Nikolaos Kartalis

Short-term Results of a Magnetic Resonance Imaging–Based Swedish Screening Program for Individuals at Risk for Pancreatic Cancer

IMPORTANCE Pancreatic cancer is the fourth leading cause of cancer-related death in Western countries. In approximately 10% of all patients with pancreatic cancer, it is possible to define a positive family history for pancreatic cancer or for one of the other related genetic syndromes. A screening program for individuals at risk is recommended; however, surveillance modalities have not been defined yet. OBJECTIVE To analyze the short-term results of a prospective clinical surveillance program for individuals at risk for pancreatic cancer using a noninvasive magnetic resonance imaging (MRI)-based screening protocol. DESIGN, SETTING AND PARTICIPANTS A prospective observational study of all patients with a genetic risk for developing pancreatic cancer who were referred to Karolinska University Hospital between January 1, 2010, and January 31, 2013, using an MRI-based surveillance program. All patients were investigated for the most common genetic mutations associated with pancreatic cancer. EXPOSURE A noninvasive MRI-based screening protocol. MAIN OUTCOMES AND MEASURES The ability of MRI to identify potential precancerous or early cancers in individuals at risk for pancreatic cancer. RESULTS Forty patients (24 women and 16 men) were enrolled. The mean age was 49.9 years. The mean length of follow-up was 12.9 months. The numbers of relatives affected by pancreatic cancer were 5 in 2 patients (5%), 4 in 5 patients (12.5%), 3 in 17 patients (42.5%), 2 in 14 patients (35%), and 1 in 2 patients (5%). In 4 patients (10%), a p16 mutation was found; in 3, a BRCA2 mutation (7.5%); and in 1, a BRCA1 mutation (2.5%). In 16 patients (40%), MRI revealed a pancreatic lesion: intraductal papillary mucinous neoplasia (14 patients, 35%) and pancreatic ductal adenocarcinoma (2 patients, 5%). One patient had a synchronous intraductal papillary mucinous neoplasia and pancreatic ductal adenocarcinoma. Five patients (12.5%) required surgery (3 for pancreatic ductal adenocarcinoma and 2 for intraductal papillary mucinous neoplasia), while the remaining 35 are under continued surveillance. CONCLUSIONS AND RELEVANCE During a median follow-up of approximately 1 year, pancreatic lesions were detected in 40% of the patients, of whom 5 underwent surgery. Although the study time was relatively short, the surveillance program in individuals at risk seems to be effective.

European evidence-based guidelines on pancreatic cystic neoplasms

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

Impact of delay between imaging and treatment in patients with potentially curable pancreatic cancer

Locoregional pancreatic ductal adenocarcinoma (PDAC) may progress rapidly and/or disseminate despite having an early stage at diagnostic imaging. A prolonged interval from imaging to resection might represent a risk factor for encountering tumour progression at laparotomy. The aim of this study was to determine the therapeutic window for timely surgical intervention.

Time-resolved computed tomography of the liver: retrospective, multi-phase image reconstruction derived from volumetric perfusion imaging

AbstractObjectiveTo assess feasibility and image quality (IQ) of a new post-processing algorithm for retrospective extraction of an optimised multi-phase CT (time-resolved CT) of the liver from volumetric perfusion imaging.MethodsSixteen patients underwent clinically indicated perfusion CT using 4D spiral mode of dual-source 128-slice CT. Three image sets were reconstructed: motion-corrected and noise-reduced (MCNR) images derived from 4D raw data; maximum and average intensity projections (time MIP/AVG) of the arterial/portal/portal-venous phases and all phases (total MIP/ AVG) derived from retrospective fusion of dedicated MCNR split series. Two readers assessed the IQ, detection rate and evaluation time; one reader assessed image noise and lesion-to-liver contrast.ResultsTime-resolved CT was feasible in all patients. Each post-processing step yielded a significant reduction of image noise and evaluation time, maintaining lesion-to-liver contrast. Time MIPs/AVGs showed the highest overall IQ without relevant motion artefacts and best depiction of arterial and portal/portal-venous phases respectively. Time MIPs demonstrated a significantly higher detection rate for arterialised liver lesions than total MIPs/AVGs and the raw data series.ConclusionTime-resolved CT allows data from volumetric perfusion imaging to be condensed into an optimised multi-phase liver CT, yielding a superior IQ and higher detection rate for arterialised liver lesions than the raw data series.Key Points• Four-dimensional computed tomography is limited by motion artefacts and poor image quality. • Time-resolved-CT facilitates 4D-CT data visualisation, segmentation and analysis by condensing raw data. • Time-resolved CT demonstrates better image quality than raw data images. • Time-resolved CT improves detection of arterialised liver lesions in cirrhotic patients.

Low tube voltage CT for improved detection of pancreatic cancer: detection threshold for small, simulated lesions

BackgroundPancreatic ductal adenocarcinoma is associated with dismal prognosis. The detection of small pancreatic tumors which are still resectable is still a challenging problem.The aim of this study was to investigate the effect of decreasing the tube voltage from 120 to 80 kV on the detection of pancreatic tumors.MethodsThree scanning protocols was used; one using the standard tube voltage (120 kV) and current (160 mA) and two using 80 kV but with different tube currents (500 and 675 mA) to achieve equivalent dose (15 mGy) and noise (15 HU) as that of the standard protocol.Tumors were simulated into collected CT phantom images. The attenuation in normal parenchyma at 120 kV was set at 130 HU, as measured previously in clinical examinations, and the tumor attenuation was assumed to differ 20 HU and was set at 110HU. By scanning and measuring of iodine solution with different concentrations the corresponding tumor and parenchyma attenuation at 80 kV was found to be 185 and 219 HU, respectively.To objectively evaluate the differences between the three protocols, a multi-reader multi-case receiver operating characteristic study was conducted, using three readers and 100 cases, each containing 0–3 lesions.ResultsThe highest reader averaged figure-of-merit (FOM) was achieved for 80 kV and 675 mA (FOM = 0,850), and the lowest for 120 kV (FOM = 0,709). There was a significant difference between the three protocols (p < 0,0001), when making an analysis of variance (ANOVA). Post-hoc analysis (students t-test) shows that there was a significant difference between 120 and 80 kV, but not between the two levels of tube currents at 80 kV.ConclusionWe conclude that when decreasing the tube voltage there is a significant improvement in tumor conspicuity.

