This is a randomized, controlled trial of preoperative chemotherapy in patients undergoing surgery for oesophageal squamous cell carcinoma (OSCC). Patients were allocated to chemotherapy, consisting ...of 2-4 cycles of cisplatin and etoposide, followed by surgery (CS group) or surgery alone (S group). Initial results reported only in abstract form in 1997, demonstrated an advantage for overall survival in the CS group. The results of this trial have been updated and discussed in the timeframe in which this study was performed.
This trial recruited 169 patients with OSCC, 85 patients assigned to preoperative chemotherapy and 84 patients underwent immediate surgery. The primary study endpoint was overall survival (OS), secondary endpoints were disease free survival (DFS) and pattern of failure. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test.
There were 148 deaths, 71 in the CS and 77 in the S group. Median OS time was 16 months in the CS group compared with 12 months in the S group; 2-year survival rates were 42% and 30%; and 5-year survival rates were 26% and 17%, respectively. Intention to treat analysis showed a significant overall survival benefit for patients in the CS group (P = 0.03, by the log-rank test; hazard ratio HR 0.71; 95%CI 0.51-0.98). DFS (from landmark time of 6 months after date of randomisation) was also better in the CS-group than in the S group (P = 0.02, by the log-rank test; HR 0.72; 95%CI 0.52-1.0). No difference in failure pattern was observed between both treatment arms.
Preoperative chemotherapy with a combination of etoposide and cisplatin significantly improved overall survival in patients with OSCC.
After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response ...of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations.
The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin area under the curve 2 mg/mL per min plus paclitaxel 50 mg/m2 of body-surface area combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4–6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET–CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12–14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed.
Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% 95% CI 17–50) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% 95% CI 4–23) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% 95% CI 17–44). PET–CT missed six of 41 TRG3 or TRG4 tumours (15% 95% CI 7–28). PET–CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas).
After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET–CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803).
Dutch Cancer Society.
Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms. We hypothesized that disturbed FA metabolism could contribute to the progression of HIV infection. Plasma ...levels of 45 FAs were analyzed with gas chromatography in healthy controls and HIV-infected patients with regard to Mycobacterium avium complex (MAC) infection. In vitro, we assessed MAC-PPD-induced release of inflammatory cytokines in peripheral and bone marrow mononuclear cells (PBMC and BMMC) according to levels of n-6 polyunsaturated fatty acids (PUFAs). While plasma saturated FAs were higher in HIV infection, PUFAs, and in particular the n-6 PUFA arachidonic acid (AA), were lower in patients with advanced disease. The ratio between AA and precursor dihomo-γ-linolenic acid, reflecting Δ5-desaturase activity, was markedly lower and inversely correlated with plasma HIV RNA levels in these patients. Depletion of AA was observed prior to MAC infection, and MAC-PPD-induced release of TNF and IL-6 in PBMC and BMMC was lower in patients with low plasma AA. Our findings suggest that dysregulated metabolism of n-6 PUFAs may play a role in the progression of HIV infection. While high AA may contribute to chronic inflammation in asymptomatic HIV-infected patients, low AA seems to increase the susceptibility to MAC infection in patients with advanced disease.
The basic principle of hot-tapping is to establish a new branch pipeline connection to an existing (mother) pipeline while under full pressure. This involves connecting the branch pipe, including a ...valve, to the mother pipeline, usually by means of welding or mechanical clamp connections, cutting a hole in the pipe wall by a machine attached to the valve, retracting the cutting head, closing the valve, and disconnecting and recovering the cutting machine.
Summary
A fractured poroelastic body is considered where the opening of the fractures is governed by a nonpenetration law, whereas slip is described by a Coulomb‐type friction law. This physical ...model results in a nonlinear variational inequality problem. The variational inequality is rewritten as a complementary function, and a semismooth Newton method is used to solve the system of equations. For the discretization, we use a hybrid scheme where the displacements are given in terms of degrees of freedom per element, and an additional Lagrange multiplier representing the traction is added on the fracture faces. The novelty of our method comes from combining the Lagrange multiplier from the hybrid scheme with a finite volume discretization of the poroelastic Biot equation, which allows us to directly impose the inequality constraints on each subface. The convergence of the method is studied for several challenging geometries in 2D and 3D, showing that the convergence rates of the finite volume scheme do not deteriorate when it is coupled to the Lagrange multipliers. Our method is especially attractive for the poroelastic problem because it allows for a straightforward coupling between the matrix deformation, contact conditions, and fluid pressure.
The aim of the present study was to describe the prevalence of clinical pulmonary manifestations in primary SS (pSS), and based on registry data, to assess quality of life (QoL) and mortality in ...these patients.
Patients with pSS consecutively included in the Norwegian systemic CTD and vasculitis registry (NOSVAR) were investigated for pulmonary manifestations when presenting with clinical pulmonary symptoms. Pulmonary involvement was defined as typical abnormalities identified with high-resolution CT (HRCT) and/or pulmonary function tests (PFTs).
