Prospective double-blinded randomized controlled trial of Microwave versus RadioFrequency Ablation for hepatocellular carcinoma (McRFA trial).

BACKGROUND: Microwave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare the efficacy of MWA versus RFA as a treatment for HCC. METHODS: Patients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed. RESULTS: A total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001). CONCLUSIONS: MWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.

Status of inflammation in relation to health related quality of life in hepatocellular carcinoma patients.

PURPOSE: Both Inflammation and health-related quality of life (HRQoL) are independent prognosticators in HCC patients. We hypothesized that inflammation can cause impairment in HRQoL and investigated the correlation between inflammatory status and HRQoL in HCC patients. METHODS: Clinical, laboratory and HRQoL (using EORTC QLQ-C30, QLQ-HCC18, C30 and HCC18 index-scores) data were prospectively collected from HCC patients at diagnosis. Correlation analyses were performed between HRQoL and inflammation-based markers including C-reactive protein (CRP), CRP/albumin ratio (CRP/alb), Glasgow Prognostic Score (GPS), Inflammation-Based Index (IBI) and Prognostic Index (PI). RESULTS: Among 445 HCC patients, higher inflammatory states were significantly correlated with worse HRQoL. For CRP and CRP/alb ratio, the HRQoL factors with higher correlations included C30 and HCC18 index-scores, certain QLQ-C30 domains and items ('physical functioning', 'role functioning', 'fatigue', 'pain', 'appetite loss') and QLQ-HCC18 items ('fatigue', 'body image', 'nutrition' and 'abdominal swelling'), where the Pearson's correlation coefficients were up to 0.416. Multivariate analyses indicated that worse HRQoL factors were significantly correlated with worse scores in GPS, IBI and PI. CONCLUSION: In HCC patients, inflammatory status correlates with HRQoL at presentation. In particular, relatively stronger correlations with CRP-based markers have been observed in HRQoL scales that assess constitutional symptoms (QLQ-C30 'physical functioning', 'role functioning', 'fatigue', 'appetite loss' and QLQ-HCC18 'fatigue' and 'nutrition') and tumor burden (QLQ-C30 'pain' and QLQ-HCC18 'abdominal swelling' and 'body image'). Future studies are warranted to evaluate whether intervention that reduces inflammation could improve HRQoL in HCC patients.

Ablative Chemoembolization for Hepatocellular Carcinoma: A Prospective Phase I Case-Control Comparison with Conventional Chemoembolization.

Purpose To evaluate the feasibility, safety, and treatment effectiveness of ablative chemoembolization (ACE) in the treatment of hepatocellular carcinoma (HCC) and compare with a similar patient cohort who underwent conventional transarterial chemoembolization (cTACE). Materials and Methods This was a prospective phase I nonrandomized study conducted between March 2013 and October 2016 in accordance to the Declaration of Helsinki and Declaration Good Clinical Practice with written informed consent. There were 36 men and eight women (median age, 64 years [interquartile range, 58-74] and 74.5 years [interquartile range, 70-80], respectively). The primary end points were treatment safety and tumor response. The secondary end points were time to progression, progression-free survival, conversion to partial hepatectomy, and viable HCC within the tumor specimen. The end points of the study group (n = 22) were compared with those of a case-matched control group (n = 22) of patients who underwent conventional cTACE during the same period by using a Pearson χ2 test. Results Treatment with ACE was successfully completed in all patients without adverse effects. The complete response (CR) rates by patient or by tumor were both 100%. The median time to progression and median progression-free survival were significantly longer in the study group than in the control group (both were 28 months vs 10 months, respectively; P < .001). The number of patient conversions to hepatectomy was seven for ACE and three for cTACE. In the tumor specimens, viable tumor was found in two of eight specimens that underwent ACE and three of three that underwent cTACE. Conclusion ACE is a feasible, safe, and well-tolerated treatment for patients with HCC; it is highly effective and may be more effective than cTACE in achieving CR. © RSNA, 2017 Online supplemental material is available for this article.

Does Intermittent Pringle Maneuver Increase Postoperative Complications After Hepatectomy for Hepatocellular Carcinoma? A Randomized Controlled Trial.