Diffusion-weighted MR imaging of pancreatic cancer: A comparison of mono-exponential, bi-exponential and non-Gaussian kurtosis models

Objectives To compare two Gaussian diffusion-weighted MRI (DWI) models including mono-exponential and bi-exponential, with the non-Gaussian kurtosis model in patients with pancreatic ductal adenocarcinoma. Materials and methods After written informed consent, 15 consecutive patients with pancreatic ductal adenocarcinoma underwent free-breathing DWI (1.5T, b-values: 0, 50, 150, 200, 300, 600 and 1000 s/mm2). Mean values of DWI-derived metrics ADC, D, D*, f, K and DK were calculated from multiple regions of interest in all tumours and non-tumorous parenchyma and compared. Area under the curve was determined for all metrics. Results Mean ADC and DK showed significant differences between tumours and non-tumorous parenchyma (both P < 0.001). Area under the curve for ADC, D, D*, f, K, and DK were 0.77, 0.52, 0.53, 0.62, 0.42, and 0.84, respectively. Conclusion ADC and DK could differentiate tumours from non-tumorous parenchyma with the latter showing a higher diagnostic accuracy. Correction for kurtosis effects has the potential to increase the diagnostic accuracy of DWI in patients with pancreatic ductal adenocarcinoma.

Computed tomography staging of pancreatic cancer: A validation study addressing interobserver agreement

BACKGROUND/OBJECTIVES Ductal adenocarcinoma in the head of the pancreas (PDAC) is usually unresectable at the time of diagnosis due to the involvement of the peripancreatic vessels. Various preoperative classification algorithms have been developed to describe the relationship of the tumor to these vessels, but most of them lack a surgically based approach. We present a CT-based classification algorithm for PDAC based on surgical resectability principles with a focus on interobserver variability. METHODS Thirty patients with PDAC undergoing pancreaticoduodenectomy were examined by using a standard CT protocol. Nine radiologists, representing three different levels of expertise, evaluated the CT examinations and the tumors were classified into four categories (A-D) according to the proposed system. For the interobserver agreement, the Intraclass Correlation Coefficient (ICC) was estimated. RESULTS The overall ICC was 0.94 and the ICCs among the trainees, experienced radiologists, and experts were 0.85, 0.76, and 0.92, respectively. All tumors classified as category A1 showed no signs of vascular invasion at surgery. In category A2, 40% of the tumors had corresponding infiltration and required resection of the superior mesenteric vein/portal vein (SMV/PV). One of two tumors in category B2 and two of three in category C required SMV/PV resection. All six patients in category D had both arterial and venous involvement. CONCLUSION There is almost perfect agreement among radiologists with different levels of expertise in regards to the local staging of PDAC. For tumors in a more advanced preoperative category, an increased risk for vascular involvement was noticed at surgery.

The added value of contrast-enhanced ultrasound in patients with colorectal cancer undergoing preoperative evaluation with extensive gadobenate dimeglumine liver MRI

ObjectivesTo evaluate the added value of pre- and intraoperative contrast-enhanced ultrasound (transabdominal, or TCEUS and intraoperative, or ICEUS, respectively) in patients with known or highly suspected colorectal cancer liver metastases (CRLM) who have previously undergone extensive gadobenate dimeglumine (Gd-BOPTA) liver MRI.MethodsFifteen patients with a total of 31 lesions were included in the comparison of TCEUS vs. MRI and nine patients with a total of 19 lesions were included in the comparison of ICEUS vs. MRI. MRI examinations were performed before TCEUS and ICEUS. The analysis was performed lesion by lesion. Sensitivity, positive predictive value (PPV) and accuracy were calculated and compared.ResultsOn comparing TCEUS with MRI, sensitivity differed significantly, with values of 87% and 100%, respectively (p value < 0.05), but there was no significant difference in PPV and accuracy. The comparison of ICEUS with MRI, however, showed no significant difference in sensitivity, PPV or accuracy.ConclusionsTransabdominal and intraoperative contrast-enhanced ultrasound have no added value in the preoperative evaluation of patients with CRLM undergoing extensive gadobenate dimeglumine liver MRI.

Multi-detector CT: Liver protocol and recent developments

Multi-detector computed tomography is today the workhorse in the evaluation of the vast majority of patients with known or suspected liver disease. Reasons for that include widespread availability, robustness and repeatability of the technique, time-efficient image acquisitions of large body volumes, high temporal and spatial resolution as well as multiple post-processing capabilities. However, as the technique employs ionizing radiation and intravenous iodine-based contrast media, the associated potential risks have to be taken into account. In this review article, liver protocols in clinical practice are discussed with emphasis on optimisation strategies. Furthermore, recent developments such as perfusion CT and dual-energy CT and their applications are presented.

A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.