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.

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/IPSbased therapies.

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.

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. Cancer 2013;119:2574-81. V C 2013 American Cancer Society.KEYWORDS: germ cell tumors; testicular cancer; age over 50; epidemiology; histology; primary site; cisplatin. INTRODUCTIONGerm cell tumors (GCTs) primarily affect adolescent and young adult men, with diagnoses in older patients, children, and women occurring much less commonly. In men, most GCTs arise in the testis but extragonadal primary tumor sites comprise up to 10% of cases, typically in midline locations such as the mediastinum, retroperitoneum, or pineal gland. The World Health Organization classification of tumors 1 categorizes GCTs in adolescents and adults into 3 histologic groups: classic seminoma with pure histology; nonseminomatous GCT (NSGCT), comprising embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, and mixed histologies (which can include seminoma); and spermatocytic seminoma.2 In most epidemiological studies, rates of seminoma slightly exceed those of NSGCT, 3,4 with spermatocytic seminoma comprising < 1% of cases. The incidence of seminoma and NSGCT differs across age groups, peaking between ages 35 and 39 years for seminoma compared with 25 to 29 years for NSGCT. 4 Nevertheless, both histologic types are rare in older men with fewer than 10% a...

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.

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.

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.

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.