Capecitabine/oxaliplatin before synchronous CRT and TME results in substantial tumor regression, rapid symptomatic response, and achievement of R0 resection.

1. Climate change is affecting species distributions and will increasingly do so. However, current understanding of which individuals and species are most likely to survive and why is poor. Knowledge of assemblage or community level effects is limited and the balance of mechanisms that are important over different time-scales is poorly described. Laboratory experiments on marine animals predominantly employ rates of change 10-100 000 times faster than climate induced oceanic warming. To address this failure we investigated differences in individual and species abilities to tolerate warming, and also how rate of warming affected survival. 2. This study identifies community level effects of thermal biology by applying a multi-species, multi-trophic level approach to the analysis of temperature limits. 3. Within species analyses of 14 species from 6 phyla showed smaller individuals survived to higher temperatures than large animals when temperatures were raised acutely. If this trend continues at slower warming rates, the early loss of larger individuals has marked consequences at the population level as larger individuals form the major reproductive component. 4. Between species comparisons showed active species survived to higher temperatures than sessile or low activity groups. Thus active groups (e.g. predators) and juvenile or immature individuals should fare better in rapid warming scenarios. This would be expected to produce short-term ecological imbalances in warming events. 5. The rate of warming markedly affected temperature limits in a wide range of Antarctic marine species. Different species survived to temperatures of 8•3-17•6 ° C when temperatures were raised by around 1 ° C day − 1 . However they only survived to temperatures between 4•0 ° C and 12•3 ° C when temperatures were raised by around 1-2 ° C week − 1 , and temperatures of only 1•0-6•0 ° C were tolerated for acclimations over periods of months. 6. Current models predicting range changes of species in response to climate change are either correlative or mechanistic. Mechanistic models offer the potential to incorporate the ecophysiological adaptation and evolutionary processes which determine future responses and go beyond simple correlative approaches. These models depend on the incorporation of data on species capacities to resist and adapt to change. This study is an important step in the provision of such data from experimental manipulations.

Summary 1.Climate change is affecting species distributions and will increasingly do so. However, current understanding of which individuals and species are most likely to survive and why is poor. Knowledge of assemblage or community level effects is limited and the balance of mechanisms that are important over different time-scales is poorly described. Laboratory experiments on marine animals predominantly employ rates of change 10-100 000 times faster than climate induced oceanic warming. To address this failure we investigated differences in individual and species abilities to tolerate warming, and also how rate of warming affected survival. 2. This study identifies community level effects of thermal biology by applying a multi-species, multi-trophic level approach to the analysis of temperature limits. 3. Within species analyses of 14 species from 6 phyla showed smaller individuals survived to higher temperatures than large animals when temperatures were raised acutely. If this trend continues at slower warming rates, the early loss of larger individuals has marked consequences at the population level as larger individuals form the major reproductive component. 4. Between species comparisons showed active species survived to higher temperatures than sessile or low activity groups. Thus active groups (e.g. predators) and juvenile or immature individuals should fare better in rapid warming scenarios. This would be expected to produce short-term ecological imbalances in warming events. 5. The rate of warming markedly affected temperature limits in a wide range of Antarctic marine species. Different species survived to temperatures of 8·3-17·6 ° C when temperatures were raised by around 1 ° C day − 1 . However they only survived to temperatures between 4·0 ° C and 12·3 ° C when temperatures were raised by around 1-2 ° C week − 1 , and temperatures of only 1·0-6·0 ° C were tolerated for acclimations over periods of months. 6. Current models predicting range changes of species in response to climate change are either correlative or mechanistic. Mechanistic models offer the potential to incorporate the ecophysiological adaptation and evolutionary processes which determine future responses and go beyond simple correlative approaches. These models depend on the incorporation of data on species capacities to resist and adapt to change. This study is an important step in the provision of such data from experimental manipulations.

No abstract

In a multivariate analysis of 154 patients receiving chemotherapy, baseline CA19-9 was an independent prognostic factor for overall survival (OS) (HR 1.8; 95% CI: 1.3 -2.5, P ¼ 0.0004). The 1-year OS was 19 and 46%, respectively, for patients with a baseline CA19-9 above or below the median value. A fall of 20% in CA19-9 level from baseline was an independent prognostic factor for OS (HR 1.9; 95% CI: 1.1 -3.4, P ¼ 0.019).

PVI 5-FU + MMC results in failure-free survival and response advantage, tolerable toxicity and better QL when compared to PVI 5-FU alone but no overall survival advantage. There is no irreversible toxicity with MMC at a cumulative dose of 28 mg/m2.

No abstract

This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n ¼ 30, CT alone n ¼ 6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m À2 day À1 for 12 weeks) with mitomycin C (MMC) (7 mg m À2 i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m À2 day À1 and concomitant pelvic radiotherapy 45 Gy in 25 fractions was commenced followed by 5.4 -9 Gy boost to tumour bed. Surgery was planned 6 weeks after chemoradiation. Postoperatively, patients received 12 weeks of MMC and 5-FU at the same preoperative doses. Between January 99 and August 01, 36 eligible patients were recruited. Median age was 63 years (range ¼ 40 -85). Following neoadjuvant chemotherapy, radiological tumour response was 27.8% (one CR and nine PRs) and no patient had progressive disease. In addition, 65% of patients had a symptomatic response including improvement in diarrhoea/constipation (59%), reduced rectal bleeding (60%) and diminished pelvic pain/tenesmus (78%). Following chemoradiation, tumour regression occurred in 80.6% (six CRs and 23 PRs; 95% CI ¼ 64 -91.8%) and only one patient still had an inoperable tumour. R0 resection was achieved in 28 patients (82%). When compared with initial clinical staging, the pathological downstaging rate in T and/or N stage was 73.5% and pathological CR was found in one patient. Neoadjuvant systemic chemotherapy as a prelude to synchronous chemoradiation can be administered with negligible risk of disease progression and produces considerable symptomatic response with associated tumour regression.