A novel delivery nanobiotechnology: engineered miR-181b exosomes improved osteointegration by regulating macrophage polarization.

BACKGROUND: Many patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice. Exosome (Exo) carrying miRNA has been proven to be a suitable nanocarrier for solving this problem. In this study, we explored whether exosomes overexpressing miR-181b (Exo-181b) could exert beneficial effect on promoting M2 macrophage polarization, thus inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro. Furthermore, we aimed to find whether Exo-181b could enhance osteointegration. RESULTS: In vitro, we firstly verified that Exo-181b significantly enhanced M2 polarization and inhibited inflammation by suppressing PRKCD and activating p-AKT. Then, in vivo, we verified that Exo-181b enhanced M2 polarization, reduced the inflammatory response and enhanced osteointegration. Also, we verified that the enhanced M2 polarization could indirectly promote the migration and osteogenic differentiation by secreting VEGF and BMP-2 in vitro. CONCLUSIONS: Exo-181b could suppress inflammatory response by promoting M2 polarization via activating PRKCD/AKT signaling pathway, which further promoting osteogenesis in vitro and promote osteointegration in vivo.

A scalable and reproducible preparation for the antitumor protein TLC, a human-derived telomerase inhibitor.

Telomerase, which is overexpressed in approximately 90% of liver cancer cells, is an ideal target for anti-liver cancer therapy. LPTS, a putative liver tumor suppressor, is the only human-derived protein that can bind telomerase directly and inhibit the extension of telomere activity. Our previous studies demonstrated that TAT-LPTS-LC (TLC), a recombinant protein fused by the C-terminal 133-328 fragment of LPTS and TAT peptides, could be delivered into cells to inhibit telomerase-positive hepatoma cell growth in vitro and in vivo with very low toxicity. In the present study, E. coli strains which expressed TLC in abundance were screened and cultured in a laboratory bioreactor. A reproducible protein separation process was built, and this process was suitable for industrial amplification. The yields of TLC protein were up to 184 mg in one batch with a purity of approximately 95%. The purified TLC protein had a similar inhibitory effect on telomerase activity in vitro compared with those purified by Ni-affinity chromatography. Furthermore, TLC protein could be delivered into the cell nucleus to increase the doubling time of the cell and suppress cell growth in telomerase-positive liver cancer cell lines. Cell growth inhibition was negatively correlated with telomere length, suggesting that TLC is a highly targeted telomerase-telomere anticancer agent. These results will contribute to future preclinical studies of the TLC protein.

The value of 99mTc-labeled galactosyl human serum albumin single-photon emission computerized tomography/computed tomography on regional liver function assessment and posthepatectomy failure prediction in patients with hilar cholangiocarcinoma.

BACKGROUND: The aim was to evaluate the value of Tc-labeled galactosyl human serum albumin (Tc-GSA) with single-photon emission computerized tomography (SPECT) in the preoperative assessment of regional liver function and prediction of posthepatectomy liver failure (PHLF) in patients with hilar cholangiocarcinoma (hCCA). METHODS: Patients with hCCA who underwent Tc-GSA SPECT/computed tomography (CT) before hepatectomy were included. The liver functional parameters of functional liver density (FLD) and predictive residual index (PRI) were calculated based on Tc-GSA SPECT/CT. PHLF was defined according to the International Study Group of Liver Surgery criteria. Univariate and multivariate analyses were used to analyze the risk factors for PHLF. The prediction of PHLF was calculated using receiver operating characteristic curve. RESULTS: A total of 34 patients were included, 23 of whom underwent preoperative biliary drainage. FLD was significantly higher in patients with drained lobes than that in patients with undrained lobes (0.615 ± 0.190 versus 0.500 ± 0.211, P < 0.05). Sixteen patients suffered PHLF. The ratio of future remnant to total morphological liver volume, future remnant FLD, and PRI differed significantly in patients with and without PHLF according to univariate analysis. PRI was identified as the only independent factor for prediction of PHLF according to multivariate analysis. With a PRI of 0.78, it was possible to predict PHLF with a sensitivity of 83% and a specificity of 93%. CONCLUSIONS: Tc-GSA SPECT/CT can accurately assess regional liver function and is better able to predict PHLF than conventional methods in patients with hCCA.

miR-21-3p regulates AGE/RAGE signalling and improves diabetic atherosclerosis.

