Serial femtosecond and serial synchrotron crystallography can yield data of equivalent quality: A systematic comparison.

For the two proteins myoglobin and fluoroacetate dehalogenase, we present a systematic comparison of crystallographic diffraction data collected by serial femtosecond (SFX) and serial synchrotron crystallography (SSX). To maximize comparability, we used the same batch of micron-sized crystals, the same sample delivery device, and the same data analysis software. Overall figures of merit indicate that the data of both radiation sources are of equivalent quality. For both proteins, reasonable data statistics can be obtained with approximately 5000 room-temperature diffraction images irrespective of the radiation source. The direct comparability of SSX and SFX data indicates that the quality of diffraction data obtained from these samples is linked to the properties of the crystals rather than to the radiation source. Therefore, for other systems with similar properties, time-resolved experiments can be conducted at the radiation source that best matches the desired time resolution.

Abdominal musculature segmentation and surface prediction from CT using deep learning for sarcopenia assessment.

PURPOSE: The purpose of this study was to build and train a deep convolutional neural networks (CNN) algorithm to segment muscular body mass (MBM) to predict muscular surface from a two-dimensional axial computed tomography (CT) slice through L3 vertebra. MATERIALS AND METHODS: An ensemble of 15 deep learning models with a two-dimensional U-net architecture with a 4-level depth and 18 initial filters were trained to segment MBM. The muscular surface values were computed from the predicted masks and corrected with the algorithm's estimated bias. Resulting mask prediction and surface prediction were assessed using Dice similarity coefficient (DSC) and root mean squared error (RMSE) scores respectively using ground truth masks as standards of reference. RESULTS: A total of 1025 individual CT slices were used for training and validation and 500 additional axial CT slices were used for testing. The obtained mean DSC and RMSE on the test set were 0.97 and 3.7 cm2 respectively. CONCLUSION: Deep learning methods using convolutional neural networks algorithm enable a robust and automated extraction of CT derived MBM for sarcopenia assessment, which could be implemented in a clinical workflow.

Three artificial intelligence data challenges based on CT and MRI.

PURPOSE: The second edition of the artificial intelligence (AI) data challenge was organized by the French Society of Radiology with the aim to: (i), work on relevant public health issues; (ii), build large, multicentre, high quality databases; and (iii), include three-dimensional (3D) information and prognostic questions. MATERIALS AND METHODS: Relevant clinical questions were proposed by French subspecialty colleges of radiology. Their feasibility was assessed by experts in the field of AI. A dedicated platform was set up for inclusion centers to safely upload their anonymized examinations in compliance with general data protection regulation. The quality of the database was checked by experts weekly with annotations performed by radiologists. Multidisciplinary teams competed between September 11th and October 13th 2019. RESULTS: Three questions were selected using different imaging and evaluation modalities, including: pulmonary nodule detection and classification from 3D computed tomography (CT), prediction of expanded disability status scale in multiple sclerosis using 3D magnetic resonance imaging (MRI) and segmentation of muscular surface for sarcopenia estimation from two-dimensional CT. A total of 4347 examinations were gathered of which only 6% were excluded. Three independent databases from 24 individual centers were created. A total of 143 participants were split into 20 multidisciplinary teams. CONCLUSION: Three data challenges with over 1200 general data protection regulation compliant CT or MRI examinations each were organized. Future challenges should be made with more complex situations combining histopathological or genetic information to resemble real life situations faced by radiologists in routine practice.

Imaging features, complications and differential diagnoses of abdominal cystic lymphangiomas.

