Prognostic Impact of Bone Marrow Fibrosis and Effects of Tyrosine Kinase Inhibitors on Bone Marrow Fibrosis in Chronic Myeloid Leukemia.

BACKGROUND: Myelofibrosis is reported in around 40% of newly diagnosed chronic myeloid leukemia (CML) patients and have an important role in the pathobiology and prognosis of CML. This retrospective study aimed to evaluate the effects of bone marrow (BM) fibrosis on disease prognosis and the effects of specific tyrosine-kinase inhibitors (TKIs) on BM fibrosis in CML patients. METHODS: The study included 96 patients (>18 years) diagnosed with chronic phase (CP) CML. The clinical and demographic information were collected from the medical files. Post-treatment BM aspirate and core biopsy samples were analyzed for the presence of fibrosis and dysplasia. RESULTS: The mean age of the study patients was 52.69 years; 47.9% of the patients were female. At the onset, 53 (63.1%) patients had BM fibrosis. The difference in the overall survival of the patients with respect to BM fibrosis grades was significant (p = .001). Within the BM fibrosis grade groups, there were significant differences between grade 0 vs. grade 2, grade 0 vs. grade 3, and grade 1 vs. grade 3 (p = .005, p = .002, and p = .003 respectively) There was no significant association between the presence of BM fibrosis at the onset and not responding to first-line therapy (p = .724). Moreover, no significant association was found between the presence of BM fibrosis at the onset and molecular (p = .623) or cytogenetic response (p = .535) to first-line therapy. Additionally, the association between the type of second-line and third-line therapy and molecular response (p = .773 and p = .424, respectively) or cytogenetic response (p = .298 and p = .641) was not significant. CONCLUSION: Although BM fibrosis seems to be a crucial complication of CML with a poor prognosis, it can be reversed via TKI treatment which may result in improved survival. It might be considered to check the BM for this complication on a regular basis during therapies to test its prognostic influence in CML patients in prospective controlled trials. Further studies focused on this issue are required to utilize BM fibrosis as a candidate prognostic factor.

Unusual Breast Metastasis from Atypical Lung Carcinoid on 68Ga-DOTATATE PET/CT.

BACKGROUND: Atypical carcinoid (AC) is one of the rarest lung neuroendocrine tumors (NETs) that rarely metastasize to the breast, and only a few cases have been reported in the literature. Positron emission tomography/computed tomography (PET/CT) with somatostatin analogs (SSAs) labeled with Gallium-68 (68Ga) now represents the gold standard for diagnosis and management of NETs. A case of an unusual metastasis to the breast from an AC detected by 68Ga-DOTATATE PET/CT was reported. CASE PRESENTATION: A 73-year-old woman was presented with a right breast lesion found on mammography screening, which revealed a metastatic neuroendocrine tumor by histopathological analysis with a tru-cut biopsy. Subsequently, 68Ga-DOTATATE PET/CT imaging performed for the initial evaluation showed increased radiotracer uptake in the lesion in the right breast as well as the nodular lesion in the middle lobe of the right lung, which was histologically confirmed to be AC. CONCLUSION: Metastasis of uncommon AC of the lung to the breast is extremely rare. However, it is essential to properly differentiate metastatic tumors from primary disease due to differences in clinical management and prognosis, and 68Ga-DOTATATE PET/CT is a unique diagnostic tool with the advantage of whole-body imaging.

An extremely rare tracheal tumor in coronavirus disease-2019 screening: Marginal zone lymphoma.

Mucosal-associated lymphoid tissue lymphoma is extremely rare due to the scarcity of lymphoid tissue in the trachea. To date, approximately 20 cases of tracheal mucosa-associated lymphoid tissue lymphoma have been reported. This case report presents a primary tracheal extranodal marginal zone lymphoma case detected incidentally during the coronavirus disease-2019 screening.

A rare case of pulmonary lymphomatoid granulomatosis complicated with venous thrombosis.

Lymphomatoid granulomatosis (LG) is Epstein-Barr virus associated and aggressive B cell lymphoproliferative disease. The most common sites of involvement are lungs, skin, kidneys, liver and central nervous system. The clinical presentation of pulmonary LG may mimic infectious diseases, malignancies or vasculitis. While treatment approach of low grade disease is watch and wait, patients with advanced stage require aggressive treatment with chemotherapy. Patients with hematological malignancy as well as solid tumors are at increased risk of venous thromboembolic events (VTE). We reported here in a case of pulmonary LG who was complicated with VTE during treatment with chemo-immunotherapy After 4 cycles of R-CHOP, she achieved complete remission for LG and was followed up without relapse for 2 years. She was anticoagulated with Low-Molecular-Weight Heparin (LMWH) during chemotherapy period, and the thrombus improved over the next several weeks. While on this paper written, patient completed her pregnancy successfully under anticoagulation prophylaxis.

