Cervical cancer screening by molecular Pap-transformation of gynecologic cytology.

BACKGROUND: Cervical cancer is one of the common cancers in women accounting for 7.9% of all cancers. In India it is the second commonest cancer in women. The immortality of the cancer cell and the relatively long time frame from acquisition of infection to development of cervical cancer was established. As major advancements like LBC, HPV testing were introduced in the recent years, screening has taken a new avatar, the Molecular pap!! The objectives of this study were: To compare gynecologic cytology and abnormal results with respect to conventional and LBC. To study the role of HPV cotesting and ancillary tests performed, that is, HPV CISH, and p16ink4a by IHC. METHODS: About 71 924 Conventional and LBC samples were included from August 2009 to December 2017. Cases for HPV testing along the conventional smears were 1539. HPV can be tested from the same LBC vial as the sample remains stable at room temperature for 6 weeks. HPV DNA PCR was carried out in our laboratory for High and Low risk genotypes. Cytology findings were also correlated with histology. RESULTS: Detection rate of SILs in LBC samples were higher (2.20%). The commonest abnormality was LSIL in LBC and ASCUS in conventional smears. Commonest HR HPV and LR HPV detected was 1 61 856 and 61 142. CONCLUSION: LBC with HPV cotesting improves sensitivity and specificity and reduces ambiguous results; allows better compliance, as a negative result of both tests allows patients to get screening every 5 years, thereby increasing screening intervals, important in a resource limited situation.

Human papillomavirus in head and neck cancer in India: Current status and consensus recommendations.

Human papillomavirus (HPV) associated head and neck squamous cell cancers (HNSCC) have become increasingly common in the West, but the same cannot be said about India. These cancers have a different biology and confer a better prognosis, however, its current role in the management of patients in India is not clearly defined. At the 35th Indian Cooperative Oncology Network conference held in September 2016, a panel of radiation, surgical and medical oncologists, pathologists, and basic scientists from across the country having experience in clinical research with respect to HPV in HNSCC reviewed the available literature from India. All the ideas and facts were thereafter collated in this report. Various topics of controversy in dealing with the diagnosis and management of HPV-associated HNSCC have been highlighted in this report in context to the Indian scenario. Furthermore, the prevalence of the same and its association with tobacco and high-risk sexual behavior has been touched on. Conclusively, a set of recommendations has been proposed by the panel to guide the practicing oncologists of the country while dealing with HPV-associated HNSCC.

Unusual ganglioglioma with extensive calcification and ossification.

Ganglioglioma is a slow-growing relatively low-grade mixed glioneuronal tumor with most cases corresponding to the WHO Grade I category. It frequently presents with seizures. The temporal lobe is the most common location followed by frontal, parietal, and occipital lobes. These generally behave in a benign fashion and have a favorable prognosis. We describe a case of a 24-year-old male presenting with convulsions and a calcified parieto-occipital mass. This mass removed from the parietal lobe showed neoplastic glial and dysplastic neuronal tissue amidst extensive areas of calcification and foci of ossification. On immunohistochemistry, the glial component expressed glial fibrillary acidic protein whereas the dysplastic neuronal component expressed synaptophysin and CD34. Epithelial membrane antigen was negative and Ki-67 showed a low proliferative index. After the surgery, the patient is free of neurological symptoms. Widespread calcification and ossification are very unusual in ganglioglioma, which prompted us to report this case.

In vivo intraocular distribution and safety of periocular nanoparticle carboplatin for treatment of advanced retinoblastoma in humans.

PURPOSE: To study the intraocular distribution and safety of polymethylmethacrylate nanoparticles loaded with carboplatin after posterior subtenon injection in humans. DESIGN: Prospective, interventional, comparative case series. METHODS: Six patients (mean age: 26.83 ± 7.5 years), scheduled to undergo planned uniocular enucleation in an institutional setting, were randomly divided into 3 groups. Each group received a 10 mg/mL posterior subtenon injection of nanoparticle carboplatin in the eye to be enucleated. Two eyes were enucleated 6, 24 and 72 hours post injection. Intravenous blood was collected during enucleation. The concentration of carboplatin reaching various intraocular tissues was determined by inductively coupled plasma atomic emission spectroscopy. The drug toxicity in the ocular tissues was assessed by histopathology and high-resolution transmission electron microscopy. RESULTS: The highest level of carboplatin was detected in retinas (8.33 ± 1.69 mg/g), up to 24 hours post treatment. The intravitreal concentration continued to increase gradually until 72 hours (3.46 ± 0.26 mg/g). The choroids and lenses showed very low levels of carboplatin after 6 hours, with negligible amounts at 72 hours. No signs of tissue damage were observed on histopathology or electron microscopy. Intravenous concentration of carboplatin was undetectable in all patients. CONCLUSION: Results may indicate an increased facilitated trans-scleral transport of nanoparticle carboplatin, with a sustained-release behavior but without any associated short-term ocular or systemic side effects in humans. The very high concentrations achieved in vitreous and retina after a single posterior subtenon injection may be clinically useful for adjunctive treatment of advanced intraocular retinoblastoma with vitreous seeds. However, further studies are needed to assess long-term toxicity and clinical efficacy.

Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane.

A critical step in apoptosis is mitochondrial outer membrane permeabilization (MOMP), releasing proteins critical to downstream events. While the regulation of this process by Bcl-2 family proteins is known, the role of ceramide, which is known to be involved at the mitochondrial level, is not well-understood. Here, we demonstrate that Bax and ceramide induce MOMP synergistically. Experiments were performed on mitochondria isolated from both rat liver and yeast (lack mammalian apoptotic machinery) using both a protein release assay and real-time measurements of MOMP. The interaction between activated Bax and ceramide was also studied in a defined isolated system: planar phospholipid membranes. At concentrations where ceramide and activated Bax have little effects on their own, the combination induces substantial MOMP. Direct interaction between ceramide and activated Bax was demonstrated both by using yeast mitochondria and phospholipid membranes. The apparent affinity of activated Bax for ceramide increases with ceramide content indicating that activated Bax shows enhanced propensity to permeabilize in the presence of ceramide. An agent that inhibits ceramide-induced but not activated Bax induced permeabilization blocked the enhanced MOMP, suggesting that ceramide is the key permeabilizing entity, at least when ceramide is present. These and previous findings that anti-apoptotic proteins disassemble ceramide channels suggest that ceramide channels, regulated by Bcl-2-family proteins, may be responsible for the MOMP during apoptosis.

Restorative Proctocolectomy with Ileo-anal Reservoir, a Histopathological, Histochemical, and Electron Microscopic Study.

This study was conducted to investigate the nature of colonic metaplasia in ileo-anal pouches and incidence/frequency of pouchitis in the same. Biopsy specimens from 8 patients with functioning ileal pouches were studied using routine histology, mucin histochemistry and electron microscopy, over a 2 - year period. All 8 patients had villous abnormalities in the form of blunting of villi and sub total or partial villous atrophy. 6 patients had an increase in the goblet cell population and Paneth cell hyperplasia. These changes were supported by electron microscopic findings of a decrease in number and flattening of ileal type microvilli and their transformed morphologic resemblance to colonic type microvilli. All the ileal pouches also had acquired colorectal type sulphomucin, when sections stained with Alcian-blue and High Iron Diamine - Alcian blue, were studied. However, no case of pouchitis as defined in literature, was found in this study.