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Summary Aims To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). Design Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. Results Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin–bilirubin (ALBI) score, liver–spleen ratio Conclusions Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.

Background and study aims : The international consensus Fukuoka guideline (Fukuoka ICG), The European evidence-based guideline on pancreatic cystic neoplasms (European EBG) and the American Gastroenterological Association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts (AGA IG) are 3 frequently cited guidelines for the risk stratification of neoplastic pancreatic cysts. The aim of this study was to assess the accuracy of detecting malignant cysts by strictly applying these guidelines retrospectively to a cohort of surgically resected pancreatic cysts. Patient and methods : 72 resected cysts were included in the analysis. Invasive carcinoma, high grade dysplasia and neuroendocrine tumour were considered as “malignant cysts” for the purpose of the study. Results : 32% of the resected cysts were malignant. The analysis showed that the Fukuoka ICG, European EBG and AGA IG had a sensitivity of 66,8%, 95,5%, 80%; a specificity of 26,8%, 11,3%, 43,8%; a positive predictive value of 31,8%, 35%, 47,1% and a negative predicted value of 61,1%, 83,3%, 77,8% respectively. The missed malignancy rate was respectively 11,3%, 1,5%, 7,7% and surgical overtreatment was respectively 48,4%, 59,1%, 34,6%. Conclusion : In this retrospective analysis, the European EBG had the lowest rate of missed malignancy at the expense of a high number of “unnecessary” resections. The Fukuoka ICG had the highest number of missed malignancy. The AGA IG showed the lowest rate of unnecessary surgery at the cost of a high number of missed malignancy. There is need to develop better biomarkers to predict the risk of malignancy.

Objectives To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. Methods A total of 359 patients who underwent gadoxetic acid–enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin [ALBI]), and scanner characteristics were analyzed using uni- and multivariate analyses. Results There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = −0.215; p < 0.001) and AST (rho = −0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = −0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). Conclusions The liver enhancement on the hepatobiliary phase of gadoxetic acid–enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands. Key Points • The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid–enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. • Signal intensity–based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. • However, absolute values might change between vendors.

Cancer during pregnancy is increasingly diagnosed due to the trend of delaying pregnancy to a later age and probably also because of increased use of non-invasive prenatal testing for fetal aneuploidy screening with incidental finding of maternal cancer. Pregnant women pose higher challenges in imaging, diagnosis, and staging of cancer. Physiological tissue changes related to pregnancy makes image interpretation more difficult. Moreover, uncertainty about the safety of imaging modalities, fear of (unnecessary) fetal radiation, and lack of standardized imaging protocols may result in underutilization of the necessary imaging tests resulting in suboptimal staging. Due to the absence of radiation exposure, ultrasound and MRI are obvious first-line imaging modalities for detailed locoregional disease assessment. MRI has the added advantage of a more reproducible comprehensive organ or body region assessment, the ability of distant staging through whole-body evaluation, and the combination of anatomical and functional information by diffusion-weighted imaging which obviates the need for a gadolinium-based contrast-agent. Imaging modalities with inherent radiation exposure such as CT and nuclear imaging should only be performed when the maternal benefit outweighs fetal risk. The cumulative radiation exposure should not exceed the fetal radiation threshold of 100 mGy. Imaging should only be performed when necessary for diagnosis and likely to guide or change management. Radiologists play an important role in the multidisciplinary team in order to select the most optimal imaging strategies that balance maternal benefit with fetal risk and that are most likely to guide treatment decisions. Our aim is to provide an overview of possibilities and concerns in current clinical applications and developments in the imaging of patients with cancer during pregnancy. ispartof: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER vol:31 issue:3 pages:423-431 ispartof: location:England status: published

Introduction: We report the case of a young female patient with a technically resectable, nonmetastatic, rectoanal, anaplastic lymphoma kinase gene (ALK)-translocated inflammatory myofibroblastic tumor (IMFT). Case Presentation: The patient was successfully treated preoperatively with the tyrosine kinase inhibitor (TKI) crizotinib, to downsize the primary tumor, followed by sphincter-sparing surgery, and adjuvant radiotherapy and crizotinib. She is now in follow-up with good sphincter function and with no evidence of active disease. Conclusion: Pre- and postoperative treatment administration of crizotinib can be given with curative intent to patients with locally advanced, nonmetastatic IMFTs to avoid mutilating surgery.

Patients with heterotaxy syndrome (HS) can present with an associated complete dorsal pancreas agenesis (DPA). They are considered to be at increased risk for developing diabetes due to a reduced functional beta cell mass (FBM) as well as for chronic pancreatitis leading to unmanageable pain. We report the case of a young woman with chronic pancreatitis due to HS and associated DPA. She presented with a severe persisting upper abdominal pain refractory to nonsurgical treatment. Unlike in previously reported cases, she had a high FBM (ie, 150% of normoglycemic controls) as determined by hyperglycemic clamp. She underwent a total pancreatectomy followed within 24 hours by an intraportal autologous islet cell transplant containing 4 × 106 beta cells (4700 islet equivalent)/kg body weight. After surgery, the pain resolved, eliminating the need for analgesics. The intraportal implant established an adequate FBM (72% of controls at posttransplant month 2), achieving glycemic control without need for insulin administration. A hyperglycemic clamp can assess the utility and efficacy of an intraportal islet cell autotransplant following total pancreatectomy in patients with HS and complete DPA.

Background Numerous publications have reported the incidental detection of occult malignancies upon routine noninvasive prenatal testing (NIPT). However, these studies were not designed to evaluate the NIPT performance for cancer detection. Methods We investigated the sensitivity of a genome-wide NIPT pipeline, called GIPSeq, for detecting cancer-specific copy number alterations (CNAs) in plasma tumor DNA (ctDNA) of patients with breast cancer. To assess whether a pregnancy itself, with fetal cell-free DNA (cfDNA) in the maternal circulation, might influence the detection of ctDNA, results were compared in pregnant (n = 25) and nonpregnant (n = 25) cancer patients. Furthermore, the ability of GIPSeq to monitor treatment response was assessed. Results Overall GIPSeq sensitivity for detecting cancer-specific CNAs in plasma cfDNA was 26%. Fifteen percent of detected cases were asymptomatic at the time of blood sampling. GIPSeq sensitivity mainly depended on the tumor stage. Also, triple negative breast cancers (TNBC) were more frequently identified compared to hormone-positive or HER2-enriched tumors. This might be due to the presence of high-level gains and losses of cfDNA or high ctDNA loads in plasma of TNBC. Although higher GIPSeq sensitivity was noted in pregnant (36%) than in nonpregnant women (16%), the limited sample size prohibits a definite conclusion. Finally, GIPSeq profiling of cfDNA during therapy allowed monitoring of early treatment response. Conclusions The results underscore the potential of NIPT-based tests, analyzing CNAs in plasma cfDNA in a genome-wide and unbiased fashion for breast cancer detection, cancer subtyping and treatment monitoring in a pregnant and nonpregnant target population.

