Nebil Bal

Germline DICER1 mutations and familial cystic nephroma

Background Multilocular cystic nephroma (CN) is a benign kidney tumour and is part of a family of kidney neoplasms including cystic partially differentiated nephroblastoma and Wilms tumour (WT). CN is rarely familial or bilateral, but it occurs in about 10% of families where pleuropulmonary blastoma (PPB) is present. Recently, germline mutations in DICER1 were found in familial PPB. Objective To search for DICER1 mutations in two families with familial CN; PPB was present in one family. Additionally, to test germline DNA from 50 children with sporadic WT for DICER1 mutations. Results Both families with multiple CN were found to have mutations in DICER1 leading to premature stop codons, predicted to result in loss of the ribonuclease and dsRNA binding domains. These domains are essential to the function of DICER1. No germline mutations were found in any of the 50 children who had developed WT. Conclusion It has been established that DICER1 mutations cause familial CN and may be implicated in bilateral CN. No germline mutations were found in the patients with WT, suggesting that DICER1 mutations are unlikely to have a major role in the aetiology of sporadic WT. These results provide further evidence implicating miRNA dysregulation in tumourigenesis.

Conventional testicular sperm extraction combined with the microdissection technique in nonobstructive azoospermic patients: a prospective comparative study

OBJECTIVE To perform conventional and microdissection testicular sperm extraction (TESE) at the same session and compare their effectiveness. DESIGN Prospective comparative study. SETTING University hospital setting. PATIENT(S) The study included 335 patients with nonobstructive azoospermia. INTERVENTION(S) Microdissection TESE was performed to 77 patient with atrophic testes. An additional 258 patients underwent conventional TESE using three incisions on three quadrants of the testis (upper, middle, and lower). Microdissection TESE was performed by enlarging the middle incision vertically when no spermatozoa could be detected using the conventional technique. MAIN OUTCOME MEASURE(S) Sperm retrieval, fertilization, clinical pregnancy rate (PR), and live birth rate were evaluated. The relation between sperm retrieval rate and FSH level and testis volume was also investigated. RESULT(S) Spermatozoa was detected in 33.7% of patients using conventional TESE. The spermatozoa detected increased to 50.8% using microdissection TESE. The increase was statistically significant. In the primary microdissection TESE group, the surgical retrieval rate was 20.8%. The overall sperm retrieval rate was 43.9%. There was a significant relation between the sperm retrieval rate and testis volume, whereas there was no relation between sperm retrieval rate and FSH levels. The overall fertilization rate, clinical PR, and live birth rate were 57.1%, 50.4%, 36.4%, respectively. CONCLUSION(S) Conventional TESE combined with microdissection TESE can be used in selected patients. Sperm retrieval rate of TESE can be low in patients with atrophic testes.

The expression of survivin and Ki-67 in meningiomas: correlation with grade and clinical outcome

Identification of proteins involving in the control of proliferation in normal cells may lead to a better understanding of cellular transformation and proliferation mechanisms. Measurement of proliferative activity may help determine the tumor grade, recurrence and malignancy. Forty meningiomas of various histological grade, diagnosed in Baskent University and Çukurova University Medical Faculty, Departments of Pathology, were graded according to WHO grading system and survivin and Ki-67 monoclonal antibodies were administered by immunohistochemical method. Findings were analyzed with statistical methods; distribution of survivin expression and Ki-67 LI values were determined for different grade meningiomas. The correlation between increasing grades of meningiomas, particularly between grades I and III, survivin and Ki-67 LI values was statistically significant. In addition, we have found a positive correlation between clinical outcome, survivin and Ki-67 LI. For over expression of survivin in some of the grade I meningiomas and no or mild expression in some of the grades II and III meningiomas, however, it has been suggested that apoptosis inhibited by survivin is not the only factor responsible for progression of meningiomas.

Leiomyoma of the Breast Parenchyma

3Department of General Surgery, Baskent University Adana Teaching and Medical Research Center, Yuregir, Adana 01250, Turkey. eiomyoma of the breast is one of the rarest benign nonepithelial tumors [1]. Most leiomyomas that do occur in the breast are found in the subareolar region [2]. Leiomyoma of the breast parenchyma in the absence of periareolar lesions is uncommon [3]. Only 13 cases of parenchymal leiomyoma of the breast have been reported to date [4]. We present a 14th case, which is the first to be reported, to our knowledge, in Turkey. The patient was initially diagnosed with fibroadenoma and was followed for 2 years before she underwent surgery. Our report documents the mammography, sonography, and histopathology findings in this case.

