Audun Elnaes Berstad

Assessment of renal allograft fibrosis by acoustic radiation force impulse quantification--a pilot study.

Chronic allograft nephropathy characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness. We evaluated if the method could reveal renal transplant fibrosis. In a prospective study, 30 adult renal transplant recipients were included. ARFI quantification, given as shear wave velocity (SWV), of the renal cortex was performed by two observers. SWV was compared to grade of fibrosis (0–3) in biopsies. The median SWV was 2.8 m/s (range: 1.6–3.6), 2.6 m/s (range: 1.8–3.5) and 2.5 m/s (range: 1.6–3) for grade 0 (n = 12), 1 (n = 10) and grades 2/3 (n = 8) fibrosis respectively. SWV did not differ significantly in transplants without and with fibrosis (grade 0 vs. grade 1, P = 0.53 and grade 0 vs. grades 2/3, P = 0.11). The mean intraobserver coefficient of variation was 22% for observer 1 and 24% for observer 2. Interobserver agreement, expressed as intraclass correlation coefficient was 0.31 (95% CI: −0.03 to 0.60). This study does not support the use of ARFI quantification to assess low‐grade fibrosis in renal transplants. ARFI quantification in its present stage of development has also high intra‐ and interobserver variation in renal transplants.

Clinical utility of microbubble contrast‐enhanced ultrasound in the diagnosis of hepatic artery occlusion after liver transplantation

To evaluate the frequency of use and the diagnostic accuracy of real‐time contrast‐enhanced ultrasound (CEUS) in the diagnosis of hepatic artery occlusion after liver transplantation. One hundred and fifty‐two liver transplantations in 142 adult subjects, comprising 80 male patients and 62 female patients, were studied. After surgery, liver circulation was routinely assessed by conventional Doppler ultrasound (US). Wherever the examiners were not confident about the state of the circulation, CEUS was performed with one or more doses of a sulfur hexafluoride (SF‐6)‐containing second‐generation contrast agent intravenously. Clinical follow up including repeat Doppler US, computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) of the liver vasculature were used as reference standards. During the first month after transplantation, Doppler US was inconclusive with regard to patency of the hepatic artery (HA) circulation in 20 (13 %) of 152 transplantations. CEUS was performed in these patients, and detected six cases of HA thrombosis (HAT) in five transplants. CEUS correctly ruled out HA occlusion in 15 transplants. All HA occlusions occurred during the first 14 days after transplantation. In the subset of transplantations examined with CEUS, the sensitivity, specificity and accuracy of CEUS were 100%. In approximately 13% of cases, conventional Doppler US did not provide sufficient visualization of the HA after liver transplantation. In these cases, correct diagnosis was achieved by supplementary CEUS.

A Novel Concept for Partial Liver Transplantation in Nonresectable Colorectal Liver Metastases: The RAPID Concept.

OBJECTIVE Selected patients with nonresectable colorectal liver metastases benefit from liver transplantation and have acceptable 5-year survival rates. However, allocating full-sized grafts to this group of patients is difficult due to the scarcity of grafts. This could be improved by utilizing small partial grafts, which mandates effective strategies to overcome the problems regarding insufficient functional liver mass. METHODS We have developed a protocol incorporating previously reported experiences from living donor transplantation and recent developments in liver surgery, facilitating transplantation of very small liver grafts. At the time of transplantation, segments 1 to 3 are resected in the recipient and orthotopically replaced by a segment 2 to 3 allograft. Portal inflow is modulated by redirecting the portal flow to the graft with concomitant focus on keeping the portal vein pressure below 20 mm Hg. A second-stage hepatectomy is performed as soon as the graft has regenerated to a sufficient volume. RESULTS A graft weighing 330 g was transplanted to a 50-year-old man weighing 92 kg, and the portal vein to the right remnant liver was closed. The volume of the liver graft was doubled 2 weeks after the first procedure, and it increased further after the second procedure, with extended right hepatectomy performed at day 23 after transplantation. There were no signs of liver failure or small-for-size syndrome. CONCLUSIONS The current protocol and ongoing study could represent a possible strategy to increase the availability of liver transplantation to patients with nonresectable liver tumors such as hepatocellular carcinoma and colorectal liver metastases.