PURPOSE: The aim of the study is to describe the imaging features, complications and differential diagnoses of abdominal cystic lymphangiomas (ACLs). RESULTS: ACLs are benign lymphatic malformations that mainly arise in the subperitoneal space and the retroperitoneum. The typical presentation of an ACL is a multilocular lesion with homogenous serous content, presenting a thin wall and septa, usually free from adjacent organ compression. Atypical findings, including fat or hemorrhagic content, septal calcifications and unilocular presentation, are not uncommon. Rarely, ACLs can be revealed by acute complications, such as infection, hemorrhage, intussusception, complications with a twisting mechanism (including torsion around its own pedicle) or spontaneous rupture, which can be diagnosed by imaging. Ultrasonography and CT are the most useful modalities in emergency situations. MRI performs best in the noninvasive characterization of cystic lesions. ACLs should be differentiated from normal anatomic structures (e.g., cisterna chyli) or pitfalls (e.g., ascites, extrapancreatic necrosis, lymphocele) that can simulate ACLs. Among other primary peritoneal cystic lesions, benign cystic mesothelioma can be difficult to differentiate from ACL. Some neoplastic peritoneal lesions may have cystic components or content that looks like fluid on imaging (such as mucinous or myxoid content) and be misdiagnosed as ACL. Nodular or thick enhancement of the wall or septa should then be considered worrisome features and should not suggest ACL. ACLs mostly require a simple follow-up. If treatment is necessary, percutaneous sclerotherapy is a safe and effective alternative to surgery. CONCLUSION: Imaging, especially MRI, allows the noninvasive diagnosis of ACL and helps to exclude potential malignant differential diagnoses.

Evaluation of severe caustic gastritis by computed tomography and its impact on management.

INTRODUCTION: Serious caustic burns of the stomach that present with no clinico-biological severity criteria (CBSC) can be treated conservatively. However, even if there are no CBSC at admission, 20% of patients still require delayed emergency surgery for peritonitis due to gastric perforation thus showing the limitations of this strategy in the diagnosis of irreversible gastric necrosis lesions. The aim of this study was to identify reliable computed tomography (CT) signs of irreversible gastric necrosis in patients with stage 3 endoscopic lesions. PATIENTS AND METHODS: In a prospective study from March 2014 to January 2017, thoraco-abdomino-pelvic CT scan was performed in 30 consecutive patients with stage 3 endoscopic gastric lesions. The CT results were concealed from the clinicians and compared to CBSC results. RESULTS: Twenty patients were treated conservatively and ten patients were operated on. Seventy percent of the patients underwent urgent delayed surgery for symptoms that developed late but before alterations in the CBSC. The CT scan showed a perfusion defect (PD) of gastric mucosal enhancement in all patients operated on for gastrointestinal distress, and could have provided an early diagnosis of irreversible gastric necrosis. CONCLUSION: CT was a more effective diagnostic tool for the diagnosis of irreversible gastric necrosis following caustic ingestion than a strategy based on digestive endoscopy and the use of CBSC. CT could eventually replace gastrointestinal endoscopy in the emergency evaluation of gastroesophageal caustic burns.

MRI for characterization of benign hepatocellular tumors on hepatobiliary phase: the added value of in-phase imaging and lesion-to-liver visual signal intensity ratio.

