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Radioembolization (RE) is an emerging treatment strategy for patients with primary hepatic malignancies and metastatic liver disease. Though RE is primarily performed in the palliative setting, a shift toward the curative setting is seen. Currently, hepatic resection and in selected cases liver transplantation are the only curative options for patients with a hepatic malignancy. Unfortunately, at diagnosis most patients are not eligible for liver surgery due to the imbalance between the necessary liver resection and the remaining liver remnant. However, in borderline resectable cases, tumor volume reduction and/or increasing the future liver remnant can lead to a resectable situation. The combination of selective tumor treatment, the induction of hypertrophy of untreated liver segments, and its favourable toxicity profile make RE an appealing strategy for downstaging. The present review discusses the possibilities for RE in the preoperative setting as a downstaging tool or as a bridge to liver transplantation.

Purpose: This meta-analysis was designed to evaluate the utility of preoperative axillary ultrasound combined with US-guided lymph node biopsy if indicated (AUS ± biopsy), in terms of staging the axilla and preventing two-step axillary surgery in the form of sentinel node biopsy (SNB) followed by completion axillary lymph node (ALN) dissection., Methods: We systematically searched electronic databases for studies that addressed preoperative assessment of ALN status by AUS ± biopsy. A pooled estimate was calculated for the false-negative rate (FNR) of AUS ± biopsy (defined as the proportion of women with a negative AUS ± biopsy result subsequently proven to have a positive axilla) and sensitivity (defined as the proportion of women with a positive AUS ± biopsy result among all women with a tumor positive axilla)., Results: The pooled FNR was 25 % (95 % confidence interval [CI] = 24-27) and the pooled sensitivity was 50 % (95 % CI = 43-57). There was substantial heterogeneity across studies for both FNR (I (2) = 69.42) and sensitivity (I (2) = 93.25), which was not explained by between-study differences in biopsy technique, mean/median tumor size, biopsy indication, or study design. Sensitivity was increased in studies with a high prevalence of ALN metastases., Conclusions: Preoperative axillary ultrasound-guided biopsy is a useful step in the process of axillary staging. Approximately 50 % of women with axillary involvement can be identified preoperatively. Still, one in four women with an ultrasound-guided biopsy-"proven" negative axilla has a positive SNB.

Background: A systematic preoperative evaluation to determine the individual resection strategy in patients with colorectal liver metastases (CRLM) was assessed as to its clinical value., Patients and Methods: From 2009 to 2011, 75 patients with CRLM who were scheduled for surgery were prospectively included and received an additional preoperative systematic evaluation in the presence of a hepatobiliary radiologist and the hepatobiliary surgeon scheduled to perform the surgery. The following items were assessed in a standardized manner: lesion detection and characterization, presence of extrahepatic disease, vascular anatomy, and resection strategy. Intraoperative findings and histopathological results were prospectively recorded., Results: Five out of 75 patients were not considered to be eligible for surgery due to additional findings, such as additional metastases or extrahepatic disease. Sensitivity and specificity for detection of individual CRLM were 80.9% (95% CI 75.7-86.1%) and 69.1% (95% CI 59.1-79.1%), respectively. Radical resections were performed in 87.1%. There was one futile laparotomy (1.4%)., Conclusion: In patients with colorectal liver metastases, standardized preoperative work-up, with subsequent planning of an individualized resection in a jointed meeting of a hepatobiliary radiologist and the surgeon who will perform the operation, leads to a high level of radical resections and a low number of futile laparotomies.

Background: Accurate preoperative localization of nonpalpable breast cancer is essential to achieve complete resection. Radioguided occult lesion localization (ROLL) has been introduced as an alternative for wire-guided localization (WGL). Although efficacy of ROLL has been established in a randomized controlled trial, cost-effectiveness of ROLL compared with WGL is not yet known. The objective of this study was to determine whether ROLL has acceptable cost-effectiveness compared with WGL., Methods: An economic evaluation was performed along with a randomized controlled trial (ClinicalTrials.gov, No. NCT00539474). Women (>18 years) with histologically proven nonpalpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomized to ROLL (n = 162) or WGL (n = 152). Empirical data on direct medical costs were collected, and changes in quality of life were measured over a 6-month period. Bootstrapping was used to assess uncertainty in cost-effectiveness estimates, and sensitivity of the results to the missing data approach was investigated., Results: In total, 314 patients with 316 invasive breast cancers were enrolled. On average ROLL required the same time as WGL for the surgical procedure (119 vs 118 min), resulted in a 7 % higher reinterventions risk, and 13 % more complications. Quality of life effects were similar (difference 0.00 QALYs 95 % CI (-0.04-0.05). Total costs were also similar for ROLL and WGL (+26 per patient 95 % CI -250-311)., Conclusion: ROLL is comparable to WGL with respect to both costs and quality of life effects as measured with the EQ5D and will therefore not lead to more cost-effective medical care.

