A clinical review of borderline glandular cells reported on liquid-based cervical cytology.

OBJECTIVE: To review the clinical outcome of women presenting with borderline glandular cells on liquid-based cervical cytology (LBC). Design Retrospective review. POPULATION AND SETTING: Women seen at a colposcopy clinic over a 26-month period referred with borderline glandular cells on LBC. METHODS: Review of the case notes and cytology, pathology and colposcopy databases of all women referred with borderline glandular cells on LBC between June 2006 and August 2008. MAIN OUTCOME MEASURES: Final histological diagnosis. RESULTS: Sixty-nine women were identified (0.19% of all smears). Twenty-seven women (39.1%) had premalignant or malignant lesions, five (7.2%) had cancers and 22 (31.9%) had intraepithelial neoplasia, 19 (27.5%) of which were cervical squamous intraepithelial neoplasia (CIN) and three (4.3%) of which were cervical glandular intraepithelial neoplasia (CGIN). No women under 35 years of age with normal and satisfactory colposcopy had premalignant or malignant lesions. Despite normal and satisfactory colposcopy, three women over 35 years had significant lesions: one high-grade CIN, one CGIN and one squamous cell carcinoma. CONCLUSIONS: On the basis of our results, it would be considered acceptable to manage women under 35 years of age with normal and satisfactory colposcopy conservatively. In women above 35 years of age, we would recommend a diagnostic 'large loop excision of the transformation zone' procedure, irrespective of the colposcopic findings.

The BSCC code of practice--exfoliative cytopathology (excluding gynaecological cytopathology).

Exfoliative cytopathology (often referred to as non-gynaecological cytology) is an important part of the workload of all diagnostic pathology departments. It clearly has a role in the diagnosis of neoplastic disease but its role in establishing non-neoplastic diagnoses should also be recognised. Ancillary tests may be required to establish a definitive diagnosis. Clinical and scientific teamwork is essential to establish an effective cytology service and staffing levels should be sufficient to support preparation, prescreening, on-site adequacy assessment and reporting of samples as appropriate. Routine clinical audit and histology/cytology correlation should be in place as quality control of a cytology service. Cytology staff should be involved in multidisciplinary meetings and appropriate professional networks. Laboratories should have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd. Consultant pathologists should sign out the majority of exfoliative cytology cases. Where specimens are reported by experienced biomedical scientists (BMS), referred to as cytotechnologists outside the UK, this must only be when adequate training has been given and be defined in agreed written local protocols. An educational basis for formalising the role of the BMS in exfoliative cytopathology is provided by the Diploma of Expert Practice in Non-gynaecological Cytology offered by the Institute of Biomedical Science (IBMS). The reliability of cytological diagnoses is dependent on the quality of the specimen provided and the quality of the preparations produced. The laboratory should provide feedback and written guidance on specimen procurement. Specimen processing should be by appropriately trained, competent staff with appropriate quality control. Microscopic examination of preparations by BMS should be encouraged wherever possible. Specific guidance is provided on the clinical role, specimen procurement, preparation and suitable staining techniques for urine, sputum, semen, serous cavity effusion, cerebrospinal fluid, synovial fluid, cyst aspirates, endoscopic specimens, and skin and mucosal scrapes.

Impact of climate change on health: what is required of climate modellers?

The potential impacts of climate change on human health are significant, ranging from direct effects such as heat stress and flooding, to indirect influences including changes in disease transmission and malnutrition in response to increased competition for crop and water resources. Development agencies and policy makers tasked with implementing adaptive strategies recognize the need to plan for these impacts. However at present there is little guidance on how to prioritize their funding to best improve the resilience of vulnerable communities. Here we address this issue by arguing that closer collaboration between the climate modelling and health communities is required to provide the focused information necessary to best inform policy makers. The immediate requirement is to create multidisciplinary research teams bringing together skills in both climate and health modelling. This will enable considerable information exchange, and closer collaboration will highlight current uncertainties and hopefully routes to their reduction. We recognize that climate is only one aspect influencing the highly complex behaviour of health and disease issues. However we are optimistic that climate-health model simulations, including uncertainty bounds, will provide much needed estimates of the likely impacts of climate change on human health.