BACKGROUND: In a previous study, we have shown that intermittent Pringle maneuver (IPM) might increase postoperative complications after hepatectomy for various indications. Complications which thought to be related to IPM were ascites, pleural effusion, wound infection and intra-abdominal collection. The aim of this study was to test the hypothesis that applying IPM during hepatectomy for hepatocellular carcinoma (HCC) could increase postoperative complications. METHODS: Between January 2013 and October 2016, eligible patients who received elective open hepatectomy for HCC were randomized to have IPM or no Pringle maneuver (NPM). Occurrence of various types of postoperative complications was specifically looked for. A routine postoperative day 5 abdominal ultrasound examination and chest X-ray were done to detect and grade any radiological ascites, pleural effusion and intra-abdominal collection. RESULTS: Fifty IPM and 50 NPM patients with histological proven HCC were recruited for final analysis. Demographics and operative parameters were comparable between the two groups. The postoperative complication rates were similar (IPM 36.0 vs. NPM 28.0%, P = 0.391). However, in the IPM group, more patients developed radiological posthepatectomy ascites (42.0 vs. 22.0%, P = 0.032) and pleural effusion (66.0 vs. 38.0%, P = 0.005). In patients with histologically proven cirrhosis, there were 28 IPM and 25 NPM patients. Again, there was no difference in postoperative complication rate but more radiological posthepatectomy ascites and pleural effusion in the IPM group. CONCLUSION: This trial was not able to detect a difference in postoperative complications whether IPM was applied or not, but use of IPM was associated with more subclinical ascites and pleural effusion. (ClinicalTrials.gov NCT01759901). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01759901.

Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces.

KEY POINTS: The gastrointestinal epithelial enterochromaffin (EC) cell synthesizes the vast majority of the body's serotonin. As a specialized mechanosensor, the EC cell releases this serotonin in response to mechanical forces. However, the molecular mechanism of EC cell mechanotransduction is unknown. In the present study, we show, for the first time, that the mechanosensitive ion channel Piezo2 is specifically expressed by the human and mouse EC cells. Activation of Piezo2 by mechanical forces results in a characteristic ionic current, the release of serotonin and stimulation of gastrointestinal secretion. Piezo2 inhibition by drugs or molecular knockdown decreases mechanosensitive currents, serotonin release and downstream physiological effects. The results of the present study suggest that the mechanosensitive ion channel Piezo2 is specifically expressed by the EC cells of the human and mouse small bowel and that it is important for EC cell mechanotransduction. ABSTRACT: The enterochromaffin (EC) cell in the gastrointestinal (GI) epithelium is the source of nearly all systemic serotonin (5-hydroxytryptamine; 5-HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5-HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The present study aimed to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of the small bowel. Piezo2 immunoreactivity localized specifically within EC cells of human and mouse small bowel epithelium. The EC cell model released 5-HT in response to stretch, and had Piezo2 mRNA and protein, as well as a mechanically-sensitive inward non-selective cation current characteristic of Piezo2. Both inward currents and 5-HT release were inhibited by Piezo2 small interfering RNA and antagonists (Gd3+ and D-GsMTx4). Jejunum mucosal pressure increased 5-HT release and short-circuit current via submucosal 5-HT3 and 5-HT4 receptors. Pressure-induced secretion was inhibited by the mechanosensitive ion channel antagonists gadolinium, ruthenium red and D-GsMTx4. We conclude that the EC cells in the human and mouse small bowel GI epithelium selectively express the mechanosensitive ion channel Piezo2, and also that activation of Piezo2 by force leads to inward currents, 5-HT release and an increase in mucosal secretion. Therefore, Piezo2 is critical to EC cell mechanosensitivity and downstream physiological effects.

Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma - clinical application of health-related quality-of-life data.

