Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery.

BACKGROUND: Major surgery is associated with postoperative insulin resistance which is attenuated by preoperative carbohydrate (CHO) treatment. The effect of this treatment on clinical outcome after major abdominal surgery has not been assessed in a double-blind randomized trial. METHODS: Patients undergoing elective colorectal surgery or liver resection were randomized to oral CHO or placebo drinks to be taken on the evening before surgery and 2 h before induction of anaesthesia. Primary outcomes were postoperative length of hospital stay and fatigue measured by visual analogue scale. RESULTS: Sixty-nine and 73 patients were evaluated in the CHO and placebo groups respectively. The groups were well matched with respect to surgical procedure, epidural analgesia, laparoscopic procedures, fasting period before induction and duration of surgery. Postoperative changes in fatigue score from baseline did not differ between the groups. Median (range) hospital stay was 7 (2-35) days in the CHO group and 8 (2-92) days in the placebo group (P = 0.344). For patients not receiving epidural blockade or laparoscopic surgery (20 CHO, 19 placebo), values were 7 (3-11) and 9 (2-48) days respectively (P = 0.054). CONCLUSION: Preoperative CHO treatment did not improve postoperative fatigue or length of hospital stay after major abdominal surgery. A benefit is not ruled out when epidural blockade or laparoscopic procedures are not used. REGISTRATION NUMBER: ACTRN012605000456651 (http://www.anzctr.org.au).

Nonsteroidal anti-inflammatory drug-induced strictures of the colon: report of a case and review of the literature.

The phenomenon of strictures of the colon induced by nonsteroidal anti-inflammatory drugs is a newly recognized pathologic entity that has gained little exposure in the surgical literature to date. A further case is reported and the clinical features of this entity are discussed. Most patients present with symptoms suggestive of malignancy, namely anemia, obstructive symptoms, or weight loss. Pathologic changes are characterized by diaphragm-like strictures with submucosal fibrosis. Surgical resection to exclude malignancy and treat symptoms along with cessation of the nonsteroidal anti-inflammatory drug is the treatment of choice.

Eosinophilic cholangitis: a case of 'malignant masquerade'.

BACKGROUND: A variety of causes of inflammatory bile duct stricture can masquerade as hilar cholangiocarcinoma. Eosinophilic cholangitis is a further example. CASE OUTLINE: A 50-year-old woman with epigastric pain and deranged liver function was found to have a stricture of the common hepatic duct on ERCP with an associated mass on MRl.The lesion was excised with reconstruction of the right and left hepatic ducts, and the patient recovered well. Histopathological examination of the resected gallbladder and bile duct showed diffuse inflammation with a predominant eosinophil infiltrate.The presence of Candida albicans in the bile duct lumen can probably be attributed to the preoperative biliary stent.There was a modest postoperative rise in peripheral eosinophil count. DISCUSSION: A literature search reveals only six previous cases of eosinophilic cholangitis, but similar infiltrates have also been seen in occasional cholecystectomy specimens. As the present patient did not have gallstones, the aetiology remains unclear. Peripheral eosinophilia is an unreliable clue to the diagnosis, which is usually likely to escape detection until the biliary stricture has been resected.

Hepatic artery infusion chemotherapy for metastatic colorectal carcinoma.

Hepatic metastases are a major cause of morbidity and will affect up to 80,000 new patients annually in the United States. Up to 20% of these patients will die with metastatic disease localized to the liver. Hepatic arterial infusion (HAI) therapy has a sound anatomical and pharmacological rationale. A number of randomized clinical trials in patients with unresected metastases have demonstrated that HAI is associated with a complete response rate in 5% of patients and partial responses up to 60%. In comparison, systemic chemotherapy is associated with a partial response in 20% of cases. No investigation comparing systemic chemotherapy with HAI has demonstrated an improvement in survival following HAI, since all investigations either allowed crossover, were under-powered with respect to survival statistics, or included patients with extrahepatic disease in the HAI arm. However, a recent investigation utilizing HAI with systemic chemotherapy following hepatic resection demonstrates improved local and systemic disease control and overall survival. This approach offers new promise for the curative treatment of the patients with metastatic colorectal carcinoma.

Gastric cancer in young patients: demographic, clinicopathological, and prognostic factors in 92 patients.