To explore the effects of miR-21-3p on diabetic atherosclerosis. Using enzyme-linked immunosorbent assay (ELISA), we also detected the levels of soluble receptor for advanced glycation endproducts RAGE (sRAGE) in the cellular supernatant of vascular endothelial cells after transfecting them with adenovirus vector having miR-21-3p mimic or inhibitor. We found decrease in the expression levels of miR-21-3p in vascular endothelial cells (VECs) induced by high-concentration glucose. We also observed that the introduction of miR-21-3p mimic significantly increased the expression of ADAM10 in the VECs. Similarly, significantly higher levels of sRAGE were found in the cultured supernatant after administration of miR-21-3p mimic in human vein endothelial cells. The production of reactive oxygen species and expression of inflammatory cytokines in VECs induced by LPS and high-concentration glucose were significantly decreased after administration of miR-21-3p. in vivo studies revealed that intravenous injection of miR-21-3p at regular intervals would reduce the area of atherosclerotic lesion and elevate the serum levels of sRAGE in atherosclerotic diabetic mice. miR-21-3p may be beneficial in diabetic atherosclerosis by promoting the cleaved form of sRAGE and inhibition of RAGE/NADPH oxidase signalling depending on the increased expression of ADAM10. SIGNIFICANCE OF THE STUDY: We identified a novel microRNA, miR-21-3p, which is characteristically at elevated levels in serum derived from diabetic patients and responsible for target degradation of ADAM10 mRNA. Further, we show that miR-21-3p aggravates the atherosclerotic lesion via dysfunction of the ectodomain shedding of molecular binding RAGE in the diabetic atherosclerotic mice.

Glomerular filtration rate measured by 99mTc-DTPA Gates method is not significantly affected by the premature or delayed initiation of image acquisition.

BACKGROUND: This study was performed to examine the effect of non-synchronization of the radiotracer injection and image acquisition on estimates of the glomerular filtration rate (GFR) by the Gates' method. METHODS: A total of 218 volunteers were selected as the research subjects. Two-sample method (GFRdt) and 99mTc-DTPA dynamic renal imaging (GFRGates) were used for determination of the GFR. We took GFRdt as the reference method, and then took the peak time of blood perfusion phase as the new time origin to ensure that all patients were unified on the time-radioactivity count rate curve. We moved the radioactivity curve on 9 time points to simulate premature (+20/+15/+10/+5 seconds), synchronous (0 seconds), and delayed (-20/-15/-10/-5 seconds) image acquisition in relation to the completion of tracer injection; we then acquired 9 GFRGates. The correlation and consistency of GFRGates and GFRdt were analyzed. Variance analysis compared the differences between different GFRGates. RESULTS: All 9 GFRGates had good correlation with GFRdt. GFRdt and GFRGates derived from -5, -10 and -15 s had the best correlation (r=0.827, P<0.01). The consistency between GFRGates derived from +20 s and GFRdt was the worst, and GFRGates derived from -15 s and GFRdt was the best. There were no significant differences between the 9 GFRGates. CONCLUSIONS: Non-synchronization of the radiotracer injection and image acquisition has no significant effect on the estimates of the GFRGates if the premature or delayed time between image acquisition and tracer injection is not more than 20 seconds.

Investigation of the Incidence of Perioperative Pulmonary Embolism in Patients with Below-Knee Deep Vein Thrombosis after Lower Extremity Fracture and Evaluation of Retrievable Inferior Vena Cava Filter Deployment in These Patients.