Mixed epithelial and stromal tumor of the kidney treated with minimally invasive surgery.

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare kidney tumor that tends to occur in middle-aged and older women and is characterized by a distinctive histological appearance. Most of them were incidentally detected. A 26-year-old female patient was referred to in our clinic due to intermittent left lower back pain for 2 months and left renal mass. Abdominal computed tomography showed a cystic enhanced heterogenic left renal mass about 5 cm in the largest diameter was extending from the renal pelvis to the ureter and causing gross hydronephrosis of the left kidney. The mass treated with transperitoneal laparoscopic nephroureterectomy and bladder cuff resection. Histopathological evaluation revealed MESTK. In our patient, MESTK successfully and without any complication be treated by minimally invasive surgery. We believe that the fact that the tumor can mimic the urothelial-cell carcinoma of the kidney in radiological appearance, as seen in our case, should be taken into consideration.

Comparison between single-photon emission computed tomography/computed tomography and ultrasound in preoperative detection of parathyroid adenoma: retrospective review of an institutional experience.

OBJECTIVE: The aim of this study was to evaluate the accuracy of technetium- 99m-methoxyisobutylisonitrile (Tc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) and ultrasound in preoperative localization of single parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (pHPT) who would be suitable for minimally invasive parathyroidectomy (MIP). METHODS: A retrospective study of 143 consecutive patients with biochemical evidence of hyperparathyroidism who underwent preoperative localization of parathyroid lesions using Tc-MIBI SPECT/CT and ultrasound, and proceeded to parathyroid surgery at our institution from January 2013 to January 2018. Of these, 125 had single adenomas and are the subject of this study. The sensitivity, positive predictive value (PPV) and accuracy of the two imaging techniques for the accurately identification and lateralization of PTAs were determined using histopathology as the criterion standard. RESULTS: Of 125 PTAs, the correct identification and lateralization were significantly higher by SPECT/CT than ultrasound. SPECT/CT and ultrasound detected lesions with histopathologically proven PTAs in 116 and 95 patients, respectively. The sensitivity, PPV and accuracy were 92.17, 94.64 and 87.60%, respectively, for SPECT/CT and 75.89, 90.43 and 70.25%, respectively, for ultrasound in lateralization analysis. CONCLUSIONS: The results of our study indicate that Tc-MIBI SPECT/CT is more accurate than ultrasound for the preoperative identification of single PTAs in patients with pHPT who are candidates for MIP.

Combination therapy with azacitidine, etoposide, and cytarabine in the treatment of elderly acute myeloid leukemia patients: A single center experience.

AIMS: The prognosis of acute myeloid leukemia (AML) in elderly patients is worse due to age and comorbidities. Lately, monotherapy with hypomethylating agents like azacitidine (Aza) has been used to prolong overall survival (OS) in AML patients. Herein, we present a retrospective study investigating treatment responses and OS of Aza in combination with etoposide (Eto) and cytarabine (ARA-C) in elderly. MATERIALS AND METHODS: In this study, therapies and outcomes of 37 newly diagnosed AML patients, >60 years old, and ineligible for intensive chemotherapy were investigated retrospectively. Patients were grouped according to the treatments they received as follows - Group 1: low-dose conventional therapies as hydroxyurea, low-dose ARA-C, or best supportive care (n = 11); Group 2: Aza alone (n = 6); Group 3: Aza in combination with Eto and ARA-C (Aza + Eto + ARA-C, n = 20). RESULTS: It was found that an Aza + Eto + ARA-C combination therapy had significantly better overall response rates (P = 0.002). Combination group had significantly better OS than Group 1 (8 months vs. 1 month, P < 0.001), the difference between combination and monotherapy was not significant. The OS was also associated with age and performance status, but the difference was still statistically significant after adjustment for these factors, especially for patients with younger age and better performance. CONCLUSIONS: We concluded that combination therapy of Aza with Eto and ARA-C increases response rates, and prolong survival for this poor prognosed patient group. We believe that larger controlled studies investigating Aza combinations with other antileukemic drugs will contribute to the development of tolerable treatment protocols for elderly AML patients.

The Predictive Role of the Neutrophil/Lymphocyte Ratio in Survival with Multiple Myeloma: A Single Center Experience.