OBJECTIVES: To evaluate the lesion-to-liver visual signal intensity ratio (SIR) before and at the hepatobiliary phase MRI (HBP-MRI) after gadobenate dimeglumine (Gd-BOPTA) injection, using several T1-weighted images (T1-WI), for the characterization of benign hepatocellular lesions. METHODS: Patients with histologically proven focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA), who underwent Gd-BOPTA-enhanced HBP-MRI from 2009 to 2017, were retrospectively identified. The lesion-to-liver SIR was visually assessed by two radiologists on HBP (post-HBP analysis) and compared with that of unenhanced sequences (pre/post-HBP analysis) on T1-WI in-phase (T1-IP), out-of-phase (T1-OP), and fat suppression (T1-FS). Lesions were classified as hyper-, iso-, or hypointense on post-HBP, and as decreasing, stable, or increasing SIR on pre/post-HBP analyses. The performance of the different T1-WI sequences for the diagnostic of FNH was evaluated on post-HBP analysis. RESULTS: Twenty-nine FNHs and 33 HCAs were analyzed. On post-HBP analysis, FNHs appeared hyper-/isointense in 89.7% of all T1-WI. HCAs appeared hypointense in 93.9%, 63.6%, and 69.7% of T1-IP, T1-OP, and T1-FS, respectively. FNHs exhibited an increasing SIR in 55.2-58.6%, a stable SIR in 44.8-58.6%, and a decreasing SIR in 0%, whereas HCAs exhibited a decreasing SIR in 66.7-93.9%, a stable SIR in 6.1-33.3%, and an increasing SIR in 0% (p < 0.0001). The specificity of T1-IP was significantly higher than that of T1-OP (p = 0.015) and T1-FS (p = 0.042). CONCLUSION: T1-IP is the most reliable sequence due to misleading tumor/liver signal ratio in the case of fatty liver when using T1-FS or T1-OP. The pre/post-HBP lesion-to-liver SIR is accurate to classify benign hepatocellular lesions and contributes to avoid biopsy. KEY POINTS: •The T1-weighted images in-phase should be systematically included in the HBP-MRI protocol, as it is the most reliable sequence especially in the case of fatty liver. •The comparison between lesion-to-liver signal intensity ratios on unenhanced and at the hepatobiliary phase sequences is useful to classify benign hepatocellular lesions in three categories without misclassification: FNH (increasing signal intensity ratio), HCA (decreasing signal intensity ration), and indeterminate lesions (stable signal intensity ratio).

Acquired diverticular disease of the jejunum and ileum: imaging features and pitfalls.

PURPOSE: To present radiological aspects of jejunoileal diverticulosis and its complications. RESULTS: Jejunoileal diverticulosis is a relatively rare and underestimated condition, which mostly affects the elderly. It is frequently asymptomatic but it can lead to significant complications requiring surgical treatment. Jejunoileal diverticulosis is far less common than colonic diverticulosis. Acquired small bowel diverticula are often numerous but the complication rate is low. Acute diverticulitis is the most frequent complication; its classic presentation involves the jejunum and is often non-severe. Diverticular hemorrhage is the second most common complication; CT scan examination is essential to determine the accurate topography of the pathological diverticula. Small bowel obstruction can occur through several mechanisms: adhesions, enterolith, and intussusception. Extra-intestinal gas without perforation and "pseudo-ischemic" appearance are non-pathological conditions that are important to diagnose in order to avoid surgery. CONCLUSION: Jejunoileal diverticulosis usually does not show any symptoms but can lead to diagnostic challenges requiring evaluation by CT. CT scan signs of these complications and some pitfalls must be known.

Irisin levels in LMNA-associated partial lipodystrophies.

AIM: The adipo-myokine irisin regulates energy expenditure and fat metabolism. LMNA-associated familial partial lipodystrophy (FPLD2) comprises insulin resistance, muscle hypertrophy and lipoatrophy. The aim of this study was to investigate whether irisin could be a biomarker of FPLD2. PATIENTS AND METHODS: This case control study included 19 FPLD2 subjects, 13 obese non-diabetic (OND) patients and 19 healthy controls (HC) of normal weight (median BMI: 26, 39 and 22 kg/m2, respectively). Serum irisin and leptin levels, body composition (DXA/MRI) and metabolic/inflammatory parameters were compared in these three groups. RESULTS: BMI and MRI intra-abdominal fat significantly differed among these three groups, whereas DXA total fat mass and leptin levels were higher in the OND group, but did not differ between HC and FPLD2. Lipodystrophy patients had higher intra-abdominal/total abdominal fat ratios than the other two groups. Irisin levels were higher in FPLD2 and OND patients than in HC (medians: 944, 934 and 804 ng/mL, respectively). However, irisin/leptin ratios and lean body mass percentages were strikingly higher, and lean mass indices lower, in FPLD2 and HC than in the OND (median irisin/leptin ratios: 137, 166 and 21, respectively). In the entire study group, irisin levels positively correlated with BMI, lean body mass and index, intra-abdominal/total abdominal fat ratio, triglyceride, cholesterol, insulin, glucose and HbA1c levels. Also, intra-abdominal/total abdominal fat ratio and lean body mass better differentiated the three groups only in female patients. CONCLUSION: Circulating irisin is similarly increased in FPLD2 and OND patients, who are characterized by higher lean body mass regardless of their clearly different fat mass. However, irisin/leptin ratios, strikingly higher in FPLD2 than in OND patients, could help to make the diagnosis and prompt genetic testing in clinically atypical cases.

