Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial.

BACKGROUND: Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery. METHODS: ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m2 on days 1, 8, and 15, and oral capecitabine 830 mg/m2 twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, folinic acid given according to local practice, and fluorouracil 400 mg/m2 bolus injection on days 1 and 15 followed by 2400 mg/m2 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m2 twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete. FINDINGS: Between Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0-12·4). 1-year overall survival was 39% (95% CI 24-61) for immediate surgery, 78% (60-100) for gemcitabine plus capecitabine, 84% (70-100) for FOLFIRINOX, and 60% (37-97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19-58) for immediate surgery and 59% (46-74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28-0·98], p=0·016). Three patients reported local disease recurrence (two in the immediate surgery group and one in the FOLFIRINOX group). 78 (91%) patients were included in the safety set and assessed for toxicity events. 19 (24%) of 78 patients reported a grade 3 or worse adverse event (two [7%] of 28 patients in the immediate surgery group and 17 [34%] of 50 patients in the neoadjuvant therapy groups combined), the most common of which were neutropenia, infection, and hyperglycaemia. INTERPRETATION: Recruitment was challenging. There was no significant difference in resection rates between patients who underwent immediate surgery and those who underwent neoadjuvant therapy. Short-course (8 week) neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Neoadjuvant chemotherapy with either gemcitabine plus capecitabine or FOLFIRINOX had the best survival compared with immediate surgery. These findings support the use of short-course neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma. FUNDING: Cancer Research UK

Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals

Postpartum psychiatric disorders

Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential

Characteristics of chromium oxides supported on TiO2 and Al2O3 for the decomposition of perchloroethylene

The effects of supports including TiO2 and Al2O3 on the molecular structure and catalytic activity of chromium oxide for the complete oxidation of perchloroethylene (PCE) have been examined with respect to the content of Cr on the catalyst surface. The results from XRD, XPS, Raman, and TPR-TPO indicate that the state of the surface species of chromium oxide strongly depends on catalyst support and Cr loading. The amount of Cr(VI) in the high oxidation state on the surface of the catalyst increased as the content of Cr increased from I to 17 wt%. while the relative ratio of Cr(VI)/Cr(III) existing on the catalyst surface decreased with respect to the Cr loading, regardless of the supports examined in the present study. The molecular structure of Cr(VI) was also altered with respect to the content of Cr and the surface nature of support. Monochromate species appeared on the surface of Al2O3 at 1 wt% of Cr loading on the catalyst surface. However, further increase in the Cr contents up to 17 wt% formed di-, tri-, and tetrachromate species of Cr(VI) and crystalline alpha-Cr2O3 on the surface of Al2O3. CrOx/TiO2 catalyst formed polymeric chromium oxide species on its surface in the wide range of Cr content of the catalyst from I to 17.4 wt%. The high degree of polymerization of chromate species on the surface of TiO2 containing the strong redox ability is contrasted with the state of the chromate species on Al2O3. The rate of PCE oxidation was enhanced as the Cr loading increased for both catalysts. CrOx/TiO2 catalyst revealed a relatively higher reaction rate than CrOx/Al2O3 at the given content of Cr and its surface density. TOF of the catalyst increased along with the degree of polymerization of the chromate species on the catalyst surface. The superior performance of CrOx/TiO2 catalyst is attributed mainly to the formation of the polychromate species containing a stronger redox ability on the surface of TiO2. This clearly suggests that the metal-oxygen-support interaction (MOSI) is critical in the present catalytic reaction system. (C) 2003 Elsevier Inc. All rights reserved.X1174sciescopu

Deactivation of chromium oxide catalyst for the removal of perchloroethylene (PCE)