BACKGROUND: The objectives of the study were to investigate and compare the incidence of perioperative pulmonary embolism (PE) in trauma patients with below-knee deep vein thrombosis (BKDVT) and above-knee DVT (AKDVT) who need major orthopedic surgery and evaluate the usage of inferior vena cava (IVC) filters in these cases with BKDVT. METHODS: Between January 2003 and December 2017, patients with pelvic and/or lower extremity fracture diagnosed with DVT by duplex ultrasound were eligible for the study. A reduced-dose anticoagulation therapy was administered in patients without absolute contraindication to anticoagulation therapy during the perioperative period. Patients who did not undergo filter insertion with BKDVT were classified as the BKDVT group, and cases with thrombosis involving the popliteal or more proximal veins were classified as the AKDVT group; the incidence of PE was analyzed. Among patients with BKDVT, cases with or without filter deployment were placed in the filter group and control group, respectively, to evaluate the value of IVC filter in these patients. RESULTS: A total of 3295 patients with pelvic and/or lower extremity fracture were diagnosed as having DVT, among which, 2070 cases did not undergo filter insertion. The incidence of PE in the BKDVT group and AKDVT group was 2.08% (24/1154) and 3.17% (29/916), respectively. A total of 366 patients with BKDVT underwent filter placement and no PE occurred. The incidence of PE in the filter group was lower than the control group. In patients without filter placement, the cases received anticoagulation therapy and those who did not, the incidence of PE was 2.21% and 1.94%, respectively, and there was no difference between the two subgroups. CONCLUSIONS: There was no difference in incidence of PE between the AKDVT and BKDVT groups. Reduced-dose anticoagulation therapy does not affect the rates of PE in trauma patients with BKDVT who require ongoing orthopedics operations. For these patients, placement of the retrievable filter may be considered.

Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLR family pyrin domain containing 3 (NLRP3) inflammasome in diabetic rats.

BACKGROUND: Heparan sulfate (HS) attenuates the inflammatory response and improves diabetic wound healing in rats. However, the specific mechanisms by which HS suppresses inflammation are not clear. Given that NLR family pyrin domain containing 3 (NLRP3) is a major receptor involved in innate immune regulation, the aim of the present study was to elucidate the effects of HS on NLRP3 and proinflammatory cytokines in diabetic wounds. METHODS: Full-thickness wounds were created on the back of diabetic rats. The experimental group received HS treatment (1 mg/kg, i.m., on Days 0 and 7), whereas the control group received vehicle (0.1% dimethylsulfoxide in 0.9% NaCl). Expression of NLRP3 and its downstream effector molecules, namely cleaved interleukin (IL)-1ß, IL-18, tumor necrosis factor (TNF)-α, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), proteinase inhibitor 9, and caspase-12, in the wound tissues was examined. RESULTS: Treatment with HS accelerated wound healing in diabetic rats. Rats treated with HS exhibited decreased activation of cleaved IL-1ß, IL-18, and TNF-α, as well as decreased expression of NLRP3 and ASC. In addition, HS increased levels of proteinase inhibitor 9 and caspase-12. CONCLUSIONS: Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLRP3 inflammasome and cleaved IL-1ß during the wound healing process in diabetic rats.

Three-Dimensional Quantitative Evaluation of the Segmental Functional Reserve in the Cirrhotic Liver Using Multi-Modality Imaging.

To quantitatively evaluate the regional functional reserve in the cirrhotic liver and to seek related index that reflects diminished segmental liver function. A 3D system for quantitative evaluation of the liver was used to fuse technetium-99m galactosyl human serum albumin single-photon emission computed tomography and computed tomography images from 20 patients with cirrhotic liver and hepatocellular carcinoma. A set of parameters reflecting liver function including morphological liver volume, functional liver volume, functional liver density (FLD), and the drug absorption rate constant for hepatic cells (GSA-K) was calculated. Differences in FLD and GSA-K in intrahepatic segments were compared in patients with a tumor embolus (Group Y) and those without such an embolus (Group N) in the right portal vein. Differences in FLD and GSA-K in tumor-bearing (T+ group) and tumor-free (T- group) segments in patients with no tumor embolus (Group N) were also compared. Eleven living donor liver transplantation donor served as the control group. The FLD of the liver as a whole was significantly lower in patients with cirrhosis than in the control group (0.53 ±â€Š0.13 vs 0.68 ±â€Š0.10, P = 0.010). The FLD in segments of the right hemiliver was significantly lower than that in segments of the left hemiliver in Group Y (0.31 ±â€Š0.21 vs 0.58 ±â€Š0.12, P = 0.002) but not in Group N (0.60 ±â€Š0.19 vs 0.55 ±â€Š0.13, P = 0.294). FLD was 0.45 ±â€Š0.17 in the T+ group and 0.60 ±â€Š0.08 in the T- group (P = 0.008). Differences in GSA-K in intrahepatic segments were not significant. In the control group, differences in FLD and GSA-K in intrahepatic segments were not significant. The segmental liver functional reserve can be quantitatively calculated. FLD, but not GSA-K, is an index that reflects diminished regional liver function caused by portal flow obstruction or tumor compression.