Non-invasive assessment of renal allograft fibrosis by dynamic sonographic tissue perfusion measurement

Background Chronic allograft nephropathy (CAN) characterized by interstitial fibrosis and tubular atrophy is a major cause of renal transplant failure. The diagnosis can currently only be verified by a graft biopsy. Purpose To evaluate whether non-invasive dynamic color Doppler sonographic parenchymal perfusion measurements are different in grafts with various degrees of biopsy proven renal transplant fibrosis. Material and Methods Forty-nine adult patients were prospectively included. Four patients were excluded. Color Doppler videos from the renal cortex were recorded. Perfusion in the renal cortex was evaluated using a software package which calculates color pixel area and flow velocity, encoded by each pixel inside a region of interest of a video sequence. The software calculates parameters that describe tissue perfusion numerically. Two of these, the perfusion intensity and tissue pulsatility index, were compared to grade of interstitial fibrosis (0–3) in biopsies. Observer agreement was evaluated in a subset of 12 patients. Results Of the 45 patients analyzed, 18 patients had grade 0, 18 had grade 1, seven had grade 2 and two had grade 3 fibrosis. The mean perfusion intensity of grade 0 was significantly higher than that of grade 2 and 3 fibrosis in the proximal cortical layer (1.65 m/s vs. 0.84 m/s, P = 0.008). No significant difference was found between grade 0 and grade 1 fibrosis. Perfusion intensity was correlated to estimated glomerular filtration rate (Pearson r 0.51, P = 0.001, R2 = 0.26 and 0.46, P = 0.001, R2 = 0.22 in the distal and proximal cortex, respectively). Inter-observer agreement of the perfusion intensity, expressed as intraclass correlation coefficient was 0.69 in the proximal part of the cortex. Intra-observer agreement was 0.85 for observer 1 and 0.82 for observer 2. Conclusion Perfusion intensity assessed by dynamic color Doppler measurements is significantly reduced in allografts with grade 2 and 3 fibrosis compared to allografts without fibrosis. Further studies involving longitudinal assessment of allografts undergoing protocol biopsies would be of interest.

Increased Mucosal Production of Monomeric IgA1 but No IgA1 Protease Activity in Helicobacter pylori Gastritis

Immunoglobulin A and IgM are subjected to epithelial transport only when they are produced as polymers with incorporated J chain. Immunocytes containing various Ig isotypes and associated J chain in gastric mucosa, as well as IgA-degrading protease activity in Helicobacter pylori cultures, were examined. Gastric body specimens from 15 H. pylori-positive and 14 H. pylori-negative patients were studied by paired immunofluorescence for IgA, IgA1, IgA2, IgG, or IgM and concurrent cellular J chain. H. pylori isolates were incubated with IgA1 or secretory IgA and examined by immunoelectrophoresis for cleavage products. A substantial increase of Ig-producing cells occurred in chronic gastritis, particularly in the IgA1 isotype, but H. pylori was shown to possess neither IgA1-specific nor nonspecific IgA-degrading protease activity. Regardless of infection status, reduced J chain expression was observed for all immunocyte isotypes (except for IgM) in inflamed compared with normal gastric body mucosa, the median positivity for IgA1 cells being reduced to 58.7% versus 87.9% (P = 0.0002), and for IgA2 cells to 48.9% versus 87.8% (P = 0.0002). This down-regulation of the J chain suggested that a large fraction of IgA monomers is produced in gastritis.

Diagnostic accuracy of computed tomography and histopathology in the diagnosis of usual interstitial pneumonia

Background The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate. Purpose To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP. Material and Methods The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses. Results There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (κ = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1). Conclusion Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP.

Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy

Pancreatoduodenectomy with superior mesenteric–portal vein resection has become a common procedure in pancreatic surgery. The aim of this study was to compare standard pancreatoduodenectomy with pancreatoduodenectomy plus venous resection at a high‐volume centre, and to examine trends in management and outcome over a decade for the latter procedure.

Molecular signatures reflecting microenvironmental metabolism and chemotherapy-induced immunogenic cell death in colorectal liver metastases

