Purpose
We explored differences in survival between primary tumor locations, hereby focusing on the role of metastatic sites in synchronous metastatic colorectal cancer (mCRC).
Methods
Data for ...patients diagnosed with synchronous mCRC between 1989 and 2014 were retrieved from the Netherlands Cancer registry. Relative survival and relative excess risks (RER) were analyzed by primary tumor location (right colon (RCC), left colon (LCC), and rectum). Metastatic sites were reported per primary tumor location. Survival was analyzed for metastatic sites combined and for single metastatic sites.
Results
In total, 36,297 patients were included in this study. Metastatic sites differed significantly between primary tumor locations, with liver-only metastases in 43%, 54%, and 52% of RCC, LCC, and rectal cancer patients respectively (
p
< 0.001). Peritoneal metastases were most prevalent in RCC patients (33%), and lung metastases were most prevalent in rectal cancer patients (28%). Regardless of the location of metastases, patients with RCC had a worse survival compared with LCC (RER 0.81, 95% CI 0.78–0.83) and rectal cancer (RER 0.73, 95% CI 0.71–0.76). The survival disadvantage for RCC remained present, even in cases with metastasectomy for liver-only disease (LCC: RER 0.66, 95% CI 0.57–0.76; rectal cancer: RER 0.84, 95% CI 0.66–1.06).
Conclusions
This study showed significant differences in relative survival between primary tumor locations in synchronous mCRC, which can only be partially explained by distinct metastatic sites. Our findings support the concept that RCC, LCC and rectal cancer should be considered distinct entities in synchronous mCRC.
The Kilo-Degree Survey is an optical wide-field survey designed to map the matter distribution in the Universe using weak gravitational lensing. In this paper, we use these data to measure the ...density profiles and masses of a sample of ∼1400 spectroscopically identified galaxy groups and clusters from the Galaxy And Mass Assembly survey. We detect a highly significant signal (signal-to-noise-ratio ∼120), allowing us to study the properties of dark matter haloes over one and a half order of magnitude in mass, from M ∼ 1013–1014.5 h
−1 M⊙. We interpret the results for various subsamples of groups using a halo model framework which accounts for the mis-centring of the brightest cluster galaxy (used as the tracer of the group centre) with respect to the centre of the group's dark matter halo. We find that the density profiles of the haloes are well described by an NFW profile with concentrations that agree with predictions from numerical simulations. In addition, we constrain scaling relations between the mass and a number of observable group properties. We find that the mass scales with the total r-band luminosity as a power law with slope 1.16 ± 0.13 (1σ) and with the group velocity dispersion as a power law with slope 1.89 ± 0.27 (1σ). Finally, we demonstrate the potential of weak lensing studies of groups to discriminate between models of baryonic feedback at group scales by comparing our results with the predictions from the Cosmo-OverWhelmingly Large Simulations project, ruling out models without AGN feedback.
In colorectal cancer surgery there is a delicate balance between complete removal of the tumor and sparing as much healthy tissue as possible. Especially in rectal cancer, intraoperative tissue ...recognition could be of great benefit in preventing positive resection margins and sparing as much healthy tissue as possible. To better guide the surgeon, we evaluated the accuracy of diffuse reflectance spectroscopy (DRS) for tissue characterization during colorectal cancer surgery and determined the added value of DRS when compared to clinical judgement.
DRS spectra were obtained from fat, healthy colorectal wall and tumor tissue during colorectal cancer surgery and results were compared to histopathology examination of the measurement locations. All spectra were first normalized at 800 nm, thereafter two support vector machines (SVM) were trained using a tenfold cross-validation. With the first SVM fat was separated from healthy colorectal wall and tumor tissue, the second SVM distinguished healthy colorectal wall from tumor tissue.
Patients were included based on preoperative imaging, indicating advanced local stage colorectal cancer. Based on the measurement results of 32 patients, the classification resulted in a mean accuracy for fat, healthy colorectal wall and tumor of 0.92, 0.89 and 0.95 respectively. If the classification threshold was adjusted such that no false negatives were allowed, the percentage of false positive measurement locations by DRS was 25% compared to 69% by clinical judgement.