Evaluation of nonpermanent inferior vena cava filter placement in patients with deep venous thrombosis after lower extremity fracture: A single-center retrospective study.

OBJECTIVE: To investigate nonpermanent inferior vena cava (IVC) filter in the prevention of perioperative pulmonary embolism (PE) in patients of lower extremity and/or pelvic bone fracture with deep vein thrombosis (DVT). METHODS: Lower extremity or pelvic bone fracture patients with lower extremity DVT hospitalized in our hospital from January 2003 to October 2014 were retrospectively analyzed. Data was analyzed for age, gender, position of fracture, position of proximal of thrombosis, indications of placement, complications, retrieval rate, and rate of entrapped filter clot. Patients who underwent IVC filter placement were selected as the filter group. The patients who did not perform IVC filter placement after 2008 and the cases between January 2003 and December 2007 were selected as control group 1 and control group 2, respectively. The incidence of perioperative symptomatic PE and mortality were analyzed. RESULTS: A total of 2763 cases complicated with DVT underwent orthopedic surgery between January 2003 and October 2014. 823 nonpermanent filters were inserted. All filters were successfully deployed with no major complications. After a mean 14.2 days indwelling time, all of temporary filters were removed. Retrieval was attempted in 556 patients with retrievable filters and was successful in 545 (98%); mean indwelling time was 16.3 days. The total retrieval rate was 90%. The incidence of PE in the filter group was significantly lower compared with the two control groups. Among the patients who received chemical anticoagulant therapy, the incidence of PE in filter group, control group 1 and control group 2 were 0.14%, 1.60% and 2.10%, respectively. The incidence of PE in filter group was also significant lower compared with control groups. CONCLUSION: Nonpermanent IVC filter placement seems like to be a safe and effective method for preventing perioperative symptomatic and fatal PE in bone fracture patients with DVT in the present retrospective study.

[A single-center retrospective study on the intraluminal implantation of inferior vena cava filter for the lower extremity trauma patients with deep venous thrombosis].

OBJECTIVE: To evaluate the application of inferior vena cava filter (IVCF) in prevention of peri-operative pulmonary embolism (PE) in lower limb bone fracture patients with deep venous thrombosis (DVT). METHODS: From January 2003 to December 2012, 2 248 cases of lower limb and pelvic fractures with DVT were retrospectively analyzed. Before the procedure of IVCF implantation began, January 2003 to December 2007, there were 1 052 cases of acute trauma patients with DVT were classified as the group of early none-IVCF. The IVCF implantation was began since January 2008. From that time to December 2012, 712 cases of bone fractures with DVT received filter implantation, which were classified as IVCF group. The other 484 patients who had not undergone filter deployment were divided as group of late none-IVCF. The baseline conditions of the three groups were significantly different in addition to the ages between group of early none-IVCF and IVCF group. The incidences of PE and mortality of PE in each group were recorded and analyzed by χ(2) test. RESULTS: There were totally 31 cases of symptomatic PE, among which 12 cases died. Totally 712 filters were deployed successfully without any major complications. The incidences of symptomatic PE were 0.14% (1/712), 2.19% (23/1 052) and 1.45% (7/484) in IVCF group, group of early none-IVCF and group of late none-IVCF, respectively. The mortality of PE were 0 (0/712), 0.86% (9/1 052) and 0.62% (3/484) in these groups. The incidence of symptomatic PE in IVCF group was significantly different from that in the group of early and late none-IVCF (χ(2) = 11.762, P = 0.001; χ(2) = 7.395, P = 0.007, respectively). The mortality of IVCF group was also significantly lower compared with the other two groups (χ(2) = 6.122, P = 0.013; χ(2) = 4.424, P = 0.035, respectively). CONCLUSION: IVCF implantation effectively prevents symptomatic and fatal PE of patients of lower limb and pelvic fractures with DVT in the peri-operative period.

[Combined use of occluder plus bare stent in the treatment of aortic dissection with tear at the area of visceral branches].

