Aysen Terzi

The effect of adipose stromal vascular fraction on transverse rectus abdominis musculocutaneous flap: an experimental study

Abstract Background: Transverse rectus abdominis musculocutaneous (TRAM) flap is one of the options in reconstruction after breast cancer surgery for breast reconstruction. Tissue necrosis often occurs in the third and fourth perfusion zones of the flap. A study was planned to find out the effects of adipose stromal vascular fraction (SVF) cells on viability of TRAM flap and the experimental model was designed to be applicable in clinical practice. Methods: Right inferior epigastric artery pedicled, 5 × 2.5 cm sized TRAM flap was used as a flap model in 30 rats in three groups (group 1: sham; group 2: phosphate-buffered saline (PBS); group 3: SVF cell injected). The viability of the flaps were assessed on the postoperative 7th day with photographs and software for the calculations. Results: The mean viable flap percentage to total flap area was recorded as 51.8% ± 11.19, 49.5% ± 10.30, 82.3% ± 9.56, in group 1, group 2, and group 3, respectively (p < 0.05). The mean capillary density was noted as 5.15 ± 0.56, 4.37 ± 0.58, and 12.40 ± 1.17 in groups 1, 2, and 3, respectively (p < 0.05). The fibrosis gradient indicated no difference between the groups (p > 0.05). The in-vivo differentiation of SVF cells to endothelial cells was noted. The blood VEGF levels showed a marked increase in the experimental group (p < 0.05). Conclusion: The adipose SVF cells were found out to improve the TRAM flap viability and decrease necrosis, especially in zone 3 and 4.

The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia

The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.

Multiple brain metastases in a patient with uterine papillary serous adenocarcinoma: Treatment options for this rarely seen metastatic brain tumor.

Background: Uterine papillary serous adenocarcinoma (UPSAC) occurs 10-fold less frequently than endometrial carcinoma, and is referred to type 2 endometrial adenocarcinoma. The prognosis of UPSAC is worse than that of type I endometrial carcinoma. Herein we report what is only the second case of UPSAC, but it should prove to be more informative than the first reported case. Case Description: A 71-year-old female had three different metastases in the brain; two of the metastases were located in the posterior fossa within the cerebellar parenchyma with perilesional edema, but no mass effect, and the third metastasis was located in the right frontal lobe, and caused hemispheric edema and subfalcine herniation. The lesion that caused mass effect was completely extirpated without any surgical complications. The patients recovery was excellent. She is able to walk independently, and use her left hand and left arm. Her Karnofsky performance score 5 months postsurgery was 80/100. Conclusion: Based on the outcome in the presented case, we think that in any UPSAC patient with a metastatic brain tumor causing mass effect the symptomatic metastatic tumor must be removed, regardless of disease grade, to ensure optimal quality of life.

An unusual case of invasive papillary carcinoma of the breast

Invasive papillary carcinoma is a rare variant of breast cancer. We report an unusual case of invasive papillary carcinoma of the breast with high nuclear grade, brisk mitosis, necrosis, extensive apocrine differentiation, and intense lymphoplasmacytic infiltrate; additionally triple-negativity for estrogen and progesterone receptors and Her2 neu. The patient underwent modified radical mastectomy and adjuvant chemotherapy. But, it was a node negative breast carcinoma. Increasing the awareness of this clinicopathologic entity would be helpful in avoiding overtreatment of patients with this cancer even if the tumor has negative morphological and immunohistochemical prognosticators.

Erdheim-Chester disease in thoracic spine: a rare case of compression fracture

A55-year-old man with back pain for about 2 months was admitted to an orthopedics department. A plain radiological examination of the thoracic spine revealed a collapse of the T2 vertebra. Preoperative magnetic resonance imaging and a computed tomography scan showed a collapse of the T2 vertebra body (Figs. 1 and 2). The lesion involving theT2 vertebra body showed heterogenous enhancement inT1-weightedmagnetic resonance images after administration of gadolinium (Fig. 2). An open bone biopsy of the T2 vertebra body was performed. Based on the histopathologic and radiological findings, the patient was diagnosed with Erdheim-Chester disease (ECD) with involvement of bone marrow (Fig. 3). Erdheim-Chester disease is an infrequent, non-Langerhans cell histiocytosis of unknown etiology that typically affects the lower extremity of long bones, causing osteosclerosis. Isolated axial skeleton involvement of ECD is extremely rare. Imaging features of ECD involvement of vertebra are not specific, so pathologic confirmation is needed. As in our case, the possibility of ECD in patients with compression fracture can be considered [1,2]. References

Intraosseous angiolipoma of the frontal bone with a unique location: A clinical and pathological case illustration and review of the literature

