Alcohol inhibits osteopontin-dependent transforming growth factor-ß1 expression in human mesenchymal stem cells.

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 ß1 (TGF-ß1) 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-ß1 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-ß1 expression in MSC. We have demonstrated that EtOH inhibits OPN-induced TGF-ß1 protein expression, decreases MZF1-dependent TGF-ß1 transcription and MZF1 transcription, and blocks OPN-induced MZF1 phosphorylation. We also found that PKA signaling enhances OPN-induced TGF-ß1 expression. Last, we showed that EtOH exposure reduces the TGF-ß1 protein levels in mouse fracture callus. We conclude that EtOH acts in a novel mechanism by interfering directly with the OPN-MZF1-TGF-ß1 signaling pathway in MSC.

Erdheim Chester disease with appendicular skeletal, renal and pleural involvement responding to Zelboraf (BRAF inhibitor) treatment: case report.

Erdheim Chester disease is a rare non-Langerhans cell histiocytosis which may involve multiple organs including bone, soft tissue, lungs, cardiovascular system, kidneys (retroperitoneum), skin, and central nervous system. Bone involvement is most common followed by other organs. This case report describes a 58-year-old man who presented with progressive renal dysfunction presumed due to obstruction. The patient failed multiple urinary tract interventions, and clinical course was complicated by recurrent low-grade fevers, and bilateral knee pain. Advanced imaging and histopathological features on bone biopsy were consistent with Erdheim Chester disease. Molecular studies of tissue showed BRAF V600 mutation. This patient was treated with Zelboraf (vemurafenib) BRAF inhibitor with subsequent improvement in renal and pleural dysfunction as well as decreased histiocytic soft tissue masses on CT.

Older age impacts radiotherapy-related outcomes in soft tissue sarcoma.

BACKGROUND: Radiation therapy (RT) is a standard component in the multimodality management of localized soft tissue sarcoma (STS). Increasing studies are focusing on biological modifiers that may influence the host's response to RT, including immunologic mechanisms known to change with the aging process. We hypothesized that the effects of RT would be influenced by age, contributing to differences in treatment outcome. METHODS: Using Surveillance, Epidemiology, and End Results (1990-2011), we identified 30,898 adult patients (>18 y) with nonmetastatic STS undergoing initial surgery. We compared patient demographics, tumor characteristics, and treatments by age. Multivariable analyses were used to analyze overall survival (OS) and disease-specific survival (DSS). Hazard ratios (HRs) were calculated based on multivariable Cox proportional hazards models. RESULTS: Mean age at diagnosis was 56.6 ± 16.8 y, and 33.6% of patients were ≥65 y. Of the total, 52.1% of patients were male and 67% were white; 59.9% of patients underwent surgery alone, 33.3% received adjuvant RT, and 6.8% neoadjuvant RT. On multivariable analysis, age, sex, year of diagnosis, histology, grade, size, marital status, and RT predicted OS, whereas age, year of diagnosis, ethnicity, histology, site, grade, RT, size, and marital status predicted DSS. In all patients, RT was associated with improved OS and DSS compared to surgery alone (median OS 136 ± 13 mo with RT versus 118 ± 9 mo without RT and 5-y OS 63.2 ± 1.4% with RT versus 60.5 ± 1.2% without, P < 0.01). Patients ≥65 y derived greater improvements in OS and DSS compared with patients <65 y. These benefits were most notable after neoadjuvant RT with patients ≥65 y having significantly better OS (HR = 0.63; 95% confidence interval = 0.53-0.75), whereas patients <65 y did not (HR = 0.96; 95% confidence interval = 0.83-1.10). In addition, interaction testing demonstrated a significant modifier effect between RT and age (P < 0.05). CONCLUSIONS: RT is associated with improved survival in patients with STS undergoing surgical treatment, but improvements in oncologic outcome with RT were greatest among older patients. Further studies into the mechanism of these age-related effects are needed.

