Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia.

Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published cases. Tissue ELISA with Adnab-9 antibody, a putative colorectal cancer risk marker, from a patient with ZES and from seven patients with acromegaly was compared to 13 controls at average risk for colorectal neoplasia. The patient with ZES without detectable colonic neoplasia and seven patients with acromegaly had increased binding of Adnab-9 in the colonic mucosa by ELISA. The difference was significant for the acromegaly patients compared to the controls (p < 0.05). The accumulated 34 instances of colorectal neoplasia in ZES patients suggests that this association may not be rare. Adnab-9 expression, detectable in both ZES and acromegaly, may reflect predisposition to colorectal neoplasia in both hyper-secretory states. Therefore, while a basis for association of colorectal neoplasia and hypergastrinemia exists, the clinical data are not compelling enough to warrant surveillance of patients with ZES. To resolve this problem, more definitive case control studies should be conducted.

Effects of fructose-1,6-diphosphate on the activity of rat liver nitric oxide synthase in vitro.

Fructose-1,6-diphosphate (FDP) was found to cause significant stimulation of nitric oxide synthase (NOS) in rat liver homogenates in vitro. This effect was more pronounced for the inducible isoform than its constitutive counterpart. Furthermore, FDP restored rat liver inducible NOS levels following their depletion by carbon tetrachloride (CCl4). This finding may have further practical implications in hepatoprotection from various noxious chemical and biological agents.

Serum gastrin levels in patients with colorectal cancer and adenomatous polyps: a prospective study.

Serum gastrin levels were measured by radioimmunoassay in 62 patients with colorectal neoplasms (40 with adenomatous polyps and 22 with cancer) and 40 controls. Fasting serum gastrin in both the polyp (73.93 +/- 6.5 pg/ml) and the cancer (99 +/- 19.7 pg/ml) groups was significantly higher than those of the control group (42.65 +/- 2.2 pg/ml). These findings suggest that hypergastrinemia may be an etiologic factor in colorectal neoplasia.

Warfarin and reduced central venous thrombosis in home total parenteral nutrition patients.

Central venous thrombosis is a potentially life-threatening complication in patients on long-term home total parenteral nutrition (HTPN). Lack of venous access due to recurrent thromboses can prevent delivery of life-saving nutritional support. The long-term anticoagulation management to prevent thromboses in patients with central venous catheters for HTPN has not been well established. We have reviewed the role of warfarin in reducing the incidence of thromboses and its safety in our HTPN patients. Ninety consecutive HTPN patients were studied retrospectively. Twenty-two thromboses occurred during 1312 patient-mo in 53 HTPN patients on minidose warfarin. A minidose of warfarin is defined as 1-2 mg and does not prolong the prothrombin time. Seven thromboses occurred over 619 mo in 18 patients on a therapeutic dose of warfarin (minidose compared to therapeutic dose, p > 0.05). A therapeutic dose of warfarin is a dose that increases the prothrombin time to 1.2-1.5 times that of control. Twelve patients who had 18 thromboses in 323 patient-mo while on minidose warfarin were subsequently converted to therapeutic warfarin. The incidence of thromboses decreased to 2 in 369 patient-mo (p < 0.005). There were no hemorrhagic complications in the minidose warfarin group and four nonfatal hemorrhagic complications in the therapeutic dose warfarin group (p > 0.05). A therapeutic dose of warfarin is effective in reducing the incidence of thromboses in patients who experience central venous thrombosis despite minidose warfarin with a minimal increase in hemorrhagic complications.

Rapid clinical assessment of kidney function based on arm muscle circumference and serum creatinine.

A midarm muscle circumference (AMC) < 10th percentile indicates severe protein-energy malnutrition. We identified 20 consecutive patients receiving specialized nutritional therapy from the Nutrition Support Service of the New England Deaconess Hospital during a 3-mo period who had AMC < 10th percentile and 24-h urine and serum creatinine determinations performed. Mean weight was 96 +/- 25% of ideal body weight (IBW), with only 7 patients < 85% IBW, reaffirming that weight is often insensitive for the identification of lean tissue loss. Twenty-four-hour urine creatinine excretion confirmed most to be severely lean body mass depleted (creatinine-height index < 60% in 17 subjects) as predicted by AMC. Sixteen patients had normal kidney function as assessed by serum creatinine levels and hospital norms (0.3-1.2 mg/dl). However, abnormal creatinine clearances were found in 15 of 20 subjects (normal 80-100 ml/min), with a mean value (53 +/- 23 ml/min) also below normal. These results suggest that the usual normal range for serum creatinine, based on well-nourished patients, should be adjusted in severely malnourished patients. Considering the upper limit of normal serum creatinine in this population to be 0.7 mg/dl, to reflect the approximately 60% reduction in lean tissue indicated by an AMC < or = 10th percentile, would identify all but 1 patient with an abnormal creatinine clearance (sensitivity 93%, specificity 67%). Use of a predictive formula (the Cockcroft-Gault equation) also identified those with kidney dysfunction but overestimated actual function to a level not usually requiring drug dose adjustment and did not obviate the need for further testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimal design of clinical outcome studies in nutrition and cancer: future directions.

Many studies have assessed the benefits of nutrition support in cancer patients. Except for studies directed at the treatment of severe malnutrition, most clinical trials have failed. Although prospective randomized controlled clinical trials (Phase III) remain the most reliable means of evaluating the efficacy of therapy, the available literature reports only results from small trials (Phase II to III), most of which appear to be contradictory and none of which conclusively answer the question being considered. To address this gap in knowledge, tools such as meta-analysis have been adapted from the field of statistics. Meta-analysis involves pooling results across several studies and provides a more precise estimate of treatment effect than can each individual study. However, clinical trials selected for meta-analysis, although broadly similar, can differ significantly in terms of therapies used and clinical populations studied. Major cancer types with differing effects on food intake and malnutrition (eg, the mechanical obstruction in head and neck cancer vs the cytokine-induced metastases associated with lung, ovarian, colon, and breast cancer) cannot be subject to the same analytic criteria. In this paper, the current state of clinical outcome trials in nutrition and cancer is examined, and the desired design for future studies is proposed. Research priorities include the conduct of Phase II clinical trials that use as outcome measures quality of life, performance status, and survival to identify optimal cancer-specific and patient-specific nutrition support. The next round of Phase III efficacy studies should establish the appropriate use of nutrition support in cancer therapy.