OBJECTIVE: To evaluate the novel method of combinedly use of occluder and bare stent in the treatment of aortic dissection with distal tear at visceral branches. METHODS: From April 2010 to September 2012, 6 patients (5 male and 1 female patients, aged from 29 to 62 years, mean 47.2 years) were diagnosed as Stanford type B aortic dissection that been revealed by CT angiography. The main tears were sealed with stent-grafts firstly, and then the tears at the visceral branch area were evaluated that impossible to close spontaneously. Atrium septal defect occluder and ventricular septal defect were implanted at the tears with the anterior disc in false lumen, while the posterior disc in the true lumen. After that, the bare stents were implanted in the true lumen to pull the occluders on the aortic wall. RESULTS: Among the 6 procedures, occluders were successfully implanted in 5 cases, and 1 failed anchoring at the tear, and the alternative method of coils embolization was applicated. After all the procedures, the immediate aortogrophy revealed that the false lumen disappeared in the 5 cases that occluders were used, and the visceral branches were all patent. No paraplegia, lesion of visceral organs or other complications occurred. All the cases were followed at least 5 months. There was one endoleak due to a non-sealed tear at the descending aorta, one new-occurred small tear in the descending aorta but with no communication to the false lumen. CONCLUSIONS: The combinedly use of occluder and bare stent in the treatment of aortic dissection with tears at the visceral branch area is a sum of two simple technique plus each other. It is easily to master. The lesions at the aortic that ordinary stent-grafting incapable to seal are successfully solved then. The huge trauma of open or hybrid procedures are avoided.

[Assessment of hepatic reserve function of cirrhosis liver using dynamic SPECT (99m)Tc-galactosyl human serum albumin scintigraphy].

OBJECTIVE: To evaluate the effectiveness of dynamic SPECT (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy on the assessment of reserve function of cirrhosis liver. METHODS: From January 2010 to December 2011, 55 patients with cirrhosis liver were enrolled in this study. The case numbers of male and female were 43 and 12 respectively and the age was (51 ± 9) years (ranging from 35 to 69 years). After routine biochemistry test, CT scan and (99m)Tc-GSA dynamic SPECT scan were performed in turn using a juxtaposed SPECT/CT system. Then the morphologic volume of liver parenchyma (MLV), functional liver volume (FLV) and the hepatic cell absorption rate constant (GSA-K) were calculated. The correlations between GSA-K and routine biochemistry test, Child-Pugh score, indocyanine green clearance rate (ICG-K) were analyzed. The patients were further divided into 3 groups according to whether there was occlusion or stenosis in the main branch of left portal vein (group 1, n = 5), right portal vein (group 2, n = 13) or not (group 3, n = 37) and the regional hepatic functions index of the 3 groups were compared. RESULTS: The value of FLV of the whole, left and right liver was (594 ± 152) ml, (244 ± 119) ml and (356 ± 171) ml, respectively. There were correlations between GSA-K and total bilirubin, prothrombintime, Child-Pugh score and ICG-K (r = -0.730--0.298, P < 0.05). The FLV and MLV ratios of involved hemiliver to uninvolved hemiliver were 0.09 ± 0.06 and 0.30 ± 0.14 in group 1, 0.57 ± 0.43 and 1.08 ± 0.63 in group 2, 0.71 ± 0.30 and 0.71 ± 0.48 in group 3. The difference in MLV-FLV ratio was signifcant between group 1 and group 3, between group 2 and group 3 (P = 0.000). CONCLUSIONS: The dynamic SPCECT (99m)Tc-GSA scintigraphy can not only assess the whole liver function of cirrhosis liver effectively, but also evaluate the variation of regional liver function accurately.

[Application of inferior vena cava filters in prevention of peri-operative pulmonary embolism in patients with bone fracture combined with deep venous thrombosis: a report of 572 cases].