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

BACKGROUND AND METHODS: 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). RESULTS: The mean age was 41, 49.3% were female, and 82.2% were white. Radiotherapy (RT) was administered to 57.5%. On multivariable analysis, age at diagnosis, sex, race, anatomic site, SEER summary stage, tumor size, surgery type, and RT predicted OS. Similar predictors of DSS were identified. The hazard ratio (HR) for OS was 0.65 (95% CI 0.48-0.88) in favor of RT and 0.62 (95% CI 0.45-0.86) for DSS. Five-year OS improved 8.4 ± 1.0% with RT (P=0.003), and five-year DSS improved 7.7 ± 1.0% with RT (P=0.015). CONCLUSIONS: In the largest study to date examining the role of RT in synovial sarcoma, we observed that RT was associated with a statistically significant improvement in oncologic outcome among SS patients. These data support the use of RT in the multi-modality treatment of patients with SS.

Phase I trial of neoadjuvant conformal radiotherapy plus sorafenib for patients with locally advanced soft tissue sarcoma of the extremity.

BACKGROUND: Despite effective local therapy with surgery and radiotherapy (RT), ~50 % of patients with high-grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when antiangiogenic targeted therapies such as sorafenib are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a phase I/II trial among patients with extremity STS amenable to treatment with curative intent. METHODS: For the phase I trial, eight patients with intermediate- or high-grade STS >5 cm in maximal dimension or low-grade STS >8 cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 twice daily, cohort 2:200/400 daily) and preoperative RT (50 Gy in 25 fractions). Sorafenib was continued during the entire period of RT as tolerated. Surgical resection was completed 4-6 weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT). RESULTS: Eight patients were enrolled in the phase I (five females, median age 44 years, two high-grade pleomorphic, two myxoid/round cell liposarcoma, four other). Median tumor size was 16 cm (range 8-29), and all tumors were located in the lower extremity. Two of five patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and supraventricular tachycardia. Radiation toxicity (grade 1 or 2 dermatitis; N = 8) and post-surgical complications (three grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (≥95 % tumor necrosis) was observed in three patients (38 %). CONCLUSION: Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (ClinicalTrials.gov identifier NCT00805727).

Anti-proliferative but not anti-angiogenic tyrosine kinase inhibitors enrich for cancer stem cells in soft tissue sarcoma.

BACKGROUND: Increasing studies implicate cancer stem cells (CSCs) as the source of resistance and relapse following conventional cytotoxic therapies. Few studies have examined the response of CSCs to targeted therapies, such as tyrosine kinase inhibitors (TKIs). We hypothesized that TKIs would have differential effects on CSC populations depending on their mechanism of action (anti-proliferative vs. anti-angiogenic). METHODS: We exposed human sarcoma cell lines to sorafenib, regorafenib, and pazopanib and assessed cell viability and expression of CSC markers (ALDH, CD24, CD44, and CD133). We evaluated survival and CSC phenotype in mice harboring sarcoma metastases after TKI therapy. We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate. RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P < 0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P < 0.05). In contrast, we observed negligible effects on viability and CSC sub-populations with pazopanib. At low doses, there was progressive CSC enrichment in vitro after longer term exposure to sorafenib although the anti-proliferative effects were attenuated. In vivo, sorafenib improved median survival by 11 days (P < 0.05), but enriched ALDHbright cells 2.5 - 2.8 fold (P < 0.05). Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib and regorafenib with a corresponding increase in ALDHbright cells (P < 0.05). Again, negligible effects from pazopanib were observed. TMA analysis of archived specimens from sarcoma patients treated with sorafenib demonstrated significant enrichment for ALDHbright cells in the post-treatment resection specimen (P < 0.05), whereas clinical specimens obtained longitudinally from a patient treated with pazopanib showed no enrichment for ALDHbright cells (P > 0.05). CONCLUSIONS: Anti-proliferative TKIs appear to enrich for sarcoma CSCs while anti-angiogenic TKIs do not. The rational selection of targeted therapies for sarcoma patients may benefit from an awareness of the differential impact of TKIs on CSC populations.

