Prognosis after surgery for multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors:Functionality matters

Background: Metastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis.Methods: Patients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival.Results: Out of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P =.001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%–76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%–91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47–6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22–7.33]) and World Health Organization grade 2 (2.95 [1.02–8.50]) were associated with liver metastases-free survival.Conclusion: Patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade.</p

The predictive accuracy of PREDICT: A personalized decision-making tool for southeast Asian women with breast cancer

10.1097/MD.0000000000000593Medicine (United States)948e59

Synthetic smooth muscle cell phenotype is associated with increased nicotinamide adenine dinucleotide phosphate oxidase activity: Effect on collagen secretion

ObjectiveSmooth muscle cells (SMCs) from prosthetic vascular grafts secrete higher levels of collagen than aortic SMCs under basal conditions and during incubation with oxidized low-density lipoprotein. We postulated that reactive oxygen species (ROS) contributed to the observed difference. The objective of this study was to assess the effect of ROS on collagen secretion by aortic and graft SMCs and explore the mechanism involved.MethodsSMCs isolated from canine aorta or Dacron thoracoabdominal grafts were incubated with 6-anilinoquinoline-5,8-quinone (LY83583), an agent that induces superoxide production. Type I collagen in the conditioned medium was measured by enzyme-linked immunosorbent assay, and superoxide anion production was measured by lucigenin assay.ResultsLY83583 stimulated a rapid increase in collagen production by graft SMCs that paralleled the LY83583-induced increase in superoxide production. The increase in both collagen and superoxide was greater in graft SMCs than aortic SMCs. Collagen and superoxide production were inhibited by superoxide scavengers. Nicotinamide adenine dinucleotide phosphate (NADPH) induced significantly more superoxide production by graft SMCs than aortic SMCs, suggesting that the NADPH oxidase system was more active in graft SMCs. NADPH oxidase inhibitors blocked the superoxide and collagen production induced by LY83583.ConclusionIn SMCs, the synthetic phenotype is associated with increased NADPH oxidase activity and elevated superoxide production in response to an oxidative stress. Superoxide, in turn, leads to increased collagen production.Clinical RelevanceThe inflammatory process after prosthetic vascular graft implantation causes oxidative stress that can stimulate collagen production by graft SMCs, contributing to the progression of intimal hyperplasia. The exaggerated response of graft SMCs to oxidative stress offers a potential target for therapeutic interventions

Effects of exercise in breast cancer patients: implications of the trials within cohorts (TwiCs) design in the UMBRELLA Fit trial

Purpose The Trials within Cohorts (TwiCs) design aims to overcome problems faced in conventional RCTs. We evaluated the TwiCs design when estimating the effect of exercise on quality of life (QoL) and fatigue in inactive breast cancer survivors. Methods UMBRELLA Fit was conducted within the prospective UMBRELLA breast cancer cohort. Patients provided consent for future randomization at cohort entry. We randomized inactive patients 12-18 months after cohort enrollment. The intervention group (n = 130) was offered a 12-week supervised exercise intervention. The control group (n = 130) was not informed and received usual care. Six-month exercise effects on QoL and fatigue as measured in the cohort were analyzed with intention-to-treat (ITT), instrumental variable (IV), and propensity scores (PS) analyses. Results Fifty-two percent (n = 68) of inactive patients accepted the intervention. Physical activity increased in patients in the intervention group, but not in the control group. We found no benefit of exercise for dimensions of QoL (ITT difference global QoL: 0.8, 95% CI = - 2.2; 3.8) and fatigue, except for a small beneficial effect on physical fatigue (ITT difference: - 1.1, 95% CI = - 1.8; - 0.3; IV: - 1.9, 95% CI = - 3.3; - 0.5, PS: - 1.2, 95% CI = - 2.3; - 0.2). Conclusion TwiCs gave insight into exercise intervention acceptance: about half of inactive breast cancer survivors accepted the offer and increased physical activity levels. The offer resulted in no improvement on QoL, and a small beneficial effect on physical fatigue.Clinical epidemiolog

The effect of neoadjuvant short-course radiotherapy and delayed surgery versus chemoradiation on postoperative outcomes in locally advanced rectal cancer patients – A propensity score matched nationwide audit-based study

Objective: To investigate differences in postoperative outcomes between short-course radiotherapy and delayed surgery (SCRT-delay) and chemoradiation (CRT) in patients with locally advanced rectal cancer (LARC). Background: Previous trials suggest that SCRT-delay could serve as an adequate neoadjuvant treatment for LARC. Therefore, in frail LARC patients SCRT-delay is recommended as an alternative to CRT. However, data on postoperative outcomes after SCRT-delay in comparison to CRT is scarce. Methods: This was an observational study with data from the Dutch ColoRectal Audit (DCRA). LARC patients who underwent surgery (2014–2017) after an interval of ≥6 weeks were included. Missing values were replaced by multiple imputation. Propensity score matching (PSM), using age, Charlson Comorbidity Index, cT-stage and surgical procedure, was applied to create comparable groups. Differences in postoperative outcomes were analyzed using Chi-square test for categorical variables, independent sample t-test for continuous variables and Mann-Whitney U test for non-parametric data. Results: 2926 patients were included. In total, 288 patients received SCRT-delay and 2638 patients underwent CRT. Patients in the SCRT-delay group were older and had more comorbidities. Also, ICU-admissions and permanent colostomies were more common, as well as pulmonic, cardiologic, infectious and neurologic complications. After PSM, both groups comprised 246 patients with equivalent age, comorbidities and tumor stage. There were no differences in postoperative complications. Conclusion: Postoperative complications were not increased in LARC patients undergoing SCRT-delay as neoadjuvant treatment. Regarding treatment-related complications, SCRT-delay is a safe alternative neoadjuvant treatment option for frail LARC patients