BACKGROUND: This investigation was undertaken to define the demographic, clinicopathological, and prognostic factors relevant to young patients with gastric adenocarcinoma. METHODS: A prospective database of all patients with gastric cancer who presented to Memorial Sloan-Kettering Cancer Center was started in 1985. Clinical, pathological, and operative records and follow-up data on 92 patients, 40 years of age or younger, with a primary diagnosis of gastric cancer were reviewed. RESULTS: The mean patient age was 35 +/- 4.9 years (range, 17-40 years), and 52 were male. The male-to-female ratio of patients younger than 30 was 0.85/1; whereas in those older than 30, the ratio was 1.45/1. Sixty-six percent of the patients were white, 15% Asian, 11% Hispanic, and 8% were black American. Nineteen percent of patients reported a family history of gastric cancer. Sixty-six patients (71%) presented with stage III or IV disease, whereas 13 patients, each, presented with stage I or II disease. Poorly differentiated lesions were present in 71%. Resection with curative intent was undertaken in 47 patients, and resection with palliative intent was performed in 24 patients. Tumor site (proximal vs. distal vs. linitus plastica), advanced T stage, and the presence of nodal disease were significant predictors of disease-free survival on both univariate and multivariate analyses. The mean survival time and disease-specific 5-year survival rates for individual Union International Contre le Cancer tumor stages were similar to those observed in older populations of patients with gastric cancer; and eight patients, who presented with early (T1/T2) node-negative tumors, are alive and well a minimum of 60 months after resection. CONCLUSIONS: The high frequency of a positive family history in young patients suggests an opportunity to identify a high-risk population for screening.

Pancreatic or duodenal resection or both for advanced carcinoma of the right colon: is it justified?

PURPOSE: The role of extended resections for locally advanced carcinomas of the right colon infiltrating duodenum and pancreas remains unclear. This investigation was undertaken to review our experience with pancreatic head or duodenal resections for advanced right-sided colon cancer. METHODS: The clinical, pathologic, and follow-up details of eight patients with bulky primary carcinomas of the right colon infiltrating the duodenum (n = 4) or pancreatic head (n = 4) surgically managed at Memorial Sloan-Kettering Cancer Center between 1986 and 1998 were reviewed. RESULTS: Six patients presented with anemia, and one patient each with epigastric pain and an abdominal mass. All patients had T4 lesions, whereas five had lymph node metastases at presentation. All patients were resected with clear pathologic margins either by right colectomy and en bloc duodenectomy (n = 4), or en bloc pancreaticoduodenectomy (n = 4). The 30-day mortality rate was zero. Six patients remained alive and free of disease at a median follow-up of 26 months, and there was one long-term survivor who was alive and free of disease at 84 months after resection. CONCLUSION: Extended resection for localized primary colonic carcinoma invading pancreas or duodenum can be undertaken safely and is associated with prolonged survival time.

Abdominal wall recurrence after colorectal resection for cancer.

PURPOSE: Disease recurrence in the abdominal wall from a primary colorectal cancer is a poorly studied and little understood phenomenon that has received renewed attention after the recognition of port site metastases in patients after laparoscopic colorectal resections. The purpose of the present study was to define the clinical, pathologic, and management issues in patients with abdominal wall metastases from colorectal cancer. METHODS: Patients presenting to Memorial Sloan-Kettering Cancer Center with a diagnosis of colorectal cancer were entered into a prospective database beginning in 1986. Review of this database showed that 31 patients presenting with recurrent disease in the abdominal wall were managed surgically at the institution between 1986 and 1998. RESULTS: A total of 31 patients (19 males) with a median age of 67 (range, 45-86) years presented with recurrent disease between 7 and 183 (median, 24) months after primary surgery. Primary tumors were located in the right colon in 17 patients, left colon in 2 patients, sigmoid colon in 7 patients, and rectum in 3 patients. Nineteen percent of primary tumors were perforated, 45 percent were poorly differentiated, 92 percent were transmural (T3 or T4), and 51 percent had lymph node metastases at presentation. Twenty-two patients presented with a symptomatic abdominal wall mass, whereas recurrence in the abdominal wall was found incidentally in 9 patients undergoing laparotomy. Four patients had isolated abdominal wall disease, whereas the remaining 27 were found to have associated intra-abdominal disease. Six patients who were left with residual intra-abdominal cancer after abdominal wall resection had a median survival time of four months. Twenty-five patients underwent a histologically complete resection of recurrence restricted to the abdominal wall alone (n = 4; median survival time, 18 months), abdominal wall and in continuity resection of adherent viscera (n = 15; median survival time, 12.5 months), or resection of abdominal wall and intra-abdominal recurrence at a distant site (n = 6; median survival time, 22 months, although only 1 patient remained alive with disease). The actual two-year and five-year disease-free survival rates were 16 and 3 percent, respectively. CONCLUSION: Abdominal wall metastases are often indicators of recurrent intra-abdominal cancer; however, aggressive resection in patients with disease restricted to the abdominal wall and associated adherent viscera can result in local disease control with little morbidity and no mortality.

