Presentation of autoimmune hepatitis (AIH) can differ from nonacute to acute autoimmune hepatitis (A‐AIH) with jaundice and acute severe autoimmune hepatitis (AS‐AIH) with jaundice and coagulopathy. ...The aim of the study was to evaluate the short‐term prognosis of different presentations of AIH and the influence of liver function improvement on short‐term prognosis. In this single‐center retrospective cohort study, AIH patients with repeatedly tested liver function at diagnosis and during at least 1 year of follow‐up were included. A‐AIH was defined as bilirubin >45 µmol and international normalized ratio (INR) <1.5. AS‐AIH was defined as bilirubin level >45 µmol/L and INR ≥1.5. Of the 81 included patients, 17 (21%) presented with A‐AIH, and 14 (17%) presented with AS‐AIH. After the start of immunosuppressive therapy, bilirubin, albumin, and INR normalized in 70%, 77%, and 69%, respectively, in a median of 2.6 months, 3 months, and 4 weeks, respectively, in patients with A‐AIH and AS‐AIH. Liver transplantation (LT)–free survival rate was 100% in nonacute AIH, 94% in A‐AIH, and 57% in AS‐AIH at 12 months after diagnosis. An increase of INR or bilirubin at 2 weeks was the best predictive factor for the need of LT within 12 months with a Youden’s index of 0.85. A‐AIH was present in 21%, and AS‐AIH was present in 17% of AIH patients. In the majority of patients, bilirubin, albumin, and INR normalized in the first months of treatment. Deterioration of liver function after 2 weeks of treatment should lead to rapid evaluation for LT and consideration of second‐line medication.
https://www.wileyhealthlearning.com/Activity/7201351/disclaimerspopup.aspx
Background
Determining the resectability of pancreatic cancer with vascular involvement on preoperative computed tomography imaging remains challenging, especially following preoperative chemotherapy ...and chemoradiotherapy. Intraoperative ultrasound (IOUS) may provide real-time additional information, but prospective multicenter series confirming its value are lacking.
Patients and Methods
This prospective multicenter study included patients undergoing surgical exploration for pancreatic cancer with vascular involvement. All patients underwent IOUS at the start of explorative laparotomy. Primary outcomes were resectability status as defined by the National Comprehensive Cancer Network and the extent of vascular involvement.
Results
Overall, 85 patients were included, of whom 74 (87%) were post preoperative chemotherapy, and mostly following FOLFIRINOX regimen (
n
= 57; 76%). On the basis of preoperative imaging, 34 (40%) patients were staged as resectable (RPC), 32 (38%) borderline resectable (BRPC), and 19 (22%) locally advanced pancreatic cancer (LAPC). IOUS changed the resectability status in 32/85 (38%) patients (
p
< 0.001), including 8/19 (42%) patients with LAPC who were downstaged (4 to BRPC, 4 to RPC), and 22/32 (69%) patients with BRPC who were downstaged to RPC. Among patients with presumed superior mesenteric artery (SMA) involvement, 20/28 (71%) had no SMA involvement on IOUS. In 15 of these 20 patients a pancreatic resection was performed, all with R0 SMA margin.
Conclusion
IOUS during surgical exploration for pancreatic cancer and vascular involvement downstaged the resectability status in over one-third of patients, which could facilitate progress during surgical exploration. This finding should be confirmed by larger studies, including detailed pathology assessment.
Trial Registration
www.trialregister.nl
(NL7621).
Purpose
To investigate the biodistribution of holmium-166 microspheres (
166
Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to ...establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume).
Materials and Methods
This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2–5 cm, or a maximum of 3 lesions of ≤ 3 cm each. The day after RFA patients undergo angiography and cone-beam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates (
99m
Tc-MAA). The perfused liver volume is segmented from the CBCT and
166
Ho-MS is administered to this treatment volume 5–10 days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60 Gy, 90 Gy and 120 Gy) until the endpoint is reached. SPECT/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of ≥ 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival.
Discussion
This study aims to find the optimal administration dose of adjuvant radioembolization with
166
Ho-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients.
Trial registration
Clinicaltrials.gov identifier: NCT03437382.
In this pilot study, we investigated the feasibility of response prediction using digital 18 FFDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant ...chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial.
Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and 18 FFDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected.
Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy, early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features.
Both multiparametric MRI and 18 FFDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.
Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Lea/c/x, sdi-Lea, ...sLea, sLex, sTn as well as mucin-1 (MUC1) and mucin-5AC (MU5AC) have gained significant interest as targets for PDAC imaging. To evaluate their PDAC molecular imaging potential, biomarker expression was determined using immunohistochemistry on PDAC, (surrounding) chronic pancreatitis (CP), healthy pancreatic, duodenum, positive (LN+) and negative lymph node (LN−) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Lea/c/x, 94% for sdi-Lea, 98% for sLea, 90% for sLex, 88% for sTn, 96% for MUC1 and 67% for MUC5AC, where all were not affected by the application of neoadjuvant therapy. Compared to PDAC, all biomarkers were significantly lower expressed on CP, healthy pancreatic and duodenal tissues, except for sTn and MUC1, which showed a strong expression on duodenum (sTn tumor:duodenum ratio: 0.6, p < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, p > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN+, as well as the distinction of LN+ from LN− tissues. To conclude, this study paves the way for the development and evaluation of Lea/c/x-, sdi-Lea-, sLea-, sLex- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic.