BACKGROUND: Recent studies have shown a positive correlation between tumor-related immune response markers and the poor outcome in solid tumors. In this study, we aimed to investigate the neutrophil/lymphocyte ratio (NLR) in multiple myeloma. To the best of our knowledge, this would be the second report concerning this topic. METHODS: We retrospectively reviewed the data for 52 multiple myeloma patients. The patients were grouped using the baseline NLR as NLR ≤ 1.72 and NLR > 1.72 using receiver operating characteristic analysis to determine a cut off. We compared the two groups in terms of both the known prognostic factors of the myeloma and the overall survival (OS). RESULTS: Our study showed that NLR is associated with C-reactive protein and ß2 microglobulin (P = 0.02 and P = 0.001, respectively). The patients with NLR > 1.72 had significantly worse stages, performance status, and kidney functions. The whole group's OS was estimated as 35.1 months while the patients with lower NLR had better OS when compared with those with NLR > 1.72 (42.75 and 26.14 months, respectively, P: 0.04). CONCLUSION: Neutrophil/lymphocyte ratio, which is associated with stage, performance status, and kidney functions, can be used in daily practice as a predictor for survival in multiple myeloma. Simply adding NLR to the routine charts may enrich our data for larger studies.

Protective effects of caffeic acid phenethyl ester on ifosfamide-induced central neurotoxicity in rats.

BACKGROUND: The aim of this study was to establish the protective effect of caffeic acid phenethyl ester (CAPE) against the ifosfamide (IFOS)-induced central neurotoxicity in rats and to determine the changes in oxidant-antioxidant status of brain tissue. METHOD: A total of 35 Wistar rats (aged 7-12 days) were used in the experiments. The study comprised of five groups. Control untreated rats (n = 7) belonged to group 1; group 2 was given intraperitoneal (IP) injection of CAPE alone (10 µmol/kg; n = 7); group 3 was treated with single IP injection of IFOS (500 mg/kg; n = 7); group 4 was treated for 2 days with IP administration of CAPE (10 µmol/kg) beginning from one day before single IP injection of IFOS (n = 7); and group 5 was treated with saline and 10% ethanol. At the 24th hour of IFOS treatment, brain tissues were removed for analysis. RESULTS: The brain catalase activity was lower in IFOS group than the other groups (p < 0.05). The levels of malondialdehyde (MDA) and protein carbonyl content in brain tissue were higher in IFOS group than the control, CAPE, ethanol, and IFOS + CAPE groups (p < 0.05). There was no significant difference between MDA and protein carbonyl content of control, CAPE, ethanol, and IFOS + CAPE groups. Immunohistochemistry showed marked activation of caspase 3 in the IFOS group at 24 h after treatment. CONCLUSION: This study revealed that pretreatment with CAPE might protect brain tissue against IFOS-induced central neurotoxicity. CAPE could be an effective course of therapy to enhance therapeutic efficacy and to lessen IFOS toxicity in clinical chemotherapy.

Relationship of CD95 and COX-2 in renal cell carcinomas with survival and other prognostic parameters: A tissue microarray study.

OBJECTIVE: To investigate the expression of cyclooxygenase-2 and cluster of differentiation 95 in renal cell carcinomas having different clinico-pathological characteristics. METHODS: The study entailed histopathological diagnoses carried out on paraffin blocks at the Department of Pathology of the Medical Hospital of Duzce University, Turkey, between 2005 and 2011. Immunohistochemical staining for cyclooxygenase-2 and cluster of differentiation 95was performed on tissue microarray using standard procedures. Each patient's age and gender as well as the tumour's grade, stage, diameter, ureteral surgical margins, vascular invasion, capsule invasion and subtype were assessed. In order to determine if the cases were still alive, relatives were telephoned and identity registration records were checked. SPSS 18 was used for statistical analysis. RESULTS: There were 49 paraffin blocks in the study.Significant correlations were found between cyclooxygenase-2 and tumour subtype (p=0.044) as well as between cyclooxygenase-2 and tumour diameter (p=0.026). There was a significant correlation between cluster of differentiation 95and the Fuhrman grade (p=0.050). CONCLUSIONS: Expression of cluster of differentiation 95and cyclooxygenase-2 may be correlated with prognostic parameters in renal cell carcinoma and may also be associated with tumour progression.

Protective effects of colchicine in an experimental rat endometriosis model: histopathological evaluation and assessment of TNF-α levels.

