Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Alkali-cation-incorporated and functionalized iron oxide nanoparticles for methyl blue removal/decomposition.

Enhancing the rate of decomposition or removal of organic dye by designing novel nanostructures is a subject of intensive research aimed at improving waste-water treatment in the textile and pharmaceutical industries. Despite radical progress in this challenging area using iron-based nanostructures, enhancing stability and dye adsorption performance is highly desirable. In the present manuscript alkali cations are incorporated into iron oxide nanoparticles (IONPs) to tailor their structural and magnetic properties and to magnify methyl blue (MB) removal/decomposition capability. The process automatically functionalizes the IONPs without any additional steps. The plausible mechanisms proposed for IONPs incubated in alkali chloride and hydroxide solutions are based on structural investigation and correlated with the removal/adsorption capabilities. The MB adsorption kinetics of the incubated IONPs is elucidated by the pseudo second-order reaction model. Not only are the functional groups of -OH and -Cl attached to the surface of the NPs, the present investigation also reveals that the presence of alkali cations significantly influences the MB adsorption kinetics and correlates with the cation content and atomic polarizability.

A clinicopathologic study of surgically resected metastatic lesions of brain: A single institutional experience.

INTRODUCTION: One of the most common tumors of the brain are metastatic lesions. They can present as cancer of unknown primary (CUP) and require careful determination of the site of origin of the primary. Histopathologic and immunohistochemical analysis helps to determine the primary site. AIM: To study the clinicopathological features of metastatic tumors of the brain. MATERIALS AND METHODS: All cases of surgically resected brain metastasis (solid tumor metastasis) from January 2013 to April 2015 were included in the study. The clinical details including age, gender, clinical features, and location were taken from medical records. The histopathology slides were retrieved and reviewed along with clinical and imaging findings from medical records. Immunohistochemistry was performed wherever necessary. RESULTS: Out of 1662 resected brain lesions during the study period, 69 accounted for central nervous system metastasis, of which 36 were brain metastasis and 33 were isolated spinal cord metastasis. In the 36 brain metastasis cases, 19 were cases with an unknown primary. Carcinoma lung (47.2%) was found to be the most common primary malignancy. Immunohistochemistry with cytokeratin (CK)7, CK20, and thyroid transcription factor (TTF) 1 as a primary panel in metastatic tumors is highly recommended. CONCLUSION: Metastatic tumors accounted for 4.1% of intracranial lesions. Histopathologic pattern and immunohistochemistry aid in the accurate diagnosis of the original site of malignancy.

A method to improve the accuracy between the presumed depth of excision and the actual depth of excision in women receiving LLETZ cervical treatment; a single-center, two-operator experience.

BACKGROUND: We aimed to determine whether continuous auditing of the presumed depth of excision and comparing with the actual depth of excision in women having large loop excision of the transformation zone (LLETZ) improves the ability to acquire the desired depth of excision. METHODS: This was a prospective study of women submitted to a single LLETZ treatment between 2017-2018. Two senior colposcopists recorded what they presumed was the depth of excision at the time of treatment and the subsequent histopathology report provided the actual excised depth. Multiple linear regression identified independently associated parameters with the difference between presumed and actual excision depth. Non-linear regression determined the learning plateau defined as the theoretical minimal score of difference one could achieve with infinite practice. RESULTS: There were significant differences in practices with the first colposcopist using an 18-mm loop and the second colposcopist a 15-mm loop in the majority of cases. The median absolute and percentage difference between the presumed and actual excised depth was 2 mm and 16.6 % and 3.5 mm and 35.4 % for the two colposcopists, respectively. A learning plateau was identified only for the first colposcopist. We found that auditing consecutive excisions decreased significantly the difference between the presumed and actual depth of excision with a learning plateau at 2.2 mm of absolute difference and 22.6 % of percentage difference and with a learning rate of 13 cervical excisions. CONCLUSION: There might be a benefit in auditing our treatment practice as there seems to be a learning plateau through this method. HIPPOKRATIA 2018, 22(3): 113-121.

