if the selective application of RT is indicated.

Giant cell tumor of bone.

EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Identify at-risk populations for giant cell tumor of bone. 2. Recognize the biology that drives giant cell tumor of bone. 3. Describe modern surgical and adjuvant techniques to effectively treat giant cell tumor of bone. 4. Recognize the complications associated with radiation therapy, poor resection, and adjuvant treatments. Giant cell tumor of bone (GCT) is a benign, locally aggressive bone tumor. Giant cell tumor of bone primarily affects the young adult patient population. The natural history of GCT is progressive bone destruction leading to joint deformity and disability. Surgery is the primary mode of treatment, but GCT has a tendency to recur locally despite a range of adjuvant surgical options. Pulmonary metastasis has been described. However, systemic spread of GCT rarely becomes progressive, leading to death. This review presents the clinicopathologic features of GCT and a historical perspective that highlights the current rationale and controversies regarding the treatment of GCT.

Alcohol Inhibits Osteopontin Dependent Transforming Growth Factor-β1 Expression in Human Mesenchymal Stem Cells

Background: Alcohol (EtOH) exposure has detrimental effects on fracture healing. Results: EtOH inhibits TGF-β1 protein expression via interference with the transcription factor myeloid zinc finger 1. Conclusion: EtOH-induced deficient fracture healing may be related to reduced TGF-β1. Significance: Further understanding of the mechanisms responsible for the effects of EtOH are crucial for the development of interventions aimed at averting morbidities related to EtOH consumption. Alcohol (EtOH) intoxication is a risk factor for increased morbidity and mortality with traumatic injuries, in part through inhibition of bone fracture healing. Animal models have shown that EtOH decreases fracture callus volume, diameter, and biomechanical strength. Transforming growth factor β1 (TGF-β1) and osteopontin (OPN) play important roles in bone remodeling and fracture healing. Mesenchymal stem cells (MSC) reside in bone and are recruited to fracture sites for the healing process. Resident MSC are critical for fracture healing and function as a source of TGF-β1 induced by local OPN, which acts through the transcription factor myeloid zinc finger 1 (MZF1). The molecular mechanisms responsible for the effect of EtOH on fracture healing are still incompletely understood, and this study investigated the role of EtOH in affecting OPN-dependent TGF-β1 expression in MSC. We have demonstrated that EtOH inhibits OPN-induced TGF-β1 protein expression, decreases MZF1-dependent TGF-β1 transcription and MZF1 transcription, and blocks OPN-induced MZF1 phosphorylation. We also found that PKA signaling enhances OPN-induced TGF-β1 expression. Last, we showed that EtOH exposure reduces the TGF-β1 protein levels in mouse fracture callus. We conclude that EtOH acts in a novel mechanism by interfering directly with the OPN-MZF1-TGF-β1 signaling pathway in MSC.

Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers

The molecules Indian hedgehog (IHH), SP7 (also known as osterix), sex-determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and TWIST1 regulate the normal differentiation of osteo- and chondrogenic cells from precursors during skeletal development and remodeling. The aberrant function of the same molecules has been implicated in the pathogenesis of bone tumors. Preliminary studies suggest that antibodies against these molecules have practical, diagnostic or prognostic utility in tumors. However, a comprehensive analysis of the expression of these molecules in a large, diverse set of bone tumors has yet to be reported. The goals of this study were to compare the immunohistochemical profiles of IHH, SP7, SOX9, RUNX2 and TWIST1 among bone tumors and to determine the optimum panel for diagnostic utility. Tissue microarrays prepared from 206 undecalcified tumors (71 osteosarcomas, 26 osteoblastomas/osteoid osteomas, 50 giant cell tumors, 5 chondromyxoid fibromas and 54 chondroblastomas) were stained with antibodies to IHH, SP7, SOX9, RUNX2 and TWIST1. The stains were scored for intensity (0−3+) and distribution. The results were analyzed by cluster analysis. Optimum antibody panels for diagnostic sensitivity and specificity were calculated. Analysis revealed six main clusters that corresponded well to tumor types and suggested a close relationship between the stromal cells of giant cell tumor and the osteoblasts of osteosarcoma. The expression profile of chondromyxoid fibroma and chondroblastoma also suggested related differentiation. The distribution of osteoblastomas and osteoid osteomas was more heterogeneous. RUNX2, SOX9 and TWIST1 represented the most sensitive and specific immunohistochemical panel to distinguish among these diagnoses with the limitation that no result could discriminate between chondroblastoma and chondromyxoid fibroma. IHH and SP7 did not yield additional utility.

Intense FDG uptake in an intra-articular localized giant-cell tumor of the tendon sheath (pigmented villonodular synovitis) mimics metastatic melanoma

We describe a patient with metastatic melanoma, one year following a clinical trial of VEGF

Perioperative radiotherapy is associated with improved survival among patients with synovial sarcoma: A SEER analysis.

We examined the outcomes of synovial sarcoma (SS) patients in a national database. We identified 1,189 patients from the Surveillance, Epidemiology, and End Results (SEER) database with data on site and extent of surgery. We excluded patients diagnosed before 1990, <18 years, or lacking pathologic confirmation. Using Kaplan–Meier and Cox proportional hazards analyses, we determined predictors of overall (OS) and disease‐specific survival (DSS).

Enteropathy-Associated T Cell Lymphoma Presenting with Acute Abdominal Syndrome: A Case Report and Review of Literature

IntroductionEnteropathy-associated T cell lymphoma (EATL) is a rare peripheral non-Hodgkins T cell lymphoma originating from intraepithelial T lymphocytes of the intestines. In general, this condition has a poor prognosis. A common initial presentation of this cancer which is a small intestinal perforation necessitating emergency surgery is of interest to practicing surgeons. The diagnosis is rarely made prior to pathological examination.MethodsWe report a case of a 39-year-old African American man who presented with acute abdomen and was found to have a deep necrotic ulcer of the jejunum during exploratory laparotomy.ResultsPathological examination and laboratory results demonstrated EATL, type 2, which is not associated with celiac disease. A review of the literature on EATL is also presented.