Comparison of Hand Drills for the Insertion of Skeletal Traction Pins.

Skeletal traction pins are inserted as part of emergent stabilization of lower extremity fractures. The purpose of this study is to compare two drill options: a reusable store-bought drill and a single-use, sterilely packaged drill. The reusable drill and disposable drill were compared by having volunteers insert traction pins within a foam bone, fully encased, knee joint model using both systems. The two drill types were evaluated on three measures: user satisfaction, time required for insertion of the pins, and cost. The disposable drill received a statistically significant higher user satisfaction score and a statistically significant faster time to pin insertion. The per-use cost of the disposable system was found to be higher. For skeletal traction pin insertion, the disposable, single-use drill was found to be superior to the reusable drill in user satisfaction and time required for traction pin insertion. Institutional cost analysis favors the disposable system because of the more predicable charge capture, while the per-use cost of the disposable system remains higher. (Journal of Surgical Orthopaedic Advances 27(4):274-276, 2018).

Clinical features, presentation, and tolerance of platinum-based chemotherapy in germ cell tumor patients 50 years of age and older.

BACKGROUND: Germ cell tumors (GCTs) primarily affect adolescent and young adult men. Detailed clinical and treatment characteristics in older men are lacking. METHODS: Patients with GCT seen over a 20-year period at Memorial Sloan-Kettering Cancer Center were identified. Primary tumor site and histology were compared for patients aged ≥ 50 years at diagnosis versus younger men. For patients aged ≥ 50, individual chart review was performed and treatment delays, changes, and toxicities were recorded for those treated with first-line chemotherapy. RESULTS: Of 4235 diagnoses of GCT, 3999 (94.4%) were made at age < 50 versus 236 (5.6%) at age ≥ 50. Compared with patients diagnosed before age 50, older men more frequently had seminoma (62.7% versus 36.7%) and less frequently, nonseminoma (34.7% versus 63.2%) (P < .0001). Predominant histology switched from nonseminoma to seminoma around age 35. Distribution of primary sites also differed for older versus younger men (testis: 89.4% versus 92.9%; retroperitoneal: 3.8% versus 0.7%; CNS 0% versus 1.7%) except for mediastinal primary tumors, which remained constant across age groups. Fifty patients age ≥ 50 received first-line platinum-based chemotherapy; 30 experienced complications leading to treatment discontinuation, delay ≥ 7 days, or regimen change. Twenty-two (44%) patients experienced neutropenic fever, 6 despite prophylactic growth factor support. Estimated 5-year survival for chemotherapy-treated patients was 84.9%. CONCLUSIONS: Men aged ≥ 50 years comprise less than 10% of GCT diagnoses and have distinct clinical and histological characteristics as compared with younger patients. Although complications from chemotherapy occur frequently in older men, prognosis remains excellent when risk-directed treatment is administered with curative intent.

Natural immunity to pluripotency antigen OCT4 in humans.

OCT4 is a transcription factor critical for the pluripotency of human embryonal stem (ES) and induced pluipotency stem (IPS) cells. OCT4 is commonly expressed in germ-cell tumors as well as putative cancer stem cells in several tumors, and is a key determinant of oncogenic fate in germ-cell tumors. The capacity of the human immune system to recognize this critical stem-cell gene is not known, but has implications for preventing tumors with ES/IPS-based therapies and targeting stem-cell pathways in cancer. Here we show that OCT4-specific T cells can be readily detected in freshly isolated T cells from most (>80%) healthy donors. The reactivity to OCT4-derived peptides resides primarily in the CD45RO(+) memory T-cell compartment and consists predominantly of CD4(+) T cells. T cells reactive against OCT4-derived peptides can be readily expanded in culture using peptide-loaded dendritic cells. In contrast to healthy donors, immunity to OCT4 was detected in only 35% of patients with newly diagnosed germ-cell tumors. However, chemotherapy of germ-cell tumors led to the induction of anti-OCT4 immunity in vivo in patients lacking such responses at baseline. These data demonstrate the surprising lack of immune tolerance to this critical pluripotency antigen in humans. Harnessing natural immunity to this antigen may allow immune-based targeting of pluripotency-related pathways for prevention of cancers, including those in the setting of ES/IPS-based therapies.

Treatment of Femoral Shaft Fractures in Patients with Klippel-Trénaunay Syndrome: A Report of 2 Cases.

CASES: Long-bone fractures in patients with Klippel-Trénaunay syndrome (KTS), a rare disorder of the venous, lymphatic, and capillary system, are difficult to treat with many complications. Two patients diagnosed with KTS presented with closed femoral shaft fractures after low-energy falls. Conservative treatment, open reduction internal fixation, and intramedullary nailing resulted in painful nonunions. Ultimately, both patients achieved pain relief and the ability to ambulate after en bloc resection and reconstruction. CONCLUSIONS: These cases demonstrate the challenges in achieving bony union when treating long-bone fractures in KTS. The feasibility of undergoing extensive resection and reconstruction to regain function is best approached with a multidisciplinary team.

Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors.