This study shows the potential of DRS for the use of tissue classification during colorectal cancer surgery. Especially the low false positive rate obtained for a false negative rate of zero shows the added value for the surgeons. Trail registration This trail was performed under approval from the internal review board committee (Dutch Trail Register NTR5315), registered on 04/13/2015, https://www.trialregister.nl/trial/5175 .
The purpose of this study was to evaluate the feasibility of electromagnetic (EM) navigation for guidance on osteotomies in patients undergoing oncologic mandibular surgery. Preoperatively, a 3D ...rendered model of the mandible was constructed from diagnostic computed tomography (CT) images. Cutting guides and patient specific reconstruction plates were designed and printed for intraoperative use. Intraoperative patient registration was performed using a cone beam CT scan (CBCT). The location of the mandible was tracked with an EM sensor fixated to the mandible. The real-time location of both the mandible and a pointer were displayed on the navigation system. Accuracy measurements were performed by pinpointing four anatomical landmarks and four landmarks on the cutting guide using the pointer on the patient and comparing these locations to the corresponding locations on the CBCT. Differences between actual and virtual locations were expressed as target registration error (TRE). The procedure was performed in eleven patients. TREs were 3.2 ± 1.1 mm and 2.6 ± 1.5 mm using anatomical landmarks and landmarks on the cutting guide, respectively. The navigation procedure added on average half an hour to the duration of the surgery. This is the first study that reports on the accuracy of EM navigation in patients undergoing mandibular surgery.
The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we ...imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.
Previous studies have shown that older patients benefited less than younger patients from surgical treatment for colorectal cancer (CRC). However, CRC care has advanced over time, and it is time to ...assess whether the difference in postoperative mortality between older and younger CRC patients is still present.
Patients with primary stage I-III CRC diagnosed between 2005 and 2016 were selected from the Netherlands Cancer Registry (N = 111,778). Trends in postoperative mortality and 1-year postoperative relative survival (RS) were analysed, stratified according to age (<75 versus ≥75 years) and tumour location (colon versus rectum). One-year postoperative RS was analysed to correct for background mortality in the older population.
Between 2005 and 2016, 30-day postoperative mortality showed a stronger decrease for older patients (from 10.0% to 4.0% for colon cancer p < 0.001 and from 8.3% to 2.7% for rectal cancer p < 0.001) compared with younger patients (from 2.0% to 0.9% for colon cancer p < 0.001 and from 1.4% to 0.7% for rectal cancer p = 0.01). Between 2005 and 2016, also 1-year RS increased more for older patients (from 84.8% to 94.6% for colon cancer and from 86.1% to 97.2% for rectal cancer) compared with younger patients (from 94.0% to 97.8% for colon cancer and from 96.3% to 98.8% for rectal cancer).
Between 2005 and 2016, differences in postoperative mortality between older and younger CRC patients decreased. One-year postoperative RS was almost equal for older and younger patients in 2015–2016. This information is crucial for shared decision-making on surgical treatment.
•Differences in mortality between older and younger CRC patients decreased.•One-year relative survival became nearly equal for older and younger patients.•Previous literature is no longer representative of the current clinical practice.
Here we demonstrate that deracemization of isoindolinones using Viedma ripening is possible starting from a racemic mixture of conglomerate crystals. Crystals of the enantiopure isoindolinones lose ...their chiral identity upon dissolution even without the need for a catalyst. This enabled complete deracemization of the reported isoindolinones without a catalyst.
No catalyst required! Complete deracemization of three isoindolinones was achieved through Viedma ripening, also without a racemization catalyst.
