Laparoscopic hysterectomy with or without pelvic lymphadenectomy or sampling in a high-risk series of patients with endometrial cancer

Background

The purpose of the study was to determine the outcome of all patients with endometrial adenocarcinoma cancer treated by laparoscopic hysterectomy at our institution, many of whom were high-risk for surgery.

Methods

Data was collected by a retrospective search of the case notes and Electronic Patient Records of the thirty eight patients who underwent laparoscopic hysterectomy for endometrial cancer at our institutions.

Results

The median body mass index was 30 (range 19–67). Comorbidities were present in 76% (29 patients); 40% (15 patients) had a single comorbid condition, whilst 18% (7 patients) had two, and a further 18% (7 patients) had more than two. Lymphadenectomy was performed in 45% (17 patients), and lymph node sampling in 21% (8 patients). Median operating time was 210 minutes (range 70–360 minutes). Median estimated blood loss was 200 ml (range 50–1000 ml). There were no intraoperative complications. Post-operative complications were seen in 21% (2 major, 6 minor). Blood transfusion was required in 5% (2 patients). The median stay was 4 post-operative nights (range 1–25 nights). In those patients undergoing lymphadenectomy, the mean number of nodes taken was fifteen (range 8–26 nodes). The pathological staging was FIGO stage I 76% (29 patients), stage II 8% (3 patients), stage III 16% (6 patients). The pathological grade was G1 31% (16 patients), G2 45% (17 patients), G3 24% (8 patients).

Conclusion

Laparoscopic hysterectomy can be safely carried out in patients at high risk for surgery, with no compromise in terms of outcomes, whilst providing all the benefits inherent in minimal access surgery.

     

Unexpected photobleaching of Alexa 488 in a fixed bacterial sample during 2-photon excitation

A sample of fixed bacterial cells was examined by immunofluorescence microscopy using an Alexa 488 conjugated secondary antibody for visualization. Excitation using visible light confirmed the expected photostability of this fluorophore; however, when using 2-photon excitation, Alexa 488 was rapidly and substantially photobleached. The unexpected instability of Alexa 488 under certain conditions may have deleterious consequences if not anticipated and accommodated in experimental protocols.     

Reinstalling antitumor immunity by inhibiting tumor-derived immunosuppressive molecule IDO through RNA interference

Tumor-derived immune suppression is a major impediment to successful immune/gene cancer therapy. In the present study, we describe a novel strategy to disrupt tumor-derived immune suppression by silencing a tolerogenic molecule of tumor origin, IDO, using small interfering RNA (siRNA). Silencing of IDO in B16F10 cells in vitro using IDO-siRNA prevented catabolism of tryptophan and inhibited apoptosis of T cells. IDO-siRNA treatment of B16F10 cells in vitro inhibited subsequent growth, tumor formation, and the size of tumor formed, by those cells when transplanted into host mice. In vivo treatment of B16F10 tumor-bearing mice successfully postponed tumor formation time and significantly decreased tumor size. Furthermore, in vivo IDO-siRNA treatment resulted in recovery of T cells responses and enhancement of tumor-specific killing. Thus, silencing IDO may break tumor-derived immune suppression. These data indicate that RNA interference has potential to enhance cancer therapy by reinstalling anticancer immunity.     

Rhodnius prolixus and Rhodnius robustus–like (Hemiptera, Reduviidae) wing asymmetry under controlled conditions of population density and feeding frequency

Habitat change in Rhodnius spp may represent an environmental challenge for the development of the species, particularly when feeding frequency and population density vary in nature. To estimate the effect of these variables in stability on development, the degree of directional asymmetry (DA) and fluctuating asymmetry (FA) in the wing size and shape of R. prolixus and R. robustus–like were measured under laboratory controlled conditions. DA and FA in wing size and shape were significant in both species, but their variation patterns showed both inter-specific and sexual dimorphic differences in FA of wing size and shape induced by nutrition stress. These results suggest different abilities of the genotypes and sexes of two sylvatic and domestic genotypes of Rhodnius to buffer these stress conditions. However, both species showed non-significant differences in the levels of FA between treatments that simulated sylvan vs domestic conditions, indicating that the developmental noise did not explain the variation in wing size and shape found in previous studies. Thus, this result confirm that the variation in wing size and shape in response to treatments constitute a plastic response of these genotypes to population density and feeding frequency.     

Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency

Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in DHFR, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and Parkinson disease.     

Examining complexities of forest cover change during armed conflict on Nicaragua’s Atlantic Coast

The effects of armed conflict on biodiversity are an emerging concern in conservation due in part to the occurrence of war in biodiversity hotspots, though few studies have addressed it. We investigate this topic by examining changes in forest cover on the Atlantic Coast of Nicaragua from 1978 to 1993, a period covering their civil war. We predict an increase in forest cover between pre- and post-conflict periods as residents abandoned agriculture plots and migrated from conflict areas. We used a remote sensing approach to detect changes in forest cover area and fragmentation at two study sites. Results confirmed that in the first 5–7 years of the conflict, reforestation was greater than deforestation, but in the latter years of the conflict deforested land almost doubled that which was reforested. Although some forest loss was due to Category 4 Hurricane Joan, several conflict-related factors were partially responsible for these results, such as mass human migration and land reform. Understanding how and why forest cover changes during periods of conflict can help conservationists protect resources both during war and in the tumultuous period following the cessation of violence when nascent governments lack the power to effectively govern and community institutions are fractured by war. In areas where the livelihoods of people are directly dependent on local resources, anticipating ecological and social impacts can help improve future conservation efforts.     

Prevalence of HIV antibody and pregnancy in Tayside, 1984-9: background to screening.

OBJECTIVE--To determine age specific prevalence of HIV antibody, incidence of pregnancy, and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for HIV antibody, from 1984 to 1989. DESIGN--Retrospective analysis of reproductive history and risk behaviour of women positive for HIV antibody and prediction of detection by screening on the basis of blood group samples, Guthrie tests, and rubella tests. SETTING--City of Dundee, where the prevalence of HIV is high, since the appearance of HIV in 1984, predominantly among heterosexual intravenous drug users. PATIENTS--All (61) women known to be positive for HIV antibody who had had clinically indicated tests, for whom case notes were available for 60. MAIN OUTCOME MEASURES--Risk assessment according to case notes and reported to the laboratory, incidence of infection, geographical location, age, date of positive test result, and reproductive history. RESULTS--With 61 infected women the overall minimum prevalence among women within the city of Dundee was 0.67/1000 and 2.9/1000 among women in their third decade. Of the 60 women whose reproductive history was available, 35 had 57 pregnancies, 36 of which occurred after seroconversion was known to have taken place, representing 8.7% of the total number of affected pregnancies reported for the United Kingdom. If antenatal screening for HIV had been performed between 1984 and 1989 it could not have detected positivity for HIV antibody in 25 (42%) women who had no pregnancies during this time. Among the remaining 35 women, screening samples taken for blood grouping could have identified a maximum of 34 (57%), samples taken to check rubella susceptibility a maximum of 22 (37%), and blood spots on Guthrie cards a maximum of 19 (32%). Retesting would have occurred in 14 women 33 times with samples taken for blood grouping, but three and four women would have been tested twice using samples taken for rubella testing and Guthrie cards respectively. Anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47 (79%) women before testing but this was increased by a further 5 (8%) who admitted to it after the test result was known. CONCLUSION--Interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of HIV antibody among women; this will be exaggerated by strategies based on anonymous testing with Guthrie cards or on samples taken for rubella testing, which do not include women who have had an earlier loss of pregnancy. Only open testing with consent will permit satisfactory attribution to