Vascular malformations of central nervous system: A series from tertiary care hospital in South India.

AIMS AND OBJECTIVES: To describe clinicopathological features of surgically resected vascular malformations (VMs) of central nervous system (CNS). MATERIALS AND METHODS: Histologically diagnosed cases of VMs of CNS during April 2010-April 2014 were included. Demographic data, clinical and radiological features were obtained. Hematoxylin and eosin slides were reviewed along with Verhoeff-Van Gieson (VVG), Masson's trichrome, periodic acid-Schiff, and Perls' stains. Morphologically, cavernomas and arteriovenous malformations (AVMs) were distinguished on the basis of vessel wall features on VVG and intervening glial parenchyma. RESULTS: Fifty cases were diagnosed as VMs of CNS with an age range of 14-62 years. These included 36 cavernomas, 12 AVMs, 2 mixed capillary-cavernous angiomas. Most of the cavernoma patients (15/36) presented with seizures, whereas AVM patients (8/12) had a headache as the dominant symptom. Twenty-nine patients were reliably diagnosed on radiological features. Microscopic evidence of hemorrhage was seen in 24/36 cavernomas and 6/12 AVMs, as opposed to radiologic evidence of 10 and 4, respectively. Reactive gliosis was seen in 16 cavernomas. CONCLUSIONS: Histological features are important for classifying the VMs of CNS as there are no specific clinical and radiological features. Type of VM has a bearing on management, prognosis, and risk of hemorrhage.

Intramedullary arachnoid cyst in an adult: Case report and review.

Arachnoid cysts in the spine are a rare entity with extradural occurrence being the commonest. Arachnoid cysts in intramedullary location are sparingly reported in elderly. We herein report a case of intramedullary arachnoid cyst in an adult female who presented with features of compressive myelopathy.

Pediatric meningiomas an aggressive subset: a clinicopathological and immunohistochemical study.

BACKGROUND: Meningiomas are uncommon neoplasms in the pediatric age group and differ in various aspects from their adult counterparts. They account for 0.4-4.6% of all primary brain tumors. AIMS: To retrospectively analyze the clinicopathological and immunohistochemical features of pediatric meningiomas. MATERIALS AND METHODS: Meningiomas in patients under 18 years of age diagnosed between January 2001 to December 2011 were analyzed retrospectively. The hematoxylin and eosin stained sections and Ki 67 labelling index (LI) were reviewed for all the cases Results: The pediatric meningiomas accounted for 1.52% of total meningiomas (15/983). The mean age at presentation was 12 years with male to female ratio of 1.5:1. The presenting symptoms were headache, seizures, and motor deficits. The histology included 9 cases (60%) of atypical meningioma (WHO grade II) followed by 4 cases (26.67%) of WHO grade-I and 2 cases (13.33%) of anaplastic meningioma (WHO grade III). Five cases had a recurrence. Ki67 LI ranged from 0.5% to 1.5% in grade I, 0.5% to 15% in grade II and 13% to 24% in grade III meningiomas. CONCLUSION: Meningiomas are rare in children and show a male preponderance. There was a higher incidence of atypical and anaplastic meningiomas in pediatric population.

Assessment of expression of epidermal growth factor receptor and p53 in meningiomas.