Chondroblastoma-like chondroma of the hand: case report.

Chondroblastoma-like chondroma is a rare tumor that almost exclusively manifests in the hand and presents with a set of unique diagnostic features. This tumor has been described in only a limited number of publications and is thus commonly omitted in the differential diagnosis of hand tumors. The diagnostic imaging and histological specimens may initially appear consistent with a number of relatively more common hand tumors, thereby delaying the diagnosis. We present the case of a 49-year-old woman with chondroblastoma-like chondroma of the hand treated with marginal excision. The physical examination, imaging, and needle biopsy made an initial case for giant cell tumor of tendon sheath until histological analysis of the excised specimen yielded the correct diagnosis.

Extraskeletal Ewing sarcoma of the sciatic nerve.

Extraskeletal Ewing sarcoma (EES) is a rare tumor diagnosed in children or young adults and is even more unusual in individuals over 30 years of age. Due to its rare occurrence and low index of suspicion, this tumor can pose diagnostic and therapeutic challenges. We present a case of a 60-year-old male with EES of the sciatic nerve, an unexpected entity given the patient's age, tumor type, and tumor location. This can mimic a nerve sheath tumor on imaging.

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.

Histologic type predicts survival in patients with retroperitoneal soft tissue sarcoma.

BACKGROUND: Histologic grade, completeness of resection, and presence of metastases are traditionally regarded as the primary factors in predicting survival for retroperitoneal soft tissue sarcoma (RPSTS). We sought to examine the importance of histologic type as a prognostic factor among patients with RPSTS. METHODS: We identified 2337 cases of RPSTS in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2004. After excluding 273 cases of age <18, identification by autopsy only, or absence of histologic confirmation, we arrived at a final study cohort of 2064 patients. 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 age, gender, race, histologic type, histologic grade, tumor size, extent of resection, and SEER summary stage. RESULTS: Among 33 histologic types, leiomyosarcoma (28.7%), well-differentiated/dedifferentiated liposarcoma (20.3%), liposarcoma not otherwise specified (NOS) (11.9%), malignant fibrous histiocytoma (MFH-11.0%), and sarcoma NOS (10.7%) were the most prevalent. Grade distribution was low, 24.2%; intermediate, 16%; high 34.3%, and unknown, 25.5%. Surgery was performed in 85.8%, and radiotherapy was administered to 22.8%. With a median follow-up of 38 mo, median OS was 78, 35, 25, 18, and 10 mo for liposarcoma, leiomyosarcoma, other histologies, MFH, and sarcoma NOS, respectively (P < 0.0001). Median DSS was 120, 53, not reached, 30, and 13 mo for liposarcoma, leiomyosarcoma, other histologies, MFH, and sarcoma NOS, respectively (P < 0.0001). On multivariate analysis, histologic type was associated with statistically significant differences in both OS and DSS. CONCLUSIONS: Histologic type is an important predictor of survival in RPSTS.

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.

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.

Radiographic and histologic response to neoadjuvant radiotherapy in patients with soft tissue sarcoma.