Background: Chemotherapy treatment induces parenchymal changes that potentially affect imaging of CRLM. The purpose of this meta-analysis was to provide values of diagnostic performance of magnetic resonance imaging (MRI), computed tomography (CT), fluorodeoxyglucose positron emission tomography (FDG-PET), and FDG-PET/CT for preoperative detection of colorectal liver metastases (CRLM) in patients treated with neoadjuvant chemotherapy., Methods: A comprehensive search was performed for original articles published from inception to 2011 assessing diagnostic performance of MRI, CT, FDG-PET, or FDG-PET/CT for preoperative evaluation of CRLM following chemotherapy. Intraoperative findings and/or histology were used as reference standard. For each imaging modality we calculated pooled sensitivities for patients who received neoadjuvant chemotherapy as well as for chemonaive patients, defined as number of malignant lesions detected divided by number of malignant lesions as confirmed by the reference standard., Results: A total of 11 papers, comprising 223 patients with 906 lesions, were included. Substantial variation in study design, patient characteristics, imaging features, and reference tests was observed. Pooled sensitivity estimates of MRI, CT, FDG-PET, and FDG-PET/CT were 85.7% (69.7-94.0%), 69.9% (65.6-73.9%), 54.5% (46.7-62.1%), and 51.7% (37.8-65.4%), respectively. In chemonaive patients, sensitivity rates were 80.5% (67.0-89.4%) for CT, 81.3% (64.1-91.4%) for FDG-PET, and 71.0% (64.3-76.9%) for FDG-PET/CT. Specificity could not be calculated because of non-reporting of "true negative lesions.", Conclusion: In the neoadjuvant setting, MRI appears to be the most appropriate imaging modality for preoperative assessment of patients with CRLM. CT is the second-best diagnostic modality and should be used in the absence of MRI. Diagnostic accuracy of FDG-PET and PET-CT is strongly affected by chemotherapy.

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10-15% of HCC patients are suitable candidates for hepatic resection and liver transplantation due to the advanced stage of the disease at time of diagnosis and shortage of donors. Therefore, several minimally invasive image-guided therapies for locoregional treatment have been developed. Tumor ablative techniques are either based on thermal tumor destruction, as in radiofrequency ablation, cryoablation, microwave ablation, laser ablation and high-intensity focused ultrasound, or chemical tumor destruction, as in percutaneous ethanol injection. Image-guided catheter-based techniques rely on intra-arterial delivery of embolic, chemoembolic or radioembolic agents. These minimally invasive image-guided therapies have revolutionized the management of inoperable HCC. This review provides a description of all minimally invasive image-guided therapies currently available, an up-to-date overview of the scientific evidence for their clinical use, and thoughts for future directions.

Background: Breast-conserving surgery (BCS) is the preferred treatment for nonpalpable breast carcinoma. The outcome, however, may be disappointing. In this study surgical outcome in a large cohort of patients diagnosed with nonpalpable breast carcinoma is evaluated., Methods: In 833 patients with 841 nonpalpable breast carcinomas the number of re-excisions and type of surgical procedures was calculated and summed per patient. Subsequently, the number of conversions to mastectomy and the number of days until complete tumor removal were analyzed. In a subgroup analysis the patients with an in situ carcinoma were compared with the patients with an invasive carcinoma., Results: The initial surgery consisted of BCS for 589 tumors (70%) and of mastectomy for 242 tumors (29%). For ten tumors (1%) the initial surgery was unknown. After BCS, 158/589 tumors (27%) required a re-excision: 116/337 (34%) for the in situ carcinomas and 63/504 (13%) for the invasive carcinomas (p = 0.0001). The number of conversions from BCS to mastectomy was 106/589 (18%): 66/241 (28%) in patients diagnosed with an in situ carcinoma versus 40/348 (11%) in patients with an invasive carcinoma (p = 0.0001). The median number of days until complete tumor removal was 28, being 38 days for the in situ carcinomas and 25 days for the invasive carcinomas (p = 0.0001)., Conclusions: There is room for improvement in the surgical treatment of nonpalpable breast carcinoma, especially the relatively favorable in situ carcinoma, as it requires significantly more excisions, mastectomies, conversions to mastectomy, and days for complete removal.

