Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS.

BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) is modulated by sex steroid hormones and affects vascular function and mood. In the Kronos Early Estrogen Prevention Cognitive and Affective Ancillary Study (KEEPS-Cog), women randomized to oral conjugated equine estrogens (oCEE) showed greater benefit on affective mood states than women randomized to transdermal 17ß-estradiol (tE2) or placebo (PL). This study examined the effect of these treatments on the platelet content of 5-HT as a surrogate measure of 5-HT synthesis and uptake in the brain. METHODS: The following were measured in a subset (n = 79) of women enrolled in KEEPS-Cog: 5-HT by ELISA, carotid intima-medial thickness (CIMT) by ultrasound, endothelial function by reactive hyperemic index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire. RESULTS: Mean platelet content of 5-HT increased by 107.0%, 84.5% and 39.8%, in tE2, oCEE and PL groups, respectively. Platelet 5-HT positively correlated with estrone in the oCEE group and with 17ß- estradiol in the tE2 group. Platelet 5-HT showed a positive association with RHI, but not CIMT, in the PL and oCEE groups. Reduction in mood scores for depression-dejection and anger-hostility was associated with elevations in platelet 5-HT only in the oCEE group (r = -0.5, p = 0.02). CONCLUSIONS: Effects of oCEE compared to tE2 on RHI and mood may be related to mechanisms involving platelet, and perhaps neuronal, uptake and release of 5-HT and reflect conversion of estrone to bioavailable 17ß-estradiol in platelets and the brain.

Molecular Docking and Interactions of Pueraria Tuberosa with Vascular Endothelial Growth Factor Receptors.

Pueraria tuberosa is known for its therapeutic potentials in cardiovascular disorders, but its effect in angiogenesis has not been studied so far. In this study, a computational approach has been applied to elucidate the role of the phytochemicals in inhibition of angiogenesis through modulation of vascular endothelial growth factor receptors: Vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, major factors responsible for angiogenesis. Metabolite structures retrieved from PubChem and KNApSAcK - 3D databases, were docked using AutoDock4.2 tool. Hydrogen bond and molecular docking, absorption, distribution, metabolism and excretion and toxicity predictions were carried out using UCSF Chimera, LigPlot(+) and PreADMET server, respectively. From the docking analysis, it was observed that puerarone and tuberostan had significant binding affinity for the intracellular kinase domain of vascular endothelial growth factor receptors-1 and vascular endothelial growth factor receptor-2 respectively. It is important to mention that both the phytochemicals shared similar interaction profile as that of standard inhibitors of vascular endothelial growth factor receptors. Also, both puerarone and tuberostan interacted with Lys861/Lys868 (adenosine 5'-triphosphate binding site of vascular endothelial growth factor receptors-1/vascular endothelial growth factor receptors-2), thus providing a clue that they may enforce their inhibitory effect by blocking the adenosine 5'-triphosphate binding domain of vascular endothelial growth factor receptors. Moreover, these molecules exhibited good drug-likeness, absorption, distribution, metabolism and excretion properties without any carcinogenic and toxic effects. The interaction pattern of the puerarone and tuberostan may provide a hint for a novel drug design for vascular endothelial growth factor tyrosine kinase receptors with better specificity to treat angiogenic disorders.

New directions in the science and technology of advanced sheet explosive formulations and the key energetic materials used in the processing of sheet explosives: Emerging trends.

This review presents the work carried out by the international community in the area of sheet explosive formulations and its applications in various systems. The sheet explosive is also named as PBXs and is a composite material in which solid explosive particles like RDX, HMX or PETN are dispersed in a polymeric matrix, forms a flexible material that can be rolled/cut into sheet form which can be applied to any complex contour. The designed sheet explosive must possess characteristic properties such as flexible, cuttable, water proof, easily initiable, and safe handling. The sheet explosives are being used for protecting tanks (ERA), light combat vehicle and futuristic infantry carrier vehicle from different attacking war heads etc. Besides, sheet explosives find wide applications in demolition of bridges, ships, cutting and metal cladding. This review also covers the aspects such as risks and hazard analysis during the processing of sheet explosive formulations, effect of ageing on sheet explosives, detection and analysis of sheet explosive ingredients and the R&D efforts of Indian researchers in the development of sheet explosive formulations. To the best of our knowledge, there has been no review article published in the literature in the area of sheet explosives.

Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose-response randomized trial.