BACKGROUND: Meningiomas represent about 30% of primary adult central nervous system tumors. Though slow growing, they recur, causing significant morbidity and mortality. OBJECTIVE: The objective of the following study is to grade meningiomas according to World Health Organization (WHO) 2007 criteria and to correlate the grade with degree of expression of epidermal growth factor receptor (EGFR) and p53. MATERIALS AND METHODS: Meningiomas diagnosed in the year 2010 in the Department of Pathology of our institute, were included in the study. Clinical and radiological findings were noted from medical records. The histopathology slides were reviewed and the tumors were graded according to WHO 2007 criteria. Tissue microarrays (TMA) were prepared and immunohistochemical analysis with epithelial membrane antigen, Vimentin, Ki67, EGFR and p53 was performed on the TMA slides. RESULTS: A total of 79 meningiomas diagnosed during the study period included 30 male and 49 female patients with an age range of 10-75 years. There was a female preponderance with M:F ratio of 1:1.63. EGFR was found to be higher in grade I (82.93%) compared with grade II (35.71%) and grade III tumors (20%) with an overall positivity of 60.81%. Mean p53 indices were higher in grade III (50%) compared with grade II (39.29%) and grade I tumors (38.46%) with an overall positivity of 39.44%. Ki67 labeling index (LI) was significantly high in grade III (16.4%) compared with grade II (6.46%) and grade I tumors (3.13%). CONCLUSION: EGFR expression and Ki67 LI correlated with grade of meningioma P < 0.0001 and P < 0.0001 respectively which were statistically significant whereas p53 expression did not correlate (P - 0.90).

Surgical outcome in patients with cervical ossified posterior longitudinal ligament: A single institutional experience.

OBJECTIVE: Ossification of the posterior longitudinal ligament (OPLL) is a complex multi-factorial disease process having both metabolic and biomechanical factors. The role of surgical intervention as well as the choice of approach weather anterior or posterior is ambiguous. The objective of this study was to assess the surgical out come and post operative functional improvement in patients with cervical OPLL at a tertiary care centre. PATIENTS AND METHODS: This prospective study included 63 patients of cervical OPLL who underwent either anterior and/or posterior surgeries in Department of Neurosurgery, Nizam's Institute of Medical Sciences, Hyderabad between June 2009 to May 2011. Patient's data including age, sex, pre and post operative functional status, radiographic findings and OPLL subtypes were recorded and analyzed over a follow up ranging up to minimum two years. RESULTS: The mean age of the patients was 51.1 (range 30-80 years) involving 14 women and 49 men. Out of 63 patients, 14 patients underwent surgery by anterior approach (corpectomy and fusion) and all of them improved (P = 0.52). 49 patients underwent surgery by posterior approach where decompressive laminectomy was performed in 40, laminectomy with instrumentation was done in 5, laminoplasty was done in 3 and 1 patient underwent both anterior and posterior surgeries. Of those who underwent posterior surgery, 40 patients improved, 7 remained the same as their preoperative status (who were having signal intensity changes on T2W MRI) and 2 patients deteriorated in the immediate post operative period and then showed gradual improvement. All the patients were followed up for 24 months. The mean pre-operative Nurick grade was 2.82 which later on improved to 2.03 post surgery (P < 0.05). Minor complications included wound infections in two patients (1.26%). CONCLUSIONS: Anterior cervical decompression and reconstruction is a safe and appropriate treatment for cervical spondylitic myelopathy in the setting of single or two level OPLL. Laminectomy or laminoplasty is indicated in patients with preserved cervical lordosis having three or more levels of involvement. Younger patients with good pre operative functional status and less than 2 levels of involvement have better outcome following anterior surgery.

Androgen-regulated miR-32 targets BTG2 and is overexpressed in castration-resistant prostate cancer.