Role of laparoscopy in the initial multimodality management of patients with near-obstructing rectal cancer.

The purpose of this study was to investigate the role of diagnostic laparoscopy in the multimodality management of locally advanced, near-obstructing rectal cancer. Fourteen patients with near-obstructing adenocarcinoma of the rectum (8 men and 6 women; mean age 49 years) underwent staging laparoscopy and formation of a sigmoid loop colostomy (n = 7), transverse colostomy (n = 4), or ileostomy (n = 3). The mean operative time was 78 minutes (range 67 to 94 minutes). All patients began a regular diet on postoperative day 1 and the median time to discharge was 4 days (range 2 to 8 days). Four patients were found to have diffuse peritoneal carcinomatosis not defined on preoperative CT scan. These patients died of disease within 6 months. Ten patients with advanced, localized pelvic disease began preoperative combined-modality treatment (5040 cGy external-beam radiation therapy in conjunction with 5-fluorouracil/leucovorin) between 8 and 13 days (median 9 days) following laparoscopy, and all underwent successful resection with clear margins in a median time of 12 weeks following laparoscopy. In the initial management of patients with near-obstructing advanced rectal cancer, laparoscopy can be both therapeutic and diagnostic by clarifying the site of the primary tumor, identifying patients with unsuspected peritoneal disease, and facilitating the formation of a defunctioning stoma with minimal morbidity. This leads to the early commencement of preoperative combined-modality treatment and does not compromise the prospects of subsequent tumor resection.

Parathyroid cancer: biology and management.

A review of all reports in the literature of parathyroid carcinoma (PTC) was undertaken to define an optimal management strategy for this rare condition. PTC is uncommon and its etiology of PTC is largely unknown although patients with familial hyperparathyroidism, multiple endocrine neoplasia type 1 and irradiation to the head and neck are at increased risk for developing the disease. PTC occurs with equal frequency in both sexes and is usually diagnosed in the fifth decade. En bloc resection of the carcinoma and the adjacent structures in the neck is the surgical treatment and is associated with an 8% local recurrence rate and a long term overall survival rate of 89% (mean follow up 69 months). In contrast simple parathyroidectomy results in a 51% local recurrence rate and 53% long-term survival rate (mean follow up 62 months). Adverse prognostic factors for survival were initial management with simple parathyroidectomy alone, the presence of nodal or distant metastatic disease at presentation and non-functioning PTC.

Anabolic and cardiovascular effects of recombinant human growth hormone in surgical patients with sepsis.

The clinical and metabolic effects of 7 days of recombinant human growth hormone (rhGH) and total parenteral nutrition (TPN) in surgical patients with sepsis were determined in a randomized controlled trial. In patients with a mean(s.e.m.) pretreatment rate of net protein catabolism (NPC) of 1.5 g per kg per day or less rhGH treatment decreased NPC from 0.93(0.14) to -0.20(0.24) g per kg per day (n = 5; P < 0.0005) and rendered these patients anabolic. TPN alone decreased NPC from 1.12(0.11) to 0.61(0.11) g per kg per day (n = 5; P < 0.001). In patients with an initial NPC of more than 1.5 g per kg per day rhGH treatment decreased NPC from 2.72(0.12) to 1.08(0.24) g per kg per day (n = 5; P < 0.001) while TPN alone decreased it from 2.41(0.32) to 1.28(0.28) g per kg per day (n = 5; P < 0.005). Use of rhGH was not associated with any adverse effects or improvement in clinical course but did decrease the mean systolic and diastolic pressures during the study period. Thus rhGH is a useful anabolic agent and may have a role in the haemodynamic management of the catabolic patient with sepsis.

Total energy expenditure during total parenteral nutrition: ambulatory patients at home versus patients with sepsis in surgical intensive care.

