CD47 expression in urothelial carcinoma and its correlation with histopathological findings.

BACKGROUND: The incidence of bladder cancers (BCs) is increasing day by day in both males and females with increased smoking. New treatment protocols are required due to the long follow-up times and high recurrence rates. CD47 (integrin-associated protein) is a membrane receptor that is effective in normal and pathophysiological events such as apoptosis, proliferation, adhesion, and immunity. Phagocytosis of both normal and tumor cells is prevented, by binding to the ligand signal regulatory protein-1 (SIRP-1)α on macrophages. Anti-CD47 antibodies can eliminate the binding and may be effective in treatment. METHODS: The study included 194 cases with urothelial carcinoma (UC) who underwent transurethral resection (TUR) of the bladder and had been followed up for one year. Cytoplasmic and membranous staining was preferred for CD47-positive staining. Staining results were compared with tumor grades, pathologic tumor stage, recurrence, and metastasis grade. RESULTS: The prevalence and intensity of CD47 staining in BCs were evaluated in this study. High-grade tumors were stained more pronouncedly compared with low-grade tumors and normal epithelium. The prevalence of CD47 staining was significant in pT2 (Pathological tumor stage 2, invades of muscularis propria) tumors, and its correlation with pTa (Pathological tumor stage a, noninvasive papillary carcinoma) tumors was significant ( P < 0.001). In the intensity evaluation, there was a significant difference between pTa and pT2 and between pT1 (Pathological tumor stage 1, invades lamina propria) and pT2 ( P = 0.003). CONCLUSION: CD47 is expressed strongly in high-grade tumors. The prevalence and intensity of CD47 staining are high in pathologic tumor stage, recurrence, and distant metastases and are considered poor prognostic markers. We believe that anti-CD47 antibodies can be used as an alternative to the current treatment or in combination with other medications, and the systemic side effects that may occur with intravesical treatment can be prevented.

Persistent pleural effusion in an infant with an unusual diagnosis: congenital alveolar rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a malignant form of neoplasm that originates from skeletal muscle. RMSs can exist anywhere in the human body but are more commonly detected in the neck region and extremities. The alveolar type is one of the subtypes of RMS that has a poor prognosis. Because the clinical manifestation of a tumour can be a painless mass, symptoms might be non-contributary to the diagnosis. Herein, a four-month-old girl was admitted to the emergency department with complaints of respiratory distress without a runny nose, cough, and fever. Recurrent effusions subsided with subsequent tube thoracostomy. Video-assisted thoracoscopic surgery (VATS) was performed to determine the aetiology of the recurrent effusion. The Tru-Cut biopsy obtained during VATS resulted in the diagnosis of alveolar rhabdomyosarcoma. Pleural effusion decreased, and the tube drainage was stopped rapidly after first vincristine, actinomycin-D, and cyclophosphamide chemotherapy cycle. Persistent and recurrent pleural effusions should alert physicians to rule out unusual diagnoses like that of our case.

Giant malignant pheochromocytoma with palpable rib metastases.

Pheochromocytoma is a rare and usually benign neuroendocrine neoplasm. Only 10% of all these tumors are malignant and there are no definitive histological or cytological criteria of malignancy. Single malignancy criteria are the presence of advanced locoregional disease or metastases. We report a case, with a giant retroperitoneal tumor having multiple metastases including palpable rib metastases, who was diagnosed as a malignant pheochromocytoma. The patient was treated with surgery. The literature was reviewed to evaluate tumor features and current diagnostic and therapeutic approaches for patients with metastatic or potentially malignant pheochromocytoma.

Higher Ki67 expression is associates with unfavorable prognostic factors and shorter survival in breast cancer.

BACKGROUND: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of this study was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2 and hormone receptor expression status in breast cancers. MATERIALS AND METHODS: Clinical and pathological features of the patients with breast cancer were retreived from the hospital records. RESULTS: In this study, 163 patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20% and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001), estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymph node positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free and overall survival compared to those of higher Ki67 levels. CONCLUSIONS: High Ki67 expression is associated with ER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The level of Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.

Orbital metastasis of endocervical stromal sarcoma: a rare tumor and an uncommon metastasis.

