We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the ...CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months.
TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS).
Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026).
Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.
The reactions of α‐pinene and of its main oxidation product, pinonaldehyde (3‐acetyl‐2,2‐dimethyl‐cyclobutyl‐ethanal), with OH radicals have been studied in the laboratory using Fourier transform ...infrared spectroscopy for real‐time monitoring of the gas‐phase chemical species and a Scanning Mobility Particle Sizer system (3071 A, TSI) for the study of the secondary aerosol formation. All gas‐phase molar yields were quantified using calibrated reference of the pure compound, except for the nitrates products. The results were: for the α‐pinene experiments in the presence of NOx, pinonaldehyde, (87±20)%; total nitrates (18±9)%; formaldehyde, (23±9)%; acetone (9±6)%; for the α‐pinene experiments in the absence of NOx: pinonaldehyde, (37±7)%; formaldehyde, (8±1)%; acetone, (7±2)%; for the pinonaldehyde experiments in the presence of NO, formaldehyde (152±56)% and acetone (15±7)%. The aerosol measurements showed that the condensed products accounted for the missing carbon in the gas‐phase balance. The partitioning of the products into the condensed phase was found to be potentially significant under experimental conditions but less than 10% for initial α‐pinene concentrations lower than 1013 molecule cm−3 and hence negligible under atmospheric conditions in the absence of aerosol seeds. On the basis of these results a comprehensive mechanism for the gas‐phase reaction of α‐pinene with OH in the presence of NOx has been proposed, including quantitative values for all the involved branching ratios.
In order to quantify the contribution of solvent use and road traffic to the total non-methane volatile organic compound (NMVOC) emissions in Germany, the composition of air in the city of Wuppertal ...was investigated during three campaigns at different locations. The measurements covered NMVOCs in the range of C
3–C
10 hydrocarbons and C
1–C
6 oxygenated compounds. An assessment of the contribution from different emission sources to the observed NMVOC concentrations was attempted with the chemical mass balance (CMB) modelling technique. Emission profiles for traffic were obtained from measurements performed in a traffic tunnel, at a downtown street intersection and during drives through the city and on motorways. Solvent emission profiles were investigated in the vicinity of different factories and workshops using solvents in Wuppertal. Apportionment analyses were performed for several receptor points located down-wind from the city centre, in residential, dense traffic and industrial areas.
The results of the present work show that traffic emission rather than solvent use determines the ambient NMVOC composition. The maximum contribution of solvent use to the NMVOC emission estimated on the basis of experimentally obtained results amounts to about 23% in the whole area of Wuppertal. It can be concluded that the contribution of solvent use to the NMVOC concentrations also in other German cities falls in the range of few to about 20%, assuming that Wuppertal can be considered as a typical German urban area with certain proportions of domestic, traffic and various industrial activities. These results are in strong disagreement with the German Emission Inventory, which states, that in the reference year 2003 about 51% of the total NMVOC emissions originate from solvent use and only 14% from traffic.
Transforming growth factor-beta1 is related to adverse events in radiochemotherapy. We investigated TGFB1 genetic variability in relation to quality of life-impairing acute organ toxicity (QAOT) of ...neoadjuvant radiochemotherapy under clinical trial conditions.
Two independent patient cohorts (n = 88 and n = 75) diagnosed with International Union Against Cancer stage II/III rectal cancer received neoadjuvant radiation doses of 50.4 Gy combined with 5-fluorouracil-based chemotherapy. Toxicity was monitored according to Common Terminology Criteria for Adverse Events. QAOT was defined as a CTCAE grade ≥2 for at least one case of enteritis, proctitis, cystitis, or dermatitis. Nine germline polymorphisms covering the common genetic diversity in the TGFB1 gene were genotyped.
In both cohorts, all patients carrying the TGFB1 Pro25 variant experienced QAOT (positive predictive value of 100%, adjusted p = 0.0006). In a multivariate logistic regression model, gender, age, body mass index, type of chemotherapy, or disease state had no significant impact on QAOT.
The TGFB1 Pro25 variant could be a relevant marker for individual treatment stratification and carriers may benefit from adaptive clinical care or specific radiation techniques.
PHOEBE was conducted during the Berlin Ozone Experiment (BERLIOZ) between 5 July and 7 August 1998 near the city of Berlin. It aimed at a quantitative understanding of the fast radical chemistry in ...rural and suburban air by simultaneous measurements of the major free radicals (OH, HO2, RO2, and NO3) and the chemical compounds and physical parameters that control the radical concentrations. Interpretation of the measurements involved models of different complexity. The methods deployed and the results are discussed in the subsequent publications of this special section. This paper outlines the aims of PHOEBE, describes the observational site at Pabstthum, and briefly summarizes the different measurements and instrument comparisons as well as the main results of the accompanying publications.
Atmospheric transformation of monoterpenes gives products that may cause environmental consequences. In this work the NO3 radical-initiated oxidation of the monoterpenes α-pinene, β-pinene, ...Δ3-carene, and limonene has been investigated. All experiments were conducted in EUPHORE, the EUropean PHOto REactor facility in Valencia, Spain. The aerosol and product yields were measured in experiments with a conversion of the terpenes in the interval from 7 to 400 ppb. The lower end of the concentrations used are close to those measured in ambient pine forest air. Products were measured using long path in situ FTIR. Aerosol yields were obtained using a DMA-CPC system. The aerosol mass yields measured at low concentrations (10 ppb terpene reacted) were <1, 10, 15, and 17% for α-pinene, β-pinene, Δ3-carene, and limonene, respectively. The total molar alkylnitrate yields were calculated to be 19, 61, 66, and 48%, and molar carbonyl compound yields were estimated to be 71, 14, 29, and 69% for α-pinene, β-pinene, Δ3-carene, and limonene, respectively. The aerosol yields were strongly dependent on the amounts of terpene reacted, whereas the nitrate and carbonyl yields do not depend on the amount of terpene converted. The principal carbonyl compound from α-pinene oxidation was pinonaldehyde. In the case of limonene, endolim was tentatively identified and appears to be a major product. The reactions with β-pinene and Δ3-carene yielded 1−2% of nopinone and 2−3% caronaldehyde, respectively. The results show that it is not possible to use generalized descriptions of terpene chemistry, e.g. in matematical models.
A kinetic and product study was performed on the reaction of OH radicals with 1-butanol in a 480 L indoor photoreactor and also in the EUPHORE outdoor smog chamber in Valencia, Spain. Long path in ...situ FTIR spectroscopy and gas chromatography with photoionization detection were used to analyze reactants and products. Using a kinetic relative rate technique, a rate coefficient of k(OH + 1-butanol) = (8.28 ± 0.85) × 10-12 cm3 s-1 was measured in 740 Torr synthetic air at 298 ± 2 K. The reaction products observed and their fractional molar yields were (in percent) butanal (51.8 ± 7.1), propanal (23.4 ± 3.5), ethanal (12.7 ± 2.2), and formaldehyde (43.4 ± 2.4). In addition, the results support the probable formation of 4-hydroxy-2-butanone. Propanal, ethanal, and formaldehyde could also be formed in secondary reactions of some of the primary aldehydic products. However, under the conditions employed in the experiments, the contribution from secondary reactions is very minor. On the basis of the product studies, a detailed atmospheric degradation mechanism was constructed and tested against experimental data by chemical box model calculations. Measured and simulated concentration−time profiles for selected reactants were in excellent agreement.
Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, ...abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.
The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic ...particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.
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