1. Carbon stable isotopes are commonly used as a research tool in physiological ecology. When elements are consumed, they are naturally enriched or depleted as the consumer processes them. The ...difference in isotopic composition between the consumer and the diet is known as the discrimination factor (Δ¹³C). 2. Mixing models are used to estimate the contribution of multiple dietary components to a consumer's tissues and discrimination must be estimated in the model. Often, discrimination factors vary depending on multiple factors, yet in many models the discrimination factor is assumed to be constant for each dietary component. 3. Few studies have evaluated the mechanistic basis of stable isotope metabolism and discrimination during macromolecule biosynthesis, despite the potential to improve estimations of discrimination factors. We tested whether ¹³C discrimination depends on the dietary concentration of ¹³C by culturing the bacterium Bacillus subtilis in a gradient of broths ranging from a δ¹³C of -11·8per thousand to -25·3per thousand. We found an increase in discrimination in whole bacterial tissue, bulk lipid, and lipid-extracted fractions as dietary the concentration of ¹³C increased, with lipids showing the greatest discrimination ranging from 2·72per thousand in the low ¹³C broths to 15·5per thousand in the high¹³C broths. 4. These findings contrast with the majority of isotopic ecology data that typically show a moderate enrichment of ¹³C as trophic level increases. This discrepancy is attributed to the de novo biosynthesis of the majority of cellular components in this study as opposed to the effects of isotopic routing seen in more metabolically complex taxa.
Radioembolization of liver malignancies with
Ho-microspheres has been shown to be safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy of
Ho ...radioembolization.
In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. The primary outcome was a response by 2 target lesions on triphasic liver CT scans 3 mo after therapy, as assessed using RECIST, version 1.1. Secondary outcomes included overall tumor response, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI.
Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27 (73%) of 37 patients, the target lesions showed complete response, partial response, or stable disease (disease control) at 3 mo (95% confidence interval CI, 57%-85%). The median overall survival was 14.5 mo (95% CI, 8.6-22.8 mo). For colorectal cancer patients (
= 23), the median overall survival was 13.4 mo (95% CI, 8.2-15.7 mo). Grade 3 or 4 toxic events after treatment (according to the Common Terminology Criteria for Adverse Events, version 4.03) included abdominal pain (in 18% of patients), nausea (8%), ascites (3%), fatigue (3%), gastric stenosis (3%), hepatic failure (3%), liver abscesses (3%), paroxysmal atrial tachycardia (3%), thoracic pain (3%), upper gastrointestinal hemorrhage (3%), and vomiting (3%). On SPECT,
Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3% ± 7.1% in the liver.
Radioembolization with
Ho-microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.
Objectives
To investigate the additional value of cervical ultrasonography over
18
F-FDG PET/CT for diagnosing cervical lymph node metastases in patients with newly diagnosed oesophageal cancer.
...Methods
Between January 2013 and January 2016, 163 patients with newly diagnosed oesophageal cancer underwent both cervical ultrasonography and
18
F-FDG PET/CT at a tertiary referral centre in the Netherlands. Retrospective clinical data analysis was performed to assess the diagnostic value of cervical ultrasonography and
18
F-FDG PET/CT for the detection of cervical lymph node metastases. Fine needle aspiration or clinical follow-up was used as reference standard.
Results
The overall incidence of patients with cervical lymph node metastases was 14%. The sensitivity of
18
F-FDG PET/CT to detect cervical lymph node metastases was 82% (95% CI 59–94%) and specificity was 91% (95% CI 85–95%). The sensitivity and specificity of cervical ultrasonography were 73% (95% CI 50–88%) and 84% (95% CI 77–90%), respectively. In patients with a negative
18
F-FDG PET/CT, 12 of 133 (9%) patients had suspicious nodes on cervical ultrasonography. In all these 12 patients the nodes were confirmed benign.
Conclusions
Cervical ultrasonography has no additional diagnostic value to a negative integrated
18
F-FDG PET/CT for the detection of cervical lymph node metastases in patients with newly diagnosed oesophageal cancer.
Key Points
•
Cervical ultrasonography has no value over PET/CT in evaluating cervical node metastases.
•
PET/CT provides greater diagnostic confidence compared to cervical ultrasonography.
•
Cervical ultrasonography during standard diagnostic work-up may be considered unnecessary.
•
Cervical lesions on PET/CT require cytopathological confirmation by FNA.
Determining the resectability of locally advanced pancreatic cancer (LAPC) after FOLFIRINOX chemotherapy is challenging because CT-scans cannot reliably assess vascular involvement. This study ...evaluates the added value of intra-operative ultrasound (IOUS) in LAPC following FOLFIRINOX induction chemotherapy.
Prospective multicenter study in patients with LAPC who underwent explorative laparotomy with IOUS after FOLFIRINOX chemotherapy. Resectability was defined according to the National Comprehensive Cancer Network guidelines. IOUS findings were compared with preoperative CT-scans and pathology results.
CT-staging in 38 patients with LAPC after FOLFIRINOX chemotherapy defined 22 patients LAPC, 15 borderline resectable and one resectable. IOUS defined 19 patients LAPC, 13 borderline resectable and six resectable. In 12/38 patients, IOUS changed the resectability status including five patients from borderline resectable to resectable and five patients from LAPC to borderline resectable. Two patients were upstaged from borderline resectable to LAPC. Tumor diameters were significantly smaller upon IOUS (31.7 ± 9.5 mm versus 37.1 ± 10.0 mm, p = 0.001) and resectability varied significantly (p = 0.043). Ultimately, 20 patients underwent resection of whom 14 were evaluated as (borderline) resectable on CT-scan, and 17 on IOUS.