OBJECTIVES: To evaluate the application of inferior vena cava filter (IVCF) in prevention of peri-operative pulmonary embolism in patients with bone fracture combined with deep venous thrombosis (DVT). METHODS: From July 2007 to April 2011, 572 cases of bone fractures consequent with DVT that confirmed by Duplex were deployed IVCF to avoid fatal pulmonary embolism in the para-operative period. There were 318 male and 254 female patients with a mean age of (51±23) years (ranging from 16 to 94 years). RESULTS: All the operations of deployment of the IVCFs were successfully. There were 174 permanent and 399 temporary IVCFs deployed. In all 399 temporary filters, 389 filters were taken out successfully. The mean station time in the IVC of the temporary filters was 22.8 days (7 to 60 days), among which, 118 were found of captured thrombus. After the follow-up of mean 16 months (3 to 40 months) of 566 patients, no pulmonary embolism occurred, but symptomatic DVT were revealed in 15 patients, and the conditions were improved after anticoagulation treatment. No serious complication of post thrombotic syndrome occurred. CONCLUSION: IVCF deployment can prevent the trauma patients with deep vein thrombosis of fatal pulmonary embolism in the peri-operative period, which may also offer a safe condition to the orthopedic operations.

Review of clinical investigation on recurrence of gastric cancer following curative resection.

OBJECTIVE: To discuss the present status and progress of clinical research on recurrence of gastric cancer after surgery, including patterns, clinicopathologic factors, prognosis, detection, diagnosis, prevention, and treatment strategies. DATA SOURCES: The data used in this review were mainly from PubMed articles published in English from 2000 to August 2011. The search terms were "gastric cancer" and "recurrence". STUDY SELECTION: Articles were selected if they involved clinicopathologic factors, detection methods, and treatment strategies of recurrence of gastric cancer. RESULTS: Peritoneal recurrence is the most common pattern in recurrence of gastric cancer. The main risk factors for recurrence of gastric cancer are tumor stage, including depth of tumor invasion and lymph node metastasis, and Borrmann classification. The prognosis of patients with recurrence is very poor, especially patients with peritoneal recurrence. Systemic chemotherapy is still the main treatment method for patients with recurrent cancer. If complete resection can be accomplished, some benefits may be obtained from surgery for recurrence. However, standard treatment for patients with recurrence has not yet been established. CONCLUSIONS: Early detection and diagnosis of recurrence is quite crucial for treatment and prognosis. The optimal therapeutic strategy for recurrence should be based on a multidisciplinary assessment and the patient's individual state and should involve combined therapy.

Predictive factors improving survival after gastric and hepatic surgical treatment in gastric cancer patients with synchronous liver metastases.

BACKGROUND: The prognosis for patients with gastric cancer and synchronous liver metastases is very poor. However, a standard therapeutic strategy has not been well established. The clinical benefit and prognostic factors after hepatic surgical treatment for liver metastases from gastric cancer remain controversial. METHODS: Records of 105 patients who underwent gastrectomy regardless of hepatic surgical treatment for gastric cancer with synchronous liver-only metastases in our center between 1995 and 2010 were retrospectively reviewed. RESULTS: The overall survival rate for the 105 patients was 42.1%, 17.2%, and 10.6% at 1, 2, and 3 years, respectively, with a median survival time of 11 months. Multivariate survival analysis revealed that the extent of lymphadenectomy (D) (P < 0.001), lymph node metastases (P < 0.001), extent of liver metastases (H) (P = 0.008), and lymphovascular invasion (P = 0.002) were significant independent prognostic factors for survival. Among patients who underwent D2 lymphadenectomy, those who underwent hepatic surgical treatment had a significantly improved survival compared with those who underwent gastrectomy alone (median survival, 24 vs. 12 months; P < 0.001). However, hepatic surgical treatment was not a prognostic factor for patients who underwent D1 lymphadenectomy (median survival, 8 vs. 8 months; P = 0.495). For the 35 patients who underwent gastrectomy plus hepatic surgical treatment, D2 lymphadenectomy (P < 0.001), lymph node metastases (P = 0.015), and extent of liver metastases (H1 vs. H2 and H3) (P = 0.017) were independent significant prognostic factors for survival. CONCLUSIONS: D2 lymphadenectomy plus hepatic surgical treatment may provide hope for long-term survival of judiciously selected patients with hepatic metastases from gastric cancer. Patients with a low degree of lymph node metastases and H1 liver metastases would make the most appropriate candidates. However, if D2 dissection cannot be achieved, hepatic surgical treatment is not recommended.

Can multimodality imaging using 18F-FDG/18F-FLT PET/CT benefit the diagnosis and management of patients with pulmonary lesions?

