Selective Interarterial Radiation Therapy (SIRT) in Colorectal Liver Metastases: How Do We Monitor Response?

Radioembolisation is a way of providing targeted radiotherapy to colorectal liver metastases. Results are encouraging but there is still no standard method of assessing the response to treatment. This paper aims to review the current experience assessing response following radioembolisation. A literature review was undertaken detailing radioembolisation in the treatment of colorectal liver metastases comparing staging methods, criteria, and response. A search was performed of electronic databases from 1980 to November 2011. Information acquired included year published, patient numbers, resection status, chemotherapy regimen, criteria used to stage disease and assess response to radioembolisation, tumour markers, and overall/progression free survival. Nineteen studies were analysed including randomised controlled trials, clinical trials, meta-analyses, and case series. There is no validated modality as the method of choice when assessing response to radioembolisation. CT at 3 months following radioembolisation is the most frequently modality used to assess response to treatment. PET-CT is increasingly being used as it measures functional and radiological aspects. RECIST is the most frequently used criteria. Conclusion. A validated modality to assess response to radioembolisation is needed. We suggest PET-CT and CEA pre- and postradioembolisation at 3 months using RECIST 1.1 criteria released in 2009, which includes criteria for PET-CT, cystic changes, and necrosis.

Carrying and spine loading.

The advantages and disadvantages of different methods of carrying objects on spine loading are still not fully understood. Previous studies have either examined the effects of carrying using physiological measures or examined isolated spine segments using biomechanical models. Additionally, most studies have been restricted to only a small number of carrying conditions. Very few studies have attempted to examine the various factors influencing spine loading together. To improve understanding of interacting factors on carrying, this study assessed the lumbar spine loads of 16 subjects as they assumed six styles of carrying at two weight levels and two activity levels (walking vs. standing). Concurrent with each trial, a subject-specific biomechanical model was used to assess spine forces over the full lumbar spine. Most carrying methods in the trials resulted in relatively low levels of spine loading. Anterior/posterior (A/P) shear loading was the only spine-loading dimension that reached biomechanically meaningful levels. Two carrying conditions, with bins carried in front of the body, significantly increased A/P shear compared with other carrying styles. This increase appeared to be due to the greater moment arms occurring in these conditions. Many of the other carrying styles produced A/P shears that were similar to those observed when carrying nothing at all. Of all the tasks, the backpack carry characteristically produced especially low spine loads. The findings of the study suggest that to achieve optimal carrying in terms of spine loading, loads should be positioned close to the body, even when carrying relatively light loads.

Pheromones enhance somatosensory processing in newt brains through a vasotocin-dependent mechanism.

We tested whether the sex pheromones that stimulate courtship clasping in male roughskin newts do so, at least in part, by amplifying the somatosensory signals that directly trigger the motor pattern associated with clasping and, if so, whether that amplification is dependent on endogenous vasotocin (VT). Female olfactory stimuli increased the number of action potentials recorded in the medulla of males in response to tactile stimulation of the cloaca, which triggers the clasp motor reflex, as well as to tactile stimulation of the snout and hindlimb. That enhancement was blocked by exposing the medulla to a V1a receptor antagonist before pheromone exposure. However, the antagonist did not affect medullary responses to tactile stimuli in the absence of pheromone exposure, suggesting that pheromones amplify somatosensory signals by inducing endogenous VT release. The ability of VT to couple sensory systems together in response to social stimulation could allow this peptide to induce variable behavioural outcomes, depending on the immediate context of the social interaction and thus on the nature of the associated stimuli that are amplified. If widespread in vertebrates, this mechanism could account for some of the behavioural variability associated with this and related peptides both within and across species.

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt insertion: a decade of experience.

BACKGROUND: Since its introduction, transjugular intrahepatic portosystemic shunt (TIPS) has been extensively used for treatment of portal hypertension. We report a decade of experience with particular emphasis on characterizing post-TIPS hepatic encephalopathy (HE). AIM: To determine the frequency of clinically evident or minimal HE post-TIPS, identify predisposing factors and determine the impact of minimal HE on quality of life. DESIGN: Prospective data collection and retrospective case notes analysis. METHODS: Of 197 patients referred for TIPS insertion, 136 patients who survived the procedure by more than 4 weeks were available for assessment. Data collected at TIPS insertion was supplemented by case note analysis. Psychometric testing was performed and health profile questionnaires administered on patients still attending. RESULTS: Most patients had alcoholic liver disease (62.4%) and bleeding varices unresponsive to endoscopic therapy (86%). Clinically evident post-TIPS HE developed in 34.5% of patients, was of similar frequency in the groups treated with polytetrafluoroethylene covered and uncovered stents, and the only significant predictor was pre-TIPS HE. Post-TIPS HE necessitating liver transplant or contributing to death occurred in only 14 (10.3%) patients. Minimal encephalopathy (abnormal psychometry) was present in 49% of patients at 26 (3-123) months after TIPS but this frequency was similar in a cohort of cirrhotics being assessed for liver transplant. However, patients with abnormal psychometry had significantly lower quality of life scores than those with normal psychometry. CONCLUSION: Although, HE is relatively common after TIPS insertion, with careful selection of patients it is usually short-lived and easily managed. Minimal HE is no more prevalent than expected in a cirrhotic population without TIPS.

