Fat necrosis and parenchymal scarring after breast-conserving surgery and radiotherapy with an intraoperative electron or fractionated, percutaneous boost: a retrospective comparison.

BACKGROUND: The aim of this retrospective analysis was to evaluate mammographic changes such as fat necroses and parenchymal scarring in the breast tissue within the first 3 years after breast-conserving surgery (BCS) and whole-breast irradiation with an additional intraoperative electron boost (IO-B) versus fractionated percutaneous boost (FP-B). METHODS: A total of 53 breast cancer patients (stage I/II) treated between 2006 and 2008 were included. All patients underwent BCS followed by fractionated whole-breast radiotherapy with a total dose and single dose of 50.4 and 1.8 Gy. Twenty patients had 10 Gy IO-B using electrons, and 33 patients were treated with a FP-B with 10.8 Gy. The IO-B was performed using the mobile linear accelerator NOVAC 7. The follow-up mammograms were focused on fat necroses, parenchymal scarring and skin thickening. RESULTS: Fat necroses occurred significantly more frequently in IO-B patients compared to FP-B patients (50.0 vs. 18.2 %). The fat necroses were mammographically detected a median of 17 versus 23 months post-surgery for the IO-B versus FP-B patients. The median size of fat necroses was 24 (14-30) mm for the IO-B group and 14 (4-53) mm for the FP-B group. Parenchymal scarring in the grade 3-4 tumor bed area was seen significantly more frequently in the IO-B patients (55.0 vs. 21.2 %). Skin thickening did not differ significantly. CONCLUSION: The IO-B led to significantly more fat necroses and local restricted parenchymal scarring in our analysis.

Synergistic effects of growth factors and mesenchymal stromal cells for expansion of hematopoietic stem and progenitor cells.

OBJECTIVE: The number of hematopoietic stem and progenitor cells (HPCs) per cord blood unit is limited, and this can result in delayed engraftment or graft failure. In vitro expansion of HPCs provides a perspective to overcome these limitations. Cytokines as well as mesenchymal stromal cells (MSCs) have been shown to support HPCs ex vivo expansion, but a systematic analysis of their interplay remains elusive. MATERIALS AND METHODS: Twenty different combinations of growth factors (stem cell factor [SCF], thrombopoietin [TPO], fibroblast growth factor-1 [FGF-1], angiopoietin-like 5, and insulin-like growth factor-binding protein 2), either with or without MSC coculture were systematically compared for their ability to support HPC expansion. CD34(+) cells were stained with carboxyfluorescein diacetate N-succinimidyl ester to monitor cell division history in conjunction with immunophenotype. Colony-forming unit frequencies and hematopoietic reconstitution of nonobese diabetic severe combined immunodeficient mice were also assessed. RESULTS: Proliferation of HPCs was stimulated by coculture with MSCs. This was further enhanced in combination with SCF, TPO, and FGF-1. Moreover, these conditions maintained expression of primitive surface markers for more than four cell divisions. Colony-forming unit-initiating cells were not expanded without stromal support, whereas an eightfold increase was reached by simultaneous cytokine-treatment and MSC coculture. Importantly, in comparison to expansion without stromal support, coculture with MSCs significantly enhanced hematopoietic chimerism in a murine transplantation model. CONCLUSIONS: The supportive effect of MSCs on hematopoiesis can be significantly increased by addition of specific recombinant growth factors; especially in combination with SCF, TPO, and FGF-1.

Serum after autologous transplantation stimulates proliferation and expansion of human hematopoietic progenitor cells.

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34(+) cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34(+), CD133(+), CD45(-)) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool.

Immediate reconstruction with an expander/implant following ablatio mammae because of breast cancer : side effects and cosmetic results after adjuvant chest wall radiotherapy.

BACKGROUND AND PURPOSE: Timing and sequencing of radiotherapy in the context of allogenous breast reconstruction have not been standardized. The aim of the present study was to assess the influence of adjuvant radiotherapy on morbidity and patient satisfaction after allogenous breast reconstruction. PATIENTS AND METHODS: 33 patients underwent mastectomy between 1999 and 2008 and had immediate breast reconstruction with an expander placement in subpectoral/epipectoral location. 24 patients had adjuvant chemotherapy. Adjuvant external-beam radiotherapy with a median dose of 50.4 Gy was given after expander filling and on average 5.2 months prior to placement of the definitive implant. 22 patients with the definitive implant were considered for analysis of capsular fibrosis rate. Questionnaires were sent to all patients to assess cosmetic outcome and satisfaction. RESULTS: Acute adverse effects were comparable to adjuvant radiotherapy after breast-conserving surgery, resulting in an erythema rate grade 1/2/3 in 21.2%/66.7%/6.1% of patients, respectively. After a mean follow-up of 24.9 months, 9.1%/18.2%/15.2%/9.1% of patients presented a capsular fibrosis grade 1/2/3/4, respectively. Severe deformation/asymmetry of the reconstructed breast was seen in 27.3%/33.3% of patients, respectively. Of the 22 patients with definitive implant, five (22.7%) lost the implant due to painful capsular fibrosis. Of these 22 patients, 50% were very satisfied or satisfied with the reconstruction result. Overall, 81% of patients would request breast reconstruction again. CONCLUSION: Adjuvant radiotherapy with the use of a subtotally filled expander prior to definitive allogenous breast reconstruction is feasible with acceptable morbidity. An interdisciplinary consultation concerning the cosmetic outcome and potential side effects is absolutely necessary.