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Background: This systematic review was performed to assess the clinical utility of the Sendai Consensus Guidelines (SCG) and Fukuoka Consensus Guidelines (FCG) for intraductal papillary mucinous neoplasm (IPMN)., Methods: A computerized search of PubMed was performed to identify all the studies which evaluated the SCG and FCG in surgically resected, histologically confirmed IPMNs., Results: Ten studies evaluating the FCG, 8 evaluating the SCG and 4 evaluating both guidelines were included. In 14 studies evaluating the FCG, out of a total of 2498 neoplasms, 849 were malignant and 1649 were benign neoplasms. Pooled analysis showed that 751 of 1801 (42%) FCG+ve neoplasms were malignant and 599 neoplasms of 697 (86%) FCG-ve neoplasms were benign. PPV of the high risk and worrisome risk groups were 465/986 (47%) and 239/520 (46%) respectively. In 12 studies evaluating the SCG, 1234 neoplasms were analyzed of which 388 (31%) were malignant and 846 (69%) were benign. Pooled analysis demonstrated that 265 of 802 (33%) SCG+ve neoplasms were malignant and 238 of 266 SCG-ve (90%) neoplasms were benign., Conclusion: The FCG had a higher positive predictive value (PPV) compared to the SCG. However, the negative predictive value (NPV) of the FCG was slightly lower than that of the SCG. Malignant and even invasive IPMN may be missed according to both guidelines., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: To assess if parameters in intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) can be used to evaluate early renal fibrosis in a mouse model of diabetic nephropathy., Materials & Methods: In a population of 38 male CD1 mice (8weeks old, 20-30g), streptozotocin induced diabetes was created in 20 mice via a single intraperitoneal injection of streptozotocin at 150mg/kg, while 18 mice served as control group. IVIM parameters were acquired at 0, 12 and 24weeks after injection of streptozotocin using a range of b values from 0 to 1200s/mm 2 . DTI parameters were obtained using 12 diffusion directions and lower b values of 0, 100 and 400s/mm 2 . DTI and IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of the right kidney was performed in all mice. Results were analyzed using an unpaired t-test with P<0.05 considered statistically significant., Results: Renal cortex fractional anisotropy (FA) was significantly lower in the diabetes group at week 12 as compared with the control group. Renal cortex apparent diffusion coefficient and tissue diffusivity were significantly higher in the diabetes group at week 12 compared with the control group at 12weeks. Blood flow was significantly decreased at the renal medulla at 24weeks. Histopathological analysis confirmed fibrosis in the diabetes group at 24weeks., Conclusion: FA is significantly reduced in diabetic nephropathy. FA might serve a potential role in the detection and therapy monitoring of early diabetic nephropathy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC)., Methods: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)., Results: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≥6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes., Conclusion: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≤7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation., Clinicaltrialsgov Identifier: NCT01029418., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To evaluate non-invasive imaging biomarkers for assessing renal fibrosis. DWI is used to assess renal function; intravoxel incoherent motion (IVIM) provides additional measures of perfusion-related diffusion (D*, blood flow; f, perfusion fraction). We aim to determine if reduced ADC seen in renal fibrosis is attributable to perfusion-related diffusion changes or to known reduction in tissue diffusivity (D)., Materials and Methods: Unilateral ureteral obstruction (UUO) was created in six mice to induce renal fibrosis. DWI was performed the day before and 7 days post-UUO. A range of b-values from 0 to 1200 s/mm(2) were used. IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of both kidneys was performed in all mice. Results were analyzed using the paired t-test with P<0.05 considered statistically significant., Results: D and f were significantly lower in the ligated kidneys at Day 7 compared to before ligation and no significant difference was found for D*. Comparing non-ligated and ligated kidneys within the same mouse at Day 7, significantly lower D values were observed in the ligated kidneys, while no significant difference was found for f and D*, although the values of f were generally lower. Histopathological analysis confirmed development of fibrosis and reduction in glomeruli in all the ligated kidneys at Day 7., Conclusion: Our study shows that the reduction in ADC seen in renal fibrosis is attributable not only to reduced D as previously encountered but also a decrease in vascularity as assessed by f. Reduction in f is possibly related to a reduction in glomeruli., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background & Aims: Hepatocellular carcinoma (HCC) is a particularly vascularized solid tumor where the Raf/MEK/ERK pathway is activated; suggesting that inhibition of this pathway may have therapeutic potential., Methods: We treated patient-derived HCC xenografts with (i) sorafenib, (ii) AZD6244 (ARRY-142886), and (iii) sorafenib plus AZD6244. Western blotting was employed to determine pharmacodynamic changes in biomarkers relevant to both angiogenesis and MEK signaling. Apoptosis, microvessel density, and cell proliferation were analyzed by immunohistochemistry., Results: We report here that sorafenib treatment resulted in suppression of tumor growth, reduction in cell proliferation, induction of apoptosis and inhibition of mTOR targets. Sorafenib-induced elevation of the insulin-like growth factor receptor 1 (IGF-1R), phospho-c-Raf Ser338, phospho-MEK Ser217/221 and phospho-ERK Thr202/Tyr204 was attenuated by co-treating cells with anti-human IGF-1R antibody or over-expression of activated mutant p70S6K. Pharmacological inhibition of the MEK/ERK pathway by AZD6244 enhanced the anti-tumor effect of sorafenib in both orthotopic and ectopic models of HCC. Such inhibition led to a further increase in pro-apoptotic Bim, apoptosis and a profound inhibition of cell proliferation., Conclusion: Our findings underscore the potential of a combined therapeutic approach with sorafenib and MEK inhibitors in the treatment of HCC.

