Anna A. Kulidjian

Continuous femoral versus posterior lumbar plexus nerve blocks for analgesia after hip arthroplasty: a randomized, controlled study.

BACKGROUND:Hip arthroplasty frequently requires potent postoperative analgesia, often provided with an epidural or posterior lumbar plexus local anesthetic infusion. However, American Society of Regional Anesthesia guidelines now recommend against epidural and continuous posterior lumbar plexus blocks during administration of various perioperative anticoagulants often administered after hip arthroplasty. A continuous femoral nerve block is a possible analgesic alternative, but whether it provides comparable analgesia to a continuous posterior lumbar plexus block after hip arthroplasty remains unclear. We therefore tested the hypothesis that differing the catheter insertion site (femoral versus posterior lumbar plexus) after hip arthroplasty has no impact on postoperative analgesia. METHODS:Preoperatively, subjects undergoing hip arthroplasty were randomly assigned to receive either a femoral or a posterior lumbar plexus stimulating catheter inserted 5 to 15 cm or 0 to 1 cm past the needle tip, respectively. Postoperatively, patients received perineural ropivacaine, 0.2% (basal 6 mL/hr, bolus 4 mL, 30-minute lockout) for at least 2 days. The primary end point was the average daily pain scores as measured with a numeric rating scale (0–10) recorded in the 24-hour period beginning at 07:30 the morning after surgery, excluding twice-daily physical therapy sessions. Secondary end points included pain during physical therapy, ambulatory distance, and supplemental analgesic requirements during the same 24-hour period, as well as satisfaction with analgesia during hospitalization. RESULTS:The mean (SD) pain scores for subjects receiving a femoral infusion (n = 25) were 3.6 (1.8) versus 3.5 (1.8) for patients receiving a posterior lumbar plexus infusion (n = 22), resulting in a group difference of 0.1 (95% confidence interval −0.9 to 1.2; P = 0.78). Because the confidence interval was within a prespecified −1.6 to 1.6 range, we conclude that the effect of the 2 analgesic techniques on postoperative pain was equivalent. Similarly, we detected no differences between the 2 treatments with respect to the secondary end points, with one exception: subjects with a femoral catheter ambulated a median (10th–90th percentiles) 2 (0–17) m the morning after surgery, in comparison with 11 (0–31) m for subjects with a posterior lumbar plexus catheter (data nonparametric; P = 0.02). CONCLUSIONS:After hip arthroplasty, a continuous femoral nerve block is an acceptable analgesic alternative to a continuous posterior lumbar plexus block when using a stimulating perineural catheter. However, early ambulatory ability suffers with a femoral infusion.

A novel patient-derived intra-femoral xenograft model of bone metastatic prostate cancer that recapitulates mixed osteolytic and osteoblastic lesions

Prostate cancer metastasizes to bone in the majority of patients with advanced disease leading to painfully debilitating fractures, spinal compression and rapid decline. In addition, prostate cancer bone metastases often become resistant to standard therapies including androgen deprivation, radiation and chemotherapy. There are currently few models to elucidate mechanisms of interaction between the bone microenvironment and prostate cancer. It is, thus, essential to develop new patient-derived, orthotopic models. Here we report the development and characterization of PCSD1 (Prostate Cancer San Diego 1), a novel patient-derived intra-femoral xenograft model of prostate bone metastatic cancer that recapitulates mixed osteolytic and osteoblastic lesions.MethodsA femoral bone metastasis of prostate cancer was removed during hemiarthroplasty and transplanted into Rag2-/-;γc-/- mice either intra-femorally or sub-cutaneously. Xenograft tumors that developed were analyzed for prostate cancer biomarker expression using RT-PCR and immunohistochemistry. Osteoblastic, osteolytic and mixed lesion formation was measured using micro-computed tomography (microCT).ResultsPCSD1 cells isolated directly from the patient formed tumors in all mice that were transplanted intra-femorally or sub-cutaneously into Rag2-/-;γc-/- mice. Xenograft tumors expressed human prostate specific antigen (PSA) in RT-PCR and immunohistochemical analyses. PCSD1 tumors also expressed AR, NKX3.1, Keratins 8 and 18, and AMACR. Histologic and microCT analyses revealed that intra-femoral PCSD1 xenograft tumors formed mixed osteolytic and osteoblastic lesions. PCSD1 tumors have been serially passaged in mice as xenografts intra-femorally or sub-cutaneously as well as grown in culture.ConclusionsPCSD1 xenografts tumors were characterized as advanced, luminal epithelial prostate cancer from a bone metastasis using RT-PCR and immunohistochemical biomarker analyses. PCSD1 intra-femoral xenografts formed mixed osteoblastic/osteolytic lesions that closely resembled the bone lesions in the patient. PCSD1 is a new primary prostate cancer bone metastasis-derived xenograft model to study metastatic disease in the bone and to develop novel therapies for inhibiting prostate cancer growth in the bone-niche.