We performed post hoc analyses on the utility of pretherapeutic and early interim 68Ga-DOTATOC PET tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to 4 cycles of 90Y-DOTATOC at 1.85 GBq/m2/cycle with a maximal kidney biologic effective dose of 37 Gy. All patients underwent 68Ga-DOTATOC PET/CT at baseline and 7 wk after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semiautomatically delineated using a customized SUV threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival and overall survival (OS) were 13.9 and 22.3 mo, respectively. An SUVmean higher than 13.7 (75th percentile) was associated with better survival (hazard ratio [HR], 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 cm3 (75th percentile) was associated with worse OS (HR, 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR, 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with progression-free survival were found. A composite score based on SUVmean and IBI allowed us to further stratify patients into 3 categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (75th percentile) was associated with worse survival (HR, 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This method can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization. ispartof: JOURNAL OF NUCLEAR MEDICINE vol:61 issue:7 pages:1014-1020 ispartof: location:United States status: published

Background: Metastatic renal cell carcinoma (mRCC) patients with bone metastases (BM) are at high risk for skeletal related events and have a poorer outcome when treated with vascular endothelial g...

Bone imaging has been intimately associated with the diagnosis and staging of multiple myeloma (MM) for more than 5 decades, as the presence of bone lesions indicates advanced disease and dictates treatment initiation. The methods used have been evolving, and the historical radiographic skeletal survey has been replaced by whole body CT, whole body MRI (WB-MRI) and [18F]FDG-PET/CT for the detection of bone marrow lesions and less frequent extramedullary plasmacytomas.Beyond diagnosis, imaging methods are expected to provide the clinician with evaluation of the response to treatment. Imaging techniques are consistently challenged as treatments become more and more efficient, inducing profound response, with more subtle residual disease. WB-MRI and FDG-PET/CT are the methods of choice to address these challenges, being able to assess disease progression or response and to detect “minimal” residual disease, providing key prognostic information and guiding necessary change of treatment.This paper provides an up-to-date overview of the WB-MRI and PET/CT techniques, their observations in responsive and progressive disease and their role and limitations in capturing minimal residual disease. It reviews trials assessing these techniques for response evaluation, points out the limited comparisons between both methods and highlights their complementarity with most recent molecular methods (next-generation flow cytometry, next-generation sequencing) to detect minimal residual disease. It underlines the important role of PET/MRI technology as a research tool to compare the effectiveness and complementarity of both methods to address the key clinical questions.

Introduction/Background* Implausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring efficient downstream clinical management of these cases. Methodology Using a large data set of 88,294 NIPT performed in our University Hospital Leuven, we retrospectively evaluated the positive predictive value (PPV) of our NIPT approach for cancer detection. In this approach, whole-genome cell-free DNA (cfDNA) data from NIPT were scrutinized for the presence of (sub)chromosomal copy number alterations (CNAs) predictive for a malignancy, using an unbiased NIPT analysis pipeline coined GIPSeq. For suspected cases, the presence of a maternal cancer was evaluated via subsequent multidisciplinary clinical follow-up examinations. The cancer-specificity of the identified CNAs in cfDNA was assessed through genetic analyses of a tumour biopsy. Result(s)* Fifteen women without a cancer history were identified with a GIPSeq result suggestive of a malignant process. Their cfDNA profiles showed either genome-wide aberrations or a single trisomy 8. Upon clinical examinations, a solid or hematological cancer was identified in 4 and 7 cases, respectively. Three women were identified as having a clonal mosaicism. For one case no underlying condition was found. These numbers add to a PPV of 73%. Based on this experience, a novel multidisciplinary care path for efficient clinical management of these cases was presented. Conclusion* The here presented approach for analysing NIPT results has an unparalleled high PPV, yet unknown sensitivity, for detecting asymptomatic malignancies upon routine NIPT. Given the complexity of diagnosing a pregnant woman with cancer, clinical follow-up should occur in a well-designed multidisciplinary setting, such as via the novel care model that we presented here. These findings have now been accepted for publication in eClinicalMedicine (online journal of The Lancet group), showing the importance of these data.

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement. ispartof: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER vol:31 issue:7 pages:961-982 ispartof: location:England status: published

Hepatocellular adenoma (HCA) is an uncommon benign liver neoplasm usually solitary and identified incidentally on imaging. We report a case of a 50-year old female who was diagnosed with multiple hepatic adenomas of the inflammatory subtype. After discontinuation of oral contraception a decrease of both the number and size of the liver lesions was seen on magnetic resonance imaging (MRI) without the need of further intervention. The major challenge in the clinical management of patients with multiple HCAs resides in the risk assessment for future complications. In the case of multiple HCAs subtype seemed to be more relevant than the actual number of lesions. Because little is known about the natural evolution in patients with multiple HCAs, we performed a review of the current literature with focus on the different subtypes and their clinical relevance. ispartof: ACTA GASTRO-ENTEROLOGICA BELGICA vol:84 issue:3 pages:505-508 ispartof: location:Belgium status: published

OBJECTIVES: To compare MR imaging with or without DWI and clinical response evaluation (CRE) in the local control evaluation of cervical carcinoma after radiotherapy. METHODS: In a multicentre university setting, we prospectively included 107 patients with primary cervical cancer treated with radiotherapy. Sensitivity and specificity for CRE and MR imaging (with pre-therapy MR imaging as reference) (2 readers) were evaluated using cautious and strict criteria for identifying residual tumour. Nested logistic regression models were constructed for CRE, subsequently adding MR imaging with and without DWI as independent variables, as well as the pre- to post-treatment change in apparent diffusion coefficient (delta ADC). RESULTS: Using cautious criteria, CRE and MR imaging with DWI (reader 1/reader 2) have comparable high specificity (83% and 89%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (63%/53%) than CRE. Using strict criteria, CRE and MR imaging with DWI both showed very high specificity (99% and 92%/95%, respectively), whereas MR imaging without DWI showed significantly lower specificity (89%/77%) than CRE. All sensitivities were not significantly different. Addition of MR imaging with DWI to CRE has statistically significant incremental value in identifying residual tumour (reader 1: estimate, 1.06; p = 0.001) (reader 2: estimate, 0.62; p = 0.02). Adding the delta ADC did not have significant incremental value in detecting residual tumour. CONCLUSIONS: DWI significantly increases the specificity of MR imaging in the detection of local residual tumour. Furthermore, MR imaging with DWI has significant incremental diagnostic value over CRE, whereas adding the delta ADC has no incremental diagnostic value. KEY POINTS: • If MR imaging is used for response evaluation, DWI should be incorporated • MR imaging with DWI has diagnostic value comparable/complementary to clinical response evaluation • Inter-reader agreement is moderate to fair for two experienced radiologist readers • Quantitative measurements of ADC early post-therapy have limited diagnostic value. ispartof: EUROPEAN RADIOLOGY vol:29 issue:1 pages:309-318 ispartof: location:Germany status: published