Gfi1b is a transcriptional repressor expressed in hematopoietic stem cells (HSCs) and megakaryocytes (MKs). Gfi1b deficiency leads to expansion of both cell types and abrogates the ability of MKs to ...respond to integrin. Here we show that Gfi1b forms complexes with β-catenin, its co-factors Pontin52, CHD8, TLE3 and CtBP1 and regulates Wnt/β-catenin-dependent gene expression. In reporter assays, Gfi1b can activate TCF-dependent transcription and Wnt3a treatment enhances this activation. This requires interaction between Gfi1b and LSD1 and suggests that a tripartite β-catenin/Gfi1b/LSD1 complex exists, which regulates Wnt/β-catenin target genes. Consistently, numerous canonical Wnt/β-catenin target genes, co-occupied by Gfi1b, β-catenin and LSD1, have their expression deregulated in Gfi1b-deficient cells. When Gfi1b-deficient cells are treated with Wnt3a, their normal cellularity is restored and Gfi1b-deficient MKs regained their ability to spread on integrin substrates. This indicates that Gfi1b controls both the cellularity and functional integrity of HSCs and MKs by regulating Wnt/β-catenin signaling pathway.
Aliment Pharmacol Ther 2011; 34: 335–343
Summary
Background Treatment failure occurs in 20% of autoimmune hepatitis patients on prednisolone and azathioprine (AZA). There is no established second ...line treatment.
Aim To assess the efficacy of mycophenolate mofetil as second line treatment after AZA‐intolerance or AZA‐nonresponse in autoimmune hepatitis and overlap syndromes.
Methods Consecutive patients from the Dutch Autoimmune Hepatitis Group cohort, consisting of 661 patients, with autoimmune hepatitis or overlap syndromes, AZA‐intolerance or AZA‐nonresponse and past or present use of mycophenolate mofetil were included. Primary endpoint of mycophenolate mofetil treatment was biochemical remission. Secondary endpoints were biochemical response (without remission), treatment failure and prevention of disease progression.
Results Forty‐five patients treated with mycophenolate mofetil were included. In autoimmune hepatitis remission or response was achieved in 13% and 27% in the AZA‐nonresponse group compared to 67% and 0% in the AZA‐intolerance group (P = 0.008). In overlap‐syndromes remission or response was reached in 57% and 14% in the AZA‐nonresponse group and 63% and 25% of the AZA‐intolerance group (N.S.); 33% had side effects and 13% discontinued mycophenolate mofetil. Overall 38% had treatment failure; this was 60% in the autoimmune hepatitis AZA‐nonresponse group. Decompensated liver cirrhosis, liver transplantations and death were only seen in the autoimmune hepatitis AZA‐nonresponse group (P < 0.001).
Conclusions Mycophenolate mofetil induced response or remission in a majority of patients with autoimmune hepatitis and azathioprine‐intolerance and with overlap syndromes, irrespective of intolerance or nonresponse for azathioprine. In autoimmune hepatitis with azathioprine nonresponse mycophenolate mofetil is less often effective.
The main challenge for radical resection in oral cancer surgery is to obtain adequate resection margins. Especially the deep margin, which can only be estimated based on palpation during surgery, is ...often reported inadequate. To increase the percentage of radical resections, there is a need for a quick, easy, minimal invasive method, which assesses the deep resection margin without interrupting or prolonging surgery. This systematic review provides an overview of technologies that are currently being studied with the aim of fulfilling this demand.
A literature search was conducted through the databases Medline, Embase and the Cochrane Library. A total of 62 studies were included. The results were categorized according to the type of technique: ‘Frozen Section Analysis’, ‘Fluorescence’, ‘Optical Imaging’, ‘Conventional imaging techniques’, and ‘Cytological assessment’. This systematic review gives for each technique an overview of the reported performance (accuracy, sensitivity, specificity, positive predictive value, negative predictive value, or a different outcome measure), acquisition time, and sampling depth.
At the moment, the most prevailing technique remains frozen section analysis. In the search for other assessment methods to evaluate the deep resection margin, some technologies are very promising for future use when effectiveness has been shown in larger trials, e.g., fluorescence (real-time, sampling depth up to 6 mm) or optical techniques such as hyperspectral imaging (real-time, sampling depth few mm) for microscopic margin assessment and ultrasound (less than 10 min, sampling depth several cm) for assessment on a macroscopic scale.
•There is a need for a method that assesses the deep resection margin during surgery•This systematic review provides an overview of techniques that fulfill this demand•The techniques were evaluated on performance, acquisition time and sampling depth•The most prevailing technique remains frozen section analysis•Methods that are promising are fluorescence, optical analysis and ultrasound
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