IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.

Many people living with diabetes also have nonalcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating (trans-signaling) soluble receptors. We investigated whether secretion of IL-6 trans-signaling coreceptors are altered in NAFLD by diabetes and whether this might associate with the severity of fatty liver disease. Secretion patterns were investigated with use of human hepatocyte, stellate, and monocyte cell lines. Associations with liver pathology were investigated in two patient cohorts: 1) biopsy-confirmed steatohepatitis and 2) class 3 obesity. We found that exposure of stellate cells to high glucose and palmitate increased IL-6 and soluble gp130 (sgp130) secretion. In line with this, plasma sgp130 in both patient cohorts positively correlated with HbA1c, and subjects with diabetes had higher circulating levels of IL-6 and trans-signaling coreceptors. Plasma sgp130 strongly correlated with liver stiffness and was significantly increased in subjects with F4 fibrosis stage. Monocyte activation was associated with reduced sIL-6R secretion. These data suggest that hyperglycemia and hyperlipidemia can directly impact IL-6 trans-signaling and that this may be linked to enhanced severity of NAFLD in patients with concomitant diabetes. ARTICLE HIGHLIGHTS: IL-6 and its circulating coreceptor sgp130 are increased in people with fatty liver disease and steatohepatitis. High glucose and lipids stimulated IL-6 and sgp130 secretion from hepatic stellate cells. sgp130 levels correlated with HbA1c, and diabetes concurrent with steatohepatitis further increased circulating levels of all IL-6 trans-signaling mediators. Circulating sgp130 positively correlated with liver stiffness and hepatic fibrosis. Metabolic stress to liver associated with fatty liver disease might shift the balance of IL-6 classical versus trans-signaling, promoting liver fibrosis that is accelerated by diabetes.

Portal vein embolization does not affect the long-term survival and risk of cancer recurrence among colorectal liver metastases patients: A prospective cohort study.

BACKGROUND: Previous studies comparing the survival outcomes of liver resections with and without preoperative portal vein embolization (PVE) for colorectal liver metastases (CLM) have linked PVE to higher rate of tumor progression, lower overall survival (OS) and lower disease-free survival (DFS). The lack of adjusted models to compare these outcomes is a limitation of these studies since patients requiring PVE may differ significantly from the ones receiving upfront surgery. MATERIALS AND METHODS: Prospective cohort study of 128 patients undergoing CLM resection. The OS analysis followed an intent-to-treat (ITT) approach. The adjusted impact of PVE on OS and DFS was evaluated using multivariate Cox regression models. RESULTS: Seventy-one patients underwent PVE before attempting a liver resection while 57 received upfront surgery (NoPVE). All NoPVE patients were resected while 14 PVE participants (19.7%) were not operated (tumor progression = 9/14). PVE patients had a significantly higher preoperative lesions count (3 [1.75-4] vs 1 [1-2.5]; p < 0.001), a higher prevalence of bilateral metastases (23.5% vs 8.8, p = 0.028) and a higher count of neo-adjuvant chemotherapy cycles compared to NoPVE patients. The OS of PVE patients was similar to NoPVE participants (44.7 months [26.9-69.5] vs 49.0 [24.9-64.8], p = 0.761). The DFS of resected PVE patients was higher than NoPVE patients (33.2 months [10.7-54.6] vs 23.4 months [14.1-58.1], p = 0.991). In the adjusted models, preoperative lesions count was the only significant predictor of overall mortality (HR+IC95 = 1.06 (1.02-1.11) p = 0.005) and cancer recurrence (HR+IC95 = 1.14 (1.03-1.27) p = 0.012). CONCLUSION: In the context of CLM, patients requiring PVE differ significantly from patients receiving upfront surgery. This confirms the need for adjusted models when comparing the clinical outcomes of both groups. Our adjusted analysis suggests that PVE is not a significant predictor of a lower OS or DFS. PVE allowed the resection of 80% of participants with initially unresectable CLM. INSTITUTIONAL PROTOCOL NUMBER: 12.106 STUDY REGISTRATION NUMBER: NCT03168230.