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

We thank Isabelle Thomassin-Nagarra et al for their interest in the ESGO/ISUOG/IOTA/ESGE consensus statement on the pre-operative diagnosis of ovarian tumors. This statement is based on a careful review of the relevant literature and available evidence as well as on structured discussions between

BACKGROUND: An isovolumetric intragastric balloon to continuously measure gastric phasic contractility was recently developed by us. We aimed to investigate the readout of this technique in relation to gastric content and gastric emptying. METHODS: In this crossover investigation, the VIPUNTM Gastric Monitoring System, which comprises a double lumen nasogastric feeding tube with integrated intragastric balloon, was used to assess phasic gastric contractility by interpretation of the pressure in an isovolumetric balloon in 10 healthy subjects. Balloon pressure was recorded in fasted state, during a 2-hour intragastric nutrient infusion (1 kcal/ml at 25, 75, or 250 ml/h) and 4 hours post-infusion, and quantified as Gastric Balloon Motility Index (GBMI), ranging from 0 (no contractility) to 1 (maximal contractility). Gastric accumulation was quantified with magnetic resonance imaging and gastric emptying with a13 C-breath test. Results are expressed as mean(SD). KEY RESULTS: GBMI was significantly lower during infusion at 250 ml/h compared to baseline (0.13(0.05) versus 0.46(0.12)) and compared to infusion at 25 (0.54(0.21)) and 75 ml/h (0.43(0.20)), all P 0 ml compared to when the stomach was empty. CONCLUSIONS AND INFERENCES: Enteral nutrition dose-dependently decreased the contractility readout. This decrease was linked to gastric accumulation of enteral nutrition. ispartof: Neurogastroenterology And Motility vol:33 issue:7 ispartof: location:England status: accepted

Over the past decade, updated definitions for the different stages of prostate cancer and risk for distant disease, along with the advent of new therapies, have remarkably changed the management of patients. The two expectations from imaging are accurate staging and appropriate assessment of disease response to therapies. Modern, next-generation imaging (NGI) modalities, including whole-body magnetic resonance imaging (WB-MRI) and nuclear medicine (most often prostate-specific membrane antigen [PSMA] positron emission tomography [PET]/computed tomography [CT]) bring added value to these imaging tasks. WB-MRI has proven its superiority over bone scintigraphy (BS) and CT for the detection of distant metastasis, also providing reliable evaluations of disease response to treatment. Comparison of the effectiveness of WB-MRI and molecular nuclear imaging techniques with regard to indications and the definition of their respective/complementary roles in clinical practice is ongoing. This paper illustrates the evolution of WB-MRI imaging protocols, defines the current state-of-the art, and highlights the latest developments and future challenges. The paper presents and discusses WB-MRI indications in the care pathway of men with prostate cancer in specific key situations: response assessment of metastatic disease, "all in one" cancer staging, and oligometastatic disease.

Background & Aims SORAMIC is a prospective phase II randomised controlled trial in hepatocellular carcinoma (HCC). It consists of 3 parts: a diagnostic study and 2 therapeutic studies with either curative ablation or palliative Yttrium-90 radioembolisation combined with sorafenib. We report the diagnostic cohort study aimed to determine the accuracy of gadoxetic acid-enhanced magnetic resonance imaging (MRI), including hepatobiliary phase (HBP) imaging features compared with contrast-enhanced computed tomography (CT). The primary objective was the accuracy of treatment decisions stratifying patients for curative or palliative (non-ablation) treatment. Methods Patients with clinically suspected HCC underwent gadoxetic acid-enhanced MRI (HBP MRI, including dynamic MRI) and contrast-enhanced CT. Blinded read of the image data was performed by 2 reader groups (radiologists, R1 and R2). A truth panel with access to all clinical data and follow-up imaging served as reference. Imaging criteria for curative ablation were defined as up to 4 lesions 4 lesions significantly more frequently than CT. Conclusions In HCC, HBP MRI provided a more accurate decision than CT for a curative vs. palliative treatment strategy. Lay summary Patients with hepatocellular carcinoma are allocated to curative or palliative treatment according to the stage of their disease. Hepatobiliary imaging using gadoxetic acid-enhanced MRI is more accurate than CT for treatment decision-making., Graphical abstract, Highlights • Comparison of gadoxetic acid-enhanced MRI vs. contrast-enhanced multi-slice CT to stratify patients with suspected HCC. • Clinical decision-making was shown to be significantly more accurate with gadoxetic acid-enhanced hepatobiliary MRI than CT. • To the best of our knowledge, this is the first study linking a clinical decision endpoint to hepatobiliary MRI criteria for HCC diagnosis. • The results of our international multicentre trial could guide recommendations on the diagnostic management of HCC.

Background Accurate staging of patients with gastric cancer is necessary for selection of the most appropriate and personalized therapy. Computed tomography (CT) is currently used as primary staging tool, being widely available with a relatively high accuracy for the detection of parenchymal metastases, but with low sensitivity for the detection of peritoneal metastases. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has a very high contrast resolution, suggesting a higher diagnostic performance in the detection of small peritoneal lesions. The aim of this study was to retrospectively evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for detection of peritoneal carcinomatosis (PC) and distant metastases in the preoperative staging of gastric cancer. Methods This retrospective study included thirty-two patients with a suspicion of gastric cancer/recurrence, who underwent WB-DWI/MRI at 1.5 T, in addition to CT of thorax and abdomen. Images were evaluated by two experienced abdominal radiologists in consensus. Histopathology, laparoscopy and/or 1-year follow-up were used as reference standard. Results For overall tumour detection (n = 32), CT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 83.3%, 100%, 100% and 82.4% respectively. For WB-DWI/MRI these values were 100%, 92.9%, 94.7% and 100%, respectively. For staging (n = 18) malignant lymph nodes and metastases, CT had a sensitivity, specificity/PPV/NPV of 50%/100%/100%/71.4%, and 15.4%/100%/100%/31.3% respectively. For WB-DWI/MRI, all values were 100%, for both malignant lymph nodes and metastases. WB-DWI/MRI was significantly better than CT in detecting tumour infiltration of the mesenteric root, serosal involvement of the small bowel and peritoneal metastases for which WB-DWI/MRI was correct in 100% of these cases, CT 0%. Conclusions WB-DWI/MRI is highly accurate for diagnosis, staging and follow-up of patients with suspected gastric cancer.