The androgen receptor (AR) signaling pathway is involved in the emergence of castration-resistant prostate cancer (CRPC). Here, we identified several androgen-regulated microRNAs (miRNAs) that may contribute to the development of CRPC. Seven miRNAs, miR-21, miR-32, miR-99a, miR-99b, miR-148a, miR-221 and miR-590-5p, were found to be differentially expressed in CRPC compared with benign prostate hyperplasia (BPH) according to microarray analyses. Significant growth advantage for LNCaP cells transfected with pre-miR-32 and pre-miR-148a was found. miR-32 was demonstrated to reduce apoptosis, whereas miR-148a enhanced proliferation. Androgen regulation of miR-32 and miR-148a was confirmed by androgen stimulation of the LNCaP cells followed by expression analyses. The AR-binding sites in proximity of these miRNAs were demonstrated with chromatin immunoprecipitation (ChIP). To identify target genes for the miRNAs, mRNA microarray analyses were performed with LNCaP cells transfected with pre-miR-32 and pre-miR-148a. Expression of BTG2 and PIK3IP1 was reduced in the cells transfected with pre-miR-32 and pre-miR-148a, respectively. Also, the protein expression was reduced according to western blot analysis. BTG2 and PIK3IP1 were confirmed to be targets by 3'UTR-luciferase assays. Finally, immunostainings showed a statistically significant (P<0.0001) reduction of BTG2 protein in CRPCs compared with untreated prostate cancer (PC). The lack of BTG2 staining was also associated (P<0.01) with a short progression-free time in patients who underwent prostatectomy. In conclusion, androgen-regulated miR-32 is overexpressed in CRPC, leading to reduced expression of BTG2. Thus, miR-32 is a potential marker for aggressive disease and is a putative drug target in PC.

Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer.

Androgen receptor (AR) is overexpressed in the majority of castration-resistant prostate cancers (CRPCs). Our goal was to study the effect of AR overexpression on the chromatin binding of the receptor and to identify AR target genes that may be important in the emergence of CRPC. We have established two sublines of LNCaP prostate cancer (PC) cell line, one overexpressing AR 2-3-fold and the other 4-5-fold compared with the control cells. We used chromatin immunoprecipitation (ChIP) and deep-sequencing (seq) to identify AR-binding sites (ARBSs). We found that the number of ARBSs and the AR-binding strength were positively associated with the level of AR when cells were stimulated with low concentrations of androgens. In cells overexpressing AR, the chromatin binding of the receptor took place in 100-fold lower concentration of the ligand than in control cells. We confirmed the association of AR level and chromatin binding in two PC xenografts, one containing AR gene amplification with high AR expression, and the other with low expression. By combining the ChIP-seq and expression profiling, we identified AR target genes that are upregulated in PC. Of them, the expression of ZWINT, SKP2 (S-phase kinase-associated protein 2 (p45)) and FEN1 (flap structure-specific endonuclease 1) was demonstrated to be increased in CRPC, while the expression of SNAI2 was decreased in both PC and CRPC. FEN1 protein expression was also associated with poor prognosis in prostatectomy-treated patients. Finally, the knock-down of FEN1 with small interfering RNA inhibited the growth of LNCaP cells. Our data demonstrate that the overexpression of AR sensitizes the receptor binding to chromatin, thus, explaining how AR signaling pathway is reactivated in CRPC cells.

Meningiomas: correlation of Ki67 with histological grade.

BACKGROUND: Meningiomas are slow-growing tumors. Grading of meningiomas based on histological features has certain limitations in predicting the exact biological behavior, necessitating ancillary techniques. OBJECTIVE: To study the Ki67 labeling index (Ki67 LI) in various histological subtypes and grades of meningioma and correlate it with various parameters for recurrence. MATERIAL AND METHODS: All intracranial and intraspinal meningiomas diagnosed between 2005 and 2008 were graded according to WHO 2007 criteria. Immunohistochemistry was performed using Ki67 (Dako, USA 1:50) in 300 cases. Statistical analysis was performed. Results : There was female predominance. The age ranged from 2-75 years including 11 children below the age of 18 years. There were 211 Grade I, 78 Grade II and 11 Grade III meningiomas. The mean Ki67 LI increased from Grade I to II and from Grade II to III and these were statistically significant. The Ki67 LI was high for the subtypes of clear cell, chordoid, papillary and rhabdoid but there was no statistical significance between the subtypes. The difference in Ki67 LI between recurrent versus non-recurrent and brain-invasive versus non-invasive meningiomas was statistically significant. CONCLUSION: High Ki67 LI indicates higher grade of meningioma. The difference in KI67 LI between recurrent and non-recurrent meningiomas was statistically significant.

Nanosilica-from medicine to pest control.