BACKGROUND Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance. METHODS In this ancillary study to the Oslo-CoMet trial, CLM and tumor-adjacent liver tissue from 46 patients were analyzed by profiling mutations (targeted sequencing), genome-wide copy number alteration (CNAs), and gene expression. RESULTS Somatic mutations and CNAs detected in CLM were similar to reported primary CRC profiles, while CNA profiles of eight metastatic pairs suggested intra-patient divergence. A CMS classifier tool applied to gene expression data, revealed the cohort to be highly enriched for CMS2. Hierarchical clustering of genes with highly variable expression identified two subgroups separated by high or low expression of 55 genes with immune-related and metabolic functions. Importantly, induction of genes and pathways associated with immunogenic cell death (ICD) was identified in metastases exposed to neoadjuvant chemotherapy (NACT). CONCLUSIONS The uniform classification of CLM by CMS subtyping may indicate that novel class discovery approaches need to be explored to uncover clinically useful stratification of CLM. Detected gene expression signatures support the role of metabolism and chemotherapy in shaping the immune microenvironment of CLM. Furthermore, the results point to rational exploration of immune modulating strategies in CLM, particularly by exploiting NACT-induced ICD.Background Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance. Methods In this ancillary study to the Oslo-CoMet trial, CLM and tumor-adjacent liver tissue from 46 patients were analyzed by profiling mutations (targeted sequencing), genome-wide copy number alteration (CNAs), and gene expression. Results Somatic mutations and CNAs detected in CLM were similar to reported primary CRC profiles, while CNA profiles of eight metastatic pairs suggested intra-patient divergence. A CMS classifier tool applied to gene expression data, revealed the cohort to be highly enriched for CMS2. Hierarchical clustering of genes with highly variable expression identified two subgroups separated by high or low expression of 55 genes with immune-related and metabolic functions. Importantly, induction of genes and pathways associated with immunogenic cell death (ICD) was identified in metastases exposed to neoadjuvant chemotherapy (NACT). Conclusions The uniform classification of CLM by CMS subtyping may indicate that novel class discovery approaches need to be explored to uncover clinically useful stratification of CLM. Detected gene expression signatures support the role of metabolism and chemotherapy in shaping the immune microenvironment of CLM. Furthermore, the results point to rational exploration of immune modulating strategies in CLM, particularly by exploiting NACT-induced ICD.

Laparoscopic Completion Pancreatectomy for Local Recurrence in the Pancreatic Remnant after Pancreaticoduodenectomy: Case Reports and Review of the Literature

Completion pancreatectomy (CP) is a surgical procedure, in which the aim is to remove the remnant pancreatic tissue after initial pancreatic resection. This technique is used as a salvage procedure after pancreaticoduodenectomy (PD) in patients, experiencing severe complications of pancreatic leakage. Although some authors have proposed not to consider CP in patients with a pancreatic fistula [1], Gueroult et al. assumed that CP may represent the only means to achieve adequate control of an ongoing infection [2]. Other reports also concluded that despite of significant morbidity and mortality CP has a role in the management of post-pancreatic surgical complications and may increase survival [3, 4]. Other clinical indication for this procedure is isolated local recurrence (ILR) of malignancy in the pancreatic remnant. However, given the low rate of resectable cases, the indications for surgery have not yet been clarified. Previously, limited experience with CP has been reported in the literature and generally by conventional, open surgery [5–13]. A review of the relevant literature revealed that no cases of laparoscopic completion pancreatectomy (LCP) after initial open PD have been reported to date. In this article, we describe two cases of LCP in our institution for ILR of malignant tumors in the pancreatic remnant after initial PD.

Choosing the Best Reconstruction Technique in Abdominal Computed Tomography: A Systematic Approach

Objective There is uncertainty regarding the effect of iterative reconstruction (IR) techniques and other reconstruction algorithms on image quality. The aim of this study was to optimize image quality in relation to radiation dose in computed tomography (CT) liver examinations by comparing images reconstructed with different abdominal filters with and without IR. Methods An anthropomorphic phantom was scanned on a Toshiba Aquilion ONE CT scanner. Images at 2 different dose levels were reconstructed with 12 different body reconstruction filters, all with both filtered back-projection and Adaptive Iterative Dose Reduction 3 dimensional. Receiver operating characteristic curves were constructed. The 2 reconstruction combinations with the highest scores from the phantom study were evaluated in a second comparison of clinical images. Six liver examinations were reconstructed with both filters and evaluated using visual grading analysis. Results Two combinations of reconstruction filters and IR were the only 2 options among the 8 best images at both dose levels (area under the curve, 0.96 and 0.94 for 15 mGy as well as 0.86 and 0.84 for 10 mGy). In the patient study, one of these filters in combination with IR scored slightly higher than the other in combination with IR (mean score, 2.60 and 2.57, respectively; P = 0.56). Iterative reconstruction did not significantly increase lesion detectability for any of the filters. Conclusions This study indicates that the preferred choice for reconstruction of CT liver examinations performed with the Toshiba Aquilion ONE should be the FC18 filter with IR, although the IR technique did not significantly improve lesion detectability and did not compensate for the dose reduction in this study.