BACKGROUND: Health-related quality-of-life (HRQOL) assessment with EORTC QLQ-C30 was prognostic for overall survival (OS) in patients with advance-stage hepatocellular carcinoma (HCC), but no data existed for early-stage patients. The HCC-specific QLQ-HCC18 has not been evaluated for prognostic value in HCC patients. Utilization of raw HRQOL data in clinical setting has been impractical and non-meaningful. Therefore we developed index scores of QLQ-C30 and QLQ-HCC18 in an attempt to enable clinical utilization of these HRQOL measurements. This study investigates the prognostic significance of QLQ-C30, QLQ-HCC18 and C30/HCC18 index-scores in patients with newly diagnosed HCC which encompasses all stages. METHODS: From 2007-2011, 517 patients were prospectively recruited. HRQOL was assessed at diagnosis using QLQ-C30 and QLQ-HCC18; C30 and HCC18 index-scores were calculated from raw HRQOL data. Cox regression was performed using continuous, dichotomized QLQ-C30 and QLQ-HCC18 variables, or index-scores, together with clinical factors to identify independent factors for OS. Various multivariate models were validated with c-index and bootstrapping for 1000 replications. RESULTS: Four hundred and seventy two patients had complete HRQOL data. Their median OS was 8.6 months. In multivariate analysis, independent prognostic HRQOL variables for OS were QLQ-C30 pain (HR 1.346 [1.092-1.661], p = 0.0055), QLQ-C30 physical functioning (HR 0.652 [0.495-0.860], p = 0.0024); QLQ-HCC18 pain (HR 1.382 [1.089-1.754], p = 0.0077) and QLQ-HCC18 fatigue (HR 1.441 [1.132-1.833], p = 0.0030). C30 index-score (HR 2.143 [1.616-2.841], p < 0.0001) and HCC18 index-score (HR 1.957 [1.411-2.715], p < 0.0001) were highly significant factors for OS. The median OS of patients with C30 index-score of 0-20, 21-40, 41-60, 61-100 were 16.4, 7.3, 3.1, 1.8 months respectively (p < 0.0001); while for HCC18 index-score: 16.4, 6.0, 2.8, 1.8 months respectively (p < 0.0001). All the multivariate models were validated, with mean optimism <0.01. The bootstrap validated c-index was 0.78. CONCLUSIONS: QLQ-C30 and QLQ-HCC18 were prognostic for OS in patients with newly diagnosed HCC irrespective of stage. Both C30 and HCC18 index-scores were highly significant prognostic factors for OS in newly diagnosed HCC patients. Index-scoring provides an effective way to summarize, analyze and interpret raw HRQOL data, and renders QLQ-C30 and QLQ-HCC18 meaningful and communicable in clinical practice. Index-scores could potentially serve as a standardized tool for future HRQOL research.

Transarterial Ethanol Ablation for Unresectable Hepatocellular Carcinoma: Analysis of Clinical and Tumor Outcomes.

PURPOSE: To evaluate survival, tumor response, and treatment toxicity of transarterial ethanol ablation (TEA) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective study involved 186 patients (146 men and 40 women; median age, 65 y [interquartile range, 57-72.3 y]). Of 186 patients, 146 (78.5%) were hepatitis B virus carriers, 18 (9.7%) were hepatitis C virus carriers, 82 (44.1%) had tumors ≥ 5 cm, and 43 (23.1%) had multifocal tumors. Overall survival (OS), complete response (CR) by European Association for the Study of the Liver criteria, time to progression (TTP), progression-free survival (PFS), and treatment toxicities were evaluated. Univariate and multivariate analyses for prognostic factors of OS were performed. RESULTS: Median OS was 25.7 months (95% confidence interval [CI], 20.9-30.5) and varied significantly between Child-Pugh A and B (28.7 mo vs 13.4 mo, P < .001), and Barcelona Clinic Liver Cancer A and B or C (37.1 mo vs 17.7 mo, P = .001). Prognostic factors for longer OS were solitary tumor, tumor size < 5 cm, > 1 treatments, and CR of all tumors at 6 months. TTP was 9.1 months (95% CI, 6.9-11.3). PFS was 8.4 months (95% CI, 7.1-9.7). CR occurred in 69.1% (159/230) of lesions and 48.9% (88/180) of patients at 6 months. Any one symptom of the postembolization syndrome of grade 2 severity occurred in < 22% (41/186) of patients. No treatment-related hepatitis or death occurred within 30 days. Transient respiratory decompensation occurred in three patients (1.6% [3/186]), and alcoholic intoxication occurred in one patient (0.5% [1/186]). CONCLUSIONS: TEA appears to be safe and effective for local control of HCC.