The effect of a wide range of feed concentration of PCE from 3 0 to 10,000 ppm on the stability of chromium oxide supported on TiO2 and Al2O3 for the removal of chlorinated volatile organic compounds (CVOCs) has been investigated over a fixed bed flow reactor. Both chromium oxide catalysts exhibited stable PCE removal activity up to 100 h of reaction time without any catalyst deactivation when 30 ppm was introduced into the reactor. However, the high concentrations of PCE from 1,000 to 10,000 ppm, significantly deactivated the catalyst, regardless of the support. The deactivation of chromium oxide catalyst was neither caused by the evaporation of chromium from the catalyst surface nor the reduction of surface area by coking which is the most suspicious deactivation mechanism in the present reaction system. It was mainly due to the phase transformation from Cr(VI), active reaction sites on the catalyst surface, to Cr(III). The phase transformation of Cr(VI) to Cr(III) is probably attributed to the relatively slow rate of re-oxidation step of Cr(III) compared to the lattice oxygen consumption step during the reaction at a high feed concentration of PCE. Although some of Cr on the catalyst surface evaporated, it was insignificant in reducing PCE removal activity of the catalyst.X115sciescopu

A pilot plant study for catalytic decomposition of PCDDs/PCDFs over supported chromium oxide catalysts

Chromium oxide catalysts supported on TiO2 and A1(2)O(3) were examined in a fixed-bed flow reactor system for the removal of PCE (perchloroethylene), a simulant of 2,3,7,8-TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), and in a pilot plant employing actual flue gas from a sintering plant for the removal of PCDDs/PCDFs (poly-chlorinated dibenzo-dioxin/poly-chlorinated dibenzo-furan). The 12.5 wt.% chromium oxides supported on TiO2 and Al2O3 revealed excellent stability and performance of PCE removal in the feed gas stream containing water vapor. In a pilot plant study, the catalysts washcoated on the honeycomb reactor revealed 93-95% of PCDDs/PCDFs removal activity over CrOx/Al2O3-HC20 (CrOX/Al2O3 catalyst washcoated on 20 cell-honeycomb), and more than 99% of the decomposition activity over CrOx/Tio(2)-HC20 (CrOx/TiO2 catalyst washcoated on 20 cell-honeycomb) at 325 C and 5000 h(-1) of reactor space velocity without the de novo synthesis of PCDDs/PCDFs. In particular, CrOx/TiO2-HC20 showed 94% of PCDDs/PCDFs decomposition activity even at 280degreesC reaction temperature. The catalyst also exhibited significant NO removal activity. The chromium oxide seems to be a promising catalyst for the removal of PCDDs/PCDFs and NOx contained in the flue gas. (C) 2002 Elsevier Science B.V. All rights reserved.X1125sciescopu

Effect of the catalyst supports on the removal of perchloroethylene (PCE) over chromium oxide catalysts

The oxidation of perchloroethylene (PCE) was investigated over chromium oxide catalysts supported on TiO2, Al2O3, SiO2, SiO2-Al2O3 and activated carbon. The phase of chromium oxide on the catalyst surface is critical for the oxidation of PCE. The catalytic activity of PCE removal enhances as the formation of Cr(VI) species on the catalyst surface increases. The surface area and the type of the catalyst supports were also essential for high performance in the PCE oxidation. In addition, the structure of Cr(VI) on the catalyst surface also plays an important role for the decomposition of PCE. The polymerized Cr(VI) mainly formed by the interaction of metals with the support is the active reaction site for the present reaction system. CrOx/TiO2 reveals the strongest PCE removal activity among the catalysts examined in the present study.X1114sciescopu

Catalytic removal of perchloroethylene (PCE) over supported chromium oxide catalysts

The oxidation of perchloroethylene (PCE) was investigated over chromium oxide catalysts supported on SiO2 SiO2-Al2O3, activated carbon, mordenite type zeolites, MgO, TiO2 and Al2O3. Supported chromium oxide catalysts were more active than any other metal oxide catalysts including noble metal examined in the present study. PCE removal activity of chromium oxide catalysts mainly depended on the type of supports and the content of metal loaded on the catalyst surface. TiO2 and Al2O3 containing high surface areas were effective for the high performance of PCE removal, since the formation of well dispersed Cr(VI) active reaction sites for the present reaction system, was enhanced even for the high Cr loading on the catalyst surface. CrOx catalysts supported on TiO2 and Al2O3 also exhibited stable PCE removal activity at a low feed concentration of PCE of 30 ppm up to 100 h at 350 degreesC. However, significant catalyst deactivation was observed at high PCE concentration of 10 000 ppm. CrOx /TiO2 revealed stronger water tolerance than CrOx/Al2O3 due to the surface hydrophobicity. (C) 2000 Elsevier Science B.V. All rights reserved.X1126sciescopu