PCSD1, a new patient-derived model of bone metastatic prostate cancer, is castrate-resistant in the bone-niche.

IntroductionProstate cancer bone metastasis occurs in 50-90% of men with advanced disease for which there is no cure. Bone metastasis leads to debilitating fractures and severe bone pain. It is associated with therapy resistance and rapid decline. Androgen deprivation therapy (ADT) is standard of care for advanced prostate cancer, however, bone metastatic prostate cancer (PCa) often becomes resistant to ADT. There are few pre-clinical models to understand the interaction between the bone microenvironment and prostate cancer. Here we report the castrate resistant growth in the bone niche of PCSD1, a patient-derived intra-femoral xenograft model of prostate bone metastatic cancer treated with the anti-androgen, bicalutamide.MethodsPCSD1 bone-niche model was derived from a human prostate cancer femoral metastasis resected during hemiarthroplasty and serially transplanted into Rag2−/−;γc−/− mice intra-femorally (IF) or sub-cutaneously (SC). At 5 weeks post-transplantation mice received bicalutamide or vehicle control for 18 days. Tumor growth of PCSD1 was measured with calipers. PSA expression in PCSD1 xenograft tumors was determined using quantitative RT-PCR and immunohistochemistry. Expression of AR and PSMA, were also determined with qPCR.ResultsPCSD1 xenograft tumor growth capacity was 24 fold greater in the bone (intra-femoral, IF) than in the soft tissue (sub-cutaneous, SC) microenvironment. Treatment with the anti-androgen, bicalutamide, inhibited tumor growth in the sub-cutaneous transplantation site. However, bicalutamide was ineffective in suppressing PCSD1 tumor growth in the bone-niche. Nevertheless, bicalutamide treatment of intra-femoral tumors significantly reduced PSA expression (p < =0.008) and increased AR (p < =0.032) relative to control.ConclusionsPCSD1 tumors were castrate resistant when growing in the bone-niche compared to soft tissue. Bicalutamide had little effect on reducing tumor burden in the bone yet still decreased tumor PSA expression and increased AR expression, thus, this model closely recapitulated castrate-resistant, human prostate cancer bone metastatic disease. PCSD1 is a new primary prostate cancer bone metastasis-derived xenograft model to study bone metastatic disease and for pre-clinical drug development of novel therapies for inhibiting therapy resistant prostate cancer growth in the bone-niche.

Upper extremity reconstruction with a humeral tumor endoprosthesis: A novel salvage procedure after multiple revisions of total shoulder and elbow replacements

Failure of revision shoulder and elbow replacement because of periprosthetic infection and fracture presents a challenging technical problem for the surgeon and a difficult decision for the patient considering limb salvage versus amputation. At present, there exist few viable options for a limb salvage procedure that provides a reasonable level of functionality and pain relief. Compromised bone stock, infection, aseptic loosening, and progressive osteolysis are among the obstacles that may preclude the surgeon from pursuing repeat revision of shoulder and elbow arthroplasty. We report the case of a 54-year-old woman with severe rheumatoid arthritis in whom revision shoulder and elbow replacements failed because of periprosthetic infection and fracture. Unfortunately, this yielded a dysfunctional flail arm and incapacitating pain. Progressive humeral and ulnar bone loss created a suboptimal condition for skeletal fixation by means of repeat revision of the total shoulder and elbow components. Previously, this patient had undergone an ipsilateral wrist fusion for chronic extensor tendon ruptures. However, she was still capable of limited hand function, including writing and grasping activities, that she did not wish to sacrifice, unless absolutely necessary. Given the patient’s strong desire to keep her arm and preserve a limited degree of function, we did not believe that forequarter amputation

Osteosarcoma: a comprehensive review

Osteosarcoma (OS) is a relatively rare tumor of bone with a worldwide incidence of 3.4 cases per million people per year. For most of the twentieth century, five-year survival rates for classic OS were very low. In the 1970s, the introduction of adjuvant chemotherapy in the treatment of OS increased survival rates dramatically. The current article reviews the various types of OS and analyzes the clinical and histological features. We also examine historical and current literature to present a succinct review of methods for diagnosis and staging, as well as treatment, and we also discuss some of the future directions of treatment.

Benign lymphoid hyperplasia (pseudolymphoma) of soft tissue

Benign lymphoid hyperplasia (pseudolymphoma) has been reported in the skin, lungs, orbit, and gastrointestinal tract, but only rarely in soft tissues. These lesions mimic lymphoma both clinically and histologically. We describe a case of a pseudolymphoma of the deep soft tissues of the lower extremity. The lesion was composed of nonencapsulated lymphoid tissue with involvement of adjacent fat and connective tissues and multiple variably sized well-polarized germinal centers. Immunohistochemical staining, flow cytometry, chromogenic in situ hybridization for κ/λ light-chain restriction, and polymerase chain reaction for T- and B-cell gene rearrangements all revealed a polyclonal population of T and B cells, consistent with a benign reactive process. So far as we know, pseudolymphoma of the deep soft tissues has been described only once previously in the medical literature.

