Jan Nilsson

Non-invasive imaging of microcirculation: a technology review.

Microcirculation plays a crucial role in physiological processes of tissue oxygenation and nutritional exchange. Measurement of microcirculation can be applied on many organs in various pathologies. In this paper we aim to review the technique of non-invasive methods for imaging of the microcirculation. Methods covered are: videomicroscopy techniques, laser Doppler perfusion imaging, and laser speckle contrast imaging. Videomicroscopy techniques, such as orthogonal polarization spectral imaging and sidestream dark-field imaging, provide a plentitude of information and offer direct visualization of the microcirculation but have the major drawback that they may give pressure artifacts. Both laser Doppler perfusion imaging and laser speckle contrast imaging allow non-contact measurements but have the disadvantage of their sensitivity to motion artifacts and that they are confined to relative measurement comparisons. Ideal would be a non-contact videomicroscopy method with fully automatic analysis software.

Limiting factors for liver regeneration after a major hepatic resection for colorectal cancer metastases.

BACKGROUND Chemotherapy before resection of colorectal metastases in the liver is extensively used and has been shown to induce histopathological changes in the liver parenchyma, although little is known about the effect of chemotherapy on liver regeneration. The aim of this study was to determine if pre-operative chemotherapy influences the regenerated liver volume after a major liver resection. PATIENTS AND METHODS This retrospective cohort study included 74 patients subjected to a major liver resection for colorectal metastases. Patients were divided into two groups depending on whether they had been treated with chemotherapy less than 3 months before surgery or not. Liver volumes were measured before and 1 year after resection. RESULTS Pre-operative chemotherapy reduced volumetric liver regeneration (83 ± 2% versus 91 ± 2%; P = 0.007) as compared with patients without chemotherapy. There was a linear correlation between regenerated volume and time interval between the end of chemotherapy to resection (P = 0.031). CONCLUSIONS Pre-operative chemotherapy in patients with colorectal liver metastases negatively affects volume regeneration after a partial hepatectomy. The time interval between chemotherapy and surgery determines the impact of these affects.

Microcirculation changes during liver resection — A clinical study

BACKGROUND In this study we aimed to evaluate effects of liver resection on hepatic microcirculation. In addition we wanted to study if histological liver damage could be detected intra-operatively. PATIENTS AND METHODS 40 patients undergoing hepatic resection were included and grouped according to if they were operated with a major or minor resection. Hepatic microcirculation measurements were made intra-operatively before and after liver resection with sidestream dark-field (SDF) imaging. Red blood cell velocity (RBCV), sinusoidal diameter and functional sinusoidal density were determined. RESULTS After hepatic resection RBCV increased in both the minor and major groups (44 μm/s, P=0.016 and 121 μm/s, P=0.002). RBCV in patients with histological damages was 225 (148-464) μm/s vs. 161 (118-329) μm/s in patients with no damage (P=0.016). CONCLUSION A hepatic resection leads to an increase of sinusoidal RBCV. SDF imaging could potentially be used to intraoperatively identify histological damages.

Laser speckle contrast imaging for intraoperative assessment of liver microcirculation: a clinical pilot study.

Background Liver microcirculation can be affected by a wide variety of causes relevant to liver transplantation and resectional surgery. Intraoperative assessment of the microcirculation could possibly predict postoperative outcome. The present pilot study introduces laser speckle contrast imaging (LSCI) as a new clinical method for assessing liver microcirculation. Methods LSCI measurements of liver microcirculation were performed on ten patients undergoing liver resection. Measurements were made during apnea with and without liver blood inflow occlusion. Hepatic blood flow was assessed by subtracting zero inflow signal from the total signal. Zero inflow signal was obtained after hepatic artery and portal vein occlusion. Perfusion was expressed in laser speckle perfusion units, and intraindividual and interindividual variability in liver perfusion was investigated using the coefficient of variability. Results Hepatic microcirculation measurements were successfully made in all patients resulting in analyzable speckle contrast images. Mean hepatic blood flow was 410±36 laser speckle perfusion units. Zero inflow signal amounted to 40%±4% of the total signal. Intraindividual and interindividual coefficients of variability in liver perfusion were 25% and 28%, respectively. Conclusion Under the conditions of this pilot study, LSCI allows rapid noncontact measurements of hepatic blood perfusion over wide areas. More studies are needed on methods of handling movement artifacts.

Diffuse Reflectance Spectroscopy for Surface Measurement of Liver Pathology

Background: Liver parenchymal injuries such as steatosis, steatohepatitis, fibrosis, and sinusoidal obstruction syndrome can lead to increased morbidity and liver failure after liver resection. Diffuse reflectance spectroscopy (DRS) is an optical measuring method that is fast, convenient, and established. DRS has previously been used on the liver with an invasive technique consisting of a needle that is inserted into the parenchyma. We developed a DRS system with a hand-held probe that is applied to the liver surface. In this study, we investigated the impact of the liver capsule on DRS measurements and whether liver surface measurements are representative of the whole liver. We also wanted to confirm that we could discriminate between tumor and liver parenchyma by DRS. Materials and Methods: The instrumentation setup consisted of a light source, a fiber-optic contact probe, and two spectrometers connected to a computer. Patients scheduled for liver resection due to hepatic malignancy were included, and DRS measurements were performed on the excised liver part with and without the liver capsule and alongside a newly cut surface. To estimate the scattering parameters and tissue chromophore volume fractions, including blood, bile, and fat, the measured diffuse reflectance spectra were applied to an analytical model. Results: In total, 960 DRS spectra from the excised liver tissue of 18 patients were analyzed. All factors analyzed regarding tumor versus liver tissue were significantly different. When measuring through the capsule, the blood volume fraction was found to be 8.4 ± 3.5%, the lipid volume fraction was 9.9 ± 4.7%, and the bile volume fraction was 8.2 ± 4.6%. No differences could be found between surface measurements and cross-sectional measurements. In measurements with/without the liver capsule, the differences in volume fraction were 1.63% (0.75-2.77), -0.54% (-2.97 to 0.32), and -0.15% (-1.06 to 1.24) for blood, lipid, and bile, respectively. Conclusion: This study shows that it is possible to manage DRS measurements through the liver capsule and that surface DRS measurements are representative of the whole liver. The results are consistent with data published earlier on the combination of liver chromophores. The results encourage us to proceed with in vivo measurements for further quantification of the livers composition and assessment of parenchymal damage such as steatosis and fibrosis grade.