Accurate and timely response assessment and follow-up by imaging are pivotal for guiding radiotherapeutic management of head and neck cancer. Primarily, post-treatment imaging should aim to detect tumour recurrence as early as possible in order to maximize success of salvage surgery and determine the need for neck dissection. Second, post-treatment imaging has a pivotal role in the differentiation of tumour recurrence from toxicity-induced complication like necrosis or ulcerations and the detection of delayed onset of locoregional, metastatic recurrence and second primary cancers.

BACKGROUND: In well-responding patients to chemoradiotherapy for locally advanced rectal cancer (LARC), a watch-and-wait strategy can be considered. To implement organ-sparing strategies, accurate patient selection is needed. We investigate the use of MRI-based radiomics models to predict tumor response to improve patient selection. MATERIALS AND METHODS: Models were developed in a cohort of 70 patients and validated in an external cohort of 55 patients. Patients received chemoradiation followed by surgery and underwent T2-weighted and diffusion-weighted MRI (DW-MRI) before and after chemoradiation. The outcome measure was (near-)complete pathological tumor response (ypT0-1N0). Tumor segmentation was done on T2-images and transferred to b800-images and ADC maps, after which quantitative and four semantic features were extracted. We combined features using principal component analysis and built models using LASSO regression analysis. The best models based on precision and performance were selected for validation. RESULTS: 21/70 patients (30%) achieved ypT0-1N0 in the development cohort versus 13/55 patients (24%) in the validation cohort. Three models (t2_dwi_pre_post, semantic_dwi_adc_pre, semantic_dwi_post) were identified with an area-under-the-curve (AUC) of 0.83 (95% CI 0.70-0.95), 0.86 (95% CI 0.75-0.98) and 0.84 (95% CI 0.75-0.94) respectively. Two models (t2_dwi_pre_post, semantic_dwi_post) validated well in the external cohort with AUCs of 0.83 (95% CI 0.70-0.95) and 0.86 (95% CI 0.76-0.97). These models however did not outperform a previously established four-feature semantic model. CONCLUSION: Prediction models based on MRI radiomics non-invasively predict tumor response after chemoradiation for rectal cancer and can be used as an additional tool to identify patients eligible for an organ-preserving treatment. ispartof: RADIOTHERAPY AND ONCOLOGY vol:142 pages:246-252 ispartof: location:Ireland status: published

Combination therapy using a BRAF and MEK inhibitor significantly improves both progression-free and overall survival in patients with BRAF V600-mutated stage IV melanoma. Dual MAPK inhibition achieves an objective response in the majority of patients. We present a case of a woman with BRAF V600E-mutated malignant melanoma and rapidly progressing liver, bone, and lymph node metastases. The patient commenced dabrafenib and trametinib with clinical and biochemical signs of response after 2 days. On day 3 she developed grade 3 liver hemorrhage, which was successfully embolized. Her anemia responded appropriately to transfusions and stabilized after interventional resolution of the hemorrhagic event. Subsequently she developed a pathological fracture of the right proximal humerus. MRI showed cystic bone metastases with stigmata of bleeding. To our knowledge, this is the first case report of a patient with hemorrhage of both liver and bone metastases of a melanoma. As the patient responded rapidly to dabrafenib and trametinib we hypothesize that the hemorrhage may be due to rapid tumor necrosis and bleeding of affected tumor supplying blood vessels. Our case demonstrates the importance of considering tumoral bleeding as a side effect of BRAF and MEK inhibition in responding melanoma patients. Mechanical intervention can be effective in resolving this treatment-related adverse event.

Background Gastro-intestinal stromal tumors (GISTs) are very rare tumors of the gastro-intestinal tract, originating from the interstitial cells of Cajal or a common cell precursor which both express type III tyrosine kinase receptors. Regorafenib is an oral multi-kinase inhibitor used to treat gastro-intestinal stromal tumors. To our knowledge this is the first case in literature to show the response of regorafenib on PET. Case presentation A 37-year-old male with lower abdominal pain and weight loss was referred to our hospital. Abdominal ultrasound and computed tomography (CT) showed diffuse peritoneal implants. Surgical specimen histology showed a GIST with c-KIT exon 11 deletion (c.1708_1728del) and treatment with imatinib 400 mg/day was initiated. Due to disease progression illustrated on baseline versus follow-up 18F–FDG-PET/CT scans therapy was switched to imatinib 800 mg/day and later to sunitinib 50 mg/day. Upon further disease progression 10 months later, third line treatment with regorafenib 160 mg/day was initiated. 18F–FDG-PET/CT showed the metabolic responses after 4 months regorafenib treatment ranging from complete response to the appearance of a new lesion in the liver. The new hypermetabolic lesion was only seen on the non-attenuation-corrected images because of breathing motion artifact. Conclusion This case illustrates that metabolic response can occur in GIST lesions without morphological response after third line regorafinib treatment. Furthermore this is the first case in literature to show regorafinib response on PET.

Background and purpose To safely implement organ preserving treatment strategies for patients with rectal cancer, well-considered selection of patients with favourable response is needed. In this study, we develop and validate an MRI-based response predicting model. Methods A multivariate model using T2-volumetric and DWI parameters before and 6 weeks after chemoradiation (CRT) was developed using a cohort of 85 rectal cancer patients and validated in an external cohort of 55 patients that underwent preoperative CRT. Results Twenty-two patients (26%) achieved ypT0-1N0 response in the development cohort versus 13 patients (24%) in the validation cohort. Two T2-volumetric parameters (ΔVolume% and Sphere_post) and two DWI parameters (ADC_avg_post and ADCratio_avg) were retained in a model predicting (near-)complete response (ypT0-1N0). In the development cohort, this model had a good predictive performance (AUC = 0.89; 95% CI 0.80–0.98). Validation of the model in an external cohort resulted in a similar performance (AUC = 0.88 95% CI 0.79–0.98). Conclusion An MRI-based prediction model of (near-)complete pathological response following CRT in rectal cancer patients, shows a high predictive performance in an external validation cohort. The clinically relevant features in the model make it an interesting tool for implementation of organ-preserving strategies in rectal cancer.