This prospective study demonstrates that IOUS may change the resectability status up to a third of patients with LAPC following FOLFIRINOX chemotherapy.
The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis.
We collected 92 biopsies from untreated head ...and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling, we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested.
Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Using Gene Set Enrichment analysis, several gene sets were found to be enriched in locoregional recurrences, although with high false-discovery rates. Previously published signatures for radiosensitivity, hypoxia, proliferation, "wound," stem cells, and chromosomal instability were not significantly correlated with outcome. However, a recently published signature for HNSCC defining a "high-risk" group was shown to be predictive for locoregional control in our dataset.
Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.
OBJECTIVETo assess the additional value of cervical ultrasonography as supplement to a negative fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) for detecting cervical lymph node ...metastases during the initial staging of patients with esophageal cancer.
METHODSPubMed/Medline, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies describing the accuracy of cervical ultrasonography and integrated F-FDG PET/CT or standalone F-FDG PET and CT for detecting cervical lymph node metastases in patients with esophageal cancer. The reference standard consisted of cytopathology and/or clinical follow-up. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of the included studies. A random effects model was used to meta-analyze the additional diagnostic value of cervical ultrasonography.
RESULTSFour diagnostic studies were eligible and included for meta-analysis, comprising 567 patients with esophageal cancer who underwent diagnostic workup before treatment. The quality of the included studies was considered reasonable; there were few concerns regarding risk of bias and applicability. In three of the four studies, cervical ultrasonography did not detect cervical lymph node metastases in addition to a negative finding on F-FDG PET/CT or standalone F-FDG PET and CT. In one study, cervical ultrasonography detected additional cervical lymph node metastases in 4% (3/74) of patients over standalone F-FDG PET and CT. Pooled estimate of the additional value of cervical ultrasonography was 1% (95% confidence interval0–5%).
CONCLUSIONCervical ultrasonography has very limited additional diagnostic value as supplement to a negative F-FDG PET/CT in the detection of cervical lymph node metastases during the initial staging of patients with esophageal cancer.
Occult metastases are detected in 10-15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in ...patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013-December 2017). Multivariable logistic regression analysis based on the Akaike Information Criteria was performed with intraoperative pathologically proven metastases as the outcome. The model was externally validated with a cohort from the University Hospital of Verona (January 2013-December 2017). For model development, 2262 patients were included of whom 235 (10%) had occult metastases, located in the liver (
= 143, 61%), peritoneum (
= 73, 31%), or both (
= 19, 8%). The model included age (OR 1.02, 95% CI 1.00-1.03), BMI (OR 0.96, 95% CI 0.93-0.99), preoperative nutritional support (OR 1.73, 95% CI 1.01-2.74), tumor diameter (OR 1.60, 95% CI 1.04-2.45), tumor composition (solid vs. cystic) (OR 2.33, 95% CI 1.20-4.35), and indeterminate lesions on preoperative imaging (OR 4.01, 95% CI 2.16-7.43). External validation showed poor discrimination with a C-statistic of 0.56. Although some predictor variables were significantly associated with occult metastases, the model performed insufficiently at external validation.
Summary
Reduced reproduction increases storage and extends lifespan in several animal species. The disposable soma hypothesis suggests this life extension occurs by shifting allocation of ingested ...nutrients from reproduction to the soma. A great deal of circumstantial evidence supports this hypothesis, but no direct tracking of nutrients has been performed in animals that are long‐lived because of direct reduction in reproduction. Here, we use the stable isotopes to track carbon and nitrogen from ingestion to somatic organs in long‐lived, ovariectomized grasshoppers. Three estimates of somatic storage (viz., quantity of hemolymph storage proteins, amount of femur muscle carbohydrates, and size of the fat body) all doubled upon ovariectomy. In stark contrast, ovariectomy did not increase the proportion of these tissues that were made from recently ingested foods. In other words, the physiology underlying relative allocation to these somatic tissues was not affected by ovariectomy. Thus, at the level of whole tissue storage, these results are consistent with a trade‐off between reproduction and longevity. In contrast, our stable isotope data are inconsistent with the prediction that enhanced storage in ovariectomized females results from a physiological shift in allocation of ingested nutrients.
Understanding how resources are allocated between survival and reproduction is fundamental to the study of the evolution of life histories. Reproductive resources can come from two intrinsic resource ...pools, stored reserves (capital) acquired before reproduction or income acquired during reproduction. The variety of reproductive strategies in insects is remarkable and reproductive allocation encompasses the complete range of allocation strategies from pure capital breeders to pure income breeders. However, most organisms probably use a blend of capital and income and this blend is likely dynamic, changing between reproductive bouts in response to internal and external conditions. We used stable isotopes to quantify the allocation of capital and income resources to reproduction in the flesh fly, Sarcopha crassipalpis and assessed how allocation patterns change over multiple bouts of reproduction.
Sarcophaga crassipalpis shifts from a slight investment of capital in the first clutch to an almost pure income breeder in the second clutch. We discuss the relationship between activity and allocation, and the potential for this system to understand how allocation patterns change in response to environmental stress.
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