Distinct cellular origins for serotonin-expressing and enterochromaffin-like cells in the gastric corpus.

BACKGROUND & AIMS: The alimentary tract contains a diffuse endocrine system comprising enteroendocrine cells that secrete peptides or biogenic amines to regulate digestion, insulin secretion, food intake, and energy homeostasis. Lineage analysis in the stomach revealed that a significant fraction of endocrine cells in the gastric corpus did not arise from Neurogenin3 (Neurog3)-expressing cells, unlike enteroendocrine cells elsewhere in the digestive tract. We aimed to isolate enriched serotonin-secreting and enterochromaffin-like (ECL) cells from the stomach and to clarify their cellular origin. METHODS: We used Neurogenic differentiation 1 (NeuroD1) and Neurog3 lineage analysis and examined the differentiation of serotonin-producing and ECL cells in stomach tissues of NeuroD1-cre;ROSA(tdTom), tryptophan hydroxylase 1 (Tph1)-cyan fluorescent protein (CFP), c-Kit(wsh/wsh), and Neurog3Cre;ROSA(tdTom) mice by immunohistochemistry. We used fluorescence-activated cell sorting to isolate each cell type for gene expression analysis. We also performed RNA sequencing analysis of ECL cells. RESULTS: Neither serotonin-secreting nor ECL cells of the corpus arose from cells expressing NeuroD1. Serotonin-secreting cells expressed a number of mast cell genes but not genes associated with endocrine differentiation; they did not develop in c-Kit(wsh/wsh) mice and were labeled with transplanted bone marrow cells. RNA sequencing analysis of ECL cells revealed high expression levels of many genes common to endocrine cells, including transcription factors, hormones, ion channels, and solute transporters but not markers of bone marrow cells. CONCLUSIONS: Serotonin-expressing cells of the gastric corpus of mice appear to be bone marrow-derived mucosal mast cells. Gene expression analysis of ECL cells indicated that they are endocrine cells of epithelial origin that do not express the same transcription factors as their intestinal enteroendocrine cell counterparts.

Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response.

BACKGROUND: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC. Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with concomitant chronic liver disease. The objectives of this study were: (1) In phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and (3) to explore potential biomarkers for response. METHODS: Major eligibility criteria included histologically confirmed advanced HCC and adequate organ function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The MTD was used in the subsequent phase II part; the primary endpoint was PFS and secondary endpoints were response and OS. In addition, exploratory analysis was conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p-AKT expressions as potential biomarkers for response. Overall survival and PFS were calculated using the Kaplan-Meier method. Reassessment CT scans were done every 6 weeks. All adverse events were reported using CTCAE v3. RESULTS: The Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36 patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD. Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was 8.89 months (95% C.I. 5.89-13.30). Grade ≥ 3 that occurred in > 10% of patients included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR 5.667, 95% CI 1.129-28.454, p = 0.035). CONCLUSIONS: In HCC patients with chronic liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The targeted PFS endpoint was not reached. However, further studies to identify appropriate patient subgroup are warranted. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.

Irreversible Electroporation of the Femoral Neurovascular Bundle: Imaging and Histologic Evaluation in a Swine Model.

PURPOSE: To evaluate imaging, histologic changes, and safety of irreversible electroporation (IRE) on the femoral neurovascular bundle in a swine model. MATERIALS AND METHODS: The study was approved by the institutional animal ethics committee. IRE was performed on the right femoral neurovascular bundle of 9 swine, which were subsequently sacrificed at 24 hours (n = 4, acute group), 7 days (n = 4, subacute group), or 21 days (n = 1, delayed group). Clinical observation, computed tomography (CT), and pathologic examination were carried out. RESULTS: After the procedure, 7 of 9 subjects were able to stand and walk, and the remaining 2 subjects could eventually do so within 1 week. The femoral vessels were patent on CT and gross examination. There was microscopic evidence of venous thrombosis in 75% of the subacute group. Except for mild perineural inflammation observed in 1 subject in the subacute group, the femoral nerves were intact on gross and histologic examination. Significant damage to the surrounding muscle and soft tissue was identified on CT and histology, manifesting as necrosis, hematoma, and inflammation. CONCLUSIONS: The ablative effect of IRE on muscle and soft tissue manifested as necrosis, hemorrhage, and inflammation. Histologic changes were observed in the perineural tissue and veins in a few subjects. The clinical implication of such changes and safety of clinical use of IRE for lesions encasing the neurovascular bundle in humans are yet to be determined.