Intraabdominal desmoid tumour presenting with perforation.

We present a rare case of a desmoid tumour presenting with perforation of the small bowel. Although desmoid is classified pathologically as a benign tumour, its infiltrative nature leads to a locally aggressive mass, which can invade surrounding structures and organs making surgical resection difficult. Some unresectable tumours show oestrogen receptor positive cells and can be managed with tamoxifen. The aetiology, investigation and management options are briefly described.

Risk factors in stage III epithelial ovarian cancer: previous sterilisation is an adverse independent prognostic indicator.

OBJECTIVES: To determine whether past history of pelvic surgery is of prognostic significance in stage III epithelial ovarian cancer. METHODS: A retrospective review of 140 women with stage III epithelial ovarian cancer. RESULTS: Sixteen women had previously undergone pelvic surgery including eight sterilisations (6%), seven hysterectomies (5%) and one ovarian cystectomy (0.7%). Women with a past history of sterilisation were significantly younger (median age, 46 years) than women without a past history of sterilisation (median age, 63 years), and also significantly younger than women with a past history of hysterectomy (median age, 58 years). In addition, the sterilisation procedure was performed at a significantly younger age than the hysterectomy procedure (p=0.008). On multivariate analysis comparing previous pelvic surgery, previous malignancy, place of surgery, interval/secondary debulking, presence of concomitant tumour, performance of bowel surgery, histological grade, histological type, size of residual disease and age, all of the following were seen to be independent variables associated with outcome survival; previous sterilisation (p=0.0012), age (p=0.0074), histological type (p=0.025), histological grade (p=0.0017) and size of residual disease (p=0.0043). CONCLUSION: Past history of sterilisation appears to be an adverse independent prognostic indicator in women presenting with stage III epithelial ovarian cancer. To have developed ovarian cancer despite the protective effects of a sterilisation procedure against environmental factors might possibly suggest a predisposition to ovarian cancer in these women. Further studies are indicated to confirm the present results.

Regional temperature and precipitation changes under high-end (≥4°C) global warming.

Climate models vary widely in their projections of both global mean temperature rise and regional climate changes, but are there any systematic differences in regional changes associated with different levels of global climate sensitivity? This paper examines model projections of climate change over the twenty-first century from the Intergovernmental Panel on Climate Change Fourth Assessment Report which used the A2 scenario from the IPCC Special Report on Emissions Scenarios, assessing whether different regional responses can be seen in models categorized as 'high-end' (those projecting 4°C or more by the end of the twenty-first century relative to the preindustrial). It also identifies regions where the largest climate changes are projected under high-end warming. The mean spatial patterns of change, normalized against the global rate of warming, are generally similar in high-end and 'non-high-end' simulations. The exception is the higher latitudes, where land areas warm relatively faster in boreal summer in high-end models, but sea ice areas show varying differences in boreal winter. Many continental interiors warm approximately twice as fast as the global average, with this being particularly accentuated in boreal summer, and the winter-time Arctic Ocean temperatures rise more than three times faster than the global average. Large temperature increases and precipitation decreases are projected in some of the regions that currently experience water resource pressures, including Mediterranean fringe regions, indicating enhanced pressure on water resources in these areas.

Primary endometrial squamous cell carcinoma.

Primary squamous cell carcinoma of the endometrium (PESCC) is rare and its pathogenesis is unclear. Identification of PESCC and its differentiation from endometrial involvement by squamous cell carcinoma is essential for correct patient management and is based on strict pathological criteria. We present a case of a 71-year-old patient satisfying the proposed diagnostic criteria for PESCC together with a review of the literature.