Among patients referred from our primary area, Oslo (n = 117), lung involvement was found in 26 patients (22%). In our total cohort (n = 216), 59 patients (27%) were affected. A higher rate of pulmonary complications and trends towards longer disease duration and higher age indicated a selection of more complicated cases referred from outside our primary area. Abnormal HRCTs were found in 50 patients (23%) and PFTs in 34 patients (16%). The Medical Outcomes Study 36-Item Short-Form Health Survey Physical Functioning subscore, was significantly reduced in patients with lung involvement (P = 0.03). Furthermore, a 4-fold increased risk of dying after 10 years of disease among patients with lung involvement (n = 10, 17%) compared with those without lung involvement (n = 7, 4.5%) (P = 0.002) was found.
We found a high population-based prevalence of clinical pulmonary involvement (22%) among patients with pSS. Moreover, patients with lung involvement had reduced QoL represented by the subscale Physical Functioning, and mortality was increased.
The purposes of this review are to assess the human exposure and human and experimental evidence for adverse effects of brominated flame-retardants (BFRs) with specific focus on intake from seafood. ...The leakage of BFRs from consumer products leads to exposure of humans from fetal life to adulthood. Fish and fish products contain the highest levels of BFRs and dominate the dietary intake of frequent fish eaters in Europe, while meat, followed by seafood and dairy products accounted for the highest US dietary intake. House dust is also reported as an important source of exposure for children as well as adults. The levels of BFRs in the general North American populations are higher than those in Europe and Japan and the highest levels are detected in infants and toddlers. The daily intake via breast milk exceeds the RfD in 10% of US infants.
BFRs including PBDEs, HBCDs and TBBP-A have induced endocrine-, reproductive- and behavior effects in laboratory animals. Furthermore, recent human epidemiological data demonstrated association between exposure to BFRs and similar adverse effects as observed in animal studies.
Fish including farmed fish and crude fish oil for human consumption may contain substantial levels of BFRs and infants and toddlers consuming these products on a daily basis may exceed the tolerable daily intake suggesting that fish and fish oil alone represent a risk to human health. This intake comes in addition to exposure from other sources (breast milk, other food, house dust). Because potential harmful concentrations of BFRs and other toxicants occur in fish and fish products, research on a wider range of products is warranted, to assess health hazard related to the contamination of fish and fish products for human consumption.
•BFRs are associated with endocrine-, reproductive- and behavioral effects.•Seafood contains the highest levels of BFRs.•The US population carry higher doses of BFRs than Europeans and Japanese.•The highest levels of BFRs are detected in infants and toddlers.•Frequent seafood eaters may exceed the safe level.
Robotic in-row weed control in vegetables Utstumo, Trygve; Urdal, Frode; Brevik, Anders ...
Computers and electronics in agriculture,
November 2018, 2018-11-00, 20181101, Letnik:
154
Journal Article
Recenzirano
•Robot for in-row weed control with single herbicide droplets.•Lab trials with 4 weed species using droplets of glyphosate and iodosulfuron.•Successful robotic field trial controlling weeds in carrot ...crop.•A ten-fold reduction in herbicide use, and reduced health and environmental impact.
Vegetables and other row-crops represent a large share of the agricultural production. There is a large variation in crop species, and a limited availability in specialized herbicides. The robot presented here utilizes systematic growing techniques to navigate and operate in the field. By the use of machine vision it separates seeded vegetable crops from weed. Each weed within the row is treated with individual herbicide droplets, without affecting the crop. This results in a significant reduction in herbicide use, and allows for the use of herbicides that would otherwise harm the crop.
The robot is tailored to this purpose with cost, maintainability, efficient operation and robustness in mind. The three-wheeled design is unconventional, and the design maintains maneuverability and stability with the benefit of reduced weight, complexity and cost.
Indoor pot trials with four weed species demonstrated that the Drop-on-Demand system (DoD) could control the weeds with as little as 7.6 μg glyphosate or 0.15 μg iodosulfuron per plant. The results also highlight the importance of liquid characteristics for droplet stability and leaf retention properties. The common herbicide glyphosate had no effect unless mixed with suitable additives. A field trial with the robot was performed in a carrot field, and all the weeds were effectively controlled with the DoD system applying 5.3 μg of glyphosate per droplet. The robot and DoD system represent a paradigm shift to the environmental impact and health risks of weed control, while providing a valuable tool to the producers.
Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment ...strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma.