Vulvar syringoma aggravated by pregnancy

Syringoma is a benign tumors of eccrine sweat gland. They appear as multiple, tiny, firm, skin-colored papules. Vulvar involvement of syringoma is rare. Only 24 cases with vulvar syringoma have been previously reported in the literature. The majority of patients with vulvar syringomas are asymptomatic. A case of syringoma of the vulva exacerbated during pregnancy is presented. The case appears remarkable for the experienced aggravated pruritic symptoms of the patient during her pregnancy.

Evaluation of malignant and benign renal lesions using diffusion-weighted MRI with multiple b values.

Background Limited data are available regarding the use of diffusion-weighted (DW) magnetic resonance imaging (MRI) with multiple b values for characterization of renal lesions. Purpose To demonstrate and compare the diagnostic performance of DW-MRI with multiple b values for renal lesion characterization. Material and Methods Sixty-three lesions (36 malignant, 27 benign) in 60 consecutive patients (48 men, 12 women; age 60 ± 12.5 years) with solid/cystic renal lesion diagnosed after MRI were included prospectively. Single-shot echo-planar DW abdominal MRI (1.5T) was obtained using seven b values with eight apparent diffusion coefficient (ADC) maps. Contrast-to-noise ratios (CNRs), signal intensities, lesion ADCs, and lesion/normal parenchyma ADC ratios were analyzed. Receiver-operating characteristic analysis was performed. Results The mean signal intensities of malignant lesions (at b0, 50, and 200s/mm2) were significantly lower than those of benign lesions (P < 0.05). The mean ADC values at all b value combinations of malignant lesions were significantly lower than those of benign lesions (P < 0.000), excluding the ADC value at b50 s/mm2. ADC with all b values could better distinguish between benign and malignant lesions. A 1.35 × 10−3 mm2/s threshold ADC value permitted this distinction with 85.2% sensitivity and 65.6% specificity. The lesion/normal parenchyma ADC ratio was more effective than the lesion ADC. Conclusion In addition to the ADC value, the signal intensity curve on DW images using multiple b values could be helpful for differentiation of malignant and benign renal lesions.

Nitric oxide synthase in gingival tissues of patients with chronic periodontitis and with and without diabetes.

BACKGROUND The purpose of this study was to evaluate the expression of inducible nitric oxide synthase (iNOS) in the gingival tissues of periodontitis patients with and without type 2 diabetes to assess whether NO plays a role in the severity of periodontitis in patients with diabetes. Patients with diabetes and healthy patients were used as controls. METHODS A total of 80 patients were evaluated in four groups (with 20 subjects each): patients with chronic periodontitis and diabetes (12 males and eight females; mean age, 52.1 +/- 6.9 years), patients with chronic periodontitis who were otherwise healthy (12 males and eight females; mean age, 43.1 +/- 8.9 years), periodontally healthy patients with diabetes (12 males and eight females; mean age 50.9 +/- 6.3 years), and systemically and periodontally healthy control subjects (12 males and eight females; mean age 29.8 +/- 9.2 years). Periodontal parameters were recorded. Immunohistochemistry was used to detect inflammation and iNOS expression in gingival tissues. RESULTS Although periodontal parameters were slightly higher in periodontitis compared to diabetic periodontitis, immunohistochemical parameters were higher in diabetic periodontitis compared to periodontitis. All periodontal parameters were higher in patients with periodontitis and with/without diabetes compared to controls and patients with diabetes. All immunohistochemical parameters were higher in patients with diabetes and periodontitis compared to patients with only diabetes or periodontitis, but there was no difference between the latter two groups. There was a correlation between the expression of iNOS and inflammatory cells in controls, patients with diabetes, and patients with periodontitis but not in patients with diabetes and periodontitis. CONCLUSIONS Inflammation and iNOS expression were more prominent in the gingiva of the patients with both diabetes and periodontitis. However, iNOS expression did not seem to have an additional detrimental effect on the course of periodontitis in patients with diabetes compared to those with periodontitis alone.

