Rectal gastrointestinal stromal tumors:Imaging features with clinical and pathological correlation

AIM:To investigate computed tomography(CT) and magnetic resonance imaging(MRI) manifestations of rectal gastrointestinal stromal tumors(GISTs) in order to enhance the recognition of these rare tumors.METHODS:Fourteen patients with pathologically proven rectal GISTs were retrospectively reviewed.Patient histories were retrospectively reviewed for patient age,gender,presenting symptoms,endoscopic investigations,operation notes and pathologic slides.All tumors were evaluated for CD117,CD34 expression,and the tumors were stratified according to current criteria of the National Institutes of Health(NIH).In all cases the first pre-operation imaging findings(CT and MRI,n = 3;MRI only,n = 8;CT only,n = 3) were analyzed by two experienced radiologists by consensus,which include:tumor size,shape,CT density(hypodense,isodense and hyperdense),MRI signal intensity(hypointense,isointense and hyperintense),epicenter(intraluminal or extraluminal),margin(well-defined or ill-defined),internal component(presence of calcifications,necrosis,hemorrhage or ulceration),pattern and degree of enhancement,invasion into adjacent structures.After review of the radiologic studies,clinical and pathological findings were correlated with radiological findings.RESULTS:The patients,13 men and 1 woman,were aged 31-62 years(mean = 51.5 ± 10.7 years).The most common initial presentation was hematochezia(n = 6).The mean tumor diameter was 5.68 ± 2.64 cm(range 1.5-11.2 cm).Eight lesions were round or oval,and 6 lesions were irregular.Eleven lesions were welldefined and 3 had ill-defined margins.Ten tumors were extraluminal and 4 were intraluminal.The density and MR signal intensity of the solid component of the lesions were similar to that of muscle on unenhanced CT(n = 6) and T1-weighted images(n = 11),and hyperintense on T2-weighted MR images.Calcification was detected in 2 tumors.Following intravenous injection of contrast media,3 lesions had mild enhancement and 11 lesions had moderate enhancement.Enhancement was homogenous in 3 lesions and heterogeneous in 11.In 1 of 11 patients who underwent both CT and MRI,the tumor was homogenous on CT scan and heterogeneous on MRI.Eight patients were classified as high risk according to the modified recurrent risk classification system of NIH.CONCLUSION:Rectal GISTs usually manifest as large,well-circumscribed,exophytic masses with moderate and heterogeneous enhancement on CT and MRI.The invasion of adjacent organs,bowel obstruction and local adenopathy are uncommon.

Comparison of total splenic artery embolization and partial splenic embolization for hypersplenism

AIM:To evaluate whether total splenic artery embolization(TSAE) for patients with hypersplenism delivers better long-term outcomes than partial splenic embolization(PSE).METHODS:Sixty-one patients with hypersplenism eligible for TSAE(n = 27,group A) or PSE(n = 34,group B) were enrolled into the trial,which included clinical and computed tomography follow-up.Data on technical success,length of hospital stay,white blood cell(WBC) and platelet(PLT) counts,splenic volume and complications were collected at 2 wk,6 mo,and 1,2,3,4 years postoperatively.RESULTS:Both TSAE and PSE were technically successful in all patients.Complications were significantly fewer(P = 0.001),and hospital stay significantly shorter(P = 0.007),in group A than in group B.Postprocedure WBC and PLT counts in group A were significantly higher than those in group B from 6 mo to 4 years(P = 0.001),and post-procedure residual splenic volume in group A was significantly less than that observed in group B at 1,2,3 and 4 years post-procedure(P = 0.001).No significant differences were observed in red blood cell counts and liver function parameters between the two groups following the procedure.CONCLUSION:Our results indicate that TSAE for patients with hypersplenism not only delivers a better longterm outcome,but is also associated with lower complication rates and a shorter hospital stay than PSE.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients:a multicenter,open-label,phase Ⅲ study

BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy tissue.This study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese patients.METHODS:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging.MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded radiologists.The primary efficacy endpoint was sensitivity in lesion detection.RESULTS:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than 1cm.Gd-EOB-DTPA improved diagnostic accuracy in lesion classification.CONCLUSIONS:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 cm.Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

IN VIVO ~1 H MAGNETIC RESONANCE SPECTROSCOPY IN EVALUATION OF HEPATOCELLULAR CARCINOMA AND ITS EARLY RESPONSE TO TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION

