Synovial sarcoma of the thoracic spine.

BACKGROUND CONTEXT: Synovial sarcoma is an uncommon malignant neoplasm occurring chiefly in young adults. It often presents as a solid well-circumscribed soft-tissue mass in the extremities of young adults. Despite its proximity to joints, it has been well established that the tumor cells do not display features of synovial differentiation but instead appear to have a primitive epithelial phenotype. There is no report of a lower thoracic paravertebral synovial sarcoma in an adult male. PURPOSE: To describe our management in a patient with a synovial sarcoma of the thoracic spine and to review previously published cases. STUDY DESIGN: Case report. METHODS: A 60-year-old man presented with a 5-month history of right upper quadrant abdominal pain radiating to his back in a band-like fashion; shortness of breath on exertion; and increasing pain when standing, sitting, or walking. Magnetic resonance imaging (MRI) demonstrated a large right-sided paraspinal mass sitting on the eighth and ninth ribs, pressing on the T9 vertebrae and abutting the T7 and T8 vertebral level exhibiting "Triple Intensity." Plain films demonstrated a right-sided paraspinal mass extending from the T7-T8 level to T10. Bone scintigraphy showed increased uptake on the right thoracic spine at T7-T8 to T10. Computed tomography (CT) imaging revealed a right paraspinal mass with lytic changes in the T9 vertebral bodies. A right-sided thoracotomy was performed, and the patient underwent subsequent radiation therapy. Absence of the tumor was shown by an MRI scan after the operation. RESULTS: Complete resolution of the patient's complaints was achieved. The diagnosis is supported by plain radiographs, bone scintigraphy, magnetic resonance and CT imaging studies, and histologic and immunohistochemical evidence. CONCLUSIONS: Synovial sarcomas are rarely present in the paravertebral region of the thoracic spine. A careful radiographic study of the tumor permitted early preliminary diagnosis, confirmed upon histopathologic analysis. Despite lytic changes, removal of a periosteal layer permitted sparing of the vertebral bodies.

Video-assisted thoracic surgery lobectomy: centers of excellence or excellence of centers?

VATS lobectomy, as defined by CALGB 39802, provides the same oncologic surgery as that performed through a thoracotomy. Standardizing the terminology is the first step that must be undertaken to standardize the operation. VATS lobectomy is the use of technology to aid in performing an established procedure. This technology and development of the skills required to perform a safe VATS lobectomy must be carefully monitored to protect the quality of the product, which ultimately is defined as patient outcome. "Center of Excellence" is a determination used in several other specialties to provide quality assurance for new procedures or technologies, or for those surgeries not widely performed, such as esophageal surgery. The authors believe that the profession should designate Centers of Excellence based on the credentialing guideline discussed earlier. The authors do believe that the current residency and fellowship training will provide, in time, ample surgeons skilled in VATS lobectomy. As these surgeons become certified and disseminate throughout the country, it is expected that VATS lobectomy will be readily available in most institutions. Over time this will allow VATS lobectomy to evolve from specific Centers of Excellence to a broader group of hospitals based on widespread availability ofa surgeon certified in VATS lobectomy. During this transition, the authors would encourage the community of surgeons performing this procedure to submit their statistics to a nationwide database. This will provide an excellent database for evidence-based medicine. Such rigorous data collection should permit thoracic surgeons to be appropriately compensated for performing these technically challenging procedures.

Airway stents.

Airway stenting has been well used in the treatment and palliation of patients with malignant stenoses and to a lesser extent in those with benign disease causing airway compromise. Stents are either constructed of silicone or metal, usually a nitinol, a nickel and titanium alloy. The different categories of stents have positive and negative attributes that play a role in choosing the proper stent. This article aims to discuss these issues with regards to malignant and benign tracheobronchial disease.

Bryostatin 1/ionomycin (B/I) ex vivo stimulation preferentially activates L-selectinlow tumor-sensitized lymphocytes.

We have shown that tumor vaccine-sensitized draining lymph node (vDLN) cells activated ex vivo with bryostatin and ionomycin (B/I) were capable of inducing antigen-specific regression of a murine mammary tumor, 4T07. vDLN cells not activated with B/I were ineffective. We hypothesized that B/I selectively activates tumor-sensitized (CD62Llow) lymphocytes, to account for the highly potent and tumor-specific activity. We hypothesized that CD8+ CD62Llow cells may be preferentially activated by B/I treatment, infiltrate the tumors and mediate tumor regression in mice. 4T07-IL2 tumor cells were injected into one hind footpad of BALB/c mice. Ten days later, vDLN were harvested and separated based on CD62L expression. After separation, cells were activated with B/I, expanded with IL2 (40 IU/ml) for 10 days, and adoptively transferred to 4T07 tumor bearing mice. Naive mice were also treated with different subsets of T cells and later were challenged with 4T07 tumor cells. To test in vitro responses to antigen, expanded lymphocytes were cultured either alone or with irradiated 4T07 tumor cells. Supernatants were harvested after 24 h and tested by ELISA for IFN-gamma. The importance of the host immune response was tested by AIT into 4T07-bearing nude athymic mice. Host mice were depleted in vivo of CD4 or CD8 T cells after vDLN AIT to ascertain the mediators of tumor regression. In order to track B/I activated vDLN cells, they were prestained with CFSE prior to adoptive transfer into tumor-bearing hosts. At various time points, tumors, spleens and lymph nodes of host mice were harvested, dual stained for activation marker expression and analyzed by flow cytometry. CD62Llow cells expanded 12-fold more than CD62Lhigh lymphocytes during the 10 day culture period. Supernatant from CD62Llow cells + 4T07 cultures contained 33-fold more IFN-gamma than supernatant from CD62Lhigh cells + 4T07 cultures (843.9 pg/ml +/- 135.8 vs 25.89 pg/ml +/- 0.01). Adoptive transfer of CD62Llow lymphocytes induced complete tumor regressions in all mice, while tumors regressed in only 17% of mice treated with CD62Lhigh lymphocytes. Naive mice that received B/I-activated CD62Llow cells were protected from future tumor challenges, while mice given CD62Lhigh cells did not exhibit the same resistance to tumor growth. Tumors in nude host mice regressed after AIT treatment. In vivo depletion of CD4 T cells after AIT did not inhibit tumor regression, but CD8 T cell depletion abrogated tumor regression. vDLN cells tracked preferentially to tumor draining lymph nodes and proliferated in vivo, persisting for at least 21 days, and were 95% CD44+ and 39% CD69+. Bryostatin 1 and ionomycin, by increasing PKC activity and intracellular calcium, respectively, mimic intracellular signals that result in T cell activation. CD62Llow cells are preferentially activated by B/I, leading to a highly effective anti-tumor T cell population.