Biliary cystadenoma (BCA) is a rare neoplasm of the bile duct with malignant potential. We report a case of intrahepatic BCA with an unusual presentation of obstructive jaundice. Computed tomography scan of the abdomen revealed a dilated common bile duct and intrahepatic ducts with internal septa. Endoscopic retrograde cholangiography showed an oval filling defect in the bile duct causing the obstruction. At laparotomy, this proved to be a multiloculated mucinous polyp in the common bile duct, with its origin in the left intrahepatic duct, detected using intraoperative choledochoscopy. A left hemihepatectomy was performed, and histology confirmed intrahepatic mucinous BCA with mesenchymal stroma. The imaging process and surgical options for BCA are discussed.

Purpose: To evaluate local experience of phased-array magnetic resonance imaging (MRI) in the staging of locally advanced prostate carcinoma with comparison to clinical staging., Methods: The study population was 21 patients who underwent preoperative MRI with pelvic phased-array coils followed by radical prostatectomy. The MRI findings were correlated with completely embedded serially sliced and whole-mounted sections of the prostate gland and clinical staging., Results: Overall accuracy of 57.1% was obtained, with specificity of 90.0% and sensitivity of 27.3%. All but one case of locally advanced disease missed by MRI was microscopic. Clinical staging in these cases also achieved accuracy of 57.1%, specificity of 90.0% and sensitivity of 27.3%., Conclusions: MRI with a phased-array coil has high specificity but low sensitivity for detection of extraprostatic disease. Phased-array MRI does not image microscopic tumour extension. It did not perform better than clinical staging and is not recommended for routine staging.

Angiomyolipoma [AML] is a rare benign lipomatous tumour of the liver. It is typically echogenic on ultrasound, hypodense on computed tomography and hyperintense on magnetic resonance imaging. Its varied imaging appearance is due to the different proportion of the three cell types which make up the tumour. This is a case report of a hepatic AML mimicking hepatocellular carcinoma [HCC] with fatty change in a hepatitis B carrier. Diagnostic difficulty and implications on subsequent management are discussed in the context of an endemic region for HCC.