Quantification of physical and biological uncertainty in the simulation of the yield of a tropical crop using present-day and doubled CO2 climates.

The impacts of climate change on crop productivity are often assessed using simulations from a numerical climate model as an input to a crop simulation model. The precision of these predictions reflects the uncertainty in both models. We examined how uncertainty in a climate (HadAM3) and crop General Large-Area Model (GLAM) for annual crops model affects the mean and standard deviation of crop yield simulations in present and doubled carbon dioxide (CO2) climates by perturbation of parameters in each model. The climate sensitivity parameter (gamma, the equilibrium response of global mean surface temperature to doubled CO2) was used to define the control climate. Observed 1966-1989 mean yields of groundnut (Arachis hypogaea L.) in India were simulated well by the crop model using the control climate and climates with values of gamma near the control value. The simulations were used to measure the contribution to uncertainty of key crop and climate model parameters. The standard deviation of yield was more affected by perturbation of climate parameters than crop model parameters in both the present-day and doubled CO2 climates. Climate uncertainty was higher in the doubled CO2 climate than in the present-day climate. Crop transpiration efficiency was key to crop model uncertainty in both present-day and doubled CO2 climates. The response of crop development to mean temperature contributed little uncertainty in the present-day simulations but was among the largest contributors under doubled CO2. The ensemble methods used here to quantify physical and biological uncertainty offer a method to improve model estimates of the impacts of climate change.

Complete cytoreduction: is epithelial ovarian cancer confined to the pelvis biologically different from bulky abdominal disease?

OBJECTIVES: The aim of this study was to determine whether site and size of tumor masses prior to complete surgical cytoreduction affect outcome survival. METHODS: A retrospective review was performed of 53 women with stage II and III epithelial ovarian cancer following complete surgical cytoreduction. RESULTS: Fifteen cases (28%) were classified as stage II and the remaining 38 cases (72%) as stage III. The overall median survival was 58 months with overall 2- and 5-year survivals of 76 and 42%, respectively. On univariate analysis, women with well differentiated tumors did significantly better than those with moderately or poorly differentiated tumours (P = 0.0009). FIGO stage did not reach statistical significance (P = 0.066). On multivariate analysis, comparing patient's age, previous history of pelvic surgery, previous history of malignancy, performance of lymphadenectomy for visibly/palpably enlarged nodes, performance of bowel resection, presence of concomitant tumors, positive pelvic and/or para-aortic lymph nodes, histological type, histological grade, and FIGO stage, only histological grade remained an independent variable affecting outcome survival (P = 0.0004; FIGO stage, P = 0.22) (hazard ratio = 6.5: well versus poor differentiation, 95% confidence interval, 1.7-25.5). CONCLUSION: When surgical cytoreduction to no visible disease has been achieved in women with stage II and III epithelial ovarian cancer, FIGO stage, i.e., site and size of tumor masses prior to surgical cytoreduction, does not appear to influence outcome survival. The aggressiveness of the remaining microscopic disease would seem to be determined largely by histological grade. Bearing in mind the retrospective nature of this study and the relatively small cohort of patients, the results would appear to suggest that it is unlikely that there are any other significant parameters (hidden factors) affecting tumor biology which are independent of tumor grade in these patients. A possible implication of this result is that complete surgical cytoreduction confers a survival benefit by producing a biologically more homogeneous tumor.

Optimal cytoreductive surgery is an independent prognostic indicator in stage IV epithelial ovarian cancer with hepatic metastases.