Giant sublingual epidermoid cyst: a report of two cases.

Epidermoid cysts are benign epithelial cysts that occur rarely in the neck. In contrast to dermoid cysts,epidermoid cysts do not include dermal attachments such as hair, hair follicles, sebaceous glands and sweat glands. They may be congenital or acquired. Acquired epidermoid cysts are either post-traumatic or iatrogenic. They rarely enlarge markedly.This study discusses epidermoid cysts in a 34-year-old woman and a 35-year-old man, both of which were giant epidermoid cysts in the sublingual space. Both patients were admitted for difficulty swallowing and cosmetic problems. The cysts of both patients had an aetiology of trauma and were documented by pathology sections and pre-operative magnetic resonance images. Both cysts were excised completely, one intraorally and one externally. Such cysts are benign and ought to be borne in mind in the differential diagnosis of oral cavity and neck cystic masses.

Nasolacrimal Duct Obstruction: Clinicopathologic Analysis of 205 Cases

Purpose: To investigate the histopathological results of lacrimal sac biopsies in patients with primary acquired nasolacrimal duct obstruction. Methods: In this prospective non-comparative study, 205 consecutive patients, who were diagnosed as primary acquired nasolacrimal duct obstruction, were included. Patients with history of trauma and/ or surgery in the periorbital area, punctum or canalicular obstruction were excluded from the study. Patients were evaluated for age, gender, history, and presenting symptoms. Lacrimal drainage system abnormalities were assessed. Lacrimal system irrigation, dacryocystography, and in selected cases dacryoscintigraphy was performed. All patients underwent external dacryocystorhinostomy. Biopsy specimens were obtained from the posterior inferior flap and examined by the same pathologist. Results: Forty-seven male and 158 females with age ranging from 6 to 81 years (mean 47.5 ± 16.2 years) were included in the study. Only one patient had the diagnosis of chronic leukemia, others had no preexisting history of systemic disease. Pathologic examination revealed chronic inflammation (n= 178), fibrosis without inflammation (n= 19), normal mucosa (n= 4), and lymphoid hyperplasia (n= 1). Three patients had abnormal pathology: Lymphoproliferative disease in the patient with chronic leukemia, granulomatous inflammation, and basosquamous cell carcinoma. Conclusion: In primary nasolacrimal duct obstruction, pathological examination of the lacrimal sac revealed chronic inflammatory changes in most patients. Even though rare, malignant or systemic disease in patients with neither specific history nor clinical or radiological finding might be observed in these cases. Thus, we recommend taking biopsy if any suspicion of abnormality of the lacrimal sac exists.

The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

IntroductionThe prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated.MethodsSeventy-three consecutive patients (median age, 61 years) with stage IIIB and IV non-small cell lung cancer, admitted between February 2004 and December 2006, were included in this study. Sixty-one patients received gemcitabine, given as two 1250 mg/m2 doses on days 1 and 8 and, cisplatin, given as a 75 mg/m2 dose on day 8. Twelve patients received vinorelbine, given as two 25 mg/m2 doses on day 1 and 8, and cisplatin, given as a 75 mg/m2 dose on day 1. Both treatment paradigms were repeated on a 21-day cycle. Tumor response was evaluated by comparing tumor size on computerized tomography scans before and after three cycles of chemotherapy. HER2 status was examined by immunohistochemical analysis of paraffin-embedded specimens.ResultsHER2 was positive in 21 of 73 patients (28.8%). Of the 21 patients with HER2 positivity, 13 (61.9%) responded to chemotherapy with either a complete response, partial remission, or evidence of stable disease. Of 52 HER2-negative patients, 48 (92.3%) exhibited a response to chemotherapy. The difference in response to therapy between HER2-positive and -negative patients was statistically significant (p = 0.003). The median overall survival duration for all patients was 13 months. Median overall survival time was 14 months for HER2-negative patients and 10 months for HER2-positive patients (log-rank p = 0.007).ConclusionNon-small cell lung cancer patients with high expression of HER2 exhibited resistance to cisplatin-based chemotherapies that are the standard treatment for this disease. Our results indicate that HER2 status may be a predictive and prognostic factor for cisplatin- based therapy response and disease survival.