Background Cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPC) for gastric peritoneal carcinomatosis (PC) is controversial, and selection criteria for this treatment modality are lacking. Methods Thirty-two patients (F/M ratio 12/20; median (range) age 58 (32-75) years) underwent CRS + HIPC with cisplatin for PC from gastric adenocarcinoma in 2010-2014. This monocentric phase-2 nonrandomized prospective study with a power of 90% aimed to improve the 1-year overall survival (OS) rate with 40% (historical reference of 52% to 72%). Median PCI score was 8 (range 1-20), number of regions involved was 6 (range 1-11). The impact of 16 prognostic factors on survival was evaluated using univariable and multivariable Cox regression models. Follow-up was complete in all patients, and closed 2 years after patient inclusion. Results All patients had complete cytoreduction (CCR-0) and histopathological R0 resection. PCI

To describe the added value of novel functional MRI techniques towards detection, staging, characterization, response monitoring and prognostication in gynaecological cancer.Functional MRI including diffusion-weighted imaging (DWI)-MRI and dynamic contrast-enhanced (DCE)-MRI adds structural, hemodynamic and physiological information to anatomical MRI. In endometrial and cervical cancer, the addition of DWI-MRI and DCE-MRI improves tumour detection as well as staging of uterine and extra-uterine pelvic spread. Quantitative assessment of DWI and DCE-MRI reflecting tissue properties of biological aggressiveness or treatment resistance may enable the prediction of risk of extra-uterine or extra-ovarian disease spread, predict risk of recurrence and assess treatment response. DWI shows high accuracy for detecting peritoneal metastases and allows for comprehensive staging of (recurrent) ovarian cancer following the clinical development of whole body DWI-MRI.The added value of DWI/DCE-MRI for characterization and staging of gynaecological malignancy is becoming increasingly established and may improve treatment stratification. Ongoing multicentre studies are expected to further consolidate its use in clinical routine. Quantitative evaluation of functional MRI may help in prognostication and risk stratification.

We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HCCs of 2.8-20.9 mm in size on liver cirrhosis received CA4P intravenously at 10 mg/kg. Tumor-diameter was measured by T2-weighted imaging (T2WI) to define microcancers (< 5 mm) versus larger HCCs. Vascular responses and tissue necrosis were detected by diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (CE-T1WI) and dynamic contrast enhanced (DCE-) MRI, which were validated by microangiography and histopathology. MRI revealed nearly complete necrosis in 5 out of 7 micro-HCCs, but diverse therapeutic necrosis in larger HCCs with a positive correlation with tumor size. Necrosis in micro-HCCs was 36.9% more than that in larger HCCs. While increased diffusion coefficient (ADCdiff) suggested tumor necrosis, perfusion coefficient (ADCperf) indicated sharply decreased blood perfusion in cirrhotic liver together with a reduction in micro-HCCs. DCE revealed lowered tumor blood flow from intravascular into extravascular extracellular space (EES). Microangiography and histopathology revealed hypo- and hypervascularity in 4 and 3 micro-HCCs, massive, partial and minor degrees of tumoral necrosis in 5, 1 and 1 micro-HCCs respectively, and patchy necrotic foci in cirrhotic liver. CD34-PAS staining implicated that poorly vascularized micro-HCCs growing on liver cirrhosis tended to respond better to CA4P treatment. In this study, more complete CA4P-response occurred unexpectedly in micro-HCCs in rats, along with CA4P-induced necrotic foci in cirrhotic liver. These may help to plan clinical applications of VDAs in patients with HCCs and liver cirrhosis. ispartof: Oncotarget vol:8 issue:33 pages:55204-55215 ispartof: location:United States status: published

Background and purpose To explore the integration of imaging and molecular data for response prediction to chemoradiotherapy (CRT) for rectal cancer. Material and methods Eighty-five rectal cancer patients underwent preoperative CRT. 18 F-FDG PET/CT and diffusion-weighted imaging (DWI) were acquired before (TP1) and during CRT (TP2) and prior to surgery (TP3). Inflammatory cytokines and gene expression were analysed. Tumour response was defined as ypT0-1N0. Multivariate models were built combining the obtained parameters. Final models were calculated on the data combination with the highest AUC. Results Twenty-two patients (26%) achieved ypT0-1N0 response. 18 F-FDG PET/CT had worse predictive performance than DWI and T2-volumetry (AUC 0.61±0.04, 0.72±0.03, and 0.72±0.02, respectively). Combining all imaging parameters increased the AUC to 0.81±0.03. Adding cytokines or gene expression did not improve the AUC (AUC of 0.72±0.06 and 0.79±0.04 respectively). Final models combining 18 F-FDG PET/CT, DWI, and T2-weighted volumetry at all TPs and using only TP1 and TP3, allowed ypT0-1N0 prediction with a 75% sensitivity, 94% specificity and PPV of 80%. Conclusions Combining 18 F-FDG PET/CT, DWI, and T2-weighted MRI volumetry obtained before CRT and prior to surgery may help physicians in selecting rectal cancer patients for organ-preservation.

Despite excellent per-lesion performance for peritoneal staging, the additional clinical value of diffusion-weighted magnetic resonance imaging (DWI/MRI) compared to computed tomography (CT) remains to be established in ovarian cancer. Our purpose was to evaluate whole body (WB)-DWI/MRI for diagnosis, staging and operability assessment of patients suspected for ovarian cancer compared to CT. One hundred and sixty-one patients suspected for ovarian carcinoma underwent 3 T WB-DWI/MRI and contrast-enhanced CT. WB-DWI/MRI and CT were compared for confirmation of the malignant nature and primary origin of the ovarian mass, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging and prediction of incomplete resection using institutional operability criteria. Interobserver agreement between two readers was determined for WB-DWI/MRI and CT. WB-DWI/MRI showed a significantly higher accuracy than CT (93 versus 82%, p = 0.001) to confirm the malignant nature of the ovarian mass and correctly identified 26 of 32 (81%) cancers of non-ovarian origin compared to 10/32 (31%) for CT (p < 0.001). WB-DWI/MRI assigned more ovarian carcinoma patients to the correct FIGO stage (82/94, 87%) compared with CT (33/94, 35%). For prediction of incomplete resection, WB-DWI/MRI showed significantly higher sensitivity (94 versus 66%), specificity (97.7 versus 77.3%) and accuracy (95.7 versus 71.3%) compared to CT (p < 0.001). Interobserver agreement was almost perfect (κ = 0.90) for WB-DWI/MRI and moderate (κ = 0.52) for CT for prediction of incomplete resection. WB-DWI/MRI was superior to CT for primary tumour characterisation, staging and prediction of incomplete resection in patients suspected for ovarian cancer

Endometrial cancer is staged according to the International Federation of Gynecology and Obstetrics (FIGO) guidelines which are developed independently from imaging [1]. Major prognostic factors for endometrial cancer comprise histologic grade and lymphovascular invasion, local tumor extent including depth of myometrial invasion and cervical stromal involvement, and extrauterine tumor spread including nodal and distant metastatic spread [2]. Although FIGO guidelines do not recommend cross-sectional imaging as routine diagnostic modalities, CT, MRI, and FDG-PET/CT have an increasing role in the management of endometrial cancer patients as they also allow assessment of distant nodal or visceral disease spread [3]. At the time of diagnosis of endometrial cancer, imaging is most important for staging of locoregional and distant tumor extent and for prognostication. The purpose of this chapter is to present a general overview of conventional and newly developed imaging concepts for endometrial cancer.