OBJECTIVE: Endometriosis is an estrogen-dependent chronic inflammatory disease observed in reproductive period. The aim of the present study is to assess the efficacy of colchicine, widely used to treat many inflammatory diseases, in an experimental rat endometriosis model. STUDY DESIGN: Experimental endometriosis was constituted with implantation of autogenous endometrial tissue. Rats were divided randomly into 2 groups as colchicine group (n = 8) and control group (n =8). Although oral 0.1 mg/kg colchicine was administered 4 weeks to the colchicine group, the same amount of saline solution was administered to the control group. Before and after 30 days of treatment period, peritoneal and tissue tumor necrosis factor α (TNF-α), the volumes and histopathological properties of the implants were evaluated. RESULTS: Although the implant volume decreased significantly in the colchicine group (89.2 ± 13.4 mm(3) to 35.2 ± 4.5 mm(3), P < .05), the implant volume increased in the control group (85.1 ± 14.2 mm3 to 110.3 ± 10.5 mm(3), P < .05). When compared to the control group, the colchicine group had significantly lower histopathologic sores (1.4 ± 0.2 vs 2.6 ± 0.4, P < .001). Although peritoneal fluid TNF-α levels were significantly decreased in the colchicine group (45.2 ± 5.3 pg/mL vs 12.1 ± 5.2 pg/mL, P < .001), the peritoneal fluid TNF-α levels were significantly increased in the control group after the treatment (44.2 ± 3.5 pg/mL vs 61.3 ± 12.2 pg/mL; P < .001). Tissue TNF-α levels were significantly lower in the colchicine group when compared to the control group (45.4 ± 8.6 pg/mL vs 71.3 ± 11.2 pg/mL; P < .001). CONCLUSION: Colchicine resulted in regression of endometrial implant volumes in experimental rat endometriosis model and decreased peritoneal and tissue TNF-α levels.

Comparison of therapeutic characteristics of islet cell transplantation simultaneous with pancreatic mesenchymal stem cell transplantation in rats with Type 1 diabetes mellitus.

Although, pancreas islet call transplantation is a new, promising method for type 1 diabetic patients, it remains as an experimental procedure applied in selected patients. The present study aimed to investigate effect of pancreatic mesenchymal stem cell transplantation simultaneous with islet cell transplantation on islet liveliness and thus on the treatment of diabetes in type 1 diabetic rats. The study used Wistar Albino Rats and was performed in a total of four groups [control (G1), mesenchymal stem cell (G2), islet (G3) and islet + mesencymal stem cell (G4)] each including 8 rats. Blood glucose level of the rats, in which diabetes model has been created using streptozotocin, was measured after 72 h. Blood samples were obtained from the rats 30 days after transplantation and then, their livers and pancreases were kept in 10% formaldehyde and the experiment was ended. Following staining with H&E, they were morphologically evaluated under a light microscope. Change in mean blood glucose level was statistically significant in G3 and G4 versus G1 and G2 (p = 0.001, p < 0.001, p < 0.001, and p < 0.001 respectively). Histological examination revealed that mean number of islet cells in the pancreases of the rats was higher in G4; difference between the groups was statistically significant (p < 0.001). Transplantation of islet cells together with mesenchymal stem cells showed beneficial effects in terms of prolonging survival of islet grafts suggesting that transplantation of mesenchymal stem cells together with islet cells during clinical islet transplantation may be beneficial in increasing the number of noninsulin-dependent patients in Type 1 diabetes.

Protective effect of colchicine on ovarian ischemia-reperfusion injury: an experimental study.

OBJECTIVE: The aim of the present study is to investigate the efficiency of colchicine in the experimental rat ovarian torsion model in the light of histological and biochemical data. STUDY DESIGN: A total of 35 Wistar albino female rats were randomly divided into 5 groups, group 1: (control-sham operated, n = 7); group 2: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion; group 3: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion; group 4: (torsion/detorsion, n = 7) 2 hours of ischemia and 2 hours of reperfusion and a signal dose of oral 1 mL/kg colchicine; and group 5: (torsion/detorsion, n = 7), 2 hours of ischemia and 5 days of reperfusion and 5 days of oral 1 mg/kg colchicine. Histopathologic evaluation was performed by a scoring that assesses congestion, bleeding, edema, and cellular degeneration in the ovarian tissue. Catalase, tissue malondialdehyde (MDA), and protein carbonyl levels were calculated. RESULTS: The histopathologic scores, MDA, and protein carbonyl levels in the control and colchicine groups were significantly lower than groups 2 and 3 (P < .001). Catalase activities were significantly higher in the control and colchicine groups than in groups 2 and 3 (P < .001). The results of the histopathologic parameters and biochemical markers showed that protective effects of colchicine treatment persisted up to 5 days. CONCLUSION: Our study results revealed that colchicine reduced ovarian ischemia-reperfusion injury in experimental rat ovarian torsion model. As the ovarian detorsion is the first choice of the treatment modality in the early phase, antioxidant and anti-inflammatory treatment modalities like colchicine might be used to reduce ovarian ischemia-reperfusion injury.