Vascular endothelial growth factor (VEGF) overexpression and increased angiogenesis have been proposed as having biologic importance in germ cell tumors (GCT). We conducted a single-institution phase II trial of sunitinib, an oral inhibitor of the VEGF receptor, in patients with relapsed or refractory GCT. A Simon's two-stage design was used to determine the number of patients for enrollment. Responses were assessed using a modified version of Response Evaluation Criteria in Solid Tumors (RECIST), taking into account tumor marker changes. Dose modifications were made according to a nomogram for adverse events. Ten patients were enrolled. The first five received sunitinib 50 mg for four consecutive weeks, followed by a two-week break (4/2). Since four of five treated on this schedule had some tumor marker decline during the four-week "on" period, with subsequent rise during the two-week break, the dose was changed to 37.5 mg continuously for patients six to ten. However, only marker stabilization (no declines) was seen. Overall, there were no objective responses: Five had stable disease and five progressive disease (PD). Sunitinib was well tolerated; only one patient required a dose reduction due to grade 3 mucositis. Two patients experienced tumor-related hemorrhage (grade 3 and grade 1). All patients developed PD within three cycles. Sunitinib is well tolerated, but at standard doses, does not demonstrate significant activity in highly refractory GCT. Correlation between sunitinib treatment and tumor marker changes on the 50 mg 4/2 schedule suggest some pathways targeted by sunitinib (ie, angiogenesis) may be important to GCT biology.

Infectious complications from high-dose chemotherapy and autologous stem cell transplantation for metastatic germ cell tumors.

High-dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly utilized in patients with relapsed and refractory germ cell tumors (GCT). Infectious complications are common after ASCT for hematologic malignancies, but their epidemiology in GCT patients has not been described. To identify infectious complications of ASCT for GCT, we conducted a retrospective study of patients treated at our institution, a tertiary-care cancer center in New York City between 1994 and 2006. Patients received ciprofloxacin prophylaxis but no routine antifungal or antiviral prophylaxis. In addition, patients were housed in shared rooms of 2 with standard precautions during hospitalizations. Overall, 107 patients with relapsed or refractory GCT were treated with 1-2 cycles of paclitaxel/ifosfamide and 1-3 cycles of high-dose carboplatin/etoposide with ASCT. Sixty (56%) of 107 patients developed 95 total infections, including 33 catheter-associated bloodstream infections. Fungal, viral, and nosocomial infections were uncommon. There were no infection-related deaths. In conclusion, serious morbidity from infection is uncommon among GCT patients receiving high-dose chemotherapy with ASCT. Isolation and aggressive antifungal and antiviral prophylaxis is not warranted in these patients.

Mechanical Considerations for Electrospun Nanofibers in Tendon and Ligament Repair.

Electrospun nanofibers possess unique qualities such as nanodiameter, high surface area to volume ratio, biomimetic architecture, and tunable chemical and electrical properties. Numerous studies have demonstrated the potential of nanofibrous architecture to direct cell morphology, migration, and more complex biological processes such as differentiation and extracellular matrix (ECM) deposition through topographical guidance cues. These advantages have created great interest in electrospun fibers for biomedical applications, including tendon and ligament repair. Electrospun nanofibers, despite their nanoscale size, generally exhibit poor mechanical properties compared to larger conventionally manufactured polymer fiber materials. This invites the question of what role electrospun polymer nanofibers can play in tendon and ligament repair applications that have both biological and mechanical requirements. At first glance, the strength and stiffness of electrospun nanofiber grafts appear to be too low to fill the rigorous loading conditions of these tissues. However, there are a number of strategies to enhance and tune the mechanical properties of electrospun nanofiber grafts. As researchers design the next-generation electrospun tendon and ligament grafts, it is critical to consider numerous physiologically relevant mechanical criteria and to evaluate graft mechanical performance in conditions and loading environments that reflect in vivo conditions and surgical fixation methods.

Extensile Fasciotomy for Compartment Syndrome of the Forearm and Hand.

PURPOSE: The purpose of this video is to demonstrate the technique of an extensile fasciotomy of the forearm and hand. METHODS: A patient presented to our hospital with a rapidly progressing infection of the right upper extremity and clinical signs and symptoms of compartment syndrome. The patient was immediately taken to the operating room for decompressive fasciotomy, debridement, drainage, and irrigation of what cultures subsequently revealed to be a virulent streptococcal infection. Important anatomical structures are identified in the video as the compartments of the forearm and hand are decompressed through volar and dorsal incisions. In the conclusion of the video, the skin is loosely approximated over the elbow and wrist flexion creases, and a bulky gauze dressing is applied including a plaster splint. RESULTS: The video is 6 minutes, 20-second duration in time, and 558,180,000 bytes in size. CONCLUSIONS: This video successfully demonstrates the anatomical approach and technique of an extensile forearm and hand fasciotomy for compartment syndrome related to a rapidly progressing infection.

TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis.

PURPOSE: We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients. PATIENTS AND METHODS: Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed. RESULTS: Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin > or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models. CONCLUSION: TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.