BACKGROUND: To avoid the complications associated with overfeeding or underfeeding, the energy requirements of patients receiving total parenteral nutrition (TPN) must be accurately prescribed. However, until recently it has not been possible to directly measure the rates of total energy expenditure (TEE) in surgical patients receiving TPN. METHODS: Values for total body water and TEE in four patients with sepsis (mean Acute Physiology and Chronic Health Evaluation [APACHE] score, 10) receiving TPN in surgical intensive care unit and in four patients with chronic intestinal failure receiving long-term TPN at home (HPN) have been determined by using the doubly labeled water technique. The values for TEE have been compared with those of resting energy expenditure obtained with indirect calorimetry (REE CAL) and calculated by using the Harris-Benedict equation (REE HB). RESULTS: In both the patients with sepsis and the patients receiving HPN the proportion of body weight made up of water was normal for patient age and gender. In patients with sepsis the REE HB significantly (p < 0.05) underestimated the REE CAL (15.39 +/- 3.80 kcal/kg/day-1 versus 31.3 +/- 1.23 kcal/kg/day-1) and was significantly less than the TEE derived by using doubly labeled water (44.62 +/- 1.09 kcal/kg/day-1; p < 0.001). In the ambulatory patients receiving HPN no difference was noted between the REE HB and the REE CAL (18.02 +/- 0.41 kcal/kg/day-1 versus 21.37 +/- 0.94 kcal/kg/day-1). The average TEE for these patients was 30.25 +/- 3.42 kcal/kg/day-1, and this was significantly greater (p < 0.006) than both REE CAL and REE HB: CONCLUSIONS: This investigation has shown that in patients with sepsis TEE constitutes 1.4 times the REE CAL or approximately 40 kcal/kg/day, whereas in HPN patients TEE can be estimated by supplying 1.4 times the REE or approximately 30 kcal/kg/day-1.

Growth hormone therapy initiated before starvation ameliorates the catabolic state and enhances the protein-sparing effect of total parenteral nutrition.

The effect of 7 days of subcutaneously administered bovine growth hormone (bGH) (0.2 mg kg-1 day-1; n = 4) or an equivalent volume of 0.15 mol l-1 saline (n = 3) on protein metabolism was assessed in lambs. The catabolic response to 48 h of starvation and subsequent hypocaloric total parenteral nutrition (TPN) was measured using primed constant intravenous infusions of [15N]urea and [14C]leucine. Following 48 h of starvation and 7 h of TPN, bGH-treated animals had a significantly decreased rate of net protein catabolism compared with controls (mean(s.e.m.) 2.4(0.2) versus 3.2(0.3) g kg-1 day-1, P < 0.01). The mean(s.e.m.) rate of whole-body protein catabolism was also significantly decreased in bGH-treated animals at 10.9(0.3) g kg-1 day-1 compared with 12.9(0.7) g kg-1 day-1 in saline-treated controls (P < 0.05). In addition, the rates of net and whole-body protein catabolism decreased significantly (P < 0.05) during the period of hypocaloric parenteral feeding to mean(s.e.m.) values of 2.3(0.2) and 8.6(0.6) g kg-1 day-1 respectively in bGH-treated animals. By contrast, in saline-treated controls net and whole-body protein catabolism continued to increase during hypocaloric parenteral feeding. There was a significant decrease (P < 0.05) in the rate of [14C]leucine uptake in tissues of the gastrointestinal tract, heart and diaphragm in bGH-treated animals compared with controls. These results demonstrate that daily administration of growth hormone decreases the catabolic response to a metabolic stress, resulting in the conservation of protein in the heart, diaphragm, gastrointestinal tract and musculoskeletal system by a primary anticatabolic action. In addition, growth hormone therapy initiated before induction of the catabolic state enhances the protein-sparing effects of TPN. Further study is justified to determine whether growth hormone therapy initiated before elective or urgent surgery in the nutritionally depleted patient may have a role in reducing the severity of the postoperative catabolic state, particularly in the patient in whom a complicated course is anticipated.

Metabolic basis for management of the septic surgical patient.

The physiologic events accompanying postoperative septic complications in surgical patients represent a coordinated response to bacterial invasion, which is aimed at maintaining the function of key organ systems. When sepsis is prolonged or overwhelming, physiologic dysfunction and multiorgan failure develop. This review outlines the pathophysiologic response to sepsis and correlates it with recent therapeutic advances in the metabolic management of the postoperative septic patient.

Passive immunization against circulating insulin-like growth factor-I (IGF-I) increases protein catabolism in lambs: evidence for a physiological role for circulating IGF-I.