10530 Background: Germline pathogenic variants (PV) in the tumor suppressor gene TP53 are associated with a high risk of developing diverse malignancies, often at young age, and predispose to Li-Fraumeni syndrome (LFS). Surveillance programs for presymptomatic PV carriers have shown survival benefit in a non-randomized trial. Here we describe the surveillance findings and clinical outcomes of adults with TP53 PV undergoing a standardized screening protocol. Methods: We identified adults with germline PV in TP53 who underwent surveillance at the University Hospitals Leuven, Belgium, between 04/2013 and 08/2020. Patients with prior cancer were allowed, while patients with an active malignancy requiring treatment at diagnosis of the TP53 PV were excluded. Surveillance was performed per modified Toronto protocol, including annual whole body diffusion-weighted MRI (WB-DWI/MRI), brain MRI, abdominal ultrasound (US), endoscopic surveillance, laboratory tests, dermatological examination and breast MRI/US in females. The primary aim was to evaluate the number and type of malignancies and premalignant lesions diagnosed during screening and to assess the proportion of malignancies detected by surveillance. Secondary outcomes were the cancer detection rate during the first year of screening, the proportion of carriers with false-positive findings, and overall survival. Results: We included 42 adults from 20 apparently unrelated families. Median age was 38y (range, 17-70y) and 23 had a history of prior cancer. After a median follow-up of 41.5mo, we diagnosed 18 cancers in 12/42 participants (29%). Overall survival was 95% in all participants, including 2 carriers who opted to discontinue surveillance. Surveillance detected 10/18 cancers (56%), the majority of whom through WB-DWI/MRI (6/10; 60%). No malignancies were identified with brain MRI. In 5/42 individuals (12%), surveillance detected a malignancy during the first year of screening. Only 2/10 cancers discovered with surveillance (1 soft tissue and 1 bone sarcoma) belong to the LFS core tumors. Cancers not detected with surveillance (8/18) were 6 non-melanoma skin cancers and 2 interval cancers (sarcoma post radiation, secondary acute leukemia). Additionally, we detected 27 premalignant lesions in 11/42 patients (26%), of whom 78% were diagnosed by colonoscopy. False-positive findings occurred in 7/42 patients (17%) and were mostly seen with WB-DWI/MRI. Conclusions: Adults with germline PV in TP53 that undergo surveillance have high cancer detection rates. The majority of malignancies were asymptomatic at diagnosis and detected with WB-DWI/MRI. Despite the high cancer incidence, few LFS core cancers were diagnosed and survival was encouraging. Increased genetic testing changes the clinical picture of germline TP53 carrier populations, justifying the transition from LFS to a wider concept of heritable TP53-related cancer syndrome.

PURPOSE: To evaluate the prognostic utility of apparent diffusion coefficient (ADC) changes at whole-body diffusion-weighted (WB-DW) MRI after one treatment cycle for aggressive non-Hodgkin lymphoma (NHL) compared with response assessment at interim and end-of-treatment fluorine 18 ((18)F) fluorodeoxyglucose (FDG) PET/CT. MATERIALS AND METHODS: This was a secondary analysis of a prospective study (ClinicalTrials.gov identifier: NCT01231269) in which participants with aggressive NHL were recruited between March 2011 and April 2015 and underwent WB-DW MRI before and after one cycle of immunochemotherapy. Volunteers were recruited for test-retest WB-DW MRI (ClinicalTrials.gov identifier: NCT01231282) to assess ADC measurement repeatability. Response assessment was based on ADC change after one treatment cycle at WB-DW MRI and Deauville criteria at (18)F-FDG PET/CT. To evaluate prognostic factors of disease-free survival (DFS), Kaplan-Meier survival analysis and univariable and multivariable Cox regression were performed; intraclass correlation coefficient (ICC) and mean difference with limits of agreement were calculated to determine inter- and intraobserver repeatability of ADC measurements. RESULTS: Forty-five patients (mean age, 58 years ± 17 [standard deviation]; 31 men) and nine volunteers (mean age, 22 years ± 3; seven men) were enrolled. Median DFS was 48 months (range, 2–48 months). Outcome prediction accuracy was 86.7% (39 of 45), 71.4% (30 of 42), and 73.8% (31 of 42) for WB-DW MRI and interim and end-of-treatment (18)F-FDG PET/CT, respectively. WB-DW MRI (hazard ratio [HR], 17.8; P < .001) and interim (HR, 5; P = .008) and end-of-treatment (HR, 4.3; P = .017) (18)F-FDG PET/CT were prognostic of DFS. After multivariable analysis, WB-DW MRI remained an independent predictor of outcome (HR, 26.8; P = .002). Intra- and interobserver agreement for ADC measurements were excellent (ICC = 0.85–0.99). CONCLUSION: Quantitative WB-DW MRI after only one cycle of immunochemotherapy predicts DFS in aggressive NHL and is noninferior to routinely performed interim and end-of-treatment (18)F-FDG PET/CT. Keywords: MR-Diffusion Weighted Imaging, Lymphoma, Oncology, Tumor Response, Whole-Body Imaging Supplemental material is available for this article. © RSNA, 2021

BACKGROUND: Correct staging of patients with colorectal cancer is of utmost importance for the prediction of operability. Although computed tomography (CT) has a good overall performance, estimation of peritoneal cancer spread is a known weakness, a problem that cannot always be overcome by Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT); especially in infiltrative and miliary disease spread. Due to its high spatial and contrast resolution magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) might have a better performance. Our aim was to evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for prediction of peritoneal cancer spread and operability assessment in colorectal cancer patients with clinically suspected peritoneal carcinomatosis (PC). METHODS: This institutional review board approved retrospective study included sixty colorectal cancer patients who underwent WB-DWI/MRI in addition to CT for clinically suspected peritoneal metastases. WB-DWI/MRI and CT were assessed for detecting PC following the peritoneal cancer index (PCI), determination of PCI-score categorized as PC 15, detection of nodal and distant metastases and estimation of overall operability. Histopathology after surgery and biopsy and/or 6 months follow-up were used as reference standard. RESULTS: For detection of PC, CT had 43.2% sensitivity, 95.6% specificity, 84.5% positive predictive value (PPV) and 75.2% negative predictive value (NPV). WB-DWI/MRI had 97.8% sensitivity, 93.2% specificity, 88.9% PPV and 98.7% NPV. WB-DWI/MRI enabled better detection of inoperable distant metastases (all 12 patients) than CT (2/12 patients) and significantly improved prediction of PCI category [WB-DWI/MRI PCI 15: 16/17 patients (94.1%) versus CT PCI 15: 2/17 patients (11.8%); p