Background: The next step in breast-conserving surgery for small breast carcinomas could be local ablation. In this study, the feasibility of ultrasound-guided laser-induced thermal therapy (LITT) is evaluated., Methods: Patients with large-core needle biopsy-proven invasive, palpable breast carcinoma (clinically or=2 cm in size (P = .026)., Conclusions: Successful LITT of invasive breast cancer seems to be feasible when confined to small (<2 cm) nonlobular carcinomas without surrounding extensive in-situ component and angioinvasion. However, to implement LITT in a curative setting, improvements in imaging to more reliably preoperatively assess tumor size and monitoring of fiber tip placement and treatment affect are essential.

The sex pheromone of feral sweet potato weevils Cylas formicarius elegantulus from Cuba was found, via solid-phase microextraction analysis, to be identical to (Z)-3-dodecenyl (E)-2-butenoate, a previously reported compound. Females emitted 20 pg pheromone d(-1). In scanning electron microscopy studies carried out on the male antenna, we identified several types of sensilla: sensilla trichoidea of type 1 (ST1) as long hairs (100-150 microm), sensilla trichoidea of type 2 as short hairs (50-60 microm), sensilla basiconica of type 1 as thick pegs (20-25 microm), sensilla basiconica of type 2 as curved pegs (10-15 microm), and sensilla basiconica of type 3 as thin and straight short pegs (15-20 microm). The same types were observed in female antennae but ST1 were far less abundant than in males. Sensilla chaetica were also found on the flagellum subsegments in both sexes. In electrophysiological tests, the crotonate function in the pheromone structure proved to be critical for activity since regular depolarizations (0.6-0.8 mV) were obtained with puffs on 1 microg of the attractant, but not with puffs of the formate, acetate, propionate, or butyrate analogue of the pheromone. In a double dual-choice olfactometer, males showed maximum activity between the 4th and the 8th hr of scotophase at a dose of 50-1000 ng of pheromone. In field tests, a correlation between the contents of the Z,E isomer in the pheromone formulation with activity was noticed, and baits containing this isomer of stereomeric purity >94% showed the highest attractivity. The presence of 5% of the Z,Z isomer in the lure did not induce any synergistic or inhibitory effect, and the alcohol precursor of the pheromone was inactive. The results show that use of a stereomerically pure pheromone may not be necessary in pest control strategies.

The purpose of this study was to evaluate the mechanism by which Escherichia coli lipopolysaccharide stimulates the secretion of phosphatidylcholine in primary cultures of rat type II pneumocytes. The stimulatory effect of lipopolysaccharide on phosphatidylcholine secretion was additive to those of terbutaline and TPA (protein kinase A and C activators respectively) and this effect was not suppressed by inhibitors of both protein kinases. On the other hand, lipopolysaccharide did not modify the increase on phosphatidylcholine secretion induced by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin, and enhanced slightly the calcium-ionophore A23187 stimulated phosphatidylcholine secretion. In addition, the stimulatory effect of lipopolysaccharide was suppressed by BAPTA, an intracellular Ca2+ chelator, and KN-62, a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results, together with the lipopolysaccharide-mediated increase in the cytosolic [Ca2+], suggest that stimulation of phosphatidylcholine secretion by lipopolysaccharide in type II pneumocytes occurs by a calcium-dependent transduction mechanism via Ca2+-calmodulin-dependent protein kinase activation.

