Background: Radiopaque breast markers cause artifacts in dedicated spiral breast-computed tomography (SBCT). This study investigates the extent of artifacts in different marker types and the ...feasibility of reducing artifacts through a metal artifact reduction (MAR) algorithm. Methods: The pilot study included 18 women who underwent contrast-enhanced SBCT. In total, 20 markers of 4 different types were analyzed for artifacts. The extent of artifacts with and without MAR was measured via the consensus of two readers. Image noise was quantitatively evaluated, and the effect of MAR on the detectability of breast lesions was evaluated on a 3-point Likert scale. Results: Breast markers caused significant artifacts that impaired image quality and the detectability of lesions. MAR decreased artifact size in all analyzed cases, even in cases with multiple markers in a single slice. The median length of in-plain artifacts significantly decreased from 31 mm (range 11–51 mm) in uncorrected to 2 mm (range 1–5 mm) in corrected images (p ≤ 0.05). Artifact size was dependent on marker size. Image noise in slices affected by artifacts was significantly lower in corrected (13.6 ± 2.2 HU) than in uncorrected images (19.2 ± 6.8 HU, p ≤ 0.05). MAR improved the detectability of lesions affected by artifacts in 5 out of 11 cases. Conclusion: MAR is feasible in SBCT and improves the image quality and detectability of lesions.
Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, ...using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease.
Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease ...and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.
The study aimed to investigate the added value of blood glucose monitoring in high-risk individuals (HRIs) participating in pancreatic cancer surveillance.
HRIs with a CDKN2A/p16 germline pathogenic ...variant (PV) participating in pancreatic cancer surveillance were included in this study. Multivariable logistic regression was performed to assess the relationship between new-onset diabetes (NOD) and pancreatic ductal adenocarcinoma (PDAC). To quantify the diagnostic performance of NOD as a marker for PDAC, receiver operating characteristic curve with area under the curve (AUC) was computed.
In total, 220 HRIs were included between 2000-2019. Median age was 61 (IQR 53-71) years and 62.7% of participants were female. During the study period, 26 (11.8%) HRIs developed NOD, of whom 5 (19.2%) later developed PDAC. The other 23 (82.1%) PDAC cases remained NOD-free. Multivariable analysis showed no statistically significant relationship between NOD and PDAC (OR 1.21; 95% CI, 0.39-3.78) and four out of five PDAC cases appeared to have NOD within three months before diagnosis. Furthermore, NOD did not differentiate between HRIs with- and without PDAC (AUC 0.54; 95% CI, 0.46-0.61).
In this study we found no added value for longitudinal glucose monitoring in CDKN2A PV carriers participating in an imaging-based pancreatic cancer surveillance program.
Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The ...aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival.
This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013-2017).
A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P < 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P < 0.001) and worse overall survival (median 12 versus 16 versus 20 months, respectively; P < 0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33 months, respectively; P = 0.470), although there was a difference in major morbidity rates (52 versus 19 versus 21 per cent, respectively; P = 0.012).
In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection.
Diffuse optical spectroscopy (DOS) has the potential to enable monitoring of tumor response during chemotherapy, particularly in the early stages of treatment. This study aims to assess feasibility ...of DOS for monitoring treatment response in HER2-negative breast cancer patients receiving neoadjuvant chemotherapy (NAC) and compare DOS with tumor response assessment by MRI.
Patients received NAC in six cycles of 3 weeks. In addition to standard treatment monitoring by dynamic contrast enhanced MRI (DCE-MRI), DOS scans were acquired after the first, third, and last cycle of chemotherapy. The primary goal was to assess feasibility of DOS for early assessment of tumor response. The predictive value of DOS and DCE-MRI compared with pathologic response was assessed.
Of the 22 patients, 18 patients had a partial or complete tumor response at pathologic examination, whereas 4 patients were nonresponders. As early as after the first chemotherapy cycle, a significant difference between responders and nonresponders was found using DOS (HbO2 86% ± 25 vs. 136% ± 25, P = 0.023). The differences between responders and nonresponders continued during treatment (halfway treatment, HbO2 68% ± 22 vs. 110% ± 10, P = 0.010). Using DCE-MRI, a difference between responders and nonresponders was found halfway treatment (P = 0.005) using tumor volume measurement calculations.
DOS allows for tumor response assessment and is able to differentiate between responders and nonresponders after the first chemotherapy cycle and halfway treatment. In this study, DOS was equally effective in predicting tumor response halfway treatment compared with DCE-MRI. Therefore, DOS may be used as a novel imaging modality for (early) treatment monitoring of NAC.
Background
CDKN2A‐p16‐Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis.
