Sylvain Terraz

‘Liver First’ Approach in the Treatment of Colorectal Cancer with Synchronous Liver Metastases

Background: In patients with synchronous colorectal liver metastases, an approach reversing the traditional therapeutic order – i.e. starting with chemotherapy first, doing the liver surgery second, and performing the colorectal surgery last – is theoretically appealing as it avoids the risk of metastatic progression during treatment of the primary tumor. The present series updates on a previously reported pilot experience. Patients and Methods: 35 patients with advanced synchronous colorectal metastases and nonobstructive colorectal tumors were treated with the reversed approach. Data were collected in a prospective database. Results: The median number of metastases was 6, the median size of the largest metastasis was 6 cm. Five patients could not complete the program (one death from sepsis during chemotherapy, 3 cases of progressive disease under treatment, and one case of vanishing liver metastases). The remaining 30 patients responded and underwent R0 liver resections with no major complications. One patient needed a Hartmann’s procedure for obstruction after a first-step hepatectomy, and 1 patient had a rectal anastomotic leak. Median survival was 44 months. Overall survival rates of the 30 patients who completed the program at 1, 2, 3, 4 and 5 years were 100, 89, 60, 44 and 31%. Conclusions: The reverse approach appeared feasible and safe, with operability and survival rates better than expected for patients with similar severity. Potential problems, in particular regrowth of vanishing metastases and primary tumors, chemotherapy-associated liver damage, and large bowel obstruction, can be minimized by careful multidisciplinary selection, planning and execution.

Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

Objective Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD). We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT) improved liver function in decompensated ALD. Design 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy) were randomized early after hospital admission to standard medical therapy (SMT) alone (n = 30), including steroids in patients with a Maddrey’s score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28). Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC) compartment. Results Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64%) from the BMMCT group and 18 patients (53%) from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49–5.4) in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001), and proliferating HPC tended to decrease in both groups (−35 and −33%, respectively). Conclusion Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. Trial Registration Controlled-Trials.com ISRCTN83972743.

Improved Long-Term Outcome of Surgery for Advanced Colorectal Liver Metastases: Reasons and Implications for Management on the Basis of a Severity Score

BackgroundThe outcome of liver resection for colorectal liver metastases (CRLM) appears to be improving despite the fact that surgery is offered to patients with more-severe disease. To quantify this assumption and to understand its causes we analyzed a series of patients on the basis of a standardized severity score and changes in management occurring over the years.MethodsPatients’ characteristics, operative data, chemotherapies and follow-up were recorded. CRLM severity was quantified according to Fong’s clinical risk score (CRS), modified to take into account the presence of bilateral liver metastases. Three periods were analyzed, in which different indications, surgical strategies and uses of chemotherapy were applied: 1984–1992, 1993–1998, and 1999–2005.ResultsBetween January 1984 and December 2005, 210 liver resections were performed in 180 patients (1984–1992, 43 patients; 1993–1998, 42 patients; 1999–2005, 95 patients). CRLM severity increased throughout the time periods, as did the use of neoadjuvant chemotherapies, repeat resections, and multistep procedures. While the disease-free survival did not improve over time, the 1-, 3- and 5-year overall survival rate increased from 85%, 30%, and 23% in the first period, to 88%, 60%, and 34% in the second period, and to 94%, 69%, and 46% in the third period.ConclusionsAnalysis according to the CRS showed that despite the fact that patients had more severe disease, the overall survival improved over the years, mainly thanks to more aggressive treatment of recurrent disease. Management of advanced CRLM should, from the start, take into account the likelihood of secondary procedures.

Dangerous halo after neoadjuvant chemotherapy and two-step hepatectomy for colorectal liver metastases

Bilobar colorectal metastases are a therapeutic challenge and require a multidisciplinary approach. The aim of this study was to describe the clinical and histological outcomes of patients having neoadjuvant chemotherapy and two‐step hepatectomy with right portal vein occlusion for advanced bilateral colorectal metastases.

Reference-Free PRFS MR-Thermometry Using Near-Harmonic 2-D Reconstruction of the Background Phase

Proton resonance frequency shift (PRFS) MR thermometry (MRT) is the generally preferred method for monitoring thermal ablation, typically implemented with gradient-echo (GRE) sequences. Standard PRFS MRT is based on the subtraction of a temporal reference phase map and is, therefore, intrinsically sensitive to tissue motion (including deformation) and to external perturbation of the magnetic field. Reference-free (or reference-less) PRFS MRT has been previously described by Rieke and was based on a 2-D polynomial fit performed on phase data from outside the heated region, to estimate the background phase inside the region of interest. While their approach was undeniably a fundamental progress in terms of robustness against tissue motion and magnetic perturbations, the underlying mathematical formalism requires a thick unheated border and may be subject to numerical instabilities with high order polynomials. A novel method of reference-free PRFS MRT is described here, using a physically consistent formalism, which exploits mathematical properties of the magnetic field in a homogeneous or near-homogeneous medium.

Complications of Elective Liver Resections in a Center With Low Mortality: A Simple Score to Predict Morbidity

OBJECTIVE To develop a score predicting the morbidity of liver resections in a center with low mortality. DESIGN, SETTING, AND PATIENTS The study was based on a prospective database of all liver resections performed at the Geneva University Hospitals between January 1, 1991, and October 30, 2009 (a total of 726 elective liver resections in 689 patients). Perioperative complications and their severity were graded according to the original classification by Clavien et al. Variables independently associated with the occurrence of complications were identified using a linear regression analysis model. A score was computed with all independent variables in an assessment population including two-thirds of the liver resections and was further validated in a population including one-third of the liver resections. RESULTS Overall mortality was 0.7% (5 of 726 liver resections). We recorded 375 different complications in 259 hepatic resections (36% of resections had ≥ 1 complication). In the assessment group, resection of 3 or more segments, an American Society of Anesthesiologists score of 3 or higher, and resection for a malignant neoplasm independently predicted the risk of complications. A score integrating these 3 factors significantly predicted the risk of postoperative complications. The score also correlated with the occurrence of major complications. CONCLUSION The score allows for identification of patients most susceptible to complications, in whom efforts against specific postoperative morbidities can be concentrated.