Endocervical stromal sarcoma (ECSS) is a very rare uterine sarcoma. The most common presentation is pelvic mass and vaginal bleeding. The mainstay of treatment is surgery. There is no consensus on the adjuvant treatment. Relapses are usually in the pelvic and abdominal regions. To a lesser extent, lung, liver and bone metastases may be seen. A 46-year-old woman had total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) performed due to endometrial polyp and leiomyoma. Six months after the TAH-BSO, she was admitted to the hospital with cough and hemoptysis. A thoracic mass was detected, and a biopsy was done. The diagnosis was low-grade ECSS metastasis. One week after thoracotomy, she was admitted to the hospital with loss of vision in the left eye. An orbital mass was detected with magnetic resonance imaging. Endometrial and cervical pathology preparations were reassessed and were compatible with ECSS. We performed mammography, thorax, and abdomen and cranial imaging to rule out other malignancies that may cause lung and orbital metastasis. Partial remission was achieved with systemic chemotherapy and orbital radiotherapy. Orbital metastasis may be seen in ECSS patients. Although we have less knowledge about the choice of chemotherapeutic agents, ifosfamide and doxorubicin are effective in treating ECSS.

Tularemia: potential role of cytopathology in differential diagnosis of cervical lymphadenitis: multicenter experience in 53 cases and literature review.

Tularemia is a zoonosis caused by Francisella tularensis. Tularemia outbreaks occurred in Central Anatolia during 2009 and 2011. We evaluated the clinical characteristics and cytomorphologies of fine needle aspirations (FNAs) from cervical lymph nodes in serologically confirmed tularemia cases. To our knowledge, this is the first large series concerning FNA morphology of Tularemia. FNA smears of 53 patients of the 290, diagnosed by microagglutination tests and PCR, were evaluated at three Pathology centers. FNAs were performed by cytopathologists or ear-nose-throat surgeons. Of all patients, 17 had also lymph node resections. FNAs showed the presence of suppuration and abscess. Rare epithelioid histiocytes and granulomas, seldom phagocytosed bacilli-like microorganisms were observed. On histopathology; granulomas, necrosis, and suppurative inflammation extending extracapsular areas were seen. Tularemia is endemic in certain areas of the Northern Hemisphere. The benefit from cytopathology is limited and cytological suspicion should be confirmed by serology. However FNA cytology is helpful in differential diagnosis of tularemia and other diseases presented with suppurative, granulomatous cervical lymphadenitis. It is also useful in providing the material for PCR and culture in early phase when the serology is negative and the treatment is more effective.

Antitumoral effects of Melissa officinalis on breast cancer in vitro and in vivo.

BACKGROUND: There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. Here we investigated the antiproliferative properties of Melissa officinalis (MO) from Turkey on breast cancer. METHODS: MO extracts were studied for cytotoxicity against breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). In vitro apoptosis studies were performed by annexin V staining and flow cytometry analyses. Immunohistochemistry for Ki-67 and caspase 7 in the tumoral tissue sections of DMBA-induced mammary tumors in rats was also performed, along with TUNEL assays to detect apoptotic cells. In vivo anticancer activity testing was carried out with reference to inhibition of growth of DMBA induced mammary tumors in rats. RESULTS: MO showed cytotoxicity against three cancer cell lines, inducing increase in Annexin-positive cells. Expression of caspase-7 protein and TUNEL positive cells were much higher in rats treated by MO, compared with the untreated control group, while expression of Ki-67 was decreased. Furthermore, in vivo studies showed that mean tumor volume inhibition ratio in MO treated group was 40% compared with the untreated rats. CONCLUSION: These results indicated that MO extrcts have antitumoral potential against breast cancer.

Pulmonary toxicity of chronic exposure to tobacco and biomass smoke in rats.

OBJECTIVE: The objective of this study was to examine the separate and combined effects of tobacco and biomass smoke exposure on pulmonary histopathology in rats. INTRODUCTION: In addition to smoking, indoor pollution in developing countries contributes to the development of respiratory diseases. METHODS: Twenty-eight adult rats were divided into four groups as follows: control group (Group I, no exposure to tobacco or biomass smoke), exposed to tobacco smoke (Group II), exposed to biomass smoke (Group III), and combined exposure to tobacco and biomass smoke (Group IV). After six months the rats in all four groups were sacrificed. Lung tissue samples were examined under light microscopy. The severity of pathological changes was scored. RESULTS: Group II differed from Group I in all histopathological alterations except intraparenchymal vascular thrombosis. There was no statistically significant difference in histopathological changes between the subjects exposed exclusively to tobacco smoke (Group II) and those with combined exposure to tobacco and biomass smoke (Group IV). The histopathological changes observed in Group IV were found to be more severe than those in subjects exposed exclusively to biomass smoke (Group III). DISCUSSION: Chronic exposure to tobacco and biomass smoke caused an increase in severity and types of lung injury. CONCLUSION: Exposure to cigarette smoke caused serious damage to the respiratory system, particularly with concomitant exposure to biomass smoke.