Comparison of techniques for volumetric analysis of the future liver remnant: implications for major hepatic resections.

OBJECTIVE: The purpose of this work was to compare measured and estimated volumetry prior to liver resection. METHODS: Data for consecutive patients submitted to major liver resection for colorectal liver metastases at two centres during 2004-2012 were reviewed. All patients underwent volumetric analysis to define the measured total liver volume (mTLV) and measured future liver remnant ratio (mR(FLR)). The estimated total liver volume (eTLV) standardized to body surface area and estimated future liver remnant ratio (eR(FLR)) were calculated. Descriptive statistics were generated and compared. A difference between mR(FLR) and eR(FLR) of ±5% was considered clinically relevant. RESULTS: Data for a total of 116 patients were included. All patients underwent major resection and 51% underwent portal vein embolization. The mean difference between mTLV and eTLV was 157 ml (P < 0.0001), whereas the mean difference between mR(FLR) and eR(FLR) was -1.7% (P = 0.013). By linear regression, eTLV was only moderately predictive of mTLV (R(2) = 0.35). The distribution of differences between mR(FLR) and eR(FLR) demonstrated that the formula over- or underestimated mR(FLR) by ≥5% in 31.9% of patients. CONCLUSIONS: Measured and estimated volumetry yielded differences in the FLR of ≥5% in almost one-third of patients, potentially affecting clinical decision making. Estimated volumetry should be used cautiously and cannot be recommended for general use.

Accuracy of preoperative automatic measurement of the liver volume by CT-scan combined to a 3D virtual surgical planning software (3DVSP).

BACKGROUND: Liver volumetry is a critical component of safe hepatic surgery, in order to minimize the risk of postoperative liver failure. Liver volumes can be calculated routinely using the time-consuming gold standard method of manual volumetry. The current work sought to evaluate an alternative automatic technique based on a novel 3D virtual planning software, and to compare it to the manual technique. METHODS: A prospective study of patients undergoing liver resection was conducted. Every patient had a pre and 2-day postoperative CT-scan. For each patient, total, remnant and resected volumes were calculated manually and automatically. Planes of resection were verified by a hepatobiliary surgeon and compared with postoperative volumes. Paired t-tests and correlation coefficients were calculated. RESULTS: A major hepatectomy was carried out in 36/43 patients. The automatic TLV (1,759 mL) and the manual TLV (1,832 mL) were significantly different (p < 0.001), but extremely highly correlated (r = 0.989). The percentages of preoperative RLV (manual 58.5%, automatic 58.9%) were similar, with an excellent correlation of 0.917. The preoperative RLV were matched with the 2-day postoperative RLV showing a significant difference (p = 0.0301). The resected volumes using both techniques (871 and 832 mL) were compared with the resected specimen volume (670 mL), showing a significant difference (p < 0.001) but a high degree of correlation (r = 0.874). CONCLUSION: The 3D virtual surgical planning software is accurate and reliable in determining the total liver and future remnant liver volumes. This technique demonstrates a good correlation with the manual technique. Future work will be required to confirm these findings and to evaluate the clinical value of the three-dimensional planning platform.

Effectiveness of ultrasound-guided corticosteroid injection for the treatment of gluteus medius tendinopathy.