Noncontrast-Enhanced Magnetic Resonance Versus Computed Tomography Angiography in Preoperative Evaluation of Potential Living Renal Donors.

RATIONALE AND OBJECTIVES: Living renal donors undergo an extensive examination program. These examinations should be as safe, gentle, and patient friendly as possible. To compare computed tomography angiography (CTA) and an extensive magnetic resonance imaging (MRI) protocol without contrast agents to observations from nephrectomy in living renal donors and to evaluate whether noncontrast-enhanced MRI can replace CTA for vessel assessment in living renal donors. MATERIAL AND METHODS: CTA and MRI results were compared to observations from nephrectomy, which served as the reference standard. Fifty-one potential kidney donors underwent imaging, and 31 donated a kidney. Comparisons in sensitivity, specificity, and accuracy were made with respect to the number of arteries, early branching, and the number of veins. Agreement was assessed using Cohen's kappa. The exact McNemar's test was used to test for statistically significant differences. RESULTS: In the assessment of more than one renal artery, the sensitivity and specificity of MRI and CTA were high and in perfect agreement compared to observations from surgery. The results for both MRI and CTA were as follows: (sensitivity 100%/specificity100%/accuracy 100%/Kappa = 1/P = 1). When comparing the ability to test for early branching we found, MRI: (sensitivity 33%/specificity 100%/accuracy 87%/Kappa = 0.45/P = 1) and CTA: (sensitivity 50%/specificity 100%/accuracy 90%/Kappa = 0.62/P = 1). When used to depict supernumerary veins, we found MRI: (sensitivity60%/specifivity100%/accuracy 93%/Kappa = 0.72/P = 1), whereas CTA showed: (sensitivity 40%/specificity 96%/accuracy 87% Kappa = 0.43/P = 1). CONCLUSIONS: In conclusion, an optimized MRI protocol that includes noncontrast-enhanced magnetic resonance angiography can be substituted for CTA for preoperative assessment of the renal vessels before living donor nephrectomy.

Fixed target matrix for femtosecond time-resolved and in situ serial micro-crystallography.

We present a crystallography chip enabling in situ room temperature crystallography at microfocus synchrotron beamlines and X-ray free-electron laser (X-FEL) sources. Compared to other in situ approaches, we observe extremely low background and high diffraction data quality. The chip design is robust and allows fast and efficient loading of thousands of small crystals. The ability to load a large number of protein crystals, at room temperature and with high efficiency, into prescribed positions enables high throughput automated serial crystallography with microfocus synchrotron beamlines. In addition, we demonstrate the application of this chip for femtosecond time-resolved serial crystallography at the Linac Coherent Light Source (LCLS, Menlo Park, California, USA). The chip concept enables multiple images to be acquired from each crystal, allowing differential detection of changes in diffraction intensities in order to obtain high signal-to-noise and fully exploit the time resolution capabilities of XFELs.

Preoperative planning of renal transplantation: a comparison of non-contrast-enhanced ultrasonography, computed tomography, and magnetic resonance angiography with observations from surgery.