BACKGROUND: Limited data exist regarding the radiographic and histologic response of soft tissue sarcoma (STS) to neoadjuvant radiotherapy (RT). METHODS: Between February 2000 and January 2009, a total of 25 patients aged >16 years with intermediate- or high-grade primary STS of all sites were treated with neoadjuvant RT followed by definitive resection. Patients receiving chemoradiotherapy were excluded. Cross-sectional images obtained before and after RT as well as pathologic specimens were reviewed for maximal change in tumor diameter and percentage tumor necrosis, respectively. Clinicopathologic variables were analyzed for their association with pathologic and radiographic response. RESULTS: There were 18 extremity (72%) and 7 retroperitoneal (28%) tumors. Median maximal tumor size was 9 cm (range, 3.3-35 cm), and 88% were of high grade. There were 21 R0 resections (84%) and 4 R1 resections (16%). Radiographically, the median percentage change in tumor diameter was 0% (range, -25 to +86%). By Response Evaluation Criteria in Solid Tumors (RECIST), 5 patients demonstrated progressive disease, 20 demonstrated stable disease, and 0 demonstrated partial/complete response. The median pathologic percentage tumor necrosis was 30% (range, 5-100%). Two tumors (8%) demonstrated near-complete pathologic response (≥95% necrosis). Near-complete pathologic response was associated with favorable oncologic outcomes, although these associations were not statistically significant. CONCLUSIONS: Radiologic and near-complete pathologic responses are rare events after preoperative RT for STS. Near-complete pathologic response may be a potentially meaningful surrogate marker for disease outcome and is not predicted by RECIST response. Knowledge of these historical response rates is important for the evaluation of novel neoadjuvant therapies for patients with STS.

Monostotic fibrous dysplasia of the distal phalanx: case report.

Monostotic fibrous dysplasia in the finger is rare. We are aware of only 4 cases, none of which involved the distal phalanx. We present a case of a 16-year-old boy with a fibrous dysplasia of the left long finger distal phalanx. Treatment consisted of curettage and bone grafting.

Multi-focal Lytic Lesions in a Patient with Myelofibrosis: A Case Report.

Myelofibrosis is a rare disorder that is classified as one of the myeloproliferative disorders. This particular disorder results in the abnormal proliferation of hematopoietic stem cells in the bone marrow. In some cases, such as ours, pathologic fractures can occur due to skeletal manifestations. We report on a rare finding of rapidly progressive lytic lesions in multiple regions throughout the body. This presentation of myelofibrosis behaving in a metastatic-like fashion has not been previously described.

Atypically presenting kaposiform hemangioendothelioma of the knee: ultrasound findings.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of early childhood and infancy. Kasabach-Merritt phenomenon, a common complication of KHE, is characterized by life-threatening thrombocytopenia, hemolytic anemia, and consumption coagulopathy. There may be atypical cases that do not present with Kasabach-Merritt phenomenon and do have atypical imaging findings. Knowledge of atypical imaging features may assist radiologists in identifying KHE. In this report, we present a 4-year-old case of KHE with atypical ultrasound findings.

Expression of epidermal growth factor receptor, but not K-RAS mutations, is present in congenital cystic airway malformation/congenital pulmonary airway malformation.

Congenital cystic airway malformation/congenital pulmonary airway malformation (CCAM/CPAM) of the lung is a rare but well-described malformative lesion of pulmonary parenchyma characterized by the abnormal maturation of airways along with an increase in terminal respiratory structures, resulting in cysts of variable sizes. Five types have been classified based on morphological analysis. Although the etiology of the lesion is still unclear, recent data suggest that bronchial atresia is a predisposing/associated anomaly. A described association between type 1 CCAM/CPAM and bronchioloalveolar carcinoma suggests that type 1 CCAM/CPAM may predispose to malignant transformation by as yet unidentified tumorigenic mechanisms. Here we studied epidermal growth factor receptor (EGFR) and K-RAS oncogene, 2 biological markers closely associated with tumorigenesis and altered in many types of tumors, including lung carcinomas. For this purpose, we used immunohistochemistry and gene sequencing in paraffin-embedded tissue. Our results demonstrate expression of EGFR in types 1 and 3 CCAM/CPAM, with a distinctive distribution and intensity, compared with that of type 2. Of special interest, mucinous areas in 2 cases of type 1 CCAM/CPAM lacked EGFR expression, whereas adjacent epithelial cystic linings were strongly positive. This supports the hypothesis that mucinous differentiation in CCAM/CPAM, always present in cases with malignant transformation, could be related to other molecular pathways. The K-RAS gene was screened for mutations usually found in lung carcinomas; however, no mutations were present in any of the studied samples. These findings support the notion that EGFR may play an important role in the pathogenesis and phenotype of CCAM/CPAM.