Pulmonary toxicity of chronic exposure to tobacco and biomass smoke in rats

OBJECTIVE: The objective of this study was to examine the separate and combined effects of tobacco and biomass smoke exposure on pulmonary histopathology in rats. INTRODUCTION: In addition to smoking, indoor pollution in developing countries contributes to the development of respiratory diseases. METHODS: Twenty-eight adult rats were divided into four groups as follows: control group (Group I, no exposure to tobacco or biomass smoke), exposed to tobacco smoke (Group II), exposed to biomass smoke (Group III), and combined exposure to tobacco and biomass smoke (Group IV). After six months the rats in all four groups were sacrificed. Lung tissue samples were examined under light microscopy. The severity of pathological changes was scored. RESULTS: Group II differed from Group I in all histopathological alterations except intraparenchymal vascular thrombosis. There was no statistically significant difference in histopathological changes between the subjects exposed exclusively to tobacco smoke (Group II) and those with combined exposure to tobacco and biomass smoke (Group IV). The histopathological changes observed in Group IV were found to be more severe than those in subjects exposed exclusively to biomass smoke (Group III). DISCUSSION: Chronic exposure to tobacco and biomass smoke caused an increase in severity and types of lung injury. CONCLUSION: Exposure to cigarette smoke caused serious damage to the respiratory system, particularly with concomitant exposure to biomass smoke.

Inter-observer agreement in laryngeal pre-neoplastic lesions.

In this series, laryngeal preneoplastic lesions were evaluated by the classifications of the World Health Organization (WHOC), Ljubljana (LC) and squamous intraepithelial neoplasia (SINC) by multiple observers. The inter-observer agreement (IA) by WHOC for laryngeal lesions had been previously evaluated, but to the best of our knowledge, there are no data for LC and SINC. H&E stained slides from 42 laryngeal biopsies were evaluated by fourteen participants according to WHOC and LC, and SINC was additionally applied by 6. The results were analyzed statistically. The diagnoses which were favored by most participants for each case, according to WHOC, were as follows: squamous cell hyperplasia (n = 5; 12%), mild dysplasia (n = 11; 26.2%), moderate dysplasia (n = 12; 28.6%), severe dysplasia (n = 7; 16.7%), carcinoma in situ (n = 5; 12%), and invasive squamous cell carcinoma (n = 2; 4.8%). There was a significant difference between the participants for all three classifications; some participants gave lower or higher scores than the others. The mean correlation coefficients (MCC) of the participants were higher for WHOC compared to LC (0.55 ± 0.15 and 0.48 ± 0.14, respectively). The mean linear-weighted kappa (wKappa) values of participants were not significantly different (0.42 ± 0.10, 0.41 ± 0.12 and 0.37 ± 0.07 for WHOC, LC and SINC, respectively). The kappa values in this series are in agreement with those in previous literature for WHOC, and the similar results obtained for LC and SINC are novel findings. Although the MCC of WHOC was higher, as the wkappa was not significantly different, the findings in this series are not in favor of any of the classifications for better IA for pre-neoplastic laryngeal lesions.

Could total thyroidectomy become the standard treatment for Graves' disease?

PURPOSE: Graves' disease is the most frequent cause of hyperthyroidism. Although treatment with antithyroid drugs or radioactive iodine is effective, surgery remains the preferred treatment for many patients. We analyzed the results of 55 prospectively followed patients who underwent total thyroidectomy for Graves' disease. METHODS: Total thyroidectomy was performed by experienced endocrine surgeons in all 55 patients. We monitored the patients postoperatively for early and late complications. RESULTS: There were 19 men, with a mean age of 42 years (range, 34-68 years) and 36 women, with a mean age of 38 years (range, 19-78 years). One patient suffered postoperative hemorrhage and subsequent wound infection, two patients had transient recurrent laryngeal nerve palsy, and 24 patients had transient hypocalcemia. The mean follow-up time was 4 years (range, 10 months to 6 years). Recurrence of hyperthyroidism was not reported in this period. CONCLUSION: Removal of all thyroid tissue offers the best chance of preventing recurrent hyperthyroidism. Total thyroidectomy is the most effective surgery for achieving the goal of treatment of Graves' disease to ensure that hyperthyroidism will not recur.

The intratumoral microvessel density and expression of bFGF and nm23-H1 in colorectal cancer.