BACKGROUND: Many candidates for kidney transplantation need to undergo vessel examination before the transplantation procedure. PURPOSE: To identify the optimal preoperative modality for the examination of vessel status without the use of contrast agents in kidney transplant candidates. MATERIAL AND METHODS: Fifty-three consecutive patients were examined and 31 patients were transplanted. Ultrasonography (US), non-contrast-enhanced computed tomography (NCCT), and non-contrast-enhanced magnetic resonance angiography (NCMRA) were compared using inspection during kidney transplantation (TX) as a reference standard. The sensitivity and specificity to severe arteriosclerotic changes and the accuracy were calculated. Kappa statistics were used to assess the agreement between TX and the different examination modalities, and McNemar's test was used to test for significant differences. RESULTS: US had higher sensitivity (1.0) and better agreement with observations from surgery (k = 0.89) than both NCCT (sensitivity = 0.60; k = 0.72) and NCMRA (sensitivity = 0.20; k = 0.30). No significant difference was found between TX and US (P = 0.3173) or TX and NCCT (P = 0.1573), but there was a significant difference between TX and NCMRA (P = 0.0455). US was inconclusive in 20% of cases, and the internal iliac artery could not be visualized in 69% of cases. CONCLUSION: Either US or NCCT can be used as the preferred preoperative imaging modality to examine vessel status before kidney transplantation, but a combination of the two is preferable. NCMRA should not be used as the sole imaging modality for preoperative imaging before kidney transplantation because of its low sensitivity in detecting severe arteriosclerotic disease without the presence of stenosis.

No effect of remote ischaemic conditioning on inflammation in a porcine kidney transplantation model.

MAIN PROBLEM: Delayed graft function after kidney transplantation is associated with decreased graft survival and increased patient mortality but the pathogenesis is poorly understood. Remote ischaemic conditioning (rIC) may prevent delayed graft function by an anti-inflammatory effect. In a porcine model of transplantation from adults to children, we investigated the inflammatory response in the transplanted kidney and the effect of rIC. METHODS: Kidneys were recovered from brain dead donor pigs(63kg) and transplanted into two groups of recipient pigs(15kg) after 22h of cold ischaemia. Recipients were randomised to either: rIC (n=8) performed before the 10-h reperfusion period or no-rIC (n=8). Non-transplanted kidneys from eight brain dead pigs served as controls. RESULTS: Compared to controls, transplantation increased the number of apoptotic cells, macrophages and neutrophils in the kidney. After transplantation, IL-10 levels increased and IL-6 levels decreased in the kidney, whereas levels of TNF-α and IL-8 were not affected. A significant rise in plasma IL-1ß and IL-6 was observed in the recipients after transplantation. Plasma IL-10 was not affected by transplantation and TNF-α and IL-8 were below detection limit. No effect of rIC was found with regards to cell infiltration or cytokine production. CONCLUSION: Renal transplantation elicits an inflammatory response in the kidney manifested as apoptotic cell death, macrophage and neutrophil infiltration, and an anti-inflammatory cytokine response 10h after transplantation. This response was not modified by rIC.

Iron overload of hematological origin: validation of a screening procedure for cardiac overload by MRI in routine clinical practice.

PURPOSE: Screening for cardiac iron overload is generally done by magnetic resonance imaging (MRI) and demonstrated by a shortening of the myocardial T2* below 20 ms at 1.5 Tesla. This measurement was validated with a specific sequence and the CMRTools(®) calculation software (reference technique). The objective of this study was to validate the use of sequences and software programs that are available in routine clinical practice to screen for iron overload. MATERIAL AND METHODS: First, a phantom of 11 tubes with a T2* between 4 and 33 ms was tested at three sites that had MRI machines of different brands. Second, the myocardial T2* values of 75 patients were measured in routine clinical practice using two methods. The first method used the reference sequence specially installed in the machines associated with the CMRTool software. The second method used the standard acquisition sequences available in the machines followed by calculation on a computer spreadsheet. RESULTS: In the phantom, the mean of the differences in T2* between each machine was 0.6 ms. Thirteen patients had a lowered T2* value with the reference technique. Three cases were poorly classified using the routine technique and corresponded with false positives of low overload (T2* between 18 and 20 ms). CONCLUSION: Screening for myocardial iron overload can be done by MRI by using sequences and calculation software available in routine clinical practice during the same examination as the one for the evaluation of hepatic iron overload.