Nanotechnology is a broad interdisciplinary area of research, development, and industrial activity that has been growing rapidly worldwide for the past decade. More ambitious uses of nanoparticles are bioremediation of contaminated environments, controlled release of fragrances, biocides, and antifungals on textiles. Silica nanocomposites have received much attention because of its thermal degradation behavior and applications in chromatography, medicine, optics, etc. Nanobiotech takes agriculture from the battleground of genetically modified organisms to the brave new world of atomically modified organisms where rice has been modified atomically. Silica has been widely applied in various industries. Application of gold-coated silica has been used in the treatment for benign and malignant tumor. Surface-modified hydrophobic as well as lipophilic nanosilica could be effectively used as novel drugs for treatment of chicken malaria and nuclear polyhedrosis virus (BmNPV), a scourge in silkworm industry. Here, the authors attempt to provide a review to explain the impact of nanosilica on basic biology, medicine, agro-nanoproducts, and use of amorphous nanosilica as biopesticide.

Pathology of fungal infections of the central nervous system: 17 years' experience from Southern India.

AIMS: To describe the pathology of central nervous system (CNS) fungal infections with particular reference to India. METHODS AND RESULTS: This was a retrospective study from 1988 to 2004 constituting 130 cases. The diagnosis was based on morphology of biopsy/autopsy material. These included aspergillosis (n=73), zygomycosis (n=40), cryptococcosis (n=2), rhodotorulosis (n=1), candidiasis (n=5), maduramycosis (n=1), pheohyphomycosis (n=3) and mixed infections (n=5). Predisposing risk factors were present in 49 (38%) patients only. The majority of the patients were immunocompetent. The commonest risk factor was diabetes mellitus, the commonest route of infection was from a contiguous site and the commonest pathology was granuloma. Culture positivity was seen in only 31%. CONCLUSION: Environmental factors in tropical countries such as India play a significant role in the pathogenesis of CNS fungal infections.

Isolated Rosai Dorfman disease of the central nervous system presenting as dural-based and intraparenchymal lesions.

OBJECTIVE: To report three patients with isolated Rosai Dorfman disease of the central nervous system. CASE REPORTS: We report two patients with dural-based lesions diagnosed imageologically as meningiomas, and one patient with multiple intraparenchymal lesions diagnosed imageologically as lymphoma. Two patients were males and one was female. All were above 35 years of age with no nodal or other system involvement. The diagnosis was established on surgically excised masses during histopathology. One patient died due to unrelated causes 10 years later and the other two are symptom-free at 21.5- and 11.5-year-follow-up. CONCLUSIONS: Awareness of the entity and consideration in the differential diagnosis of dural-based/intraparenchymal lesions is necessary for diagnosis and prognosis.

Bilateral trigonal lateral ventricular mirror image meningiomas : a case report.

A seventeen year old male patient presented with clinical features suggestive of raised intracranial pressure. CT Scan and MRI of brain revealed two mass lesions, one in trigone of each lateral ventricle. They were imageologically alike, appearing as mirror image masses. Both ware totally excised through occipitoparietal transventricular approach on the respective side of the lesion. Postoperative period was uneventful. Repeat CT Scan showed no residue of the lesions. Histopathological examination showed meningioma. To the best of our knowledge this is the first published report on bilateral trigonal meningiomas.

Diastematomyelia in adults. Modern imaging and operative treatment.

Diastematomyelia, an uncommon dysraphic state usually seen in children, is a rarity in adults; only 19 reports have been published in the literature so far. Two cases of diastematomyelia in adults are presented and the relevant literature is reviewed. Both of these were investigated by computed tomography and magnetic resonance imaging. These two procedures are proved to be complementary to each other in understanding this anomaly. Both patients exhibited associated congenital abnormalities of the neuroectoderm in the form of hyperpigmentation, hypertrichosis, lipomatosis, and dermal sinus that were demonstrated with clarity by the neuroimaging modalities used. Operative correlation was performed in both patients, where findings correlated very well with the preoperative radiological evaluation.