Impact on renal function after endovascular aneurysm repair with uncovered supra-renal fixation assessed by serum cystatin C.

OBJECTIVE: Supra-renal fixation in endovascular aneurysm repair (SR-EVR) is used to improve the proximal seal of aortic stent grafts and appears to have minimal effect on serum creatinine. Serum cystatin C (CC) is a more sensitive marker of renal injury and, unlike creatinine, is unaffected by non-renal influence. The aim of this study was to assess the true renal effect of SR-EVR using this superior renal index. METHODS: Consecutive patients undergoing SR-EVR were prospectively recruited and compared to control groups undergoing open aneurysm repair (OR) and colorectal resection (CR). Serum CC and creatinine clearance (CrC) were determined pre-operatively and at 3, 6 and 12 months post-surgery. Renal function was compared using analyses of covariance (ANCOVA). RESULTS: Sixty-five patients (M:F; 52:13, median age 74 years) were enrolled (24 SR-EVR, 28 OR, 13 CR). Pre-operative renal function and risk factors were comparable (CC 1.04mg/l, SR-EVR; 0.96mg/l, OR; 0.97mg/l, CR). Adjusting for baseline renal function, there was no significant difference in CC or CrC between study and both control groups at 3, 6 or 12-months post-operatively. CONCLUSION: Using cystatin C as a more sensitive renal index, there was no detectable evidence of kidney dysfunction at up to one-year following EVR with uncovered bare-metal supra-renal fixation.

The mid-term effect of bare metal suprarenal fixation on renal function following endovascular abdominal aortic aneurysm repair.

OBJECTIVE: The aim of this study was to assess the mid term effect of proximal bare metal fixation design on renal function in patients undergoing endovascular repair (EVR) of abdominal aortic aneurysm (AAA). METHODS: Consecutive EVR patients for AAA from December 1995-2001 were included and grouped to either infrarenal (Group 1) or uncovered suprarenal (Group 2) fixation. Peri-operative renal function and at 6, 12 and 24 months was determined by serum creatinine (sCr mmol l(-1)) and Cockroft-Gault creatinine clearance (CrC ml min(-1)). Changes in renal function were compared using non-parametric analysis. RESULTS: Of the 179 EVR procedures during this six-year period, paired renal data was available for 135 patients at a minimal follow-up of 6 months (Gp1, n = 63; Gp2, n = 72). Median pre-EVR sCr and CrC were 113, 57 in Group 1 and 108, 58 in Group 2, p = NS. There was no significant deterioration in renal function within or between either group at 2 years post-EVR: median sCr, CrC values were 118, 56 (Group 1) and 111, 56 (Group 2), all p = NS. CONCLUSION: This study suggests mid-term renal function remains unaffected following EVR of AAA, irrespective of proximal fixation type. Designs to improve stent durability and EVR applicability do not appear to compromise renal function.

Bis(tBuSATE) phosphotriester prodrugs of 8-azaguanosine and 6-methylpurine riboside; bis(pom) phosphotriester prodrugs of 2'-deoxy-4'-thioadenosine and its corresponding 9alpha anomer.

As an extension of previous work with bis(POM) nucleotide prodrugs, we report the synthesis and biological evaluation in tumor cell culture of the bis(pivaloyloxymethyl) phosphotriester prodrug of slightly cytotoxic 2'-deoxy-4'-thioadenosine and its alpha-anomer. We have experienced need for an alternative phosphate masking group, particularly with purine nucleosides. Accordingly, we report synthesis and biological evaluation of the bis(tBuSA TE) phosphotriester prodrugs of 8-azaguanosine and 6-methylpurine riboside, nucleoside analogs with moderate to significant cytotoxicity. All four prodrugs were examined in tumor cell culture in parallel with the parent nucleosides. Synthetic routes and biological data are presented.

The Vanguard endovascular stent-graft: mid-term results from a single centre.