CT and MRI imaging at the acute phase of inaugural non-traumatic hepatic haemorrhages.

PURPOSE: Although rare, non-traumatic hepatic haemorrhage is a known complication of liver tumors. In cases where the haemorrhage is the first clinical event, diagnostic work-up is critical. MATERIAL AND METHODS: This retrospective study was conducted between July 2001 and March 2011. Acute phase CT-scan and MRI imaging in patients diagnosed with non-traumatic liver hematomas were interpreted with particular attention to the radio-semiotic characteristics of hematomas and liver lesions. Those findings were then confronted to the patients' final diagnoses. RESULTS: Twelve patients were included (mean age of 42 years). In seven of them a suspect liver lesion was discovered in the acute CT-Scan or MRI imaging. All lesions were strongly hyper vascular.The haemorrhage revealed hepatocarcinoma in four patients, liver adenoma in two and focal nodular hyperplasia in an other. CONCLUSION: It is important in spontaneous liver haemorrhage to consider the high probability of hepatocarcinoma or potentially malignant lesions even when the patient has no known hepatic disorders, and especially in young patients. The results of this study show that imaging is a key issue at the acute phase of inaugural non-traumatic hepatic haemorrhages and requires a simple but complete triphasic injected protocol.

Cochlear implant with a non-removable magnet: preliminary research at 3-T MRI.

OBJECTIVE: To perform preliminary tests in vitro and with healthy volunteers to determine the 3-T MRI compatibility of a cochlear implant with a non-removable magnet. METHODS: In the in vitro phase, we tested six implants for temperature changes and internal malfunctioning. We measured the demagnetisation of 65 internal magnets with different tilt angles between the implant's magnetic field (bi) and the main magnetic field (b0). In the in vivo phase, we tested 28 operational implants attached to the scalps of volunteers with the head in three different positions. RESULTS: The study did not find significant temperature changes or electronic malfunction in the implants tested in vitro. We found considerable demagnetisation of the cochlear implant magnets in the in vitro and in vivo testing influenced by the position of the magnet in the main magnetic field. We found that if the bi/b0 angle is <90°, there is no demagnetisation; if the bi/b0 angle is >90°, there is demagnetisation in almost 60 % of the cases. When the angle is around 90°, the risk of demagnetisation is low (6.6 %). CONCLUSION: The preliminary results on cochlear implants with non-removable magnets indicate the need to maintain the contraindication of passage through 3-T MRI. KEY POINTS: • Magnetic resonance imaging can affect cochlear implants and vice versa. • Demagnetisation of cochlear implant correlates with the angle between bi and b0. • The position of the head in the MRI influences the demagnetisation. • Three-Tesla MRI for cochlear implants is still contraindicated. • However some future solutions are discussed.

Computed tomography of the parathyroids: the value of density measurements to distinguish between parathyroid adenomas of the lymph nodes and the thyroid parenchyma.

PURPOSE: To compare the densities of parathyroid adenomas, lymph nodes and the thyroid parenchyma during multi-phase cervico-thoracic computed tomography to determine the differentiating threshold values. MATERIALS AND METHODS: This study comprises 30 patients operated for a parathyroid adenoma after computed tomography without injection and then 45 and 70 seconds after the injection of an iodine based contrast product (350 mgI/mL, 150 mL, 3 mL/s). The density of the adenomas, lymph nodes and thyroid was measured during the three phases (D0, D45, D70). The relative enhancement (RE) at 45 seconds was calculated: RE=(D45-D0)/D0. RESULTS: A significant difference was found in the spontaneous density of the parathyroid adenomas of the thyroid (P<0.01) with a threshold value of 75 HU. A significant difference is found in the enhancement after injection of the adenomas and lymph nodes (P<0.01). The adenomas present an enhancement peak at 45 seconds while the maximum enhancement of the lymph nodes is at 70 seconds. At 45 seconds, a threshold value of 114 HU and an RE 125% allows them to be distinguished (sensitivity and specificity 0.96). CONCLUSION: Measurement of the densities can differentiate between the parathyroid adenomas, lymph nodes and thyroid.