Value of contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in detection and presurgical assessment of pancreatic cancer: A prospective study

Background and Aim:  Positron Emission Tomography (PET) using 18F‐fluorodeoxyglucose (FDG) associated with computed tomography (CT) is increasingly used for the detection and the staging of pancreatic cancer, but data regarding its clinical added value in pre‐surgical planning is still lacking. The aim of this study is to investigate the performance of FDG PET associated with contrast‐enhanced CT in detection of pancreatic cancer.

Validation of fast MR thermometry at 1.5 T with gradient-echo echo planar imaging sequences: phantom and clinical feasibility studies.

The purpose of this work was to validate in phantom studies and demonstrate the clinical feasibility of MR proton resonance frequency thermometry at 1.5 T with segmented gradient‐echo echo planar imaging (GRE‐EPI) sequences during liver tumour radiofrequency (RF) ablation. Classical GRE acquisitions and segmented GRE‐EPI acquisitions were performed at 1.5 T during simultaneous RF heating with an MR‐compatible RF electrode placed in an agar gel phantom. Temperature increments were calculated and compared with four optical temperature probe measurements using Bland– Altman analysis. In a preliminary clinical feasibility study, the rapid GRE‐EPI sequence (echo train length = 13) was used for MR temperature monitoring of RF ablation of liver tumours in three patient procedures. For phantom experiments, the Bland–Altman mean of differences between MR and optical probe temperature measurements was <0.4°C, and the 95% limits of agreement value was <1.4°C. For the in vivo studies, respiratory‐triggered GRE‐EPI acquisitions yielded a temperature accuracy of 1.3 ± 0.4°C (acquisition time = 0.6 s/image, spatial coverage of three slices/respiratory cycle). MR proton resonance frequency thermometry at 1.5 T yields precise and accurate measurements of temperature increment with both classical GRE and rapid GRE‐EPI sequences. Rapid GRE‐EPI sequences minimize intra‐scan motion effects and can be used for MR thermometry during RF ablation in moving organs. Copyright

Hybrid Ultrasound/Magnetic Resonance Simultaneous Acquisition and Image Fusion for Motion Monitoring in the Upper Abdomen

ObjectivesThe combination of ultrasound (US) and magnetic resonance imaging (MRI) may provide a complementary description of the investigated anatomy, together with improved guidance and assessment of image-guided therapies. The aim of the present study was to integrate a clinical setup for simultaneous US and magnetic resonance (MR) acquisition to obtain synchronized monitoring of liver motion. The feasibility of this hybrid imaging and the precision of image fusion were evaluated. Materials and MethodsUltrasound imaging was achieved using a clinical US scanner modified to be MR compatible, whereas MRI was achieved on 1.5- and 3-T clinical scanners. Multimodal registration was performed between a high-resolution T1 3-dimensional (3D) gradient echo (volume interpolated gradient echo) during breath-hold and a simultaneously acquired 2D US image, or equivalent, retrospective registration of US imaging probe in the coordinate frame of MRI. A preliminary phantom study was followed by 4 healthy volunteer acquisitions, performing simultaneous 4D MRI and 2D US harmonic imaging (Fo = 2.2 MHz) under free breathing. ResultsNo characterized radiofrequency mutual interferences were detected under the tested conditions with commonly used MR sequences in clinical routine, during simultaneous US/MRI acquisition. Accurate spatial matching between the 2D US and the corresponding MRI plane was obtained during breath-hold. In situ fused images were delivered. Our 4D MRI sequence permitted the dynamic reconstruction of the intra-abdominal motion and the calculation of high temporal resolution motion field vectors. ConclusionsThis study demonstrates that, truly, simultaneous US/MR dynamic acquisition in the abdomen is achievable using clinical instruments. A potential application is the US/MR hybrid guidance of high-intensity focused US therapy in the liver.

How Reliable Is Sonography in the Assessment of Sialolithiasis

OBJECTIVE The purpose of this study was to determine the value of sonography for the diagnosis of salivary gland calculi. SUBJECTS AND METHODS In this study, 82 salivary glands in 79 consecutively registered patients with acute or recurrent parotid or submandibular gland swelling were examined with 7.5-12 MHz linear probes. All sonographic examinations were performed by two experienced radiologists without knowledge of the final diagnosis. The reference standard was digital sialography and sialendoscopy with or without surgery for 54 salivary glands and digital sialography alone for 28 glands. RESULTS Sialolithiasis was present in 44 glands and was absent in 38 glands as confirmed by the final diagnosis. The overall sensitivity, specificity, accuracy, and positive and negative predictive values of sonography in the detection of calculi were 77%, 95%, 85%, 94%, and 78%, respectively. False-negative sonographic findings were associated with calculi with a diameter less than 3 mm in nondilated or dilated salivary ducts; most calculi with a diameter of 3 mm or greater were correctly identified. False-positive findings were caused by ductal stenosis with wall fibrosis, which was erroneously interpreted as lithiasis. CONCLUSION Because of its limited sensitivity and limited negative predictive value, sonography does not allow reliable exclusion of small salivary gland calculi. Therefore, further diagnostic investigations are recommended to detect calculi in patients with normal sonographic findings and suspected lithiasis.