Supine MRI for regional breast radiotherapy: Imaging axillary lymph nodes before and after sentinel-node biopsy

Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p < 0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible

Automatic coronary artery calcium scoring on radiotherapy planning CT Scans of breast cancer patients: Reproducibility and association with traditional cardiovascular risk factors

Objectives Coronary artery calcium (CAC) is a strong and independent predictor of cardiovascular disease (CVD) risk. This study assesses reproducibility of automatic CAC scoring on radiotherapy planning computed tomography (CT) scans of breast cancer patients, and examines its association with traditional cardiovascular risk factors. Methods This study included 561 breast cancer patients undergoing radiotherapy between 2013 and 2015. CAC was automatically scored with an algorithm using supervised pattern recognition, expressed as Agatston scores and categorized into five categories (0, 1-10, 11-100, 101-400, >400). Reproducibility between automatic and manual expert scoring was assessed in 79 patients with automatically determined CAC above zero and 84 randomly selected patients without automatically determined CAC. Interscan reproducibility of automatic scoring was assessed in 294 patients having received two scans (82% on the same day). Association between CAC and CVD risk factors was assessed in 36 patients with CAC scores >100, 72 randomly selected patients with scores 1-100, and 72 randomly selected patients without CAC. Reliability was assessed with linearly weighted kappa and agreement with proportional agreement. Results 134 out of 561 (24%) patients had a CAC score above zero. Reliability of CVD risk categorization between automatic and manual scoring was 0.80 (95% Confidence Interval (CI): 0.74-0.87), and slightly higher for scans with breath-hold. Agreement was 0.79 (95% CI: 0.72-0.85). Interscan reliability was 0.61 (95% CI: 0.50-0.72) with an agreement of 0.84 (95% CI: 0.80-0.89). Ten out of 36 (27.8%) patients with CAC scores above 100 did not have other cardiovascular risk factors. Conclusions Automatic CAC scoring on radiotherapy planning CT scans is a reliable method to assess CVD risk based on Agatston scores. One in four breast cancer patients planned for radiotherapy have elevated CAC score. One in three patients with high CAC scores don't have other CVD risk factors and wouldn't have been identified as high risk

Health-related quality of life of early-stage breast cancer patients after different radiotherapy regimens

Purpose To evaluate and compare health-related quality of life (HRQL) of women with early-stage breast cancer (BC) treated with different radiotherapy (RT) regimens. Methods Data were collected from five prospective cohorts of BC patients treated with breast-conserving surgery and different RT regimens: intraoperative RT (IORT, 1 x 23.3 Gy; n = 267), external beam accelerated partial breast irradiation (EB-APBI, 10 x 3.85 Gy; n = 206), hypofractionated whole breast irradiation(hypo-WBI, 16 x 2.67 Gy; n = 375), hypo-WBI + boost(hypo-WBI-B, 21-26 x 2.67 Gy; n = 189), and simultaneous WBI + boost(WBI-B, 28 x 2.3 Gy; n = 475). Women >= 60 years with invasive/in situ carcinoma <= 30 mm, cN0 and pN0-1a were included. Validated EORTC QLQ-C30/BR23 questionnaires were used to asses HRQL. Multivariable linear regression models adjusted for confounding (age, comorbidity, pT, locoregional treatment, systemic therapy) were used to compare the impact of the RT regimens on HRQL at 12 and 24 months. Differences in HRQL over time (3-24 months) were evaluated using linear mixed models. Results There were no significant differences in HRQL at 12 months between groups except for breast symptoms which were better after IORT and EB-APBI compared to hypo-WBI at 12 months (p < 0.001). Over time, breast symptoms, fatigue, global health status and role functioning were significantly better after IORT and EB-APBI than hypo-WBI. At 24 months, HRQL was comparable in all groups. Conclusion In women with early-stage breast cancer, the radiotherapy regimen did not substantially influence long-term HRQL with the exception of breast symptoms. Breast symptoms are more common after WBI than after IORT or EB-APBI and improve slowly until no significant difference remains at 2 years posttreatment.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

CONSORT extension for the reporting of randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE): checklist with explanation and elaboration

Randomised controlled trials are increasingly conducted as embedded, nested, or using cohorts or routinely collected data, including registries, electronic health records, and administrative databases, to assess if participants are eligible for the trial and to facilitate recruitment, to deliver an embedded intervention, to collect trial outcome data, or a combination of these purposes. This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE). The extension was developed to look at the unique characteristics of trials conducted with these types of data with the goal of improving reporting quality in the long term by setting standards early in the process of uptake of these trial designs. The extension was developed with a sequential approach, including a Delphi survey, a consensus meeting, and piloting of the checklist. The checklist was informed by the CONSORT 2010 statement and two reporting guidelines for observational studies, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the REporting of studies Conducted using Observational Routinely collected Data (RECORD) statement. The extension includes eight items modified from the CONSORT 2010 statement and five new items. Reporting items with explanations and examples are provided, including key aspects of trials conducted using cohorts or routinely collected data that require specific reporting considerations