It has previously been reported that intratumoral microvessel density (IMD), and the expression of bFGF and nm23-H1 are useful prognostic markers in colorectal cancer (CRC). In this study, a total of 100 CRCs were evaluated histopathologically, and IMD, bFGF and nm23-H1 expression were assessed by immunohistochemistry. IMD of patients increased with grade and stage, and this increase was statistically significant (p<0.05). A significantly higher incidence of high bFGF expression scores was also associated with increasing grade and stage (p<0.05). However, there was no significant difference between the grades in nm23-H1 expression (p=0.234). nm23-H1 expression occurred with lower incidence in stages C1, C2 and D than in stages B1 and B2 (p<0.05). Thus, a negative correlation was found between nm23-H1 expression and stage or lymph node metastasis (LNM) (p<0.05). IMD and bFGF expression were positively correlated with grade, stage, LNM, and lymphovascular invasion. Although positive correlation was found between IMD and bFGF, nm23-H1 expression negatively correlated with both of them. As a result, in clinical practice, increased IMD and bFGF expression and decreased nm23-H1 expression may provide valuable information in characterizing the malignant phenotype.

Preoperative localization of parathyroid adenomas with technetium-99m methoxyisobutylisonitrile imaging: relationship with P-glycoprotein expression, oxyphilic cell content, and tumoral tissue volume.

UNLABELLED: In addition to tumor size, it has been suggested that P-glycoprotein (P-gp) expression and/or oxyphilic cell content in parathyroid adenomas has an important influence on the results of technetium 99m methoxyisobutylisonitrile (Tc-99m MIBI) parathyroid imaging. AIM: In this study, we compared the results of MIBI parathyroid imaging and immunohistochemical analysis (IHA) of P-gp expression, oxyphilic cell content, and tumoral tissue volume in parathyroid adenomas. We also evaluated the relationship between MIBI and ultrasound (US) results, operation findings, serum biochemical values. MATERIALS AND METHODS: Forty (40) patients (36 female and 4 male; mean age, 53.2 +/- 8.16 years) with hyperparathyroidism who had undergone surgery were included in this study. Preoperatively, "double phase" parathyroid scintigraphy with Tc-99m MIBI (including imaging of the neck and mediastinum) was performed in all patients. Thirty-two (32) of the patients had also neck US. Serum parathormon (PTH), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured preoperatively. In resected parathyroid tissues, P-gp expression and percentage of oxyphilic cell content were analyzed with IHA in 34 patients. RESULTS: Three (3) of the resected parathyroid tissues were hyperplastic parathyroid tissue, whereas 31 of the tissues were parathyroid adenoma (mean volume, 1.99 +/- 1.93 mL). In Tc-99m MIBI parathyroid scintigraphy, 70% of the parathyroid adenoma/hyperplastic parathyroid tissue was detected in correct localization; at US, this rate was 46.8%. According to the resected parathyroid tissue localization at surgery, sensitivity, accuracy, positive predictive value, and prevalence in scintigraphy were 82.3%, 70%, 82.3%, and 85%, respectively. Those were 60%, 46.8%, 68.2%, and 78.1% for US, respectively. No significant correlation and no concordance was found between MIBI and US results (kappa, -0.103, r = -0.11; p: 0.53). Interestingly, significant correlation was found between tumoral volume and ALP level (r = 0.42; p = 0.010) and between PTH and ALP levels (r = 0.72; p < 0.001). Significant correlation was also found between patient age and tumoral volume (r =-0.37; p = 0.02) and between PTH and serum Ca levels (r = 0.32; p = 0.04). In 23 of 34 patients in whom histopathological examination was done MIBI was positive and in 13 of these patients (56.5%), P-gp expression was positive. When the histopathological results and MIBI results were compared, there was no significant correlation and concordance between P-gp expression (kappa = 0.09, r = 0.10; p = 0.54), oxyphilic cell content (r = -0.17; p = 0.33), and tumoral tissue volume (r = -0.14; p = 0.38). In 12 of 19 patients (63%) who had parathyroid tissue < 1 mL and in 15 of 24 patients (62.5%) who had oxyphilic cell content < 10%, lesions were also detected correctly with MIBI scintigraphy. CONCLUSIONS: Present study results suggest that MIBI scintigraphy was clearly superior to US as a diagnostic tool. However, P-gp expression, oxyphilic cell content, and tumoral volume may have not a main effect on MIBI parathyroid scintigraphy results in parathyroid adenoma.

Spontaneous renal laceration as the presenting feature of polyarteritis nodosa in a patient with familial Mediterranean fever after hepatitis A infection.