Here, we report a case of a 16-year-old female patient was referred with scalp swelling and headache. Her neurological examination was normal and imaging of the skull revealed a well-defined lytic lesion measuring 15 mm × 6 mm to the right of the frontal bone. She was operated on with a prediagnosis of Langerhans cell histiocytosis. A wide excision with negative margins was made and the defect was reconstructed with a titanium plate. Subsequently, the lesion was histopathologically diagnosed as an angiolipoma of the frontal bone. The postoperative period was uneventful and she remained well during 1-year follow-up with no evidence of recurrence. Angiolipomas are rare benign lipomatous lesions located mostly in subcutaneous tissue of the forearm or trunk and frequently occur before puberty or in young adults. They are not common in bones. To the best of our knowledge, this is the first angiolipoma of the frontal bone reported.

Significance of Antibody-Mediated Vascular Rejection (AMVR) on Graft Survival: Correlation with Pure Antibody-Mediated Rejection (AMR)

Introduction Traditionally, endarteritis accepted to associate with cellular rejection. Nevertheless, some of the patients with AMR also had endarteritis at the same time. The risk of graft loss was nine times higher in AMVR than T cell-mediated rejection without endarteritis. However, the importance of the endarteritis on the graft survival in recipients with AMR is controversial. Thus we aimed to understand the prognostic value of the presence of endarteritis in recipients with AMR. Materials and Methods Among 155 recipients 72 (46,5%)had pure AMR (Group 1) while 83 (53,5%) had both AMR and endarteritis (Group 2). Endarteritis graded according to Banff. First indication biopsies of all cases reevaluated and the intensity of interstitial, glomerular and peritubular capillary (PTC) inflammation, neutrophil, macrophage and lymphocyte infiltration graded. HLA-DR expression in the arteries, PTCs, and tubules examined. The loss of DR expression on PTCs accepted as the destruction of PTCs. Follow-up biopsies analyzed for the development of interstitial fibrosis (IF), transplant glomerulopathy (TG) and transplant arteriopathy (TA). Results The extensity of the PTC and arterial C4d expression and the degree of PTC destruction found higher in Group 2 compared to Group 1 (P<.001).The degree of the interstitial eosinophil, plasma, and macrophage infiltration found higher in Group 2 patients than Group 1 (p<.001). Also, the intensity of inflammatory cells and neutrophils in both glomeruli and PTCs found higher in Group 2 compared to Group 1 (p<.001). Compared to Group 1 patients, Group 2 patients showed a higher incidence of IF, TG and TA in follow-up biopsies (p<.01).The development of IF and TG increases with the increasing degree of glomerulitis, PTC-itis, C4d expression and PTC destruction (p<.01). Also, the time of the development of IF and TG decreased with increasing intensity of PTC and interstitial infiltration, glomerulitis, PTC destruction and C4d expression (p<.01). The presence of the eosinophil and macrophage infiltration on the wall of arteries of recipients with AMVR rises the risk of the development of TG and TA (p<.01). Also, patients who had arterial C4d staining had a higher risk of TG, TA and graft loss (p<.001). The response to rejection therapy was lower in Group 2 recipients compared to Group 1 patients (p<.001). Overall the 3- and 5-year graft survival was 98%, and 85% respectively for Group 1 patients while it was 57%, and 27% respectively for Group 2 (p<.001). Conclusion Our results have underlined the importance of the presence of endarteritis in AMR. We showed that the course of AMVR are noticeably different from pure AMR, with AMVR having the worst outcome through leading the early development of IF, TG, and TA via augmenting inflammatory and fibrotic pathways. Thus the development of new treatment strategies for AMVR could salvage many kidney allografts.

Comparison of Recipients with Early and Later Presentation Polyomavirus Nephropathy (PVN) with Regard to Histological Findings and Graft Survival: What is the Influence of CD4/CD8 Ration on the Presenting Time of PVN