PURPOSE: To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels. METHODS: 71 hysterectomized women with or without oophorectomy with total testosterone <31 ng/dl and/or free testosterone <3.5 pg/ml received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly intramuscular injections of placebo, 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Total testosterone was measured in serum by LC-MS/MS, and free testosterone levels were measured by equilibrium dialysis. Cognitive function was evaluated using a comprehensive battery of standardized neuropsychological tests at baseline and 24 weeks. RESULTS: 46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample. The five groups were similar at baseline. Mean on-treatment nadir total testosterone concentrations were 15, 89, 98, 134, and 234 ng/dl in the placebo, 3, 6.25, 12.5, and 25 mg groups, respectively. No significant changes in spatial ability, verbal fluency, verbal memory, or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function, age, and education. Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores. CONCLUSION: Short-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function.

A comparative study of cervical cancer screening methods in a rural community setting of North India.

CONTEXT: Pap smear testing as a conventional cervical screening approach has limitations for implementation and aided visual cervical testing has varying results in different regions. AIMS: The aim of this study is to demonstrate the performance of aided visual cervical screening tests as against conventional Pap smear testing in a rural community setting of North India. SETTINGS AND DESIGN: This was a rural community based cross-sectional study. MATERIALS AND METHODS: All 7603 ever married women of age 30-59 years surveyed in a pocket of Dadri Tehsil, Uttar Pradesh, India were targeted for screening by Pap, visual inspection of cervix using acetic acid (VIA) and visual inspection of cervix using Lugol's iodine (VILI) methods. Screen positives were referred to colposcopy and confirmation by histology. STATISTICAL ANALYSIS USED: Detection of histological cervical intraepithelial neoplasia (CIN) II + and CIN III + assessed separately by sensitivity, specificity and likelihood ratio's and predictive values. Analysis of data was performed by using IBM SPSS statstics software version 16.0. RESULTS: A total of 65.6%(4988/7604) eligible women of 30-59 years age group in the target population were screened. Out of 4988, further analysis was performed on 4148 after excluding those who did not complete all screenings, who lost to follow-up and had missing histology results. Screen positivity rates by Pap (ASCUS and above), VIA and VILI were 2.6%, 9.7% and 13.5% respectively. Sensitivity and specificity of detecting the CIN III+ lesions were 87.5 and 98.8% for Pap, 50.0% and 96.7% for VIA and 50.0% and 95.7% for VILI respectively. CONCLUSIONS: VIA screening demonstrated as a feasible primary screening test for detecting high grade CIN and as to perform better when the Pap test is not feasible.

Human papillomavirus viral load on careHPV testing of self-collected vaginal samples vs. clinician-collected cervical samples.

OBJECTIVE: To compare viral load on careHPV DNA testing in self-collected vaginal (VHPC) and clinician-collected cervical (CHPC) samples for the detection of high-grade cervical intra-epithelial neoplasia (CIN). STUDY DESIGN: Cross-sectional study. Ever-married women aged 30-59 years were targeted for cervical screening. On attendance for screening, vaginal self-sampling was performed by the woman, and an auxiliary nurse midwife subsequently performed a per-speculum examination, collected a CHPV sample and a Pap smear, and made a visual inspection of the cervix with acetic acid. The ratio of viral load expressed in relative light units to positive controls set at a cut-off of 1pg/ml was used for careHPV quantitative assessment. The median viral load was compared using non-parametric tests. Receiver operating characteristic (ROC) curves were constructed for the detection of CINII+ and CINIII+ in CHPV and VHPV samples. RESULTS: Overall, the median viral load in the 4658 women screened was higher in CHPV samples compared with VHPV samples (9.8-fold higher in cases of high-grade CIN). The median viral load was significantly higher among Pap-positive women compared with Pap-negative women in both CHPV and VHPV samples (p<0.01). Assessment by ROC analysis for the detection of high-grade CIN did not differ significantly between CHPV and VHPV samples. CONCLUSION: Viral load on careHPV testing was comparable between self- and clinician-collected samples for the detection of high-grade CIN. The self-sampling approach may be an option for screening in low-resource countries.

CareHPV cervical cancer screening demonstration in a rural population of north India.

