Search

Background and Objectives: Currently, standard treatment of soft tissue sarcoma (STS) is wide local excision and adjuvant radiation, but radiation may be unnecessary in superficial STS. The primary objective is to assess local recurrence rates in patients treated with surgical management alone for superficial STS., Methods: A retrospective cancer registry review of patients treated with surgery alone for superficial STS at the Tom Baker Cancer Center (TBCC) was performed. Patient and tumor characteristics as well as recurrence data were collected., Results: Sixty-one patients met study criteria. Local and overall recurrence rates were 7/61 (11.5%) and 12/61 (19.7%), respectively. The proportion with a T2 tumor was 38.8% versus 33.3% (P = 0.69), with Grade 2 or 3 tumors was 59.2% versus 83.3% (P = 0.14), and with resection margins <1 cm was 28.6% versus 75.0% (P = 0.008) for patients without and with recurrence, respectively. Median time to recurrence was 1.7 (0.4-5.2) years., Conclusions: Surgical resection alone appears to be a viable option for superficial STS that can save patients from potential side effects of radiation. The association between recurrence and inadequate margins (<1 cm) requires additional treatment be offered to this subset of patients., (© 2015 Wiley Periodicals, Inc.)

Background and Objectives: The role of surgical management in duodenal lymphoma is controversial due to the rarity of this tumor subtype. A retrospective review of a provincial cancer registry was performed to assess the rationale for surgical management in duodenal lymphoma., Methods: Patient demographics, presentations, pathologies, surgical interventions, treatment, and associated disease-specific survival were assessed and descriptively presented., Results: From 1985 to 2005, 23 patients (mean age 58 years [22-82]) were diagnosed. The most common histology was large B-cell lymphoma (74%). A significant proportion presented in a complicated fashion: obstruction (30%), perforation (17%), and hemorrhage (4%). Eight patients (35%) were treated with surgery alone, eight (35%) with surgery and chemotherapy, five (22%) with chemotherapy alone, and two (9%) with supportive care. Of those treated with surgery, indications were mostly emergent conditions including obstruction (58%), perforation (33%), and hemorrhage (8%). Overall median follow-up was 14 months (1-168 months) and overall median survival was 12 months (1-168 months). There were no significant differences in survival by histology, stage, or treatment type., Conclusions: Chemotherapy continues to represent the therapeutic mainstay for GI lymphomas. However, in duodenal lymphoma, a high proportion of patients require surgery mainly because of complicated presentations.

Indoleamine 2,3-dioxygenase (IDO) is an intracellular tryptophan-catabolizing enzyme possessing various immunosuppressive properties. Here, we report the use of this enzyme to suppress the proliferation of peripheral blood mononuclear cells (PBMC) co-cultured with IDO-expressing fibroblasts of an allogeneic skin substitute in vitro. Fetal foreskin fibroblasts populated within collagen gel (FPCG) were treated with interferon-gamma (IFN-gamma) conjugated with a temperature-sensitive polymer to induce the expression of IDO mRNA and protein. SDS-PAGE showed successful conjugation of IFN-gamma with the temperature-sensitive polymer. Expression of IDO mRNA was evaluated by Northern analysis. IDO enzyme activity was evaluated by the measurement of kynurenine levels. The results of Northern blot analysis showed an induction of IDO mRNA expression when treated with polymer-conjugated IFN-gamma. Kynurenine levels, as a measure of IDO bioactivity, were significantly higher in IFN-gamma-treated fibroblasts than in controls (P < 0.001). In a lasting effect experiment, the expression of IDO mRNA in FPCG treated with polymer-conjugated IFN-gamma was significantly longer than in those treated with free (non-conjugated) IFN-gamma (P < 0.001). IFN-gamma radiolabeling showed a prolonged retention of IFN-gamma within collagen gel in its polymer-conjugated form, compared to its free form. Presence of IDO protein in FPCG was demonstrated by Western analysis even 16 days after removal of the conditioned medium (containing released IFN-gamma). To demonstrate the immunosuppressive effects of IDO on the proliferation of PBMC, IDO-expressing FPCG treated with polymer-conjugated IFN-gamma were co-cultured with PBMC for a period of 5 days. The results showed a significant reduction in proliferation of PBMC co-cultured with IFN-gamma-treated IDO-expressing fibroblasts, compared to those co-cultured with non-IDO-expressing fibroblasts (P < 0.001). The addition of an IDO inhibitor (1-methyl-D-tryptophan) reversed the suppressive effects of IDO on PBMC proliferation. In conclusion, IDO expression in FPCG suppresses the proliferation of immune cells in vitro. The use of a temperature-sensitive polymer further prolongs the effect of IFN-gamma on the expression of IDO. Therefore, modulating IDO levels in situ might be an alternative for prolonging the survival of skin allografts.

Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme, is an intracellular enzyme possessing various immunosuppressive properties. Here, we report the possible use of this enzyme to suppress proliferation of immune cells cocultured with IDO-expressing fibroblasts of an allogenic skin substitute. Fetal skin fibroblasts embedded within bovine collagen were treated with cytokine interferon-gamma (IFN-gamma) to induce expression of IDO mRNA and protein. Expression of IDO mRNA was evaluated by Northern analysis. IDO enzyme activity was evaluated by measurement of kynurenine and tryptophan levels in the IFN-gamma untreated and treated fibroblasts. The results of Northern analysis showed a dose-dependent increase in expression of IDO mRNA in response to various concentrations of IFN-gamma used. The levels of kynurenine and tryptophan measured, as the bioactivity of IDO, were significantly different in the IFN-gamma treated fibroblasts, compared to those of controls (P < 0.001). In a lasting effect experiment, the expression of IDO mRNA was gradually reduced to an undetectable level within 32 h of IFN-gamma removal. The results of Western blot analysis, however, revealed a significantly longer (192 h) lasting effect of IFN-gamma on IDO protein level, relative to that of mRNA expression. To demonstrate immunosuppressive effects of IDO on proliferation of immune cells, IDO-expressing fibroblasts were cocultured with peripheral blood mononuclear cells (PBMC) for a period of 5 days. The results of (3)H-thymidine incorporation showed a significant reduction in proliferation of PBMC when cocultured with IDO-expressing fibroblasts, compared to those cocultured with non-IDO-expressing fibroblasts (P < 0.001). Furthermore, addition of IDO-inhibitor (1-methyl-d-tryptophan) reversed the suppressive effects of IDO on PBMC proliferation in a dose-dependant fashion. To test the viability of immune cells cocultured with IDO-expressing fibroblasts, FACS analysis of the PI stained PBMC was conducted and no significant difference was found between these cells and the controls. In another set of experiments, we showed that migration rate and subsequent proliferation of IDO-expressing fibroblasts are also the same as those of control cells. In conclusion, IDO-expressing allogenic fibroblasts embedded within collagen gel suppress the proliferation of allogenic immune cells, while they still remain viable in this IDO-induced tryptophan-deficient culture environment., (Copyright 2003 Wiley-Liss, Inc.)