Objective To investigate the value of in vivo proton magnetic resonance spectroscopy （MRS） in the assessment of hepatocelhilar carcinoma （HCC） and monitor its metabolic change shortly after transcatheter arterial chemoembolization （TACE）. Mothoda In this prospective study, 28 consecutive patients with large HCC （ ≥3 cm in diameter） confirmed by fine needle aspiration biopsy were recruited. The ^1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1.5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor. The technical success rate of IH MRS in liver was high （33/41, 80% ）, closely related to breath motion, location of lesion, and size of voxeL In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended （ choline-to-lipid ratios from 0.352±0. 080 to 0. 167±0. 030, P = 0. 026; from 0. 205±0. 060 to 0. 070±0. 020, P = 0. 042, respectively ） ; yet lipid resonance peak ascended. Conclusions In vivo tH MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. IH MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.

Xuefu Zhuyu decoction improves neurological dysfunction by increasing synapsin expression after traumatic brain injury

Xuefu Zhuyu decoction has been used for treating traumatic brain injury and improving post-traumatic dysfunction, but its mechanism of action needs further investigation. This study established rat models of traumatic brain injury by controlled cortical impact. Rat models were intragastrically administered 9 and 18 g/kg Xuefu Zhuyu decoction once a day for 14 or 21 days. Changes in neurological function were assessed by modified neurological severity scores and the Morris water maze. Immunohistochemistry, western blot assay, and re- verse-transcription polymerase chain reaction were used to analyze synapsin protein and mRNA expression at the injury site of rats. Our results showed that Xuefu Zhuyu decoction visibly improved neurological function of rats with traumatic brain injury. These changes were accompanied by increased expression of synaptophysin, synapsin I, and postsynaptic density protein-95 protein and mRNA in a dose-de- pendent manner. These findings indicate that Xuefu Zhuyu decoction increases synapsin expression and improves neurological deficits alder traumatic brain injury.

Effect of b value on monitoring therapeutic response by diffusion-weighted imaging

AIM： To explore the diffusion gradient b-factor that optimizes both apparent diffusion coefficient （ADC） measurement and contrast-to-noise （CNR） for assessing tumor response to transarterial chemoembolization （TACE） in a rabbit model. METHODS： Twelve New Zealand white rabbits bearing VX2 tumors in the liver were treated with TACE. Diffusion-weighted imaging （DWI） with various b values was performed using the same protocol before and 3 d after treatment with TACE. ADC values and CNR of each tumor pre- and post-treatment with different b factors were analyzed. Correlation between ADC values and extent of necrosis in histological specimens was analyzed by a Pearson＇s correlation test.RESULTS： The quality of diffusion-weighted images diminished as the b value increased. A substantial decrease in the mean lesion-to-liver CNR was observed on both pre- and post-treatment DW images, the largest difference in CNR pre- and post-treatment was manifested at a b value of 1000 s/mm^2 （P = 0.036 ）. The effect of therapy on diffusion early after treatment was shown by a significant increase in ADCs （P = 0.007）, especially with large b factors （≥ 600 s/mm^2）. The mean percentage of necrotic cells present within the tumor was 76.3%-97.5%. A significant positive correlation was found between ADC values and the extent of necrosis with all b values except for b200, a higher relative coefficient between ADC values and percentage of necrosis was found on DWI with bl000 and b2000 （P = 0.002 and 0.006, respectively）. CONCLUSION： An increasing b value of up to 600 s/mm^2 would increase ADC contrast pre- and post-treatment, but decrease image quality. Taking into account both CNR and ADC measurement, diffusion-weighted imaging obtained with a b value of 1000 s/mm^2 is recommended for monitoring early hepatic tumor response to TACE.

Total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism

AIM:To study the safety and feasibility of total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis.METHODS:Fifteen consecutive patients with hypersplenism due to cirrhosis were enrolled in this study from January 2006 to June 2010.All patients underwent total embolization of the main splenic artery.Clinical symptoms,white blood cell(WBC) and platelet(PLT) counts,splenic volume,and complications of the patients were recorded.The patients were followed up for 1 and 6 mo,and 1,2,3 years,respectively,after operation.RESULTS:Total embolization of the main splenic artery was technically successful in all patients.Minor complications occurred in 13 patients after the procedure,but no major complications were found.The WBC andPLT counts were significantly higher and the residual splenic volume was significantly lower 1 and 6 mo,and 1,2,3 years after the procedure than before the procedure(P < 0.01).Moreover,the residual splenic volume increased very slowly with the time after embolization.All patients were alive during the follow-up period.CONCLUSION:Total embolization of the main splenic artery is a safe and feasible procedure and may serve as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis.