Histopathological findings obtained from reduction mammoplasty specimens.

BACKGROUND/AIM: Reduction mammoplasty is a common surgical procedure. We report the incidence of nonproliferative and proliferative breast lesions in breast reduction specimens from a single institution over a 6-year period. MATERIALS AND METHODS: The histopathology reports of all patients were analyzed. The clinical and histopathological findings of the patients were recorded. RESULTS: Between 2004 and 2010, 106 patients underwent breast reduction. Fifty-six patients (52.8%) had proliferative breast lesions, 84 patients (79.2%) had nonproliferative lesions, 8 patients (7.5%) had columnar cell lesions without atypia, 61 patients (57.5%) had columnar cell lesions with atypia, 5 patients (4.7%) had atypical ductal hyperplasia, and 6 patients (5.6%) had lobular carcinoma in situ. No invasive breast cancer was identified. CONCLUSION: In Turkey, there is limited evidence regarding the role of histopathological analysis in reduction mammoplasty. Moreover, none of the previous studies determined columnar cell lesion rates in reduction mammoplasty patients. The detection of significantly elevated columnar cell lesions, with or without atypia, especially in patients under the age of 40, increases the importance of screening tests, especially in Turkey, which has a high incidence of breast cancer in early ages, and addresses the need to starting screening tests early in these patients.

Zofenopril attenuates injury induced by ischemia-reperfusion on rat ovary.

AIM: The aim of the study was to investigate the effectiveness of zofenopril in an experimental model of ovarian torsion in rats with histologic and biochemical assessments. MATERIAL AND METHODS: Experimental procedures were performed on 35 female rats (Wistar albino). Rats were randomly divided into five groups as: sham (sham operated, n = 7); vehicle group 1 (torsion-detorsion, n = 7) with 2 h ischemia and 2 h reperfusion; vehicle group 2 (torsion-detorsion, n = 7) with 2 h ischemia and 5 days' reperfusion; zofenopril group 1 (torsion-detorsion, n = 7) with 2 h ischemia, 2 h reperfusion and a signal dose of oral 15 mg/kg zofenopril; and zofenopril group 2 (torsion-detorsion, n = 7) with 2 h ischemia, 5 days' reperfusion and 5 days' oral 15 mg/kg zofenopril. A scoring of histopathologic evaluation was performed on the ovaries according to congestion, bleeding, edema, and cellular degeneration. Biochemical assessments included catalase, tissue malondialdehyde and protein carbonyl. RESULTS: Compared with the vehicle groups, histopathologic scores, tissue malondialdehyde and protein carbonyl levels, which reflect oxidative stress markers, were significantly lower in the zofenopril groups. Furthermore, catalase levels were significantly increased in the zofenopril group. CONCLUSION: Our study results revealed that zofenopril attenuates injury induced by ischemia-reperfusion on rat ovary.

Does Omegaven have beneficial effects on a rat model of ovarian ischemia/reperfusion?

OBJECTIVE: The beneficial effects of omega-3 fatty acids on an intestinal ischemia/reperfusion (I/R) model was shown previously. Therefore, we aimed to examine the potential beneficial effects of parenteral omega-3 fatty acids, a safe and inexpensive product, on a rat model of ovarian I/R. STUDY DESIGN: A group of 39 rats was divided into six groups. Group 1 (Sham Group; n=6) underwent two laparotomies with a 3-h interval and their ovaries were removed 3h later. Group 2 (torsion-detorsion Group; n=7) had their ovaries torsioned clockwise and fixed at 720°; 3h later a detorsion operation was done and after another 3h, their ovaries were removed. Group 3 (n=7) and Group 4 (n=7) received the same treatment as Group 2; however, half an hour prior to detorsion, these rats received Omegaven at 1mL/kg and 5mL/kg, respectively. Group 5 (n=6) and Group 6 (n=6) received the same treatment as Group 1; however, half an hour prior to the second laparotomy, these rats received Omegaven at 1mL/kg and 5mL/kg, respectively. One ovary from each rat was evaluated histologically by hematoxylin and eosin (H&E) staining and the other ovary was homogenized and evaluated for total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI). RESULTS: While we failed to show any significant relationship among groups in oxidative parameters, there was a significant worsening in the torsion-detorsion group in histological evaluation. High Omegaven doses, but not low doses, improved tissue injury scores of torsioned and detorsioned ovaries to the levels observed in the control group. CONCLUSION: Omegaven improves the detrimental effects of ovarian I/R when used in sufficient doses. Its effects and dose adjustment on women with ovarian torsion must be investigated by further studies.