Older Age Modifies Oncologic Outcome Following Radiotherapy in Soft-tissue Sarcoma: A Subtype-specific SEER Analysis.

BACKGROUND: Given the immune-mediated mechanisms of radiotherapy (RT), we hypothesized that age would affect response to RT in patients with soft-tissue sarcoma (STS) undergoing surgery. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results Program (1990-2011), we identified 15,380 patients with non-metastatic STS. Stratified by age (≥65 years) and histological subtype, we assessed predictors of overall (OS) and disease-specific survival (DSS). RESULTS: Treatment with RT was associated with improved OS and DSS compared to surgery alone (p<0.05). Multivariate analysis also demonstrated that older patients obtained significant improvements in OS following RT, while younger patients did not. Results for DSS were similar, with older patients with leiomyosarcoma, sarcoma not otherwise specified, and myxoid liposarcoma, in particular, showing greater improvements in DSS after RT than younger patients (p<0.05). Interaction testing demonstrated an impact of year of diagnosis on outcomes but not receipt of RT. CONCLUSION: Among patients with STS undergoing surgery, age appears to impact oncological outcomes after RT.

Interfascicular Renal Cell Carcinoma Metastasis to the Ulnar Nerve: A Case Report.

BACKGROUND: Metastatic solid tumors to the hand and peripheral nerves are exceedingly rare independent occurrences. Their occurrence together has never been reported in the literature. METHODS: We present a case report of a 69 year old male with a previous history of renal cell carcinoma (RCC) presenting with a rapidly-growing painful mass located at the right volar ulnar wrist, found to have endoneural solid tumor metastatic RCC to the ulnar nerve. RESULTS: Preoperative MRI imaging of the wrist revealed a heterogeneous mass on the volar aspect of the wrist extending along the length of the ulnar artery and nerve to the level of Guyon's canal. Pathologic examination of an incisional biopsy of the mass was consistent with metastatic renal clear cell carcinoma cells, which were infiltrating nerve and surrounding soft tissue. The patient underwent local radiation therapy to the wrist and hand with interval decrease in size of the mass and symptom improvement. CONCLUSION: Solid tumor metastasis, although exceedingly rare, must be considered in the differential diagnosis of a patient with previous cancer history presenting with a wrist or hand mass associated with peripheral neuropathy.

Antinociception depends on the presence of G protein gamma2-subunits in brain.

We have shown previously [Hosohata, K., Logan, J.K., Varga, E., Burkey, T.H., Vanderah, T.W., Porreca, F., Hruby, V.J., Roeske, W.R., Yamamura, H.I., 2000. The role of the G protein gamma2 subunit in opioid antinociception in mice. Eur. J. Pharmacol. 392, R9-R11] that intracerebroventricular (i.c.v.) treatment of mice with a phosphorothioate oligodeoxynucleotide antisense to the gamma2 subunit (Ggamma2) of the heterotrimeric G proteins (antisense ODN) significantly attenuates antinociception by a delta-opioid receptor agonist. In the present study, we examined the involvement of Ggamma2 in antinociception mediated by other (mu- or kappa-opioid, cannabinoid, alpha2-adrenoreceptor) analgesic agents in a warm (55 degrees C) water tail-flick test in mice. Interestingly, i.c.v. treatment with the antisense ODN attenuated antinociception by each analgesic agent. Missense phosphorothioate oligodeoxynucleotide treatment, on the other hand, had no effect on antinociception mediated by these agonists. The antinociceptive response recovered in 6 days after the last antisense ODN injection, indicating a lack of nonspecific tissue damage in the animals. These results suggest a pervasive role for the G protein gamma2 subunits in supraspinal antinociception.