To evaluate the feasibility of whole-body diffusion-weighted MRI (WB-DWI/MRI) for detecting primary tumour, nodal and distant metastases in pregnant women with cancer. Twenty pregnant patients underwent WB-DWI/MRI in additional to conventional imaging. Reproducibility of WB-DWI/MRI between two readers was evaluated using Cohen’s κ statistics and accuracy was compared to conventional imaging for assessing primary tumour site, nodal and visceral metastases. Both WB-DWI/MRI readers showed good–very good agreement for lesion detection (primary lesions: κ=1; lymph nodes: κ=0.89; distant metastases: κ=0.61). Eight (40 %) patients were upstaged after WB-DWI/MRI. For nodal metastases, WB-DWI/MRI showed 100 % (95 % CI: 83.2–100) sensitivity for both readers with specificity of 99.4 % (96.9–100) and 100 % (80.5–100) for readers 1 and 2, respectively. For distant metastases, WB-DWI/MRI showed 66.7 % (9.4–99.2) and 100 % (29.2–100) sensitivity and specificity of 94.1 % (71.3–99.9) and 100 % (80.5–100) for readers 1 and 2, respectively. Conventional imaging showed sensitivity of 50 % (27.2-72.8) and 33.3 % (0.8–90.6); specificity of 100 % (98–100) and 100 % (80.5–100), for nodal and distant metastases respectively. WB-DWI/MRI is feasible for single-step non-invasive staging of cancer during pregnancy with additional value for conventional imaging procedures. • In our study, WB-DWI/MRI was more accurate than conventional imaging during pregnancy. • WB-DWI/MRI improves diagnostic assessment of patients with cancer during pregnancy. • Accurate imaging and oncologic staging improves treatment and outcome.

Summary Background Hodgkin's lymphoma is one of the most common lymphoid neoplasms in young adults, but the low abundance of neoplastic Hodgkin/Reed-Sternberg cells in the tumour hampers the elucidation of its pathogenesis, biology, and diversity. After an incidental observation that genomic aberrations known to occur in Hodgkin's lymphoma were detectable in circulating cell-free DNA, this study was undertaken to investigate whether circulating cell-free DNA can be informative about genomic imbalances in Hodgkin's lymphoma. Methods We applied massive parallel sequencing to circulating cell-free DNA in a prospective study of patients with biopsy proven nodular sclerosis Hodgkin's lymphoma. Genomic imbalances in Hodgkin/Reed-Sternberg cells were investigated by fluorescence in-situ hybridisation (FISH) on tumour specimens. Findings By non-invasive prenatal testing, we observed several genomic imbalances in circulating cell-free DNA of a pregnant woman, who was subsequently diagnosed with early-stage nodular sclerosis Hodgkin's lymphoma stage IIA during gestation. FISH on tumour tissue confirmed corresponding genomic imbalances in Hodgkin/Reed-Sternberg cells. We prospectively studied circulating cell-free DNA of nine nodular sclerosis Hodgkin's lymphoma cases: eight at first diagnosis and one at first relapse. Seven patients had stage IIA disease and two had stage IVB disease. In eight, genomic imbalances were detected, including, among others, gain of chromosomes 2p and 9p, known to occur in Hodgkin's lymphoma. These gains and losses in circulating cell-free DNA were extensively validated by FISH on Hodgkin/Reed-Sternberg cells in biopsy samples. Initiation of chemotherapy induced normalisation of circulating cell-free DNA profiles within 2–6 weeks. The cell cycle indicator Ki67 and cleaved caspase-3 were detected in Hodgkin/Reed-Sternberg cells by immunohistochemistry, suggesting high turnover of Hodgkin/Reed-Sternberg cells. Interpretation In early and advanced stage nodular sclerosis Hodgkin's lymphoma, genomic imbalances in Hodgkin/Reed-Sternberg cells can be identified by massive parallel sequencing of circulating cell-free DNA at diagnosis. The rapid normalisation of circulating cell-free DNA profiles on therapy initiation suggests a potential role for circulating cell-free DNA profiling in early response monitoring. This finding creates several new possibilities for exploring the diversity of Hodgkin's lymphoma, and has potential implications for the future clinical development of biomarkers and precision therapy for this malignancy. Funding KU Leuven-University of Leuven and University Hospitals Leuven.

Background The aim of the study was to retrospectively evaluate the symptom control, tumour response, and complication rate in patients with liver-predominant metastatic neuroendocrine tumours treated with transarterial chemoembolization using doxorubicin-eluting superabsorbent polymer (SAP) microspheres. Patients and methods Patients with neuroendocrine liver metastases who underwent hepatic transarterial chemoembolization using doxorubicin-eluting SAP-microspheres (50–100 μm Hepasphere/Quadrasphere Microsphere® particles, Merit Medical, South Jordan, Utah, USA) were included in this study. Pre-and post-procedure imaging studies were evaluated to assess short and intermediate-term tumour response using modified RECIST criteria. Symptom relief and procedure-related complications were evaluated. Results A total of 27 embolization procedures were performed on 17 patients. Twelve of 17 patients (70%) were symptomatic, including carcinoid syndrome (n = 8) and severe, uncontrollable hypoglycemia (n = 4). Eight of 12 patients (67%) had complete symptom relief, and the remaining 4 (33%) had partial relief. One patient developed ischemic cholecystitis (6%). No other hepatobiliary complications occurred. Short-term and intermediate-term imaging follow-up was available for 15/17 patients (88%) and 12/14 patients (86%) respectively. At short-term follow-up (< 3 months), 14 patients (93%) showed partial response and the remaining patient had progressive disease (7%). At intermediate-term imaging follow-up (> 3 months), partial response, stable disease and progressive disease were found respectively in 7 (58%), 3 (25%) and 2 (17%) patients. Conclusions Chemoembolization with doxorubicin-eluting SAP-microspheres is a safe and effective treatment option for neuroendocrine liver metastases and is associated with a low complication rate. In particular, no clinically evident liver necrosis or bile duct complications were encountered.

ispartof: ENDOSCOPY vol:50 issue:7 pages:E184-E185 ispartof: location:Germany status: published