OBJECTIVES: The aim of this study was to determine the value of optimal cytoreduction in stage IV epithelial ovarian cancer. METHODS: A retrospective review was performed of 37 women with stage IV epithelial ovarian cancer treated by radical surgery. RESULTS: Optimal surgery to less than 2 cm tumor deposits was performed in 16 of the 37 cases (43%) and tumor debulking to less than 1 cm tumor deposits in 6 cases (16.2%). Twenty-three cases (62%) were designated stage IV because of the presence of liver metastases alone. Although no patients died within 2 weeks of surgery, 7 of the 37 cases (22%) failed to survive more than 50 days after primary surgery. The overall median survival was 11 months with overall 2- and 5-year survivals of 23 and 9%, respectively. On multivariate analysis comparing age, histological type, tumor grade, place of surgery, secondary surgical procedure, performance of bowel surgery, presence of liver metastases, and optimal cytoreduction, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained highly significant (P = 0.0029 and 0.0086, respectively). Even when assessing only the 27 cases who were designated as having stage IV disease because of the presence of liver metastases, by multivariate analysis, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained significant (P = 0.023 and 0.036, respectively). Site of metastases designating stage IV status was not associated with a reduced likelihood of achieving optimal debulking (P = 0.18). CONCLUSION: Optimal cytoreduction in women with stage IV epithelial ovarian cancer with or without hepatic metastases is associated with a more favorable outcome survival.

Effects of temperature and glycerides on the enhancement of Agkistrodon piscivorus piscivorus phospholipase A2 activity by lysolecithin and palmitic acid.

The effect of temperature and various glycerides to modulate the ability of lysolecithin and fatty acid to promote high phospholipase A2 activity was studied using dipalmitoylphosphatidylcholine large unilamellar vesicles as substrate. The length of the lag phase prior to the accumulation of sufficient hydrolysis products (lysolecithin and fatty acid) to support high phospholipase activity was shortest at temperatures near the thermotropic phase transition of the phospholipid substrate. A reduction in the lag phase correlated with a reduction in the requirement for hydrolysis products at the phase transition temperature, where the bilayer exists in a state of fluctuating domains of gel and liquid crystal. Dipalmitoylglycerol and tripalmitoylglycerol also reduced the length of the lag phase. This reduction was both concentration-dependent and temperature-dependent relative to the phase transition in the presence of the glycerides. As with the effect of temperature, the ability of di- and triglycerides to decrease the lag time correlated with a decrease in the amount of reaction products necessary to promote high phospholipase activity. This effect coincided with the tendency of the glycerides to form domains in the bilayer. Glycerides that did not form domains either had no effect (monopalmitoylglycerol) or increased the length of the lag phase (dicaprylglycerol). These data suggest that the effect of the reaction products to increase phospholipase A2 activity is aided by the presence of fluctuations in lipid domains within the bilayer.

MUC1 expression in primary breast cancer: the effect of tamoxifen treatment.

This was a non-randomised single institution retrospective study. Forty-six banked frozen tumour specimens were obtained from a group of patients who had undergone 3 weeks of neoadjuvant treatment with tamoxifen between biopsy and surgery. Fifty-one comparison specimens were randomly selected from a group of concomitantly treated primary breast cancer patients who did not receive neoadjuvant tamoxifen. Specimen selection was not based on prognostic factors: hormone receptor status, patient age, or menopausal status. MUC1 expression and cell cycle distribution were assessed by flow cytometry. S-phase fraction of MUC1 positive and MUC1 negative cells were compared. A lower percentage of cells expressed MUC1 following 3-week tamoxifen treatment 18.2% versus 28.5% (p = 0.03, Mann-Whitney) and lower levels of MUC1 expression were seen following tamoxifen treatment 31,519 molecules/cell versus 39,387 (p = 0.04, Mann-Whitney). MUC1 positive cells, irrespective of treatment group, had a greater proportion of cells in S-phase of the cell cycle 27.9% versus 16.8% (p = 0.0004, Mann-Whitney) and demonstrated more cases of aneuploidy 80.65% versus 42.6% (p < 0.0001). MUC1 levels in primary tumours treated neoadjunctively with 3 weeks of tamoxifen were lower than a comparison group which did not receive tamoxifen. MUC1 should be explored further as an intermediate biomarker for assessment of treatment and prognosis.