OBJECTIVE: To compare cervical careHPV screening in a rural community setting with other methods of cervical screening for the detection of high-grade cervical intra-epithelial neoplasia (CIN). STUDY DESIGN: Cross-sectional study. All ever-married women aged 30-59 years surveyed in an administrative area of Uttar Pradesh, India were targeted for screening by careHPV (cervical and vaginal samples), Pap test and visual inspection of the cervix following application of acetic acid (VIA). Women who screened positive were referred for colposcopy and the results were confirmed histologically. Sensitivity, specificity and predictive values for the detection of histological CINII+ and CINIII+ were assessed for each screening test. RESULTS: Sixty-five percent (5032/7704) of the women invited for cervical screening agreed to participate in the study. Screen-positive rates for cervical careHPV, vaginal careHPV, Pap test and VIA were 3%, 2%, 3% and 6%, respectively. Data for women who did not complete all screening modes, women lost to follow-up and women with missing histological results were excluded before data analysis, resulting in a final sample size of 4658. Cervical careHPV had high sensitivity (85%) for the detection of CINIII+ lesions and moderate sensitivity (53%) for the detection of CINII+ lesions. Sensitivities for the detection of CINIII+ and CINII+ were 54% and 41% for vaginal careHPV, 62% and 44% for Pap test, and 8% and 22% for VIA, respectively. CONCLUSION: Cervical careHPV testing is superior to VIA and Pap test for the detection of high-grade CIN in a rural community setting.

Density functional theoretical modeling, electrostatic surface potential and surface enhanced Raman spectroscopic studies on biosynthesized silver nanoparticles: observation of 400 PM sensitivity to explosives.

Interaction of adsorbate on charged surfaces, orientation of the analyte on the surface, and surface enhancement aspects have been studied. These aspects have been explored in details to explain the surface-enhanced Raman spectroscopic (SERS) spectra of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (HNIW or CL-20), a well-known explosive, and 2,4,6-trinitrotoluene (TNT) using one-pot synthesis of silver nanoparticles via biosynthetic route using natural precursor extracts of clove and pepper. The biosynthesized silver nanoparticles (bio Ag Nps) have been characterized using UV-vis spectroscopy, scanning electron microscopy and atomic force microscopy. SERS studies conducted using bio Ag Nps on different water insoluble analytes, such as CL-20 and TNT, lead to SERS signals at concentration levels of 400 pM. The experimental findings have been corroborated with density functional computational results, electrostatic surface potential calculations, Fukui functions and ζ potential measurements.

An insight into potential of nanoparticles-assisted chemotherapy of cancer using gemcitabine and its fatty acid prodrug:a comparative study.

Gemcitabine (dFdC) mediated cancer treatment faces obstacles, due to its high hydrophilicity. A valuable strategy was executed by synthesizing lipophilic fatty acid derivative of dFdC i.e., 4-(N)-stearoyl gemcitabine (C18dFdC), built-in into polymeric poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) and compared with that of parent drug. Encapsulation of derivative within NPs was higher (68.24 +/- 3.64%) than dFdC and showed comparatively sustained drug release (19.87 +/- 1.73% within 12 hours), with a proof of increased biological half life. The cytotoxicity and flow cytometric analysis displayed enhanced MCF-7 cell inhibition by C18dFdC-NPs with higher uptake compared to dFdC-NPs. Interestingly, like gemcitabine, C18dFdC-NPs did not induce appreciable differences in blood parameters and in vivo tissue toxicity study demonstrating safe use of derivative at 40 mg/kg dose. In conclusion, the preclinical data obtained in vitro and in vivo demonstrate the C18dFdC-nanocarrier as an advantageous and promising delivery system for cancer treatment along with the potential to improve the clinical outcome of gemcitabine chemotherapy.

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults.

OBJECTIVE: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E ε4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals. METHODS: Participants were cognitively healthy adults with (FH+) (n = 60) and without (FH-) (n = 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline. RESULTS: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH × APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FH+ and FH- subjects who were APOE4-. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. CONCLUSION: Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade.

Transplantation of adult-sized kidneys in low-weight pediatric recipients achieves short-term outcomes comparable to size-matched grafts.