Evaluation of carotid angioplasty and stenting for radiation-induced carotid stenosis.

BACKGROUND AND PURPOSE: We aimed to evaluate the procedural safety, clinical, and angiographic outcome of carotid angioplasty and stenting for high-grade (≥70%) radiation-induced carotid stenosis (RIS) using atherosclerotic stenosis (AS) as a control. METHODS: In this 6-year prospective nonrandomized study, we compared the carotid angioplasty and stenting outcome of 65 consecutive patients (84 vessels) with RIS with that of a control group of 129 consecutive patients (150 vessels) with AS. Study end points were 30-day periprocedural stroke or death, ipsilateral ischemic stroke, technical success, procedural characteristics, instent restenosis (ISR; ≥50%) and symptomatic ISR. RESULTS: The median follow-up was 47.3 months (95% confidence interval, 26.9-61.6). Imaging assessment was available in 74 vessels (RIS) and 120 vessels (AS) in 2 years. Comparing RIS group with AS group, the rates of periprocedural stroke or death were 1.5% (1/65) versus 1.6% (2/129; P=1); ipsilateral ischemic stroke rates were 4.6% (3/65) versus 4.7% (6/129; P=1); the annual risks of ipsilateral ischemic stroke were 1.2% (3 patient/254.7 patient year) versus 1.2% (6 patient/494.2 patient year; P=0.89); technical success rates were both 100%. Stenting of common carotid artery and the use of multiple stents was more common in the RIS group (P=0 in both cases); ISR rates were 25.7% (19/74) versus 4.2% (5/120; P<0.001); symptomatic ISR rates were 6.8% (5/74) versus 0.8% (1/120; P=0.031). CONCLUSIONS: The safety, effectiveness, and technical difficulty of carotid angioplasty and stenting for RIS are comparable with that for AS although it is associated with a higher rate of ISR. CLINICAL TRIAL REGISTRATION: This trial was not registered as enrollment started in 2006.

Unresectable hepatocellular carcinoma: randomized controlled trial of transarterial ethanol ablation versus transcatheter arterial chemoembolization.

PURPOSE: To compare effectiveness of transarterial ethanol ablation (TEA) and transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma and determine whether TEA leads to better overall survival and tumor response than TACE. MATERIALS AND METHODS: In this institutional review board-approved preregistered randomized controlled trial (n = 200), informed consent was obtained. Primary outcome was overall survival; secondary outcomes were time to progression (TTP), progression-free survival (PFS), tumor response at computed tomography, and treatment-related toxicity. Eligible patients were randomized at a 1:1 ratio. Treatment included transcatheter delivery of ethiodized oil-ethanol mixture (2:1 ratio by volume up to 60 mL) for TEA and cisplatin-ethiodized oil emulsion (0.5 mg cisplatin per milliliter up to 30 mg), followed by 1-mm gelatin-sponge pellets, for TACE. Study was terminated after interim analysis (n = 98); 90 patients were available for analysis. Overall survival, TTP, and PFS were analyzed with Kaplan-Meier method; differences were compared with log-rank test. RESULTS: Study was terminated prematurely after interim analysis, which showed no difference in overall survival; this was unlikely to change with further patient accrual. Median overall survival in TEA and TACE was 24.3 months (95% confidence interval [CI]: 12.8, 32.7) and 20.1 months (95% CI: 9.3, 31.2), respectively (P = .358). Median TTP and PFS for intralesional progression were longer with TEA than TACE (TTP, 34.6 months [95% CI: 28.2, 41] vs 26.05 months [95% CI: 18.7, 33.3]; PFS, 14.8 months [95% CI: 10.2, 19.5] vs 9.3 months [95% CI: 7.1, 11.5]) (P = .028 and 0.029, respectively). Complete response rate on a tumor basis was persistently and significantly higher with TEA at 3 months (62 of 88 [70%] vs 39 of 76 [51%], P = .012), 6 months (64 of 88 [73%] vs 41 of 76 [54%], P = .012), and 12 months (66 of 88 [75%] vs 45 of 76 [59%], P = .031). CONCLUSION: Although there was no significant difference in overall survival, TEA demonstrated better complete tumor response, longer time to intralesional progression, and longer PFS.

