Derya Karakoc

Combined Long-Term Steroid and Immunosuppressive Treatment Regimen in Granulomatous Mastitis

Background: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of the breast. It is related to various etiological factors. The treatment of IGM is challenging as there is a lack of consensus in the literature and treatment options vary widely. Conservative treatment with antibiotics, glucocorticoids and immunosuppressive drugs, and surgery are used in the management of the disease. In this article we report our experience with IGM patients receiving immunosuppressive treatment. Patients and Methods: The medical records of patients with IGM receiving systemic therapy at the Hacettepe University Hospital between October 2007 and May 2010 were reviewed. 15 cases of histopathologically proven IGM were identified. The data was examined for risk factors and success of treatment. Results: 14 patients were given prednisolone together with azathioprine, and 1 patient who was pregnant at the time of diagnosis received only prednisolone (30 mg/day). 11 (73%) patients had a complete response to systemic therapy. 2 patients had a relapse, of whom 1 required surgical drainage and 1 was treated with a higher dose of glucocorticoids. Conclusion: Systemic therapy is a safe and effective treatment for IGM. The addition of azathioprine to glucocorticoid therapy permits quick tapering of the steroid doses and increases the treatment success.

The effect of hepatectomy on coagulation: an evaluation by thromboelastography

Objectives Liver has a major role in coagulation. The hemostatic derangements measured by the mostly used coagulation parameters as prothrombin time, activated partial thromboplastin time, and thrombocyte count do not always correlate with the bleeding associated with liver diseases and these factors do not measure the thrombotic risks. So, thromboelastography is used in new clinical and laboratory research. The aim of this study is to study the effect of different levels of hepatectomy on coagulation. Methods Laparatomy, 40% hepatectomy, and 70% hepatectomy was performed in three different groups of rats. Prothrombin time, international normalized ratio, activated partial thromboplastin time, thrombocyte count, fibrinogen levels, and thromboelastography parameters were obtained at the 0, 6, and 24th hour of the study. Results Fibrinogen level at the 24th hour was greater than the early hours in both of the hepatectomy groups. Prothrombin time and international normalized ratio values were significantly higher in hepatectomy groups than in the sham group. There were no statistically significant difference in the clotting time, clot formation time, &agr;-angle, and maximum clot firmness values in any of the thromboelastography channels, in any of the study times, in between the sham, 40% hepatectomy, and 70% hepatectomy groups. Conclusion There is no difference between 40 and 70% hepatectomy when the coagulopathy is evaluated. The coagulation derangements as reflected by the increase in fibrinogen and prolongation of prothrombin time and activated partial thromboplastin time after hepatectomy were not supported by thromboelastography parameters in this study.

Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis, Management, and Controversies

In this article, we aimed to review the literature on the clinics and management of nonfunctional pancreatic neuroendocrine tumors (NPNET). Pancreatic neuroendocrine tumors (PNET) are rare tumors with a <1/100,000 incidence and constitute approximately 2 to 10% of all pancreatic tumors. Nonfunctional PNETs are difficult to detect at early stages since they have no symptoms. Except those detected accidentally during different diagnoses, the majority of PNETs are detected in the advanced stages, with symptoms related to tumor size or liver metastasis. We reviewed the studies published in the English medical literature through PubMed and summarized the clinical features and current approaches to the treatment and follow-up of the NPNET. The common imaging techniques used for the detection of tumor localization, size, locoregional, and metastatic involvement are contrasted computed tomography, magnetic resonance imaging, endoscopic ultrasonography, and somatostatin receptor scintigraphy. Surgical resection is the only curative treatment. However, in advanced locoregional disease and liver metastasis, interventive ablative therapies such as palliative reductive surgery, selective hepatic arterial embolization, radiofrequency ablation; and systemic therapies, such as peptide receptor radionuclide therapy, chemotherapy, somatostatin analogous therapy, interferon, VEGF inhibitor, and mTOR inhibitor may be used as symptom relieving or may improve progression-free survival and total survival. Current knowledge on NPNET shows that the treatment should be personalized considering the prognostic features and life expectancy of the patient.

Thyroid surgery: what has changed from (1970 to 2004): a Turkish perspective.

BACKGROUND Turkey is an endemic region for goiter. The aim of this study was to evaluate the changing factors concerning thyroid disease and thyroid surgery in a referral center in Turkey. METHODS This study was a retrospective evaluation of reports of patients who underwent surgery for thyroid disease at Hacettepe University Medical School between the years 1970 and 1974, 1980 and 1984, 1990 and 1994, and 2000 and 2004. RESULTS A total of 1,270 patients were included in the study. There were 140, 141, 402, and 587 patients in the 1970-1974, 1980-1984, 1990-1994, and 2000-2004 groups, respectively. In the past decade, the use of ultrasonography has increased significantly; more thyroid cancer cases have been diagnosed and more extensive surgical procedures have been applied. CONCLUSIONS During the past 40 years, significant changes have occurred in the treatment of thyroid disease, particularly diagnostic tools, pathologies, and surgical procedures.