PURPOSE: Despite initial enthusiasm for endovascular aortic repair, few descriptions of longer-term follow-up of any endovascular device have been published. This paper represents the experience of a single centre with the Vanguard device over a 5-year period. METHODS: Fifty-five patients with a median age of 71 years (range 45-87 years) and aneurysm diameter of 59 mm (45-84 mm) received a bifurcated Vanguard stent-graft between December 1995 and July 1999. Follow-up was according to the Eurostar criteria (clinical assessment, plain film radiography and computed tomography) at 1, 3, 6, 12, 18 and 24 months and then annually thereafter. RESULTS: All primary stent deployments were successful. Median duration of surgery was 120 min (70-360 min). Median post-operative stay was 3 days (1-19 days) with a peri-operative mortality of 5.5%. In the follow-up period (median 40 months, range 6-64 months) there was one aneurysm associated death, and 14 deaths due to other causes. There have been three device migrations, 12 occluded graft limbs, four type II endoleaks and nine type III endoleaks. At 48 months, this has resulted in a survival rate of 67%, an endoleak free survival of 81% and intervention free survival of 59% (Kaplan-Meier). CONCLUSION: Medium term results with the Vanguard device appear to be at least equivalent to open repair with regard to morbidity and mortality. Nevertheless, several delayed complications appear to be related to endograft limb distortion. Important lessons have been learnt in relation to the deployment of bifurcated endografts to reduce the incidence of secondary limb related problems.

Preoperative portal vein embolisation for primary and metastatic liver tumours: volume effects, efficacy, complications and short-term outcome.

BACKGROUND: The aim of portal vein embolisation is to induce hyperplasia of normal tissue when resection of a cancerous portion of the liver is contraindicated only by the volume of liver that would remain following operation. METHODS: Eight patients with inoperable liver tumours (3 women and 5 men, median age 69.5 years, 3 colorectal hepatic metastasts, 2 choloangiocarcinomas and 3 hepatocellular cancers) were selected for portal vein embolisation. Selected portal branches were occluded with microparticles and coils. Liver volumes were determined by magnetic resonance imaging (MRI) before embolisation and again before operation. RESULTS: Embolisation was successfully performed in all 8 patients, 7 by the percutaneous-transhepatic route, while one patient required open cannulation of a mesenteric vein. Management was altered in 6 patients who proceded to 'curative' resection; projected remaining liver volumes increased (Wilcoxon's matched pairs test p=0.02) from a median of 361 cc to a median of 550 cc; two patients had disease progression such that operation was no longer indicated. In one patient a misplaced coil unintentionally occluded a portal branch to normal liver. CONCLUSIONS: Portal vein embolisation produced appreciable hyperplasia of the normal liver and extended the option of 'curative' operation to 6 out of the 8 cases attempted. Complications can occur. The long-term results following operation are unknown.

A new stent-graft for transjugular intrahepatic portosystemic shunts.

The transjugular intrahepatic portosystemic shunt (TIPSS) has become an effective method of treatment for the complications of portal hypertension, however shunt dysfunction is common. Covered stent-grafts have been tested in animal models, and customized or "home-made" devices have been deployed in several institutions. We report the use of a new commercially available TIPSS stent-graft in six patients undergoing primary shunting as well as two cases of revision or secondary TIPSS. The device has proved relatively easy to handle and appears to have the technical features likely to improve primary patency. Further follow-up is required to properly assess shunt patency and re-intervention rates.

Fos-like immunoreactivity in brain regions of domestic rams following exposure to rams or ewes.

Limbic and basal forebrain-hypothalamic regions from male sheep differing in sexual performance were quantified for fos-like immunoreactivity. Rams classified as high-sexually performing (HP), low-sexually performing (LP), and male-oriented (MO) received noncontact sensory stimulation from either ewes in estrus (HP, n=5; LP, n=4; MO, n=4) or other males (HP, n=5; LP, n=4; MO, n=5) for a 4-h period on each of 3 consecutive days. Following exposure to stimulus animals on the third day, rams were euthanized and their brains were perfused with a 1% paraformaldehyde/1.5% glutaraldehyde solution and sections were analyzed for fos-like immunoreactivity. Brain regions analyzed were the medial amygdala (meAMY), medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), and ventromedial hypothalamic nucleus (VMH). Fos-like immunoreactivity differed between groups in the mPOA and BNST but not in the meAMY or VMH. LP rams exposed to estrous ewes had more (P<.05) neurons staining positive for fos and fos-related antigens (FRA) in the mPOA and BNST than LP rams exposed to other rams or MO rams exposed to either estrous ewes or other rams. Numbers of neurons staining positive for FRA in the mPOA and BNST of LP rams exposed to estrous ewes, however, were not different (P>.05) from HP rams exposed to either estrous ewes or other rams. The similar fos-like immunoreactivity in areas important for the display of sexual behavior in HP and LP rams may reflect similar sensory input in these two groups of rams; however, LP rams, in contrast to HP rams, do not appear to respond similarly to the same sensory stimulus.

