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Colorectal cancer is the second most common cause of death from cancer in the UK. It is estimated that between 2 to 3 per cent of colorectal cancer occurs in patients younger than the age of 40 years. It remains unclear from the literature whether this group of patients has a worse prognosis from colorectal cancer than the population as a whole. There are no large series that report a 10-year survival in young patients diagnosed with colorectal cancer. The authors’ objective was to assess patients diagnosed with colorectal cancer younger than the age of 40 years to determine whether the 5- and 10-year survival rates in a tertiary referral center compares favorably with survival rates obtained at other centers and the population as a whole. A retrospective observational study was conducted and an analysis of the patient's notes was made, specifically looking at age at diagnosis, nature and duration of symptoms, predisposing risk factors for colorectal cancer, the site within the bowel of the colorectal cancer, the type of curative resection performed, Dukes’ stage, and details of 5- and 10-year follow-up to assess survival. Forty-nine patients age 40 years or younger received treatment for colorectal cancer at St. Mark's Hospital from 1982 to 1992. The overall 5- and 10-year survival was 58 per cent and 46 per cent respectively. The study provides more evidence to support the fact that young patients with colorectal cancer seem to present with more advanced disease. Despite this, the overall 5-year relative survival rate is comparable if not better than other studies, supporting recent evidence that the prognosis in this group of patients is no worse than for colorectal cancer in the population as a whole.

OBJECTIVE: To ascertain the effect of delayed tumor necrosis factor α (TNF-α) on the evolution of systemic and pulmonary injury after the onset of sepsis. DESIGN: Prospective controlled trial. INTERVENTION: Anesthetized swine were made septic with a 1-hour infusion of live Pseudomonas aeruginosa, following which a treatment group received an infusion of anti—TNF-α monoclonal antibody (5mg/kg). Control animals received 0.9% saline. RESULTS: Delayed anti—TNF-α treatment had no effect on septic pulmonary hypertension or decline in cardiac output. Late recovery in systemic arterial hypotension was associated with a reversal of arterial acidosis (P<.05 by τ test and analysis of variance with Tukey's Studentized Range Test) compared with unprotected septic animals. Septic animals had a significant increase in mean (±SEM) plasma lactate levels at 5 hours compared with baseline values (3.8±0.7 vs 2±0.4, P<.05), but remained unchanged from baseline following anti—TNF-α treatment (1.5±0.1 vs 1.6±0.2, not significant). Characteristic septic neutropenia was dramatically reversed by anti—TNF-α treatment and was associated with downregulation (P<.05 by τ test and analysis of variance) of polymorphonuclear neutrophil (PMN) leukocyte CD18 adhesion receptors and reduction (P<.05 by τ test and analysis of variance) in lung PMN sequestration measured by myeloperoxidase activity. The mean (±SEM) decrease in bronchoalveolar lavage protein indicated an attenuated permeability injury in anti—TNF-α animals (septic animals at 5 hours compared with baseline value, 1044 ±270 vs 149 ±28 μg/mL; control animals at 5 hours compared with baseline value, 217±83 vs 129±19 μg/mL; P<.05 by τ test and analysis of variance). CONCLUSIONS: These data show that delayed anti—TNF-α treatment reversed metabolic acidosis associated with sepsis. Furthermore, anti—TNF-α treatment reversed septic neutropenia, reduced PMN sequestration, and was associated with attenuated lung injury in a model of fulminant sepsis. This supports evidence of PMN-mediated tissue injury in sepsis and suggests mechanisms for potential therapeutic benefit of anti—TNF-α treatment in clinical practice.(Arch Surg. 1994;129:80-89)

A substantial increase in pulmonary vascular resistance is associated with sepsis and its sequelae (sepsis syndrome and septic shock). It is postulated that increased resistance may result from sepsis-induced endothelial cell injury or altered vasoreactivity secondary to pulmonary hypertension. We, therefore, tested the hypothesis that sepsis causes endothelial cell injury and that increased pulmonary pressure alters vascular reactivity. Young swine (15–25 kg) were anesthetized and ventilated. Septic animals received a 1-hr infusion of livePseudomonas aeruginosa(n= 11), and the control cohort received 0.9% NaCl (n= 7). All animals were studied for 300 min following the infusion. Postmortem branches of peripheral pulmonary arteries were prepared and tested in a vessel myograph. Ring segments were set to 90% of the circumference the vessels would have at pressures of 20, 30, 40, or 50 mmHg (L90), corresponding to varying pulmonary pressures observed in sepsis. A high dose of potassium was used to obtain maximum possible contraction. Prostaglandin was used to precontract the vessels before testing endothelial cell responses to acetylcholine or bradykinin. Sodium nitroprusside was added at the end of each experiment to obtain maximum possible smooth muscle relaxation. No differences in contraction or relaxation were observed when vessels were set to different pressures (i.e., 20 vs 50 mmHg). Maximum possible contraction to KCl was significantly decreased after 300 min of sepsis compared to control. No differences between groups were found in contractility to prostaglandin. Bradykinin-induced EDRF/NO production, mediated by BK2receptors, was not altered inPseudomonassepsis (97–98% of total relaxation control and 91–95% septic cohort). Response to acetylcholine was significantly decreased after sepsis (89–95% of total relaxation control and 51–61% of septic cohort relaxation). Decreased response to acetylcholine could not be attributed to decreased smooth muscle sensitivity to nitric oxide because the response to bradykinin plus sodium nitroprusside was not altered following sepsis. Vessel reactivity was not altered by increasing pressure settings reflective of changing pulmonary pressurein vivo.These results strongly suggest a sepsis-induced alteration in pulmonary artery endothelial cell receptor sensitivity to acetylcholine, independent of changing pulmonary arterial pressures. This is the first time this decrease has been shown in pseudomonas sepsis.