Tumor necrosis factor alpha and interleukin-1beta increase surfactant secretion in type II pneumocytes in a time- and dose-dependent manner. This stimulatory effect was additive to that of lipopolysaccharide, suggesting that cytokines and lipopolysaccharide may exert their actions through different signal transduction pathways. Tumor necrosis factor alpha and interleukin-1beta did not modify the increase on phosphatidylcholine secretion induced by the direct protein kinase C activator tetradecanoylphorbol 13-acetate, whereas this effect was inhibited by the protein kinase C inhibitors bisindolylmaleimide (2 x 10(-6) M) and 1-(5-isoquinolinylsulphonyl)-2-methyl piperazone (10(-4) M). In addition, the stimulatory effect of tumor necrosis factor alpha and interleukin-1beta was not suppressed by the intracellular Ca2+ chelator BAPTA (5 x 10(-6) M) or by KN-62 (3 x 10(-5) M), a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results suggest that tumor necrosis factor alpha or interleukin-1beta stimulate phosphatidylcholine secretion via protein kinase C activation in a Ca2+-independent manner.

Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vitamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition.

A rat model of endotoxic shock was used to evaluate the effects of dimethylthiourea, a putative hydroxyl radical scavenger, in the alterations of lung phosphatidylcholine biosynthesis found during endotoxemia. Treatment of rats with dimethylthiourea, just before lipopolysaccharide injection, resulted in a decreased lipid peroxidation and an increase in phosphatidylcholine biosynthesis, although it did not prevent the body weight loss or the increase in lung weight and lung protein content associated with the lung injury induced by lipopolysaccharide. Our results suggest that phosphatidylcholine biosynthesis is impaired by processes in which hydroxyl radicals are implicated, although other oxygen free radical species, not removed by dimethylthiourea, can be also involved in lipopolysaccharide mediated lung injury.

The mechanisms involved in cellular activation and damage by bacterial endotoxins are not completely defined. In particular, there is little information about possible intracellular targets of endotoxins. Recently, the participation of a microtubule associated protein in endotoxin actions on macrophages has been suggested. In the present work, we have studied the effect of E. coli lipopolysaccharide on the polymerization of microtubular protein in vitro. Electrophoretic analysis of the polymerization mixtures showed that the endotoxin inhibited the polymerization when present at high concentrations. At lower concentrations, LPS selectively displaced the microtubule associated protein MAP-2 from the polymerized microtubules. Electron microscopy showed that LPS binds to microtubules of tubulin + MAPs and to microtubules of purified tubulin (without MAPs) polymerized with taxol. Gel filtration experiments confirmed the binding of LPS to tubulin, and by ligand blot assays an interaction LPS-MAP-2 was detected. The ability of LPS to interact with microtubular proteins suggests a possible participation of microtubules on the cellular effects of endotoxins.

Alterations in pulmonary surfactant are partly responsible for the respiratory insufficiency seen under septic shock process. We have used an experimental model of LPS-induced shock in rats to examine the cells responsible for the pulmonary surfactant synthesis and its relationship to lung injury. (14C)Choline incorporation into phosphatidylcholine was significantly reduced in lung homogenates or type II cells obtained from LPS-treated animals. Addition of LPS in vitro fails to increase (14C)choline incorporation in type II cells obtained from LPS-treated animals. We suggest that this depression of pulmonary phosphatidylcholine synthesis may partly explain the occurrence of respiratory failure with septic shock.

The interaction between lipopolysaccharide from E. coli 0111:B4 and rat alveolar type II pneumocytes and its influence on the functional properties of the cells and their membranes were studied. Type II cells were isolated by a novel procedure involving digestion of the lung connective tissue with elastase and Percoll-gradient centrifugation. Binding of (14C)lipopolysaccharide to type II cells resulted in a partially reversible; non-specific, high affinity process. (14C)Choline incorporation into phosphatidylcholine by type II cells was stimulated by lipopolysaccharide, the maximum effect being observed at 10-20 micrograms/ml. 45Ca2+ uptake by type II cells was also increased by lipopolysaccharide. Using plasma membranes from lung homogenates an increase of membrane microviscosity versus the amount of lipopolysaccharide was shown. These results indicate that E. coli lipopolysaccharide interacts with alveolar type II cells by binding reversibly to particular ingredients of the membrane bilayer and induces a modification of ion permeability and fluidity of the membrane.