Low-weight pediatric recipients are disadvantaged by scarcity of size-matched donors. ASK have been successfully used for pediatric recipients. We report the results of renal transplantation using ASK in low-weight pediatric recipients and compare outcomes in weight-matched and unmatched donor-recipient pairs. The outcomes of renal transplants using ASK grafts in low-weight (<20 kg) recipients from a single center over a 10-yr period were reviewed. Two groups, comprising recipients of grafts from weight-matched and mismatched donors, were compared. Primary outcome was one-yr graft survival. Secondary outcomes were one- and two-yr calculated eGFR, changes in recipient body weight, perioperative cardiovascular stability, rates of AR and DGF. Twenty-three low-weight recipients were transplanted. Eleven received ASK grafts from high-weight donors and 12 grafts from low-weight donors. One patient in each group had early graft loss. No significant difference was observed in rates of DGF, AR, one-yr graft or patient survival and perioperative cardiovascular parameters. ASK with considerable donor:recipient weight discrepancies can be safely transplanted into small pediatric recipients with comparable outcomes to grafts with less weight discrepancy.

The management of splenic artery aneurysm in patients awaiting liver transplantation.

Splenic artery aneurysms (SAAs) are the third most common forms of intra-abdominal aneurysm, and the most commonly encountered visceral aneurysms in the general population. SAAs occur more commonly in patients with portal hypertension and liver failure and, as such, are often encountered in patients undergoing high-resolution abdominal imaging as part of a work-up for liver transplantation. While rupture rates of between 2% and 10% have been reported in the literature, little is known about the natural history and behavior of these lesions in patients with liver disease. Interventional management options pose a challenge given the high anesthetic and surgical risk of such patients. This study was conducted to study the management of all SAAs diagnosed among patients presenting for a liver transplant assessment at a single center over a three-yr period. We discuss the presentation and management options, with elective and emergent presentation of SAA in patients with end-stage liver disease.

Midlife predictors of Alzheimer's disease.

Factors contributing to increased risk for Alzheimer's disease (AD) include age, sex, genes, and family history of AD. Several risk factors for AD are endogenous; however, accumulating evidence implicates modifiable risk factors in the pathogenesis of AD. Although the continued task of identifying new genes will be critical to learning more about the disease, several research findings suggest that potentially alterable environmental factors influence genetic contributions, providing targets for disease prevention and treatment. Here, we review midlife risk factors for AD, and address the potential for therapeutic intervention in midlife.

Synthesis, characterization and evaluation of 1,2-bis(2,4,6-trinitrophenyl) hydrazine: a key precursor for the synthesis of high performance energetic materials.

1,2-Bis(2,4,6-trinitrophenyl) hydrazine (3) is one of the precursors in the synthesis of an important energetic material viz., hexanitrazobenzene. The simple and convenient lab scale synthesis of title compound (3) was carried out by the condensation of picryl chloride (2) with hydrazine hydrate at 30-50 degrees C in methanol based on the lines of scanty literature reports. Picryl chloride was synthesized by the reaction of picric acid (1) with phosphorous oxychloride based on the lines of reported method. The synthesized compound (3) was characterized by IR and 1H NMR spectral data. Some of the energetic properties of the synthesized compound have also been studied. The theoretically computed energetic properties of the title compound (3) indicated the superior performance in comparison to tetranitrodibenzo tetraazapentalene (TACOT) and hexanitrostilbene (HNS) in terms of velocity of detonation.

Food consumption pattern in cervical carcinoma patients and controls.

BACKGROUND: The uterine cervix is the second most common site of cancer among Indian women.Though the human papillomavirus has been demonstrated to be a causative agent for this cancer, a variety of other risk factors are in play, such as sexual and reproductive patterns, socioeconomic, hygienic practices, and diet. The accumulated evidence suggests that cervical cancer is preventable and is highly suitable for primary prevention. The dietary intake of antioxidants and vitamins like vitamin A, carotenoids, vitamin C, folacin and tocopherol is found to have protective effects against cancer of the cervix. Dietary data regarding cervical cancer are still scanty. OBJECTIVE: The present study was therefore undertaken to study the dietary pattern among uterine cervical cancer patients and normal controls. MATERIALS AND METHODS: A total of 60 consecutive patients and 60 controls were enrolled from a referral hospital during the year 2004. A schedule inclusive of the food frequency pattern and 24-h dietary recall along with the general information was administered to all the enrolled subjects to describe findings on the food consumption pattern along with other important factors. RESULTS: The mean intake of energy, protein, vitamins, etc., between the cases and controls was not significantly different except for the vitamin C level. Serum vitamin E was found to have lower average in patients as compared to controls. The nutrient intake of cervical cancer patients and controls was grossly deficient in the socioeconomic group studied. With regard to the macronutrient intake, calorie and protein intakes showed a deficit of around 50% when compared to RDA. CONCLUSION: The food consumption profile was not significantly different between cervical cancer patients and normal controls.