Splenectomy-Induced Leukocytosis Promotes Intratumoral Accumulation of Myeloid-Derived Suppressor Cells, Angiogenesis and Metastasis

ABSTRACT Background: Enlargement of the spleen is commonly observed in animal models of cancer. Here, in a breast cancer model, it was aimed to determine the effect of splenectomy on circulating and tumor-infiltrating myeloid-derived suppressor cells (MDSCs), tumor angiogenesis, and metastasis. Methods: Mice were inoculated with 4T1 breast cancer cells and underwent splenectomy or sham laparotomy. Tumor growth and survival of animals were followed. Macroscopic and histopathological analyses were performed to determine splenomegaly and metastasis. Immunophenotyping of myeloid cells was performed with flow cytometric analysis of CD11b, Gr-1, F4/80, CD206, CD11c, and F4/80 markers. Suppressive function of MDSCs on T cell proliferation was studied in cocultures. Tumor angiogenesis and granulocytic myeloid cell infiltration in the metastatic foci were studied by CD31 and Ly6G immunohistochemistry, respectively. Results: The mice bearing breast tumors underwent total splenectomy at an early time point of tumorigenesis when only low levels of MDSCs had accumulated in the spleen. Circulating and tumor-infiltrating MDSCs, and tumor-associated macrophages (TAMs) were increased following splenectomy. Nevertheless, splenectomy could only lead to a temporary deceleration in tumor growth but favored lung metastasis and angiogenesis in the long run. Conclusion: Our data demonstrated a link among splenectomy-induced leukocytosis, accumulation of circulating and tumor-infiltrating MDSC, and enhanced angiogenesis and metastasis. Therefore, as a part of oncological surgery, favorable and unfavorable facets of the splenectomy must be considered to improve therapeutic efficacy.

Familyal adenomatöz polipozis ile ilişkili iki desmoid tümör olgusu ve literatürün değerlendirilmesi

Uzak metastaz yapmazlar ancak lokal invazif ilerleyen cevre yapilara basi yapabilen tumorlerdir. Sporadik desmoid tumorlere nazaran FAP ile iliskili desmoid tumorler daha cok karinda ve karin on duvarinda gorulurler; ciddi mortalite morbidite sebebidirler. Literaturde, desmoid tumorle ayni anlamda kullanilan malign fibromatozis, mezenterik fibromatozis gibi farkli adlandirmalar mevcuttur. Biz bu calismada desmoid tumor terimini kullandik.

Renal Cell Carcinoma Metastasis to Focal Nodular Hyperplasia Focus on Liver in a Patient With Von Hippel-Lindau Disease

Von Hippel-Lindau disease is an autosomal dominant disorder occurring in 1 of 36,000 births and associated with various tumors and cysts in the central nervous system and other visceral organs. At present, metastasis from renal cell carcinoma (RCC) and neurologic complications are the most common causes of death from Von Hippel-Lindau disease. We report a case of Von Hippel-Lindau disease diagnosed during a screening and was found to have metastasis of RCC to a focal nodular hyperplasia lesion on the liver. In the literature, misdiagnosis of benign liver lesions as metastases of RCC has been reported, but there has not been a case reported to have a metastasis of RCC within a benign liver lesion. To our knowledge, this is the first case of RCC metastasis to a benign lesion of the liver.

Laparoscopic splenectomy for haematological diseases.

Abstract Purpose: To show the utility of laparoscopic splenectomy for hematologic diseases. Patients and Methods: Ten patients with hematologic diseases who were operated between February 1997 and October 1998 were analysed retrospectively. Technique: The operations were performed by four trocars, hilar vessels were divided by clips and bag was used for splenic retrival. Results: All operations were completed successfully. No accessory spleens were found. Intraoperative complication, other than a bag tear in one operation did not occur. Postoperative complications occurred in two patients. The first one was a portal vein thrombosis and the second one was a peritonitis. All patients responded hematologically to the operation. Conclusion: With appropriate surgical technique and patient follow up, laparoscopic splenectomy is a safe, adventa-geous and efficaceus operation for hematologic diseases.