Ketamine-related cholangiopathy: a retrospective study on clinical and imaging findings.

PURPOSE: Ketamine is a commonly abused recreational drug in Southeast Asia. There are emerging reports on ketamine abuse causing liver injury and biliary dilatation. This retrospective study aims to investigate the clinical and radiological features of this condition. METHODS: A retrospective search in the database of our institute was performed from January 2008 to February 2014 for patients who were ketamine abusers, with deranged liver function and/or epigastric pain, and had computed tomography of the abdomen or magnetic resonance cholangiopancreatography. Patient demographics, clinical data, and radiological findings were reviewed. RESULTS: Twenty-six patients (11 male and 15 female) were included in this study. Eighteen (69 %) patients had fusiform dilatation of the common bile ducts (CBDs) without evidence of intrinsic or extrinsic obstruction, and non-dilated intrahepatic ducts. The degree of CBD dilatation correlated with duration of abuse. In five patients who achieved abstinence, the CBD dilatation showed improvement. CONCLUSIONS: Ketamine-related cholangiopathy manifested as fusiform dilatation of the CBD without evidence of obstructive lesions. Severity of CBD dilatation appears to be correlated with the duration of ketamine, and the condition is potentially reversible in abstinent patients.

Malignant presternal goitre.

Goitres usually enlarge and descend caudad into the substernal space and are not palpable. We report on a patient whose goitre spread downward but anterior to the sternum. The thyroid mass was subsequently removed and was proven to be a papillary thyroid carcinoma. The mechanism by which a presternal goitre develops is probably due to invasion and erosion of the strap muscles and the cervical linea alba. The clinical implication of this presentation is complete extirpation of the presternal goitre with a cuff of the strap muscles.

SM22α deficiency: promoting vascular fibrosis via SRF-SMAD3-mediated activation of Col1a2 transcription following arterial injury.

Vascular fibrosis, characterized by increased Type I collagen expression, significantly contributes to vascular remodeling. Our previous studies show that disrupting the expression of SM22α (aka SM22, Tagln) induces extensive vascular remodeling following arterial injury, involving oxidative stress, inflammation, and chondrogenesis within the vessel wall. This study aims to investigate the molecular mechanisms underlying the transcription of Col1a2, a key fibrotic extracellular matrix marker. We observed upregulation of COL1A2 in the arterial wall of Sm22-/- mice following carotid injury. Bioinformatics and molecular analyses reveal that Col1a2 transcription depends on a CArG box in the promoter, activated synergistically by SRF and SMAD3. Notably, we detected enhanced nuclear translocation of both SRF and SMAD3 in the smooth muscle cells of the injured carotid artery in Sm22-/- mice. These findings demonstrate that SM22 deficiency regulates vascular fibrosis through the interaction of SRF and the SMAD3-mediated canonical TGF-ß1 signal pathway, suggesting SM22α as a potential therapeutic target for preventing vascular fibrosis.

Notch signaling differentially regulates the cell fate of early endocrine precursor cells and their maturing descendants in the mouse pancreas and intestine.

