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Intensive preoperative and postoperative chemotherapy combined with complete resection of both primary and metastatic pulmonary osteosarcomas is justified, with a goal of 100% tumor necrosis and excision. Although current treatment regimens allow effective salvage therapy for a few patients with pulmonary metastases, more effective systemic treatment is needed.

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Background Patient-specific cutting blocks have been touted as a more efficient and reliable means of achieving neutral mechanical alignment during TKA with the proposed downstream effect of improved clinical outcomes. However, it is not clear to what degree published studies support these assumptions. Questions/purposes We asked: (1) Do patient-specific cutting blocks achieve neutral mechanical alignment more reliably during TKA when compared with conventional methods? (2) Does patient-specific instrumentation (PSI) provide financial benefit through improved surgical efficiency? (3) Does the use of patient-specific cutting blocks translate to improved clinical results after TKA when compared with conventional instrumentation? Methods We performed a systematic review in accordance with Cochrane guidelines of controlled studies (prospective and retrospective) in MEDLINE 1 and EM-BASE 1 with respect to patient-specific cutting blocks and their effect on alignment, cost, operative time, clinical outcome scores, complications, and survivorship. Sixteen studies (Level I-III on the levels of evidence rubric) were identified and used in addressing the first question, 13 (Level I-III) for the second question, and two (Level III) for the third question. Qualitative assessment of the selected Level I studies was performed using the modified Jadad score; Level II and III studies were rated based on the Newcastle-Ottawa scoring system. Results The majority of studies did not show an improvement in overall limb alignment when PSI was compared with standard instrumentation. Mixed results were seen across studies with regard to the prevalence of alignment outliers when PSI was compared with conventional cutting blocks with some studies demonstrating no difference, some showing an improvement with PSI, and a single study showing worse results with PSI. The studies demonstrated mixed results regarding the influence of PSI on operative times. Decreased operative times were not uniformly observed, and when noted, they were found to be of minimal clinical or financial significance. PSI did reliably reduce the number of instrument trays required for processing perioperatively. The accuracy of the preoperative plan, generated by the PSI manufacturers, was found lacking, often leading to multiple intraoperative changes, thereby disrupting the flow of the operation and negatively impacting efficiency. Limited data exist with regard to the effect of PSI on postoperative function, improvement in pain, and patient

Much work has been done to develop tumor-targeting antibodies by selecting a phage antibody library on cancer cell lines. However, when tumor cells are removed from their natural environment, they may undergo genetic and epigenetic changes yielding different surface antigens than those seen in actual cases of cancer. We developed a strategy that allows selection of phage antibodies against tumor cells in situ on both fresh frozen and paraffin-embedded tissues using laser capture microdissection. By restricting antibody selection to binders of internalizing epitopes, we generated a panel of phage antibodies that target clinically represented prostate cancer antigens. We identified AL-CAM/MEMD/CD166, a newly discovered prostate cancer marker, as the target for one of the selected antibodies, demonstrating the effectiveness of our approach. We further conjugated two single chain Fv fragments to liposomes and demonstrated that these nanotargeting devices were efficiently delivered to the interior of prostate cancer cells. The ability to deliver payload intracellularly and to recognize tumor cells in situ makes these antibodies attractive candidates for the development of targeted cancer therapeutics.