Successful adoptive immunotherapy with vaccine-sensitized T cells, despite no effect with vaccination alone in a weakly immunogenic tumor model.

Tumor cell vaccines have been successful at inducing immunity in naïve mice, but only in a few reports has vaccination alone induced regression of established tumors and, generally, only when they are very small. Clinically, vaccinations alone may not be able to cause regression of established human cancers, which tend to be weakly immunogenic. We hypothesized that pharmacologic ex vivo amplification of a vaccination-induced immune response with subsequent adoptive immunotherapy (AIT) to tumor-bearing animals would be more effective in treatment of these animals than vaccination alone. The 4T1 and 4T07 mammary carcinomas are derived from the same parental cell line, but 4T1 is much less immunogenic and more aggressive than 4T07. Vaccination with either 4T1, 4T1-IL-2, or 4T07-IL-2 was not effective as treatment for established 4T1 tumors. However, 4T1 or 4T07-IL-2-vaccine-sensitized draining lymph node (DLN) cells, activated ex vivo with bryostatin 1 and ionomycin and expanded in culture, induced complete tumor regressions when adoptively transferred to 4T1 tumor-bearing animals. This was effective against small tumors as well as more advanced tumors, 10 days after tumor cell inoculation. Furthermore, as would be required for this approach to be used clinically, vaccine-DLN cells obtained from mice with established progressive 4T1 tumors (inoculated 10 days before vaccination) also induced regression of 4T1 tumors in an adoptive host. In none of these experiments was exogenous IL-2 required to induce tumor regression. The response to tumor cell vaccine can be amplified by ex vivo pharmacologic activation of sensitized T cells, which can then cure an established, weakly immunogenic and highly aggressive tumor that was resistant to vaccination alone.

Costimulation of T cell receptor-triggered IL-2 production by Jurkat T cells via fibroblast growth factor receptor 1 upon its engagement by CD56.

Recent studies have demonstrated that neural cell adhesion molecule (NCAM) is involved in multiple adhesive interactions with several different classes of ligands on the cell surface and in the extracellular matrix. One of these ligands is fibroblast growth factor receptor (FGFR) that is expressed on neural cells. While it is known that CD56 is a molecular isoform of NCAM expressed on human NK cells and a subset of T cells, it remains poorly characterized, with its ligand unidentified. Therefore, we were prompted to examine if CD56 molecules on NK cells interact with FGFR expressed on T cells. We demonstrate that ligation of FGFR1 beta on J.C2-14 Jurkat T cells by CD56 on fixed NK-92 cells costimulates TCR/CD3-triggered IL-2 production. CD56-binding mAbs inhibited the costimulatory effect of NK-92 cells in 50-75%. Flow cytometric analysis and cell adhesion assays showed that FGFR1 beta/Fc and FGFR2 beta/Fc chimeric proteins bind to NK-92 cells. The binding of FGFR1 beta/Fc protein to CD56 molecules was verified by immunoprecipitation of CD56 with anti-CD56 mAb followed by Western blotting with FGFR1 beta/Fc. These findings suggest that ligation of FGFR1 by CD56 may contribute to the interaction between NK cells and T cells that we have postulated in our previous studies.

Sentinel node mapping identifies vaccine-draining lymph nodes with tumor-specific immunological activity.

BACKGROUND: Adoptive immunotherapy (AIT) with 4T07-IL2 vaccine-draining lymph node (DLN) cells induced regression of established 4T07 mammary carcinomas, but contralateral non-DLN were inactive. These experiments were performed to determine whether mapping with isosulfan blue (IB), as described for identification of sentinel nodes, would identify vaccine-DLN with antitumor activity. METHODS: Ten days after vaccination with 4T07-IL-2, .1 ml of 1% IB was injected into the vaccination site (footpads or flanks). After 3 minutes, mice were euthanized, and the blue-stained nodes were collected. With flank vaccination, IB identified both an inguinal and an axillary node. We also collected DLNs blindly in mice not receiving IB dye. DLN cell suspensions were then activated with bryostatin 1, ionomycin, and IL-2, expanded in culture, and adoptively transferred to mice bearing established 4T07 flank tumors. RESULTS: Complete tumor regression occurred in nearly all mice treated with popliteal or inguinal DLNs collected with or without IB. IB-stained axillary DLNs cured 100% of tumor-bearing mice, whereas none of the mice treated with blindly collected axillary DLNs were cured. CONCLUSION: We have shown that IB identifies immunologically active DLNs, does not interfere with expansion of lymphocytes in vitro, and, more importantly, has no detrimental effect on the ability of lymphocytes to induce tumor regression in vivo. For axillary DLNs, use of IB mapping identified immunologically active lymph nodes that could not otherwise be found.