Notch signaling inhibits differentiation of endocrine cells in the pancreas and intestine. In a number of cases, the observed inhibition occurred with Notch activation in multipotential cells, prior to the initiation of endocrine differentiation. It has not been established how direct activation of Notch in endocrine precursor cells affects their subsequent cell fate. Using conditional activation of Notch in cells expressing Neurogenin3 or NeuroD1, we examined the effects of Notch in both organs, on cell fate of early endocrine precursors and maturing endocrine-restricted cells, respectively. Notch did not preclude the differentiation of a limited number of endocrine cells in either organ when activated in Ngn3(+) precursor cells. In addition, in the pancreas most Ngn3(+) cells adopted a duct but not acinar cell fate; whereas in intestinal Ngn3(+) cells, Notch favored enterocyte and goblet cell fates, while selecting against endocrine and Paneth cell differentiation. A small fraction of NeuroD1(+) cells in the pancreas retain plasticity to respond to Notch, giving rise to intraislet ductules as well as cells with no detectable pancreatic lineage markers that appear to have limited ultrastructural features of both endocrine and duct cells. These results suggest that Notch directly regulates cell fate decisions in multipotential early endocrine precursor cells. Some maturing endocrine-restricted NeuroD1(+) cells in the pancreas switch to the duct lineage in response to Notch, indicating previously unappreciated plasticity at such a late stage of endocrine differentiation.

Intra-arterial revascularisation therapy for acute ischaemic stroke: initial experience in a Hong Kong hospital.

OBJECTIVES: To assess the outcome of acute ischaemic stroke patients who received intra-arterial therapy in our unit. DESIGN: Case series. SETTING: A tertiary hospital in Hong Kong. PATIENTS: Patients with ischaemic stroke due to large artery occlusion treated within 6 hours from symptom onset between January 2007 and May 2011. INTERVENTION: Acute intra-arterial revascularisation therapy. MAIN OUTCOME MEASURES: Primary outcome was functional independence (modified Rankin Scale score of ≤ 2) at 3 months. Secondary outcome was rate of recanalisation. Safety outcomes were symptomatic intracranial haemorrhage and 3-month mortality. RESULTS: Twenty-one patients with a mean age of 67 years fulfilled the inclusion criteria. Their mean National Institutes of Health Stroke Scale score was 18. The mean onset-to-puncture time was 212 minutes. Nine received intra-arterial tissue plasminogen activator alone, 11 had an adjunctive mechanical thrombectomy, and one received balloon angioplasty without tissue plasminogen activator. At the end of the procedure, thrombolysis grade 2a or better was attained in 18 (86%) of the patients, and 8 (38%) achieved functional independence at 3 months. Rates of symptomatic intracranial haemorrhage and 3-month mortality were 10% and 24%, respectively. CONCLUSION: In this setting, intra-arterial revascularisation therapy appeared safe and efficacious for this selected group of ischaemic stroke patients with large artery occlusions. Experience gained from this pilot study may help improve clinical outcomes of such patients.

Intracranial aneurysms: midterm outcome of pipeline embolization device--a prospective study in 143 patients with 178 aneurysms.

PURPOSE: To evaluate the midterm clinical and angiographic outcomes after pipeline embolization device (PED) placement for treatment of intracranial aneurysms. MATERIALS AND METHODS: This prospective nonrandomized multicenter study was approved by the review boards of all involved centers; informed consent was obtained. Patients (143 patients, 178 aneurysms) with unruptured saccular or fusiform aneurysms or recurrent aneurysms after previous treatment were included and observed angiographically for up to 18 months and clinically for up to 3 years. Study endpoints included complete aneurysm occlusion; neurologic complications within 30 days and up to 3 years; clinical outcome of cranial nerve palsy after PED placement; angiographic evidence of occlusion or stenosis of parent artery and that of occlusion of covered side branches at 6, 12, and 18 months; and clinical and computed tomographic evidence of perforator infarction. RESULTS: There were five (3.5%) cases of periprocedural death or major stroke (modified Rankin Scale [mRS] > 3) (95% confidence interval [CI]: 1.3%, 8.4%), including two posttreatment delayed ruptures, two intracerebral hemorrhages, and one thromboembolism. Five (3.5%) patients had minor neurologic complications within 30 days (mRS = 1) (95% CI: 1.3%, 8.4%), including transient ischemic attack (n = 2), small cerebral infarction (n = 2), and cranial nerve palsy (n = 1). Beyond 30 days, there was one fatal intracerebral hemorrhage and one transient ischemic attack. Ten of 13 patients (95% CI: 46%, 93.8%) completely recovered from symptoms of cranial nerve palsy within a median of 3.5 months. Angiographic results at 18 months revealed a complete aneurysm occlusion rate of 84% (49 of 58; 95% CI: 72.1%, 92.2%), with no cases of parent artery occlusion, parent artery stenosis (<50%) in three patients, and occlusion of a covered side branch in two cases (posterior communicating arteries). Perforator infarction did not occur. CONCLUSION: PED placement is a reasonably safe and effective treatment for intracranial aneurysms. The treatment is promising for aneurysms of unfavorable morphologic features, such as wide neck, large size, fusiform morphology, incorporation of side branches, and posttreatment recanalization, and should be considered a first choice for treating unruptured aneurysms and recurrent aneurysms after previous treatments. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120422/-/DC1.