The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales.

The epidemiology of herpes zoster and post-herpetic neuralgia (PHN) was quantified from a variety of data sources and the potential cost-effectiveness of vaccination assessed. The annual incidence and severity of zoster increases sharply with age, as measured by physician consultation and hospitalisation rates, average length of stay, average proportion of cases developing PHN and the age-specific case-fatality ratio. Combining these data with information on health related quality of life results in an estimated loss of 20000 quality adjusted life years (QALYs) annually in England and Wales from herpes zoster (17400 due to PHN). The current cost of treating herpes zoster associated disease is estimated to be 47.6m pounds annually. Since both the health and economic burden are high, vaccination of the elderly is expected to be cost-effective under most scenarios, the attractiveness of immunisation increasing with age due to the increased burden of disease in the very elderly.

Low-sexually performing rams but not male-oriented rams can be discriminated by cell size in the amygdala and preoptic area: a morphometric study.

Brain regions of male sheep behaviorally classified as high-sexually performing (n=10), low-sexually performing (n=8) or male-oriented (n=9) were examined to determine if differences in reproductive behavior were associated with differences in density or sizes of neurons. High-sexually performing rams actively mounted estrous ewes, low-sexually performing rams failed to mount or had long latencies to mounting estrous ewes, and male-oriented rams mounted other rams in preference to ewes in estrus. Cell densities and sizes were quantified in Nissl stained sections through the medial amygdala (meAMY), preoptic area (POA), bed nucleus of the stria terminalis (BNST), ventromedial hypothalamic nucleus (VMH), lateral geniculate nucleus (LG) and medial geniculate nucleus (MG). Multivariate discriminant analysis based on soma sizes within nuclei of known importance for reproductive behavior and/or gonadotropin release (meAMY, POA, BNST and VMH) discriminated (Wilks Lambda P<0.05) low-performing rams from high-performing and male-oriented rams, but did not discriminate (Wilks Lambda P=0.14) between high-performing and male-oriented rams. Cell size in the parvocellular and magnocellular layers of the LG along with cells of the MG, structures without a specific role in reproduction, did not discriminate any of the three behaviorally defined groups of rams (Wilks Lambda P=0.57). Density of cells present in structures important for the display of reproductive behavior (POA, meAMY, BNST) and/or gonadotropin release (POA, VMH) had no discriminating power nor did density of cells in structures important for the processing of visual (LG) or auditory (MG) stimuli. In conclusion, significant differences in sizes of cells located within nuclei that are specifically important for the display of male reproductive behavior were found in low-sexually performing rams compared to high-sexually performing and male-oriented rams. These differences may result from neuron development in utero or occur later as a consequence of endocrine factors or behavioral experience. Neuronal cell size is a critical variable that determines excitability to synaptic inputs because cell surface area varies exponentially with cell diameter. Relatively small differences in neuron diameter could relate to functionally important differences in neuronal excitability.

Percutaneous ablation of an internal iliac aneurysm using tissue adhesive.

We report the percutaneous injection of tissue adhesive (Tisseal, Immuno, Vienna, Austria) to ablate a 12-cm internal iliac aneurysm. The complex history of this lesion included previous surgery for a ruptured aortic aneurysm, attempted repair of the internal iliac aneurysm, and several embolization procedures. These factors precluded further open repair or transcatheter techniques and dictated the choice of a more direct approach.

Corticosteroid actions from neuronal membrane to behavior: neurophysiological mechanisms underlying rapid behavioral effects of corticosterone.

Investigation of the rapid suppression of male courtship clasping behavior by corticosterone in roughskin newts (Taricha granulosa) has led to the identification of a specific neuronal membrane receptor for this stress steroid. This paper describes studies of the neurophysiological effects of the rapid, membrane receptor mediated action of corticosterone on neurons that are involved in the control of clasping. In freely behaving newts, medullary neurons, including reticulospinal neurons, process clasp-triggering sensory signals and participate in control of clasping movements. Corticosterone injection causes these brainstem neurons to show selective depression of clasping-related sensorimotor function. These corticosterone effects appear in 3-10 min and are closely associated with the simultaneous depression of clasping. In addition to these functionally specific effects, corticosterone simultaneously causes widespread, primarily depressive effects on neuronal activity and excitability in the medulla and elsewhere in the brain. Thus, the membrane actions of corticosterone lead to diverse neural effects, including changes in membrane excitability as well as specific, network-level actions that are apparent only during behavior. These rapid corticosterone effects strongly interact with actions of the neuropeptides vasotocin and corticotropin-releasing factor, such that the form and magnitude of the steroid's effects depend on the prevailing neuroendocrine state of the brain.