OBJECTIVE: The objective of our study was to evaluate the effectiveness of ultrasound-guided corticosteroid injection for the treatment of gluteus medius tendinopathy. SUBJECTS AND METHODS: We prospectively evaluated 54 consecutive patients (48 women, six men; mean age, 54.7 years; mean body mass index, 26 kg/m2) with a clinical diagnosis of gluteus medius tendinopathy. Pain assessment using a 10-cm visual analog scale (VAS) was obtained as part of the initial clinical evaluation of all patients. A hip ultrasound study was performed followed by a gluteus medius peritendinous ultrasound-guided injection of 30 mg of triamcinolone combined with 3 mL of bupivacaine 0.5% using an anterior oblique coronal plane. One month after treatment, participants were reassessed clinically, and they were asked to quantify their pain using the VAS pain score and their satisfaction with the outcome of the injection using a 4-point rating scale (very satisfied, somewhat satisfied, somewhat dissatisfied, or very dissatisfied). Statistical analysis included a paired Student's t test (comparison of pain levels before and after treatment, p=0.05) and a multivariate analysis of covariance. RESULTS: There was a 55% average reduction of pain level before versus after treatment (mean VAS pain score, 6.4 vs 2.9 cm, respectively; p<0.001). One month after treatment, 72% of the patients showed a clinically significant improvement in pain level, which was defined as a reduction in the VAS pain score of >or=30%. Seventy percent of patients were satisfied with the results of the intervention. No correlation was shown between treatment outcome and any of the clinical variables or ultrasound findings. CONCLUSION: Our study shows that a peritendinous ultrasound-guided corticosteroid injection may be an effective treatment of gluteus medius tendinopathy.

Accuracy and rate of coronary artery segment visualization with CT angiography for the non-invasive detection of coronary artery stenoses.

OBJECTIVES: To evaluate CT coronary angiography (CTA) when compared with catheter coronary angiography (CCA), for the detection of coronary artery stenoses and rate of optimal coronary artery segment visualization. METHOD: Retrospective, two-center study enrolling 26 patients who underwent CCA and ECG-gated 16-detector CTA (slice thickness 0.6 mm; rotation 500 ms). RESULTS AND CONCLUSION: 283 segments were available for postprocessing. Sensitivity, specificity, and positive predictive value were, respectively, 80, 100, and 100%, for detecting more than 50% luminal stenoses, when optimally visualized segments were considered, in comparison to CCA. Negative predictive value was excellent (98%). Rate of non-optimally visualized coronary segments was 26%. Most clinical benefits of coronary CT angiography should probably be obtained when it is performed to exclude significant stenoses on selected populations of patients with a low pre-test probability of severe coronary artery disease, and under optimal conditions of controlled heart rate and minimal presence of calcium.

Gadolinium-enhanced pulmonary magnetic resonance angiography in the diagnosis of acute pulmonary embolism: a prospective study on 48 patients.

OBJECTIVE: Gadolinium-enhanced pulmonary magnetic resonance angiography (MRA) can be an option in patients with a history of previous adverse reaction to iodinated contrast material and renal insufficiency. Radiation is also avoided. The aim of this study is to prospectively compare the diagnostic value of MRA with that of a diagnostic strategy, taking into account catheter angiography, computed tomography angiography (CTA), and lung scintigraphy [ventilation-perfusion (VQ)]. MATERIAL AND METHODS: Magnetic resonance angiography was done in 48 patients with clinically suspected pulmonary embolism (PE) using fast gradient echo coronal acquisition with gadolinium. Interpretation was done with native coronal images and multiplanar maximum intensity projection reconstructions. Results were compared to catheter angiography (n=15), CTA (n=34), VQ (n=45), as well as 6-12 months clinical follow-ups, according to a sequenced reference tree. RESULTS: The final diagnosis of PE was retained in 11 patients (23%). There were two false negatives and no false positive results with MRA. Computed tomography angiography resulted in no false negatives or false positives. Magnetic resonance angiography had a sensitivity of 82% and a specificity of 100%. CONCLUSION: In our study, pulmonary MRA had a sensitivity of 82% and a specificity of 100% for the diagnosis of PE, with slightly less sensitivity than CTA. In the diagnostic algorithm of PE, pulmonary MRA should be considered as an alternative to CTA when iodine contrast injection or radiation is a significant matter.

MR imaging-guided focused ultrasound surgery of breast cancer: correlation of dynamic contrast-enhanced MRI with histopathologic findings.