Surgical ablation of hepatocellular carcinoma with 2.45-GHz microwave: a critical appraisal of treatment outcomes.

OBJECTIVE: To evaluate the efficacy and safety of a new generation of 2.45-GHz microwave to ablate hepatocellular carcinoma by surgical approach. DESIGN; Case series with prospective follow-up. SETTING: A university teaching hospital in Hong Kong. PATIENTS: From March 2009 to January 2011, 26 consecutive patients (19 men and 7 women) with a median age of 63 (range, 49-79) years with hepatocellular carcinoma were recruited. Five (19%) of the patients had recurrent hepatocellular carcinoma after previous treatment. INTERVENTION: Microwave ablation for hepatocellular carcinomas (one tumour, n=24; two tumours, n=2) using a laparoscopic (n=16) or open approach (n=10). MAIN OUTCOME MEASURES: Operative mortality and morbidity, rate of incomplete ablation, recurrence rate, and survival rate. RESULTS: The median tumour diameter was 3.8 cm (range, 2.0-6.0 cm). Complications occurred in five (19%) of the patients; only one was ablation-related, and there was no operative mortality. One (4%) of the patients experienced incomplete ablation. Recurrent tumours were noted in 11 (42%) of the patients (5 were local, 2 were remote, and 4 were multifocal) after a median follow-up of 14 (range, 4-26) months. The failure rate for local disease control was 23%, and was 14% if patients with recurrent hepatocellular carcinoma were excluded. All but one patient survived until the time of censorship. The mean survival was 25 (standard deviation, 1) months. CONCLUSION: This new-generation microwave technique is safe and effective for local ablation of hepatocellular carcinoma. It is a valuable treatment option for patients who are not candidates for hepatectomy.

Comparison of Survival Outcomes in Transarterial Ethanol Ablation and Liver Resection for Solitary Hepatocellular Carcinoma ≤ 5 cm in Patients Stratified by Liver Function.

PURPOSE: To compare the survival outcomes of patients treated with transarterial ethanol ablation (TEA) with those treated with liver resection (LR) for solitary HCC less than 5 cm in diameter, in patients stratified according to liver function using ALBI grade. MATERIALS AND METHODS: This retrospective study approved by the Institutional Committee included all treatment-naïve patients with solitary HCC (≤ 5 cm) and Child-Pugh score 5, and who had received TEA (33 patients) or LR (192 patients) between 2004 and 2012. Treatment outcomes were compared between patients treated with TEA and LR after a period of at least 7 years of follow-up. Comparison was repeated for those patients with ALBI grade 2 or 3. RESULTS: Both overall survival (OS, months) and recurrence-free survival (RFS months) were significantly longer in the LR group (OS: LR 129.7[119.5, 140], TEA 69.1[55.9, 82.3], P < 0.0001; RFS: LR 91.3[43.5, 139.1], TEA 13.8 [11, 16.5], P < 0.0001). In patients with ALBI grade 2 or 3, there was no significant difference between the groups in OS or RFS (OS: LR 43.1[0, 91.2], TEA 55.4 [43.7, 67.2], P = 0.65; RFS: LR 17.8 [11.4, 24.2], TEA 11.9 [6.7, 17.1], P = 0.132). Transient epigastric discomfort and low-grade fever without consequence occurred in 8 patients (8/33 or 24.2%) in the TEA group. CONCLUSION: The overall survival after LR for HCCs ≤ 5 cm was superior to that after TEA but similar when compared in patients with ALBI grade 2 or 3, the ALBI grade is useful for patient selection for TEA or LR for HCCs ≤ 5 cm.