Impact of repeated abdominal surgery on wound healing and myeloid cell dynamics

BACKGROUND Even though wound dehiscence is a surgical complication, under certain medical conditions, repetition of the laparotomy (LT) (relaparotomy) can become inevitable. In addition to the risks associated with this surgical operation, relaparotomy can interfere with the tissue healing and contribute to the development of chronic wounds. METHODS In an experimental relaparotomy wounding model, this study investigated the impact of repeated surgery on wound healing and on the immune cells of myeloid origin. RESULTS The first repeat of the LT triggered fibrosis and marginally interfered with the wound healing; however, the second operation completely abrogated the healing process. Splenomegaly was observed as an indicator of the chronic inflammation and the systemic effect of repeated laparotomies. In the blood stream, the spleen, and the liver, these repeated surgeries exhibited a major impact on the CD11b+Ly6C+Ly6G- monocytes. On the other hand, especially, whespecially the second relaparotomy resulted in a massive purging of neutrophil granulocytes into the circulation. These CD11b+Ly6C+Ly6G+ neutrophils that were disseminated on repeated abdominal laparotomies had a proinflammatory character that positively influenced T cell proliferation and displayed a high capacity for production of reactive oxygen species. CONCLUSIONS The repetition of abdominal LT not only interferes with the wound healing but also contributes to the development of imperfectly healing wounds which have systemic impact on immune compartments.

The effects of cancer-associated fibroblasts obtained from atypical ductal hyperplasia on anti-tumor immune responses

Breast cancer is the most common cancer among woman. A total of 255 180 of new invasive breast cancer cases are estimated to be diagnosed in 2017 in US. In addition, 63 410 cases of in situ breast lesion cases are estimated for women (Cancer Facts & Figures‐2017). Atypical ductal hyperplasia (ADH) is thought as a precursor lesion in the development of breast cancer. It is characterized by small atypical ductal lesions that do not possess sufficient features for a definitive diagnosis of ductal carcinoma in situ (DCIS). Patients diagnosed with ADH have four‐fold increased risk of breast cancer development; however, only 15% of them develop invasive breast cancer. Since the presence of ADH cannot be diagnosed by any imaging modalities, both male and female cases of such lesions are incidental and rare. Fibroblasts constitute one of the most important cells in the stroma and turn into cancer‐associated fibroblasts (CAFs) in the tumor microenvironment. Unlike their normal counterparts, CAFs express alpha‐smooth muscle actin (α‐SMA) and display a characteristic morphology. Progression from normal to preneoplastic and then to neoplastic states involves reciprocal secretory communication with activated myofibroblasts. CAFs not only play an active role in tumor initiation and progression both by soluble factors and direct cell‐to‐cell contact, but also sculpt the tumor microenvironment by suppressing anti‐tumor immune responses directly or by recruiting immunosuppressive cells. Phenotypic and functional features of fibroblasts in cancer microenvironment are well documented; however, fibroblasts found in purgatory lesions such as ADH have never been investigated before, to the best of our knowledge. In the present study, normal breast tissue and the one with ADH were obtained from patients undergoing reduction mammoplasty. Breast tumor tissues were obtained from patients undergoing mastectomy. All fibroblast cells were isolated using a previously described protocol. All human breast tissues used for these experiments were obtained in compliance with the laws and institutional guidelines, as approved by the institutional review board from Hacettepe University School of Medicine (Approval number: GO 16/ 64‐20) Characterizations of fibroblasts were done by immunocytochemistry stainings with vimentin, pan‐cytokeratin and α‐SMA. Cells (7 × 10 cells/300 μL in each well) were planted in eight‐well chamber slides, and immunocytochemical/morphological analyses were performed when the cells reached a surface confluency of >80%. Immunocytological characterization of these fibroblasts demonstrated strong vimentin (a mesenchymal cell‐marker) and α‐SMA expression as well as a characteristic CAF‐like morphology. These features are similar with those of CAFs isolated from patients with invasive breast carcinoma (Figure 1A,C,D,F). In contrast, normal fibroblasts (NFs) isolated from normal mammary tissue did not express α‐SMA (Figure 1I). NFs, CAFs, and fibroblasts obtained from ADH lesions were shown to be negative for cytokeratin (an epithelial cell‐marker; Figure 1B,E,H). One of the mechanisms that CAFs utilize to suppress anti‐tumor immune responses is the inhibition of T cell proliferation. We investigated the effects of CAFs, NFs, or fibroblasts from ADH on CD4 T cell proliferation by CFSE (Carboxyfluorescein succinimidyl ester) proliferation assays. Isolation of CD4 T cells was accomplished (from PMBCs) by a magnetic bead‐based negative selection protocol. CD4 T cells were activated by CD3/CD28 magnetic beads. Activated T cells were cultured with conditioned Received: 22 August 2017 | Revised: 31 August 2017 | Accepted: 13 September 2017 DOI: 10.1111/tbj.13139