Assessment of hemodynamics in precancerous lesion of hepatocellular carcinoma:Evaluation with MR perfusion

AIM: To investigate the hemodynamic changes in a precancerous lesion model of hepatocellular carcinoma (HCC). METHODS: Hemodynamic changes in 18 Wistar rats were studied with non-invasive magnetic resonance (MR) perfusion. The changes induced by diethylnitrosamine (DEN) developed into liver nodular lesions due to hepatic cirrhosis during the progression of carcinogenesis. The MR perfusion data [positive enhancement integral (PEI)] were compared between the nodular lesions corresponding well with MR images and pathology and their surrounding hepatic parenchyma. RESULTS: A total of 46 nodules were located by MR imaging and autopsy, including 22 dysplastic nodules (DN), 9 regenerative nodules (RN), 10 early HCCs and 5 overt HCCs. Among the 22 DNs, 6 were low-grade DN (lGDN) and 16 were high-grade DN (HGDN). The average PEI of RN, DN, early and overt HCC was 205.67 ± 31.17, 161.94 ± 20.74, 226.09 ± 34.83, 491.86 ± 44.61 respectively, and their liver parenchyma nearby was 204.84 ± 70.19. Comparison of the blood perfusion index between each RN and its surrounding hepatic parenchyma showed no statistically significant difference (P = 0.06). There were significant differences in DN (P = 0.02). During the late hepatic arterial phase, the perfusion curve in DN declined. DN had an iso-signal intensity at the early hepatic arterial phase and a low signal intensity at the portal venous phase. Of the 10early HCCs, 4 demonstrated less blood perfusion and 6 displayed minimally increased blood flow compared to the surrounding parenchyma. Five HCCs showed significantly increased blood supply compared to the surrounding parenchyma (P = 0.02). CONCLUSION: Non-invasive MR perfusion can detect changes in blood supply of precancerous lesions.

Protective effects of Bushen Tiansui decoction on hippocampal synapses in a rat model of Alzheimer's disease

Bushen Tiansui decoction is composed of six traditional Chinese medicines：Herba Epimedii,Radix Polygoni multiflori,Plastrum testudinis,Fossilia Ossis Mastodi,Radix Polygalae,and Rhizoma Acorus tatarinowii.Because Bushen Tiansui decoction is effective against amyloid beta（Aβ） toxicity,we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer＇s disease.To test this hypothesis,we used a previously established animal model of Alzheimer＇s disease,that is,microinjection of aggregated Aβ25–35 into the bilateral brain ventricles of Sprague-Dawley rats.We found that long-term（28 days） oral administration of Bushen Tiansui decoction（0.563,1.688,and 3.375 g/m L;4 m L/day） prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins,including postsynaptic density protein 95,the N-methyl-D-aspartate receptor 2 B subunit,and Shank1.These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins.Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze（i.e.,increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency） following intraventricular injections of aggregated Aβ25–35 compared with those measures in untreated Aβ_（25–35）-injected rats.Overall,these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.

Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse xenograft model using magnetic resonance spectroscopy and principal components analysis

AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect. METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm3 , the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. 1H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiationtreated pancreatic tumor tissues were compared. RESULTS: Compared with 1H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the 1H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased. CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.

Genome-wide analysis of hippocampal transfer RNA-derived small RNAs identifies new potential therapeutic targets of Bushen Tiansui formula against Alzheimer’s disease

Objective:Bushen Tiansui formula(BSTSF),a traditional Chinese medicine prescription,has been widely used to treat Alzheimer’s disease(AD).However,the mechanisms underlying its effects remain largely unknown.In this study,a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs(tsRNAs)in the hippocampus,to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs,a novel small non-coding RNA.Methods:To generate a validated AD model,oligomeric amyloid-β_(1-42)(Aβ_(1-42))was injected intracerebroventricularly into rats.The Morris water maze(MWM)test was used to evaluate rat cognitive performance,and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus.Potential targets were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs.Results:The learning and memory deficits of Aβ_(1-42)-induced AD rats,assessed by MWM tests,were clearly ameliorated by BSTSF treatment.A total of 387 tsRNAs were detected in the rat hippocampus.Among them,13 were significantly dysregulated in AD rats compared with sham control rats,while 57 were markedly altered by BSTSF treatment,relative to untreated AD rats(fold change>2 and P<0.05).Moreover,six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR.Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles,via multiple signaling pathways and Gene Ontology biological functions,including cyclic adenosine monophosphate and retrograde endocannabinoid signaling.Conclusion:This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aβ_(1-42)-induced AD rats,demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.