Management of soft tissue tumors of the upper extremity: a review

Introduction: Management of malignant tumors of the hand and wrist is challenging and is generally approached by limb salvage or amputation. With advances in care, amputation has been superseded by limb salvage as the treatment of choice. Methods: A narrative literature review was performed to identify articles on the topic of management of soft tissue tumors of the upper extremity, including surgical management, adjuvant radiation therapy, and chemotherapy. Results: A total of 29 articles were selected. Earlier reports favored radical tumor resection, which often led to amputation, whereas later articles demonstrated limb salvage as the preferential treatment modality. Conclusions: Given the detrimental effects on function and psychologic outcomes, amputation has been superseded by limb salvage in most cases, although it can occasionally be the only option. A variety of adjuvant therapies have been described, including radiation or brachytherapy, chemotherapy, and regional hyperthermia. Radiation treatment, and specifically brachytherapy, is beneficial to select patients. Controversy surrounds chemotherapy in certain subtypes, and regional hyperthermia requires further investigation.

Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer

Objective Bone metastasis occurs in up to 90% of men with advanced prostate cancer and leads to fractures, severe pain and therapy-resistance. Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients. Thus, the special environment of the bone makes the disease more complicated and incurable. A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments. The microstructural changes in the femurs of mice implanted with PCSD1, a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen, were determined. Methods Quantitative micro-computed tomography (micro-CT) and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone (Control) into the right femurs of Rag2−/−γc−/− male mice. Results Bone lesions formed only in femurs of mice injected with PCSD1 cells. Bone volume (BV) was significantly decreased at the proximal and distal ends of the femurs (p < 0.01) whereas BV (p < 0.05) and bone shaft diameter (p < 0.01) were significantly increased along the femur shaft. Conclusion PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur, and, in contrast, induced aberrant bone formation leading to osteoblastic lesions along the femur shaft. Therefore, the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion. Our approach can be used to determine if different bone regions support more therapy resistant tumor growth, thus, requiring novel treatments.

MP87-10 GENOMIC ANALYSIS OF A LONGITUDINAL SERIES OF SURGICAL PROSTATE CANCER BONE METASTASES AND XENOGRAFTS FROM THE SAME PATIENT REVEALED SELECTION OF A PROGRESSIVELY THERAPY RESISTANT METASTATIC CLONE

METHODS: We used a panel of cell lines i.e 786-0, A498 (VHL -) and Caki-1, Caki-2, ACHN (VHL +) for CCC and LNCaP, VCap, PC3, DU145, 22RV1 for PCa. Tumor/normal corresponding tissues pairs from 42 and 41 CCC and PCa patients, respectively, were also used. DNPH1 isoforms expression was measured by RTqPCR and Western blot. Since no specific chemical inhibitors are available, the role of DNPH1 isoforms in vitro and in vivo was evaluated using siRNAs and expressing vectors (wild-type or inactive, dead active site). In vivo, we used the tumor xenografted nude mice model to assess the role and the underlying mechanisms of DNPH1 in tumor growth. RESULTS: We show that CCC and PCa express only isoforms 1 and 2. These are 174 and 148 aminoacids long, respectively, and are identical till aminoacid 126. DNPH1 expression was deregulated in 71% of CCC cases but upregulated in 75% of PCa cases, regardless of the stage. Both isoforms behave similarly but isoform 1 represented 80% of total DNPH1 expression. In CCC cell lines, the transfection with wildtype DNPH1 expressing vectors decreased cell growth up to 60% by stimulating cell proliferation and inhibiting apoptosis, while the transfection with the inactive vector had no effect. In PCa cells, siRNAs targeting DNPH1 isoforms 1 and 2 decreased cell growth dosedependently by up to 50% through inhibition of cell proliferation and induction of apoptosis. We are currently evaluating the effect of both isoforms in nude mice xenografted with CCC cell lines transfected with the DNPH1 expressing vector and in PCa-bearing nude mice treated with in vivo siRNAs. First results corroborate in vitro observations. CONCLUSIONS: Our results show the opposite tumor suppressor/oncogene properties of DNPH1 in CCC and PCa and should allow to design new therapeutic options for these refractory diseases.

Isolated peroneal tenosynovial lipoma arborescens: multimodality imaging features

Synovial lipoma arborescens is a rare and benign fatty proliferative lesion of the synovium that is most commonly seen within the suprapatellar pouch of the knee, but increasingly reported to involve tendon sheaths, including those of the ankle. We present the third known case of tenosynovial lipoma arborescens isolated to the peroneal tendon sheath without ankle joint involvement. To our knowledge, this is the first to report this entity utilizing a unique combination of radiographic, sonographic, and MR imaging, along with intraoperative and histologic correlation. Knowledge of this case is important when interpreting radiographic or sonographic images of this condition to raise the possibility of the rare entity of lipoma arborescens involving the peroneal tendon sheath.