To evaluate whole-body MRI with diffusion-weighted sequence (WB-DWI/MRI) for staging and assessing operability compared with CT and FDG-PET/CT in patients with suspected ovarian cancer. Thirty-two patients underwent 3-T WB-DWI/MRI, (18) F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and CT before diagnostic open laparoscopy (DOL). Imaging findings for tumour characterisation, peritoneal and retroperitoneal staging were correlated with histopathology after DOL and/or open surgery. For distant metastases, FDG-PET/CT or image-guided biopsies were the reference standards. For tumour characterisation and peritoneal staging, WB-DWI/MRI was compared with CT and FDG-PET/CT. Interobserver agreement for WB-DWI/MRI was determined. WB-DWI/MRI showed 94 % accuracy for primary tumour characterisation compared with 88 % for CT and 94 % for FDG-PET/CT. WB-DWI/MRI showed higher accuracy of 91 % for peritoneal staging compared with CT (75 %) and FDG-PET/CT (71 %). WB-DWI/MRI and FDG-PET/CT showed higher accuracy of 87 % for detecting retroperitoneal lymphadenopathies compared with CT (71 %). WB-DWI/MRI showed excellent correlation with FDG-PET/CT (kappa = 1.00) for detecting distant metastases compared with CT (kappa = 0.34). Interobserver agreement was moderate to almost perfect (kappa = 0.58-0.91). WB-DWI/MRI shows high accuracy for characterising primary tumours, peritoneal and distant staging compared with CT and FDG-PET/CT and may be valuable for assessing operability in ovarian cancer patients. aEuro cent Whole-body MRI with diffusion weighting (WB-DWI/MRI) helps to assess the operability of suspected ovarian cancer. aEuro cent Interobserver agreement is good for primary tumour characterisation, peritoneal and distant staging. aEuro cent WB-DWI/MRI improves mesenteric/serosal metastatic spread assessment compared with CT and FDG-PET/CT. aEuro cent Retroperitoneal/cervical-thoracic nodal staging using qualitative DWI criteria was reasonably accurate. aEuro cent WB-DWI/MRI and FDG-PET/CT showed the highest diagnostic impact for detecting thoracic metastases

To evaluate the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance (MR) and diffusion-weighted imaging (DWI) sequences for defining benignity or malignancy of solitary pulmonary lesions (SPL).First, 54 consecutive patients with SPL, clinically staged (CT and PET or integrated PET-CT) as N0M0, were included in this prospective study. An additional 3-Tesla MR examination including DCE and DWI was performed 1 day before the surgical procedure. Histopathology of the surgical specimen served as the standard of reference. Subsequently, this functional method of SPL characterisation was validated with a second cohort of 54 patients.In the feasibility group, 11 benign and 43 malignant SPL were included. Using the combination of conventional MR sequences with visual interpretation of DCE-MR curves resulted in a sensitivity, specificity and accuracy of 100%, 55% and 91%, respectively. These results can be improved by DWI (with a cut-off value of 1.52 × 10(-3) mm(2)/s for ADChigh) leading to a sensitivity, specificity and accuracy of 98%, 82% and 94%, respectively. In the validation group these results were confirmed.Visual DCE-MR-based curve interpretation can be used for initial differentiation of benign from malignant SPL, while additional quantitative DWI-based interpretation can further improve the specificity.• Magnetic resonance imaging is increasingly being used to help differentiate lung lesions. • Solitary pulmonary lesions (SPL) are accurately characterised by combining DCE-MRI and DWI. • Visual DCE-MRI assessment facilitates the diagnostic throughput in patients with SPL. • DWI provides additional information in inconclusive DCE-MRI (type B pattern).

A new hypermetabolic lesion onWe present a case of acute and nodular radiation-induced injury of the left liver after neo-adjuvant chemoradiotherapy for distal esophageal cancer, which resembles a hepatic metastasis on

A rare case of hepatocellular tumor extension in the right heart was reported. The patient presented with clinical signs of a vena cava superior syndrome. Computed tomography and transthoracic echocardiography demonstrated a large tumoral mass lesion extending from the left liver lobe into the inferior vena cava right atrium and right ventricle. The patient was treated with best supportive care. ispartof: CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY vol:2016 ispartof: location:Egypt status: published

Cholangiocellular carcinoma (CC) originates from topographically heterogeneous cholangiocytes. The cylindrical mucin-producing cholangiocytes are located in large bile ducts and the cuboidal non–mucin-producing cholangiocytes are located in ductules containing bipotential hepatic progenitor cells (HPCs). We investigated the clinicopathological and molecular features of 85 resected CCs (14 hilar CCs [so-called Klatskin tumor], 71 intrahepatic CCs [ICCs] including 20 cholangiolocellular carcinomas [CLCs], which are thought to originate from HPCs]) and compared these with the different cholangiocyte phenotypes, including HPCs. Immunohistochemistry was performed with biliary/HPC and hepatocytic markers. Gene expression profiling was performed in different tumors and compared with nonneoplastic different cholangiocyte phenotypes obtained by laser microdissection. Invasion and cell proliferation assay were assessed using different types of CC cell lines: KMC-1, KMCH-1, and KMCH-2. Among 51 ICCs, 31 (60.8%) contained only mucin-producing CC features (muc-ICCs), whereas 39.2% displayed histological diversity: focal hepatocytic differentiation and ductular areas (mixed-ICCs). Clinicopathologically, muc-ICCs and hilar CCs showed a predominantly (peri-)hilar location, smaller tumor size, and more lymphatic and perineural invasion compared with mixed-ICCs and CLCs (predominantly peripheral location, larger tumor size, and less lymphatic and perineural invasion). Immunoreactivity was similar in muc-ICCs and hilar CCs and in mixed-ICCs and CLCs. S100P and MUC1 were significantly up-regulated in hilar CCs and muc-ICCs compared with mixed-ICCs and CLCs, whereas NCAM1 and ALB tended to be up-regulated in mixed-ICCs and CLCs compared with other tumors. KMC-1 showed significantly higher invasiveness than KMCH-1 and KMCH-2. Conclusion: Muc-ICCs had a clinicopathological, immunohistochemical, and molecular profile similar to that of hilar CCs (from mucin-producing cholangiocytes), whereas mixed-ICCs had a profile similar to that of CLCs (thought to be of HPC origin), possibly reflecting their respective cells of origin. (HEPATOLOGY 2012;55:1876–1888)

Aim: Hepatocellular carcinomas (HCC) have a strong biological heterogeneity. Current prognostic scores do not include histology. Information on the behavior of HCC based on histology has been characterized on retrospective data and large tissue specimens. We aimed to assess the additional value of needle biopsy and keratin 19 (K19) assessment in a prospective manner. Methods: Between 2003 and 2008, all patients with a confirmed diagnosis of HCC by a percutaneous or laparoscopic needle biopsy at the time of diagnosis, and of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, were included. The exclusion criterion was a palliative setting. Biopsies were scored for microvascular invasion, differentiation, K19, epithelial cell adhesion molecule and α-fetoprotein staining. Clinical and radiological features were registered at time of biopsy. The added value of K19 was assessed using Cox proportional hazards regression. Results: Of 74 patients screened, we included 58 patients. Based on the BCLC, 41% presented with early disease (BCLC A), 16% with intermediate disease (BCLC B) and 43% with advanced disease (BCLC C). In nine patients (16%), K19 staining was positive. Median follow up was 54 months (range 1–74) and 43 patients (72%) died. BCLC classification predicted the prognosis accurately, but histology offered additional prognostic information. In multivariate analysis, K19 was a strong predictor of overall survival (hazard ratio 4.57, 95% confidence interval 1.86–10.6), which improved predictive performance. No needle tract dissemination was observed. Conclusion: Despite the possible problem of sampling error, needle biopsy offered additional prognostic information. This is especially the case for K19 staining.