In this investigator-initiated, open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who had stage IB– IVA resectable gastric or gastro-oesophageal adenocarcinoma (as defined by the American Joint Committee on Cancer, sixth edition), with a WHO performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and kidney function. Patients were enrolled from 56 hospitals in the Netherlands, Sweden, and Denmark, and were randomly assigned (1:1) with a computerised minimisation programme with a random element to either perioperative chemotherapy (chemotherapy group) or preoperative chemotherapy with postoperative chemoradiotherapy (chemoradiotherapy group). Randomisation was done before patients were given any preoperative chemotherapy treatment and was stratified by histological subtype, tumour localisation, and hospital. Patients and investigators were not masked to treatment allocation. Surgery consisted of a radical resection of the primary tumour and at least a D1+ lymph node dissection. Postoperative treatment started within 4–12 weeks after surgery. Chemotherapy consisted of three preoperative 21-day cycles and three postoperative cycles of intravenous epirubicin (50 mg/m2 on day 1), cisplatin (60 mg/m2 on day 1) or oxaliplatin (130 mg/m2 on day 1), and capecitabine (1000 mg/m2 orally as tablets twice daily for 14 days in combination with epirubicin and cisplatin, or 625 mg/m2 orally as tablets twice daily for 21 days in combination with epirubicin and oxaliplatin), received once every three weeks. Chemoradiotherapy consisted of 45 Gy in 25 fractions of 1·8 Gy, for 5 weeks, five daily fractions per week, combined with capecitabine (575 mg/m2 orally twice daily on radiotherapy days) and cisplatin (20 mg/m2 intravenously on day 1 of each 5 weeks of radiation treatment). The primary endpoint was overall survival, analysed by intention-to-treat. The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02.
Between Jan 11, 2007, and April 17, 2015, 788 patients were enrolled and randomly assigned to chemotherapy (n=393) or chemoradiotherapy (n=395). After preoperative chemotherapy, 372 (95%) of 393 patients in the chemotherapy group and 369 (93%) of 395 patients in the chemoradiotherapy group proceeded to surgery, with a potentially curative resection done in 310 (79%) of 393 patients in the chemotherapy group and 326 (83%) of 395 in the chemoradiotherapy group. Postoperatively, 233 (59%) of 393 patients started chemotherapy and 245 (62%) of 395 started chemoradiotherapy. At a median follow-up of 61·4 months (IQR 43·3–82·8), median overall survival was 43 months (95% CI 31–57) in the chemotherapy group and 37 months (30–48) in the chemoradiotherapy group (hazard ratio from stratified analysis 1·01 (95% CI 0·84–1·22; p=0·90). After preoperative chemotherapy, in the total safety population of 781 patients (assessed together), there were 368 (47%) grade 3 adverse events; 130 (17%) grade 4 adverse events, and 13 (2%) deaths. Causes of death during preoperative treatment were diarrhoea (n=2), dihydropyrimidine deficiency (n=1), sudden death (n=1), cardiovascular events (n=8), and functional bowel obstruction (n=1). During postoperative treatment, grade 3 and 4 adverse events occurred in 113 (48%) and 22 (9%) of 233 patients in the chemotherapy group, respectively, and in 101 (41%) and ten (4%) of 245 patients in the chemoradiotherapy group, respectively. Non-febrile neutropenia occurred more frequently during postoperative chemotherapy (79 34% of 233) than during postoperative chemoradiotherapy (11 4% of 245). No deaths were observed during postoperative treatment.
Postoperative chemoradiotherapy did not improve overall survival compared with postoperative chemotherapy in patients with resectable gastric cancer treated with adequate preoperative chemotherapy and surgery. In view of the poor postoperative patient compliance in both treatment groups, future studies should focus on optimising preoperative treatment strategies.
Dutch Cancer Society, Dutch Colorectal Cancer Group, and Hoffmann-La Roche.
Background and purpose - There is no consensus on best method of fixation in hip arthroplasty. We investigated different modes of fixation in primary total hip arthroplasty (THA) and the influence of ...age and sex, to assess need for a differentiated approach.
Patients and methods - The study was based on data from the Norwegian Arthroplasty Register in the period 2005-2017. Included were all-cemented, all-uncemented, reverse hybrid (uncemented stem and cemented cup), and hybrid (cemented stem and uncemented cup) THA designs that were commonly used, contemporary and well documented, using different causes of revision as endpoints.
Results - From the included 66,995 primary THAs, 2,242 (3.3%) were revised. Compared with all-cemented THAs, all-uncemented had a higher risk of revision due to any cause (RR 1.4; CI 1.2-1.6), mainly due to an increased risk of periprosthetic fracture (RR 5.2; CI 3.2-8.5) and dislocation (RR 2.2; CI 1.5-3.0). Women had considerably higher risk of revision due to periprosthetic fracture after all-uncemented THA (RR 12; CI 6-25), compared with cemented. All-uncemented THAs in women of age 55-75 years (RR 1.3; CI 1.0-1.7) and over 75 years of age (RR 1.8; CI 1.2-2.7), and reverse hybrid THAs in women over the age of 75 (RR 1.5; CI 1.1-1.9) had higher risk of revision compared with cemented. Hybrid THAs (RR 1.0; CI 0.9-1.2) and reverse hybrid THAs (RR 1.0; CI 0.7-1.3) had similar risk of revision due to any cause as cemented THAs.
Interpretation - Uncemented stems (all-uncemented and reverse hybrid THAs) had increased risk of revision in women over 55 years of age, mainly due to periprosthetic fracture and dislocation, and should probably not be used in THA in these patients.
PDF
