Disseminated neoplasia in blue mussels, Mytilus galloprovincialis, from the Black Sea, Romania

Disseminated neoplasia, also called leukemia or hemic neoplasia, has been detected in 15 species of marine bivalve mollusks worldwide. The disease is characterized by the presence of single anaplastic cells with enlarged nuclei and sometimes frequent mitosis, in hemolymph vessels and sinuses. The neoplastic cells gradually replace normal hemocytes leading to the increased mortality of animals. The neoplasia reaches epizootic prevalences in blue mussels, Mytilus trossulus, in some areas, whereas prevalences in Mytilus edulis are generally very low. Mytilus galloprovincialis was suggested to be resistant to the disease although very low prevalences were documented from Spain in the Atlantic Ocean and Italy in the Mediterranean Sea. A case of disseminated neoplasia was discovered in M. galloprovincialis from among 200 specimens studied from the coast of the Romanian Black Sea. Histological preparation revealed the presence of large anaplastic cells with lobed nuclei. This observation extends the geographic range of marine bivalve mollusks with disseminated neoplasia to include the Black Sea

A novel therapeutic strategy for pancreatic neoplasia using a novel RNAi platform targeting PDX-1

Bi-functional shRNA (bi-shRNA), a novel RNA interference (RNAi) effector platform targeting PDX-1 utilizing a systemic DOTAP-Cholesterol delivery vehicle, was studied in three mouse models of progressive pancreatic neoplasia. Species-specific bi-functional PDX-1 shRNA (bi-shRNAPDX-1) lipoplexes inhibited insulin expression and secretion while also substantially inhibiting proliferation of mouse and human cell lines via disruption of cell cycle proteins in vitro. Three cycles of either bi-shRNA<sup>mousePDX-1</sup> or shRNA<sup>mousePDX-1</sup> lipoplexes administered intravenously prevented death from hyperinsulinemia and hypoglycemia in a lethal insulinoma mouse model. Three cycles of shRNA<sup>mousePDX-1</sup> lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of pancreatic neoplasia. Moreover, three cycles of the bi-shRNA<sup>humanPDX-1</sup> lipoplexes resulted in near complete ablation of tumor volume and considerably improved survival in a human PANC-1 implanted SCID-mouse model. Human pancreatic neoplasia specimens also stained strongly for PDX-1 expression. Together, these data support the clinical development of a novel therapeutic strategy using systemic bi-shRNA<sup>PDX-1</sup> lipoplexes against pancreatic neoplasia

Early discharge of low-risk women from cervical screening

Background: The Scottish Cervical Screening Programme currently offers three-yearly screening to all women between the ages of 20 and 60. However, previous studies have indicated that well-screened women over the age of 50 are likely to be at low risk of cervical neoplasia. This study aimed to explore the implications of discharging these women from screening in a typical area of Scotland. Methods: A case–control study of the screening histories of women with and without screen-detected cervical neoplasia between ages 50 and 59 in Lanarkshire was carried out, as well as a cross-sectional study of the prevalence of adequate screening histories among women currently aged 50 in Lanarkshire. Routine screening programme statistics were used to estimate the effects of introducing an early discharge policy. Results: Women reaching the age of 50 with two recent, consecutive, negative smears had reduced odds of screen-detected neoplasia in the subsequent decade. The estimated odds ratio for all screen-detected neoplasia (CIN 1–3, adenocarcinoma in situ and invasive carcinoma) was 4.4 [95 per cent confidence interval (CI) 1.6–13.2, p = 0.002]. The estimated odds ratio for screen-detected high-grade CIN and invasive squamous carcinoma was 17.0 (95 per cent CI 2.4–243.0, þ = 0.0004). A total of 54.0 per cent (95 per cent CI 47.9–59.9 per cent) of screening participants currently aged 50 fulfilled the definition of adequate screening. Discharging these women might be expected to reduce screening workload by approximately 10 per cent, but those discharged would be at increased risk of neoplasia. Conclusion: Now that full screening histories are available in all health board areas since 1990, the identification of a low-risk group within the screened population could be the first step towards a screening programme targeted more closely on those with the greatest capacity to benefit

Early tumor response to intraarterial or intravenous administration of carboplatin to treat naturally occurring lower urinary tract carcinoma in dogs.