PURPOSE: Dual-tracer, (18)F-fluorodeoxyglucose and (18)F-fluorodeoxythymidine ((18)F-FDG/(18)F-FLT), dual-modality (positron emission tomography and computed tomography, PET/CT) imaging was used in a clinical trial on differentiation of pulmonary nodules. The aims of this trial were to investigate if multimodality imaging is of advantage and to what extent it could benefit the patients in real clinical settings. METHODS: Seventy-three subjects in whom it was difficult to establish the diagnosis and determine management of their pulmonary lesions were prospectively enrolled in this clinical trial. All subjects underwent (18)F-FDG and (18)F-FLT PET/CT imaging sequentially. The images were interpreted with different strategies as either individual or combined modalities. The pathological or clinical evidence during a follow-up period of more than 22 months served as the standard of truth. The diagnostic performance of each interpretation and their impact on clinical decision making was investigated. RESULTS: (18)F-FLT/(18)F-FDG PET/CT was proven to be of clinical value in improving the diagnostic confidence in 28 lung tumours, 18 tuberculoses and 27 other benign lesions. The ratio between maximum standardized uptake values of (18)F-FLT and (18)F-FDG was found to be of great potential in separating the three subgroups of patients. The advantage could only be obtained with the full use of the multimodality interpretation. Multimodality imaging induced substantial change in clinical management in 31.5% of the study subjects and partial change in another 12.3%. CONCLUSION: Multimodality imaging using (18)F-FDG/(18)F-FLT PET/CT provided the best diagnostic efficacy and the opportunity for better management in this group of clinically challenging patients with pulmonary lesions.

The value of vesicant 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in gastric malignancies.

AIM: The value of vesicant 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the detection and staging of primary gastric malignancies was studied prospectively. METHODS: Thirty-eight patients with suspected gastric tumour were imaged with three-dimensional PET after the injection of 18F-FDG. During the PET study, vesicant was given orally in order to extend the stomach with CO(2) gas. Surgical operation (n=31) or gastric endoscopy with biopsy (n=7) was undertaken 3-26 days after the PET study. The PET results were compared with clinical (computed tomography/magnetic resonance imaging/ultrasound), surgical and histological staging. RESULTS: PET correctly diagnosed 83.3% of primary malignant (25/30) and benign (7/8) lesions, and corrected 11 clinically and five surgically mis-staged cases. Five primaries were false-negatives in quantitative analysis, but qualitative PET readings revealed positive lymph nodes, thereby providing a correct diagnosis in two of the five. PET misdiagnosed seven N1, one N2 and one false-positive case. The focal uptake of 18F-FDG was correlated with the differentiation, size and depth of invasion of the gastric tumours. CONCLUSIONS: 18F-FDG PET is useful for the detection and staging of primary gastric malignancies, and the administration of vesicant may improve the diagnostic confidence.

[Value of FDG PET for mediastinal lymph node staging in non-small cell lung cancer].

BACKGROUND: To evaluate the diagnostic significance of FDG PET in preoperative mediastinal lymph node staging for NSCLC. METHODS: Whole-body FDG PET imaging was performed in 70 patients with NSCLC. All patients received thoracic CT examination 2 weeks before PET scan or 1 week after PET scan, and then were given thoracotomy with hilar and mediastinal lymph nodes dissection. After intravenous administration of 18F-FDG (150µCi/kg), PET scan was performed in 3-7 bed positions with 2D acquisition and OSEM reconstruction. For quantitative evaluation, a region of interest (ROI) was placed over the mediastinal lymph node which had abnormal uptake of radiation activity, then the standardized uptake value (SUV) were calculated. If SUV≥2.5 or uptake activity was higher than the blood pool of mediastinal on the basis of visual inspection, it was considered to be positive. RESULTS: The sensitivity, specificity and accuracy of PET were 100%, 93% and 94%, respectively. The positive lymph nodes diagnosed by PET correctly corresponded to pathological results. PET changed the clinical staging of 12 patients. The sensitivity, specificity and accuracy of CT were 70%, 77% and 76%, respectively. CONCLUSIONS: PET is an effective modality for accurate mediastinal lymph node staging in patients with NSCLC. It is valuable for determining clinical treatment.