Current imaging modalities frequently misjudge disease stage in colorectal, gastric and pancreatic cancer. As treatment decisions are dependent on disease stage, incorrect staging has serious ...consequences. Previous preclinical research and case reports indicate that prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging might provide a solution to some of these challenges. This prospective clinical study aims to assess the feasibility of
FDCFPyL PET/CT imaging to target and visualize primary colon, gastric and pancreatic cancer. In this prospective clinical trial, patients with colon, gastric and pancreatic cancer were included and underwent both
FDCFPyL and
FFDG PET/CT scans prior to surgical resection or (for gastric cancer) neoadjuvant therapy. Semiquantitative analysis of immunohistochemical PSMA staining was performed on the surgical resection specimens, and the results were correlated to imaging parameters. The results of this study demonstrate detection of the primary tumor by
FDCFPyL PET/CT in 7 out of 10 patients with colon, gastric and pancreatic cancer, with a mean tumor-to-blood pool ratio (TBR) of 3.3 and mean SUV
of 3.6. However, due to the high surrounding uptake, visual distinction of these tumors was difficult, and the SUV
and TBR on
FFDG PET/CT were significantly higher than on
FDCFPyL PET/CT. In addition, no correlation between PSMA expression in the resection specimen and SUV
on
FDCFPyL PET/CT was found. In conclusion, the detection of several gastrointestinal cancers using
FDCFPyL PET/CT is feasible. However, low tumor expression and high uptake physiologically in organs/background hamper the clear distinction of the tumor. As a result,
FFDG PET/CT was superior in detecting colon, gastric and pancreatic cancers.
A substantial fraction of familial colorectal cancer (CRC) and polyposis heritability remains unexplained. This study aimed to identify predisposing loci in patients with these disorders.
...Homozygosity mapping was performed using 222 563 SNPs in 302 index patients with various colorectal neoplasms and 3367 controls. Linkage analysis, exome and whole-genome sequencing were performed in a family affected by microsatellite stable CRCs. Candidate variants were genotyped in 10 554 cases and 21 480 controls. Gene expression was assessed at the mRNA and protein level.
Homozygosity mapping revealed a disease-associated region at 1q32.3 which was part of the linkage region 1q32.2-42.2 identified in the CRC family. This includes a region previously associated with risk of CRC. Sequencing identified the p.Asp1432Glu variant in the MIA3 gene (known as TANGO1 or TANGO) and 472 additional rare, shared variants within the linkage region. In both cases and controls the population frequency was 0.02% for this MIA3 variant. The MIA3 mutant allele showed predominant mRNA expression in normal, cancer and precancerous tissues. Furthermore, immunohistochemistry revealed increased expression of MIA3 in adenomatous tissues.
Taken together, our two independent strategies associate genetic variations in chromosome 1q loci and predisposition to familial CRC and polyps, which warrants further investigation.
The combination of alpha-1 antitrypsin (AAT) deficiency, ANCA-vasculitis, and aortic aneurysm has been rarely described in literature. We report an eventually fatal case in a 70-year-old patient who ...initially presented with giant cell arteritis and ANCA associated glomerulonephritis. Several years later, he presented with aortic dissection due to large vessel vasculitis, raising the suspicion of AAT deficiency, as two first-line relatives had chronic obstructive pulmonary disease, while they never smoked. This diagnosis was confirmed by AAT electrophoresis and immunohistochemistry on a temporal artery biopsy. Considering AAT deficiency in these cases might lead to a more timely diagnosis.
Background
Targeted molecular imaging may improve tumor cell identification during diagnosis and resection of pancreatic ductal adenocarcinoma (PDAC). Although many molecular imaging biomarkers are ...(over)expressed in PDAC, intertumoral heterogeneity of biomarker expression hampers universal tracer administration. Preoperative, patient-specific screening and selection of the most optimal biomarker could therefore improve tumor delineation.
Objective
This study evaluated whether fine-needle biopsy (FNB) specimens could be used to preoperatively predict biomarker expression in the corresponding primary PDAC specimen.
Methods
Expression of previously identified PDAC biomarkers α
v
β
6
, CEACAM5, EGFR, mesothelin, Le
a/c/x
, and sdi-Le
a
on FNB and corresponding primary tumor (PT) specimens (
n
= 45) was evaluated using immunohistochemistry and quantified using a semi-automated image analysis workflow.
Results
Biomarker expression on FNB and PT tissues showed high concordance (∆H-score ≤ 50), i.e. was present in 62% of cases for α
v
β
6
, 61% for CEACAM5, 85% for EGFR, 69% for mesothelin, 76% for Le
a/c/x
, and 79% for sdi-Le
a
, indicating high concordance. Except for α
v
β
6
, biomarker expression on FNB tissues was positively correlated with PT expression for all biomarkers. Subgroup analyses showed that neoadjuvant therapy (NAT) had no major and/or significant effect on concordance, expression difference and, except for mesothelin, correlation of biomarker expression between FNB and PT tissues.
Conclusion
This study demonstrated that biomarker expression in FNB tissues is predictive for PT expression, irrespective of the application of NAT. These findings thereby provide the foundation for the clinical application of an FNB-based biomarker-screening workflow, eventually facilitating a patient-specific approach of molecular imaging tracer administration in PDAC.
Graphical Abstract
PDF