We report a life-threatening spontaneous renal laceration with no history of bleeding diathesis or any trauma in a patient with FMF after acute hepatitis A virus (HAV) infection. Right nephrectomy was inevitable and histological investigation of the removed right kidney revealed a polyarterits nodosa (PAN). This case underlines the possibility that simultaneous PAN and immunsupressive treatment besides colchicine should be considered for patients with FMF. Also, patients with FMF who are not immune may be vaccinated for HAV which could be a predisposing mechanism for vasculitic hemorrhage.

Do vascular endothelial growth factor and basic fibroblast growth factor promote phenytoin's wound healing effect in rat? An immunohistochemical and histopathologic study.

BACKGROUND: This study was designed to determine the possible correlation between phenytoin and vascular endothelial growth factor and basic fibroblast growth factor in the wound healing process. METHODS: Sixty Wistar albino rats were divided into four groups, each containing 15 animals. The experimental groups received a daily phenytoin treatment (10 mg) for 3 or 7 days following 3-cm dorsal skin incisions on the midline; the control group incisions were treated with 0.5 mL of saline solution during the same time periods. After completion of treatments, all animals were killed, and skin tissue samples were obtained. RESULTS: Histopathologic examination of all groups revealed that there were significantly increased (p<0.05) amounts of fibroblasts, collagen deposition, and blood vessels in the phenytoin-treated groups when compared to the control groups. Although immunolocalization of vascular endothelial growth factor and basic fibroblast growth factor was weak in the 3-day phenytoin treatment groups, they were strongly expressed in the 7-day treatment group when compared to the control groups. CONCLUSION: The findings of this study demonstrate that the tissue alterations of the wound healing process could be accelerated by phenytoin and the potential local pathways of vascular endothelial growth factor and basic fibroblast growth factor.

Positive effects of phenytoin on experimental colonic anastomoses.

BACKGROUND AND AIMS: Anastomotic dehiscence following colorectal surgery is a significant cause of morbidity and mortality. Phenytoin has wound-healing promoting and collagenase inhibitory effects. This study assessed these effects on healing of experimental colonic anastomoses in a rat model. MATERIALS AND METHODS: Ninety Wistar rats weighing 240-290 g were divided into six groups: 3rd-day control group (n=15), 3rd-day oral administration of phenytoin (n=15), 3rd-day rectal administration of phenytoin (n=15), 7th-day control group (n=15), 7th-day oral administration of phenytoin (n=15), and 7th-day rectal administration of phenytoin (n=15). In oral phenytoin groups the agent was given at 10 mg/kg daily per orogastric route by 4-F fine feeding catheter; in rectal phenytoin RAP groups the agent was administered at 10 mg/0.5 cc daily to the anastomoses transrectally via a fine anal catheter. RESULTS: There were significantly higher anastomosis bursting pressure values and hydroxyproline contents in phenytoin groups than in controls. In histopathological examination it was seen that phenytoin treatment caused greater collagen deposition, fibroblast, and blood vessel ingrowth than in controls. Immunohistochemical analysis showed the stimulatory effect of phenytoin in expression of vascular endothelial growth factor and basic fibroblast growth factor. Anastomosis bursting pressure, histopathological analysis, hydroxyproline content, and immunohistochemical results were better in the groups with rectal administration than in those with oral administration. CONCLUSION: These results had showed us that phenytoin administration resulted in enhanced stability of colonic anastomoses during the first postoperative week and rectal administration showed better results than oral administration.

Effect of nifedipine on the healing of left colonic anastomoses in rats.

PURPOSE: Ca(2+) channel blockers inhibit collagenase production and have a vasodilatatory effect. They also restrict the formation of ischemia-reperfusion induced free oxygen radicals. The aim of this study was to assess the effect of nifedipine on the healing of colonic anastomoses in a rat model. METHODS: Sixty Wistar rats weighing 240-290 g were divided into four groups of 15 rats each: a 3rd day control group (group A), a 3rd day treatment group (group B), a 7th day control group (group C), and a 7th day treatment group (group D). The treatment groups were given Nifedipine 3 mg/kg per day orally as three divided doses. RESULTS: The bursting pressure values of the anastomoses in the treatment groups were significantly higher than those in the control groups ( P < 0.05). The hydroxyproline content was also significantly higher in the treatment groups than in the control groups ( P < 0.05). Histologic examination confirmed that nifedipine treatment significantly increased collagen deposition and fibroblast ingrowth compared with controls ( P < 0.05). CONCLUSIONS: These results clearly showed that nifedipine enhanced the stability of colonic anastomoses during the first postoperative week.