Plasma amyloid beta protein is elevated in late-onset Alzheimer disease families.

OBJECTIVE: Plasma A beta levels are elevated in early-onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late-onset AD (LOAD). METHODS: We measured plasma A beta in first-degree relatives of patients with LOAD in a cross-sectional series and in extended LOAD families. We screened these subjects for pathogenic mutations in early-onset AD genes and determined their ApoE genotypes. RESULTS: Plasma A beta is significantly elevated in the LOAD first-degree relatives in comparison to unrelated controls and married-in spouses. These elevations are not due to ApoE epsilon 4 or pathogenic coding mutations in the known early-onset AD genes. CONCLUSIONS: The findings provide strong evidence for the existence of novel, as yet unknown genetic factors that affect late-onset Alzheimer disease by increasing A beta.

Advances in science and technology of modern energetic materials: an overview.

Energetic materials such as explosives, propellants and pyrotechnics are widely used for both civilian and military explosives applications. The present review focuses briefly on the synthesis aspects and some of the physico-chemical properties of energetic materials of the class: (a) aminopyridine-N-oxides, (b) energetic azides, (c) high nitrogen content energetic materials, (d) imidazoles, (e) insensitive energetic materials, (f) oxidizers, (g) nitramines, (h) nitrate esters and (i) thermally stable explosives. A brief comment is also made on the emerging nitration concepts. This paper also reviews work done on primary explosives of current and futuristic interest based on energetic co-ordination compounds. Lead-free co-ordination compounds are the candidates of tomorrow's choice in view of their additional advantage of being eco-friendly. Another desirable attribute of lead free class of energetic compounds is the presence of almost equivalent quantity of fuel and oxidizer moieties. These compounds may find wide spectrum of futuristic applications in the area of energetic materials. The over all aim of the high energy materials research community is to develop the more powerful energetic materials/explosive formulations/propellant formulations in comparison to currently known benchmark materials/compositions. Therefore, an attempt is also made to highlight the important contributions made by the various researchers in the frontier areas energetic ballistic modifiers, energetic binders and energetic plasticizers.

Surgery for hilar cholangiocarcinoma: the Leeds experience.

AIM: To review the experience with hilar cholangiocarcinoma and to determine the results of a radical surgical approach in a UK centre. METHODS: A 10-year review of all patients treated surgically for proximal bile duct carcinoma at a single surgical unit was conducted. Patient demographics, disease details and histopathology reports were reviewed. From January 1993 through December 2003, 106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61 patients received surgical exploration. RESULTS: Tumours were staged as follows (UICC 6th edition): stage IB, n=10 IIA, n=9; IIB, n=20; III, n=8; IV, n=14. Out of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver resection with bile duct resection), 5 were considered unresectable and 12 underwent liver transplantation (LT). The caudate lobe was excised in 34 of the patients and regional lymphadenectomy was systematically carried out. Para-aortic lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17 and hepatic artery resection was performed in 4 cases. Negative histologic margins (R0) were achieved in 20 patients and microscopic margin involvement (R1) was seen in 16. In the remaining 8 resected patients, localised metastasis were found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic lymph nodes in 2); nevertheless the resection was performed and it was considered R2. Overall survival at 3 and 5 years for patients who underwent a resection was 43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial survival rates for patients who underwent R0 resection were 78%, 64% and 45% respectively, including the postoperative deaths (n=3). The median survival time was 41.1 months. The 1-, 3- and 5-year actuarial survival rates for R1 resection and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival time for these groups was 15.4 and 6.8 months respectively. The actuarial survival rate at 1, 3 and 5 years for well-differentiated tumours (G1) was 73%, 54% and 40% (median 39.7 months). The figures for G2 were 60%, 48% and 0%. The figures for G3 (poorly differentiated) were 16% and 0% at three years (p=0.03).The overall survival at 3 and 5 years for those patients who had a liver transplant was 41% and 20% including early postoperative mortality. The tumour grading (presence of poorly differentiated tumour) was found to be the only independent factor affecting the survival time producing a hazard ratio of 4.3 (p=0.0034, 95% confidence interval 0.1007-6.342). CONCLUSIONS: Radical surgical resection is the best treatment for hilar cholangiocarcinoma. R0 resection provides acceptable 5-year survival, but R1 resection may also provide acceptable palliation. In our experience TNM stage and tumour grade were the main determinants of long-term survival.