BackgroundSurvival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.ObjectiveTo describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).AnimalsClient-owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).MethodsRetrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.ResultsIntraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).Conclusion and clinical importanceThis study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow-up time was short and the impact on long-term outcome and survival was not determined

Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia

BACKGROUND: Cervical intra-epithelial neoplasia (CIN) typically occurs in young women of reproductive age. Although several studies have reported the impact that cervical conservative treatment may have on obstetric outcomes, there is much less evidence for fertility and early pregnancy outcomes. OBJECTIVES: To assess the effect of cervical treatment for CIN (excisional or ablative) on fertility and early pregnancy outcomes. SEARCH METHODS: We searched in January 2015 the following databases: the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12, 2014), MEDLINE (up to November week 3, 2014) and EMBASE (up to week 52, 2014). SELECTION CRITERIA: We included all studies reporting on fertility and early pregnancy outcomes (less than 24 weeks of gestation) in women with a history of CIN treatment (excisional or ablative) as compared to women that had not received treatment. DATA COLLECTION AND ANALYSIS: Studies were classified according to the treatment method used and the fertility or early pregnancy endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model and inter-study heterogeneity was assessed with I(2). Two review authors (MK, AM) independently assessed the eligibility of retrieved papers and risk of bias. The two review authors then compared their results and any disagreements were resolved by discussion. If still unresolved, a third review author (MA) was involved until consensus was reached. MAIN RESULTS: Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in treated and untreated women with an intention to conceive (88% versus 95%, RR 0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the number of women requiring more than 12 months to conceive (14% versus 9%, RR 1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95% CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4 studies, 1103 participants, low quality) was similar for treated and untreated women, CIN treatment was associated with an increased risk of second trimester miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies, 2,182,268 participants, low quality). The number of ectopic pregnancies (1.6% versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7 studies, 38,208 participants, low quality) were also higher in treated women.The results should be interpreted with caution. The included studies were often small with heterogenous design. Most of these studies were retrospective and of low or very low quality (GRADE assessment) and were therefore prone to bias. Subgroup analyses for the individual treatment methods and comparison groups and analysis to stratify for the cone length was not possible. AUTHORS' CONCLUSIONS: This meta-analysis suggests that treatment for CIN does not adversely affect fertility, although treatment was associated with an increased risk of miscarriage in the second trimester. These results should be interpreted with caution as the included studies were non-randomised and many were of low or very low quality and therefore at high risk of bias. Research should explore mechanisms that may explain the increase in mid-trimester miscarriage risk and stratify this impact of treatment by the length of the cone and the treatment method used

Can malignant and inflammatory pleural effusions in dogs be distinguished using computed tomography

Computed tomography (CT) is the primary imaging modality used to investigate human patients with suspected malignant or inflammatory pleural effusion, but there is a lack of information about the clinical use of this test in dogs. To identify CT signs that could be used to distinguish pleural malignant neoplasia from pleuritis, a retrospective case‐control study was done based on dogs that had pleural effusion, pre‐ and postcontrast thoracic CT images, and cytological or histopathological diagnosis of malignant or inflammatory pleural effusion. There were 20 dogs with malignant pleural effusion (13 mesothelioma, 6 carcinoma; 1 lymphoma), and 32 dogs with pleuritis (18 pyothorax; 14 chylothorax). Compared to dogs with pleuritis, dogs with malignant pleural effusions were significantly older (median 8.5 years vs. 4.9 years, P = 0.001), more frequently had CT signs of pleural thickening (65% vs.34%, P = 0.05), tended to have thickening of the parietal pleura only (45% vs. 3%, P = 0.002) and had more marked pleural thickening (median 3 mm vs. 0 mm, P = 0.03). Computed tomography signs of thoracic wall invasion were observed only in dogs with malignant pleural effusions (P = 0.05). There were no significant differences in pleural fluid volume, distribution or attenuation, degree of pleural contrast accumulation, amount of pannus, or prevalence of mediastinal adenopathy. Although there was considerable overlap in findings in dogs with malignant pleural effusion and pleuritis, marked thickening affecting the parietal pleural alone and signs of thoracic wall invasion on CT support diagnosis of pleural malignant neoplasia, and may help prioritize further diagnostic testing

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial

Peer reviewedPublisher PD

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment

Treatment for CIN is usually undertaken in an outpatient colposcopy clinic to remove the pre-cancerous cells from the cervix. It commonly involves lifting the cells off the cervix with electrically heated wire (diathermy) or laser, or destroying the abnormal cells with freezing methods (cryotherapy). This is potentially a painful procedure. The purpose of this review is to determine which, if any, pain relief should be used during cervical colposcopy treatment. We identified 17 trials and these reported different forms of pain relief before, during and after colposcopy. Evidence from two small trials showed that women having a colposcopy treatment had less pain and blood loss if the cervix was injected with a combination of a local anaesthetic drug and a drug that causes blood vessels to constrict (narrow), compared with placebo. Although taking oral pain-relieving drugs (e.g. ibuprofen) before treatment on the cervix in the colposcopy clinic is recommended by most guidelines, evidence from two small trials did not show that this practice reduced pain during the procedure. Most of the evidence in this field is of a low to moderate quality and further research may change these findings. Additionally, we were unable to obtain evidence with regards to dosage of the local anaesthetic drug or method of administering local anaesthetic into the cervix. There is need for high-quality trials with sufficient numbers of participants in order to provide the data necessary to estimate these effects