Improved GFR and renal plasma perfusion following remote ischaemic conditioning in a porcine kidney transplantation model.

Delayed graft function (DGF) complicates approximately 25% of kidney allografts donated after brain death (DBD). Remote ischaemic conditioning (rIC) involves brief, repetitive, ischaemia in a distant tissue in connection with ischaemia/reperfusion in the target organ. rIC has been shown to induce systemic protection against ischaemic injuries. Using a porcine kidney transplantation model with donor (63 kg) recipient (15 kg) size mismatch, we investigated the effects of recipient rIC on early renal plasma perfusion and GFR. Brain death was induced in donor pigs (n = 8) and kidneys were removed and kept in cold storage until transplantation. Nephrectomized recipient pigs were randomized to rIC (n = 8) or non-rIC (n = 8) with one kidney from the same donor in each group. rIC consisted of 4 × 5 min clamping of the abdominal aorta. GFR was significantly higher in the rIC group compared with non-rIC (7.2 ml/min vs. 3.4 ml/min; ΔGFR = 3.7 ml/min, 95%-CI: 0.3-7.2 ml/min, P = 0.038). Renal plasma perfusion in both cortex and medulla measured by dynamic contrast-enhanced magnetic resonance imaging (MRI) was significantly higher over time in the rIC group compared with non-rIC. This experimental study demonstrated a positive effect of rIC on early graft perfusion and function in a large animal transplantation model.

Brief report: new legislation supports students with intellectual disabilities in post-secondary funding.

With the passage of the Higher Education Opportunities Act (HEAO) of 2008, students with intellectual disabilities who are enrolled in a federally approved Comprehensive Transition and Postsecondary Program on a college campus will be eligible for some forms of federal student financial aid. This Brief Report discusses the forms of aid available, the impact upon higher functioning students with ASDs, the impact upon colleges and the potential conflict between HEOA and Individuals with Disabilities Education Act.

Safety and efficacy of sorafenib in hepatocellular carcinoma: the impact of the Child-Pugh score.

BACKGROUND: Sorafenib increases median survival and time to radiological progression in patients with advanced hepatocellular carcinoma, but its benefit for Child-Pugh B patients remains uncertain. AIM: To evaluate the safety and efficacy of sorafenib in real-life clinical practice conditions and to assess the influence of Child-Pugh class B on safety and efficacy. METHODS: All patients treated with sorafenib for advanced hepatocellular carcinoma in our institution were included prospectively. Adverse events, overall survival and time to progression were recorded. A case control study was performed to compare outcome of patients with comparable stages of hepatocellular carcinoma, but a different Child-Pugh class. RESULTS: From March 2007 to May 2009, 120 patients were included. Overall survival was 11.1 months, Child-Pugh A patients (n=100) had significantly higher median survival than Child-Pugh B patients (n=20) (13 vs. 4.5 months, P=0.0008). In multivariate analysis, Child-Pugh class B, α-fetoprotein level and total size of lesions were independent predictive factors of death. Patients with radiological progression in the first 3 months had shorter median survival (5.4 vs. 17.4 months). In a case control study, time to symptomatic progression (2.5 vs. 3.6 months), frequency of adverse events and discontinuation of sorafenib were not correlated with Child-Pugh class. CONCLUSIONS: Patients with advanced hepatocellular carcinoma treated with sorafenib had a median survival of 11 months. Sorafenib therapy must be considered with caution in Child-Pugh B patients due to their poor survival. Radiological assessment of tumour progression at an early stage may be advantageous when tailoring sorafenib therapy.