Incisional hernia after open resections for colorectal liver metastases – incidence and risk factors

BACKGROUND Incisional hernia is one of the most common complications after laparotomy. The aim of this retrospective study was to investigate incidence, location and risk factors for incisional hernia after open resection for colorectal liver metastases including the use of perioperative chemotherapy and targeted therapy evaluated by computed tomography. METHODS Patients operated for colorectal liver metastases between 2010 and 2013 were included. Incisional hernia was defined as a discontinuity in the abdominal fascia observed on computed tomography. RESULTS A total of 256 patients were analyzed in regard to incisional hernia. Seventy-eight patients (30.5%) developed incisional hernia. Hernia locations were midline alone in 66 patients (84.6%) and involving the midline in another 8 patients (10.3%). In multivariate analysis, preoperative chemotherapy >6 cycles (hazard ratio 2.12, 95% confidence interval 1.14-3.94), preoperative bevacizumab (hazard ratio 3.63, 95% confidence interval 1.86-7.08) and incisional hernia from previous surgery (hazard ratio 3.50, 95% confidence interval 1.98-6.18) were found to be independent risk factors. CONCLUSIONS Prolonged preoperative chemotherapy and also preoperative bevacizumab were strong predictors for developing an incisional hernia. After an extended right subcostal incision, the hernia location was almost exclusively in the midline.

Diffuse reflectance spectroscopy of liver tissue

Diffuse reflectance spectroscopy (DRS) with a fiber-optic contact probe is a cost-effective, rapid, and non-invasive optical method used to extract diagnosis information of tissue. By combining commercially available VIS- and NIR-spectrometers with various fiber-optic contact-probes, we have access to the full wavelength range from around 400 to 1600 nm. Using this flexible and portable spectroscopy system, we have acquired ex-vivo DRS-spectra from murine, porcine, and human liver tissue. For extracting the tissue optical properties from the measured spectra, we have employed and compared predictions from two models for light propagation in tissue, diffusion theory model (DT) and Monte Carlo simulations (MC). The focus in this work is on the capacity of this DRS-technique in discriminating metastatic tumor tissue from normal liver tissue as well as in assessing and characterizing damage to non-malignant liver tissue induced by preoperative chemotherapy for colorectal liver metastases.

Concurrent biliary drainage and portal vein embolization in preparation for extended hepatectomy in patients with biliary cancer.

Background Patients with perihilar cholangiocarcinoma and gallbladder cancer extending into the hilum often present with jaundice and a small future liver remnant (FLR). If resectable, preoperative biliary drainage and portal vein embolization (PVE) are indicated. Classically, these measures have been performed sequentially, separated by 4–6 weeks. Purpose To report on a new regime where percutaneous transhepatic biliary drainage (PTBD) and PVE are performed simultaneously, shortening the preoperative process. Material and Methods Six patients were treated with concurrent PTBD and PVE under general anesthesia. Results Surgical exploration followed the combined procedure after 35 days (range, 28–51 days). The FLR ratio increased from 22% to 32%. Three patients developed cholangitis after the procedure. Conclusion The combined approach of PTBD and PVE seems feasible, but more studies on morbidity are warranted.

Cardiovascular disease in systemic lupus erythematosus is associated with increased levels of biomarkers reflecting receptor-activated apoptosis

BACKGROUND AND AIMS There is convincing evidence that adaptive immune responses affect the development of atherosclerosis and thrombosis and several autoimmune diseases are associated with increased cardiovascular risk. However, our understanding of the underlying mechanisms remains limited. We investigated how biomarkers reflecting four aspects of autoimmunity: apoptosis, inflammation, tissue degradation and repair, associate with cardiovascular disease (CVD) in subjects with systemic lupus erythematosus (SLE). METHODS We investigated 484 well-characterized SLE patients, 69 of whom had CVD (coronary artery disease, cerebrovascular disease or peripheral artery disease), and 253 controls. Occurrence of carotid plaques was investigated with ultrasound. Plasma levels of biomarkers reflecting apoptosis (Fas, TNF receptor 1, TRAIL receptor 2), inflammation (IL-6, IL-8, monocyte chemotactic protein-1), tissue degradation (matrix metalloproteinase (MMP)-1, MMP-3, MMP-7), and tissue repair (platelet-derived growth factor, epidermal growth factor and stem cell factor) were analyzed by Proximity Extension Assay. RESULTS Subjects with SLE had markedly elevated plasma levels of biomarkers reflecting apoptosis, inflammation and tissue degradation as compared to controls. SLE patients with CVD had higher levels of Fas, TNF receptor 1, TRAIL receptor 2, MMP-1 and -7 than those without CVD. The same associations were found for the presence of a carotid plaque. When controlling for the factors included in the Framingham risk score, all biomarkers except MMP-1 remained associated with the presence of a carotid plaque, while only TRAIL receptor 2 levels remained significantly associated with CVD. CONCLUSIONS Our findings argue that the cardiovascular risk in SLE is associated with increased cell death by apoptosis and tissue degradation.