Objective
...To assess the cost‐effectiveness of surveillance, as compared to no surveillance.
Methods
In 2000, a surveillance program was initiated at Leiden University Medical Center with annual MRI and optional endoscopic ultrasound. Data were collected on the resection rate of screen‐detected tumors and on survival. The Kaplan–Meier method and a parametric cure model were used to analyze and compare survival. Based on the surveillance and survival data from the screening program, a state‐transition model was constructed to estimate lifelong outcomes.
Results
A total of 347 mutation carriers participated in the surveillance program. PDAC was detected in 31 patients (8.9%) and the tumor could be resected in 22 patients (71.0%). Long‐term cure among patients with resected PDAC was estimated at 47.1% (p < 0.001). The surveillance program was estimated to reduce mortality from PDAC by 12.1% and increase average life expectancy by 2.10 years. Lifelong costs increased by €13,900 per patient, with a cost‐utility ratio of €14,000 per quality‐adjusted life year gained. For annual surveillance to have an acceptable cost‐effectiveness in other settings, lifetime PDAC risk needs to be 10% or higher.
Conclusion
The tumor could be resected in most patients with a screen‐detected PDAC. These patients had considerably better survival and as a result annual surveillance was found to be cost‐effective.
Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper ...insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumor activity. We observed the temporal changes of peripheral immune subsets including NKT cells, central memory CD4
T cells, CD8
T cells and regulatory T cells (Treg) during the course of BCG. Gene expression analysis revealed enriched immune pathways involving in T cell activation and chemotaxis, as well as a more diversified T cell receptor repertoire in post-BCG tissues. Moreover, tissue multiplexed-immunofluorescence (mIF) showed baseline densities of non-Treg and CD8
PD-1
T cells were predictive of response and better recurrence-free survival after BCG. Remarkably, post-BCG tissues from responders were found to be infiltrated with more active CD8
PD-1
T cells and non-Treg CD4
FOXP3
T cells; but increased exhausted CD8
PD-1
T cells were found in non-responders. Taken together, we identified predictive biomarkers for response and uncovered the post-treatment expansion of exhausted PD-1
CD8
T cells as key to BCG resistance, which could potentially be restored by combining with anti-PD-1 immunotherapy.
Practice variation exists in venous resection during pancreatoduodenectomy, but little is known about the potential causes and consequences as large studies are lacking. This study explores the ...potential causes and consequences of practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer in the Netherlands.
This nationwide retrospective cohort study included patients undergoing pancreatoduodenectomy for pancreatic cancer in 18 centers from 2013 through 2017.
Among 1,311 patients undergoing pancreatoduodenectomy, 351 (27%) had a venous resection, and the overall median annual center volume of venous resection was 4. No association was found between the center volume of pancreatoduodenectomy and the rate of venous resections, nor between patient and tumor characteristics and the rate of venous resections per center. Female sex, lower body mass index, neoadjuvant therapy, venous involvement, and stenosis on imaging were predictive for venous resection. Adjusted for these factors, 3 centers performed significantly more, and 3 centers performed significantly fewer venous resections than expected. In patients with venous resection, significantly less major morbidity (22% vs 38%) and longer overall survival (median 16 vs 12 months) were observed in centers with an above-median annual volume of venous resections (>4).
Patient and tumor characteristics did not explain significant practice variation between centers in the Netherlands in venous resection during pancreatoduodenectomy for pancreatic cancer. The clinical outcomes of venous resection might be related to the volume of the procedure.
MRI surveillance in a cohort of CDKN2A-p16-Leiden mutation carriers with a 20% lifetime risk of PDAC led to increased resection rates and improved survival. Patients with screen-detected PDAC were ...evaluated for main pancreatic duct (MPD) abnormalities in this retrospective review.
Since 2000 annual MRI and optional EUS was performed in mutation carriers. Data of patients with screen-detected PDAC was collected on gender, age at diagnosis, site of tumor, size, outcome of surgery, pathology findings and survival. All MRIs were re-evaluated for MPD abnormalities.
23 PDAC were detected in 22 (10%) of 217 mutation carriers, 10 (45%) males and 12 (55%) females. The mean age at diagnosis was 59.8 years (range 39.2–74.3 years). Revision of the MRI/MRCP revealed a lesion and dilatation of the MPD in 8 of the 22 patients. In 5 of 7 patients with PDAC detected during follow-up, the previous MRI showed MPD dilatation without evidence of tumor. The mean size of PDAC was 12.3 mm (range 5–19 mm). All tumors were resectable.
MPD dilation is common in patients with screen-detected PDAC. Abnormalities on MRI during surveillance of high-risk individuals requires intense follow-up or prompt treatment, as early treatment results in a better prognosis.
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