Faculty Bibliography

The role of human growth hormone (hGH) as a nutritional adjunct for cancer patients is controversial because of its potential mitogenic effects on tumor growth. No studies to date have examined the effect of hGH on human tumor response in vivo. In Vitro: Athymic mice were injected (s.c.) daily with hGH (GH, n=14) or saline (CTL, n=14). On Day 10, serum was collected and added to human pancreatic carcinoma cells in culture. In Vivo: Athymic mice were inoculated (s.c.) with human pancreatic carcinoma cells. On Day 14, mice were randomized to receive daily either hGH (GH, n=14) or saline (CTL, n=12). On Day 29, animals received [3H]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics analyzed. Data are expressed as mean +/- SEM. Statistical analysis was performed by unpaired t test and/or ANOVA where appropriate. In Vitro: Serum from GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Serum for GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Growth hormone had no significant effect on tumor growth rate (mm3/day) (1.45 +/- 0.47 CTL vs 1.57 +/- 0.66 GH), final tumor weight (mg) (0.19 +/- 0.15 CTL vs 0.17+/- 0.06 GH), DNA Index (1.5 +/- 0.1 CTL vs 1.5 +/- 0.1 GH), percent S phase (20.3 +/- 3.3 CTL vs 22.1 +/- 3.0 GH), or tumor FSR (%/day) (51.1 +/- 17.8 CTL vs 70.2 +/- 61.1 GH). Growth hormone significantly elevated serum IGF-1 levels (ng/ml) (176 +/- 48 CTL vs 222 +/- 53 GH, P<0.005) and liver FSR (%/day) (62.8 +/- 17.8 CTL vs 79.7 +/- 12.7 GH, P<0.005). Serum of GH-treated mice increased human pancreatic cell growth in vitro. In vivo, GH administration raised serum IGF-1 levels and increased liver protein FSR, without tumor growth, cell cycle kinetics, or protein FSR

BACKGROUND: Cancer cachexia is a significant cause of postoperative morbidity and mortality in patients with tumors of the upper gastrointestinal tract. Standard parenteral nutrition (TPN) has failed to alter this. The anabolic effect of insulin has been well documented, and its positive effect on protein economy in cancer patients has been recently demonstrated. This study examines the effect of high-dose insulin and parenteral nutrition on protein kinetics in postoperative cancer patients. METHODS: Eleven patients underwent surgery for pancreatic, esophageal, or gastric carcinoma. Postoperatively, patients received standard TPN for 4 days (1 g/kg/day amino acids, 1,000 kcal/day dextrose, 100 g/day lipid), and hyperinsulinemic parenteral nutrition for 4 days (same as standard TPN plus 1.44 U/kg/day regular human insulin) in a crossover design. All patients received both treatments, and the order of treatment was determined randomly. Euglycemia was maintained during insulin infusion via a variable 30% dextrose infusion. Patients underwent protein metabolic studies after each treatment period and rates of whole body and skeletal muscle protein synthesis, breakdown, and net balance were determined by radioisotopic tracer methods using 14C-leucine and 3H-phenylalanine. RESULTS: Compared with standard TPN (STD), hyperinsulinemic TPN (INS) resulted in a significant increase in skeletal muscle protein synthesis (INS: 52.04 +/- 10.22 versus STD: 26.06 +/- 6.71 nmol phe/100 g/min, p < 0.05) and net balance of protein (INS: 7.75 +/- 4.61 versus STD: -15.10 +/- 6.44 nmol phe/100 g/min, p < 0.01), but no difference in skeletal muscle protein breakdown (INS: 44.29 +/- 11.54 versus STD: 41.17 +/- 5.89 nmol phe/100 g/min). Whole-body net balance of protein also significantly increased with insulin-based TPN, compared with standard TPN (INS: 0.04 +/- 0.05 versus STD: -0.08 +/- 0.07 mumol leu/kg/min, p < 0.05), but no difference in whole-body protein synthesis (INS: 2.52 +/- 0.15 versus STD: 2.49 +/- 0.15 mumol leu/kg/min) or whole-body protein breakdown (INS: 2.48 +/- 0.16 versus STD: 2.58 +/- 0.19 mumol leu/kg/min) was observed. Patients received significantly more calories during the hyperinsulinemic TPN period than during the standard TPN period. There was no difference in total, essential, or branched-chain amino acids, and no difference in serum free fatty acids, triglycerides, or cholesterol was observed between the two treatment periods. CONCLUSION: High-dose insulin in conjunction with hypercaloric parenteral nutrition causes improved skeletal muscle protein synthesis, skeletal muscle protein net balance, and whole-body protein net balance compared with standard TPN in postoperative cancer patients

Late infection of devitalized pancreatic and peripancreatic tissue has become the major cause of morbidity in severe acute pancreatitis. Previous experience found that peritoneal lavage for periods of 48 to 96 hours may reduce early systemic complications but did not decrease late pancreatic sepsis. A fortunate observation led to the present study of the influence of a longer period of lavage on late sepsis. Twenty-nine patients receiving primary nonoperative treatment for severe acute pancreatitis (three or more positive prognostic signs) were randomly assigned to short peritoneal lavage (SPL) for 2 days (15 patients) or to long peritoneal lavage (LPL) for 7 days (14 patients). Positive prognostic signs averaged 5 in both groups but the frequency of five or more signs was higher in LPL (71%) than in SPL (47%). Eleven patients in each group had early computed tomographic (CT) scans. Peripancreatic fluid collections were shown more commonly in LPL (82%) than in SPL (54%) patients. Longer lavage dramatically reduced the frequency of both pancreatic sepsis (22% LPL versus 40% SPL) and death from sepsis (0% LPL versus 20% SPL). Among patients with fluid collections on early CT scan, LPL led to a more marked reduction in both pancreatic sepsis (33% LPL versus 83% SPL) and death from sepsis (0% LPL versus 33% SPL). The differences were even more striking among 17 patients with five or more positive prognostic signs. In this group the incidence of pancreatic sepsis was 30% LPL versus 57% SPL and of death from sepsis 0% (LPL) versus 43% (SPL) (p = 0.05). In these patients, overall mortality was also reduced (20% LPL versus 43% SPL). When 20 patients treated by LPL were compared with 91 other patients with three or more positive prognostic signs who were treated without lavage or by lavage for periods of 2 to 4 days, the frequency of death from pancreatic sepsis was reduced from 13% to 5%. In those with five or more signs, the incidence of sepsis was reduced from 40% to 27% (p = 0.03) and of death for sepsis from 30% to 7% (p = 0.08). These findings indicate that lavage of the peritoneal cavity for 7 days may significantly reduce both the frequency and mortality rate of pancreatic sepsis in severe acute pancreatitis

The sensitivities and specificities of the mean cell volume (MCV), the red cell distribution width (RDW), and blood smear hypersegmentation for B12 deficiency were reviewed in 515 patients whose B12 levels were determined. 61 patients had B12 levels less than 200 pg/ml. 43 patients were defined as B12 deficient (n = 13) or non-B12 deficient (n = 30). Hypersegmentation was more sensitive (91%) than MCV greater than 95 fl (62%) or RDW greater than 15% (54%) in detecting B12 deficiency. The MCV and the RDW should not be relied on when screening for B12 deficiency; examination of the blood smear for hypersegmentation is essential