Introduction PVN is a common complication occurring around 12 months after transplant (Tx). Although unusual, the number of patients with late-presenting PVN is too much to underestimate. Thus, we aimed to understand if there are any differences between early and late-presenting PVN with regard to histological findings and graft survival. Materials and Methods All indication and follow-up biopsies of 71 patients with PVN re-evaluated and examined for the development of interstitial fibrosis (IF). Interstitial plasma cells, neutrophils, and CD3, CD4, CD8, HLA-DR positive cells, and macrophages graded. Patients separated into four groups in regards to the time of the development of PVN after Tx [Group A: <12 months (n:35), Group B: 12-24 months (n:13), Group C: 24-48 months (n:15), Group D: >48 months (n:8)]. Also, recipients correlated in two groups as Group 1 (n:48) early PVN (⩽12 months) and Group 2 (n: 23) late PVN (>12 months). Results The mean interval between the diagnosis of PVN and Tx was 17±22 months. Group 1 had higher mean hemodialysis (HD) time before Tx than Group 2 (p<.05). At the same time with PVN, CMV viremia was found in 27 patients. The mean viral load in urine and plasma at diagnosis was found higher in Group 1 than those Group 2 (p<0,01). Group 1 showed lower stages and higher degrees of polyoma viral load (Pvl) in biopsy compared to Group 2 (p<.05). Viral load in urine, plasma, and biopsy found to increase from Group A to Group D. Compared to Group 2; Group 1 showed higher degrees of interstitial neutrophil, plasma, macrophage, lymphocyte, DR-positive cell infiltration and lower degrees of the CD4/CD8 ratio (p<.01). All inflammatory cell types in interstitium found to increase from Group A to Group D. Interstitial CD4/CD8 ratio showed a significant negative correlation with Pvl (r=-0.320, p=.01), viremia (r=-0.602, p<.001) and viruria (r=-0.748, p<.001). Total 43 patients (60.6%) developed IF during follow-up, and 31 (43.7%) cases lost their graft at a mean time of 18±14 months after PVN. The risk of the development of IF increases from Group A to Group D (p<.01). Compared to Group 2 (28.7±16 months), the mean time of the graft loss after PVN was significantly early in Group 1 (13.3±9 months). The mean time of graft loss also decreases from group A to D (p<.05). Positive correlation found between the graft loss and CD4/CD8 ratio (r=0.391, p<.05). Conclusion This study pointed out that late-onset PVN is not uncommon. Recipients with late-onset PVN had a better prognosis than early-onset cases. Although the cause of late-onset PVN remains unclear, it is possible that host cells could influence the time of the onset of PVN. We showed that lower CD4 and higher CD8 proportions were risk factors for early-onset of PVN and poor graft survival. Contrarily patients who had high CD4/CD8 ratio developed late-onset PVN and better graft survival.

Platelet-rich plasma decreases fibroblastic activity and woven bone formation with no significant immunohistochemical effect on long-bone healing: An experimental animal study with radiological outcomes

Purpose: This study aimed to analyze the immunohistochemical effect of platelet-rich plasma (PRP) on healing of long-bone fractures in terms of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), the Ki-67 proliferation index, and radiological and histological analyses. Methods: Sixteen adult rabbits, whose right femoral diaphysis was fractured and fixed with Kirschner wires, were randomly divided into two groups, control and PRP (groups A and B, respectively). PRP was given to group B at 1 week postoperatively, and all animals were euthanized after 12 weeks. Radiographic evaluations were performed periodically. Cortical callus formation, chondroid and woven bone area percentages, osteoblastic and fibroblastic activities, and mature bone formation were examined. The depths of BMP-2 and VEGF staining were measured. The Ki-67 proliferation index was also calculated. Results: The mean radiological union score of group B was significantly higher than that of group A. There were also statistically significant differences between groups A and B in terms of cortical callus formation, woven bone area percentage, fibroblast proliferation, and mature bone formation. Group B had significantly more cortical callus and mature bone formation with less woven bone and fibroblast proliferation. Immunohistochemical analysis revealed no statistically significant difference between the groups in terms of BMP-2 and VEGF staining and the Ki-67 index. Conclusions: PRP had no effect on BMP-2 or VEGF levels with no increase in the Ki-67 proliferation index, although its application had a positive effect on bone healing by increasing callus and mature bone formation with decreased woven bone and fibroblast proliferation.

Recurrence of Primary Vascular Leiomyosarcoma Five Years after Initial Diagnosis in the Lower Extremity

Primary leiomyosarcomas of vascular origin are rare tumors. They frequently arise within the inferior vena cava; however, the peripheral vein was also affected. To date, only a few hundred cases have been reported in the world literature. Although it is an extremely aggressive tumor, the symptoms may be unspecific, especially in the lower extremities. In this report, we present a case of primary vascular leiomyosarcoma, arising from the short saphenous vein, with symptoms mimicking thrombus in the initial diagnosis. The diagnosis of leiomyosarcomas was confirmed by standard H&E staining and immunohistochemical staining. Recurrence of the tumor has been observed five years after surgical treatment. Due to its rarity, experience in the management of this type of tumor is limited. The mainstay of treatment for these tumors is complete surgical resection. The purpose of the presented case is to discuss the clinicopathological features and management options of this tumor, under the light of the most recent literatures.