PURPOSE: To assess the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters to monitor residual tumor following non-invasive MRI-guided focused ultrasound surgery (MRIgFUS) of breast tumors. METHODS: DCE-MRI data were acquired before and after the MRIgFUS treatment of small breast tumors (d < 3.5 cm) for 17 patients. The lesion was surgically resected and the presence of residual tumor was determined by histopathological analysis. The percentage of residual tumor was correlated with three DCE-MRI parameters measured at the maximally enhancing site of each tumor: increase in signal intensity (ISI), maximum difference function (MDF) and positive enhancement integral (PEI). RESULTS: A good correlation was found between the ISI (r = 0.897), MDF (r = 0.789) and PEI (r = 0.859) parameters and the percentage of residual viable tumor determined by histopathology. A receiver operator characteristic curve analysis yielded a cutoff value for ISI at 20% with a sensitivity of 77% and a specificity of 100%. CONCLUSION: These results suggest that parameters from DCE-MRI data could provide a reliable non-invasive method for assessing residual tumor following MRIgFUS treatment of breast tumors.

Feasibility of magnetic resonance imaging-guided focused ultrasound surgery as an adjunct to tamoxifen therapy in high-risk surgical patients with breast carcinoma.

PURPOSE: To evaluate the feasibility of treating breast neoplasms with use of magnetic resonance (MR) imaging-guided focused ultrasound (US) surgery. MATERIALS AND METHODS: Twenty-four female patients, each with a single biopsy-proven breast carcinoma, who were considered to be at increased surgical risk or who had refused surgery underwent MR imaging-guided focused US surgery as an adjunct to their chemotherapeutic regimen of tamoxifen. Follow-up included routine studies to rule out metastatic disease and MR studies with and without contrast material infusion in the treated breast (10 days and 1, 3, and 6 months after the treatment session). Percutaneous biopsy was performed after 6-month follow-up, and if residual tumor was present, a second MR imaging-guided focused US surgery treatment session was performed, followed by repeat biopsy 1 month later. RESULTS: Twenty-three of 24 patients completed the protocol, with only one minor complication associated with the treatment sessions (second-degree skin burn resolved with local treatment). Follow-up MR studies demonstrated a varying hypointense treatment margin (range, 1-11 mm), which represents destruction of tissue beyond the visible tumor. Absence of enhancement may be an indicator of tumor destruction (18 of 19 patients with negative biopsy results) whereas persistent enhancement suggested tumor residue (three of five patients with residual tumor). Overall, 19 of 24 patients (79%) had negative biopsy results after one or two treatment sessions. CONCLUSION: MR imaging-guided focused US surgery of breast tumors is a safe, repeatable, and promising method of focal tumor destruction.

MR imaging-guided focused US ablation of breast cancer: histopathologic assessment of effectiveness-- initial experience.

PURPOSE: To evaluate the effectiveness of noninvasive magnetic resonance (MR) imaging-guided focused ultrasonographic (US) ablation of breast carcinomas. MATERIALS AND METHODS: Before undergoing tumor resection, 12 patients with invasive breast carcinomas were treated with MR imaging-guided focused US ablation consisting of multiple sonications of targeted points that were monitored with temperature-sensitive MR imaging. The patients were treated with either one of two focused US systems. The effectiveness of the treatment was determined at histopathologic analysis of the resected mass that was performed to determine the volumes of necrosed and residual tumor. Complications resulting from the procedure were assessed by means of questionnaires, medical examinations, and MR image analysis. RESULTS: US ablation was well tolerated by the patients, and with the exception of minor skin burns in two patients, no complications occurred. Histopathologic analysis of resected tumor sections enabled quantification of the amount of necrosed and residual tumor and visualization of the surrounding hemorrhage. In three patients treated with one of the US systems, a mean of 46.7% of the tumor was within the targeted zone and a mean of 43.3% of the cancer tissue was necrosed. In nine patients treated with the other US system, a mean of 95.6% of the tumor was within the targeted zone and a mean of 88.3% of the cancer tissue was necrosed. Residual tumor was identified predominantly at the periphery of the tumor mass; this indicated the need to increase the total targeted area (ie, with an increased number of sonications). CONCLUSION: Thermal coagulation of small breast tumors by means of MR imaging-guided focused US appears to be a promising noninvasive ablation procedure.