Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO) RAPIDO collaborative investigators; Bahadoer

Recent studies have claimed that interleukin 1-containing preparations increase skeletal protein degradation similar to that seen during infection and inflammation. However, preparations employed have contained other products of activated macrophages, including tumor necrosis factor-alpha. In the present report, we investigated the capability of recombinant-derived murine and human interleukins 1-alpha and 1-beta and human tumor necrosis factor-alpha to affect skeletal protein synthesis and degradation both in vitro and in vivo. Partially purified products of Staphylococcus albus-stimulated human blood monocytes increased skeletal protein degradation both in vivo and in vitro. However, none of the recombinant interleukin 1 nor the human tumor necrosis factor-alpha preparations had any impact on skeletal protein balance. Both recombinant interleukin 1 and tumor necrosis factor-alpha stimulated the production of prostaglandin E2 (PGE2). Furthermore, a polyclonal antibody to human interleukin 1 eliminated the lymphoproliferative response to partially purified monocyte preparations (interleukin 1 activity), but failed to abrogate the increased skeletal protein degradation in vitro. This study demonstrates that although interleukin 1 and tumor necrosis factor-alpha induce a PGE2 response by skeletal muscle in vitro, some macrophage product distinct from either interleukin 1 or tumor necrosis factor-alpha is responsible for the accelerated skeletal protein degradation seen with partially purified human blood monocyte products. Elevated PGE2 levels do not appear to regulate skeletal protein balance in vitro.

The incidence, the median time to first appearance, and the clinical pattern of pouchitis were prospectively studied in 180 patients operated on for ulcerative proctocolitis with a continent ileostomy (CI; 84 patients) and a pelvic pouch (PP; 96 patients). Median follow-up for CI patients was 8.5 years (range, 2-15 years) and for PP patients, 5 years (range, 1-8 years). Pouchitis, with symptoms severe enough to require treatment, developed in 33% (28 of 84) of CI and 47% (45 of 96) of PP patients. The cumulative risk of developing one or more episodes of pouchitis over a 5-year follow-up was 34% in CI patients and 51% in PP patients. The median time to first appearance of pouchitis was 5 and 12 months, respectively. Eighty-six per cent of CI patients with pouchitis (24 of 28) and 71% of PP patients (32 of 45) experienced their initial episode within the first 2 years. Sixty-four per cent (18 of 28) of the CI patients and 76% (34 of 45) of PP patients had one single or a few short-lasting episodes of pouchitis with various symptom-free intervals, whereas 18% of patients in each group (5 of 28 CI patients, 8 of 45 PP patients) had frequent relapses. Most of these patients responded promptly to metronidazole treatment. Eighteen per cent (5 of 28) of CI patients and 6% (3 of 45) of PP patients had long-lasting episodes with a poor response to treatment. In this long-term study the pouch inflammation proved eventually to be Crohn's disease in four patients (2.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.