Primed constant infusions of [14C]urea were used to determine the acute effect of passive immunization against circulating free and protein-bound insulin-like growth factor-I (IGF-I) on the rate of net protein catabolism (NPC) in castrated male lambs fasted for 48 h. Following an intravenous bolus of 50 ml IGF-I antiserum, the rate of NPC increased to a peak 30 min after injection of 1.69 +/- 0.16 g/kg per day from a baseline value of 1.45 +/- 0.22 g/kg per day (P < 0.05, n = 4). In three animals given 50 ml equivalents of the purified immunoglobulin fraction, NPC increased from 1.31 +/- 0.20 to 1.59 +/- 0.16 g/kg per day (P < 0.05). A similar trend was observed in animals given 25 ml antiserum (n = 4). The rate of NPC did not increase following a bolus of non-immune serum in control animals and the rate of NPC in the treated lambs returned to control levels within 60 min of antibody injection. Plasma insulin and glucose concentrations in both the treated and control groups were unchanged throughout the study. These data suggest that circulating IGF-I has a physiological role in regulating whole body protein turnover during starvation and possibly other catabolic states. The effect of immunoneutralization of circulating IGF-I is transient and this suggests that while IGF-I has an endocrine role in the regulation of protein turnover, other regulatory mechanisms are involved.

Synergistic effect of insulin-like growth factor-I administration on the protein-sparing effects of total parenteral nutrition in fasted lambs.

Using primed constant isotopic infusions, we investigated the effects of recombinant human insulin-like growth factor-I (IGF-I) infusion on protein kinetics in both fasted and parenterally fed (TPN) lambs. Infusion of IGF-I at a dose of 50 micrograms/kg.h in fasted animals increased (P less than 0.005) the mean plasma IGF-I concentration from 77.5 +/- 9.7 to 454.4 +/- 51.4 ng/ml. During IGF-I infusion the rate of net protein catabolism (NPC) was decreased (P less than 0.005) by 17% from 3.5 +/- 0.2 to 2.9 +/- 0.2 g/kg.day, and the rate of appearance (Ra) of leucine in plasma decreased (P less than 0.01) from 5.0 +/- 0.4 to 3.4 +/- 0.4 mumol/kg.min. In addition, the fractional synthetic rate of protein in cardiac and diaphragmatic muscle increased by 100% (P less than 0.05) during the same period. After 3 h of TPN, the rate of NPC was decreased (P less than 0.01) in the TPN animals compared to that in their fasted counterparts (1.89 +/- 2.27 vs. 4.1 +/- 0.2 g/kg.day, respectively). The rate of NPC was further decreased after another 300 min of TPN to 0.76 +/- 0.27 g/kg.day. However, the Ra of leucine was not changed compared to the initial value. Infusion of IGF-I concurrently with TPN reversed (P less than 0.001) the rate of NPC from 1.02 +/- 0.21 g/kg.day after 180 min of TPN alone to a state of net protein gain of 0.14 +/- 0.19 g/kg.day after a further 300 min of combined IGF-I and TPN infusion. The Ra of leucine decreased (P less than 0.01) from 3.9 +/- 0.8 to 2.5 +/- 0.47 mumol/kg.min during IGF-I and TPN infusion. Similarly, the fractional synthetic rates of protein in cardiac muscle, diaphragm, adductor muscle, psoas muscle, and hepatic tissue were increased (P less than 0.05) compared to those in animals that received only TPN. The protein-sparing effects of IGF-I and TPN were synergistic, and the infusion of both agents resulted in the induction of a protein anabolic state within 60 min of commencing IGF-I infusion. In contrast, neither IGF-I nor TPN alone resulted in a state of net protein anabolism, and neither had an effect on protein kinetics until 120 min into the infusion. Consequently, IGF-I shows considerable potential as an anticatabolic agent when used synergistically with nutritional support.

Total parenteral nutrition in surgical illness: how much? How good?

Using primed constant infusions of isotopes and indirect calorimetry, we assessed protein, glucose, and fat kinetics in severely ill surgical patients suffering from sepsis, major trauma, gastrointestinal cancer, or nutritional depletion from benign disease. We also assessed the effect of 5 days of total parenteral nutrition (TPN) on abnormal metabolism in these states. In the basal state, patients with sepsis, trauma, or cancer had an elevated rate of net protein catabolism due to an increased rate of whole-body protein catabolism, whereas whole-body protein synthesis was not impaired. TPN had no impact on the elevated rate of whole-body protein catabolism in these conditions but decreased the rate of net protein catabolism, suggesting that increased substrate availability optimizes whole-body protein synthesis. Consequently, few surgical patients became anabolic while receiving TPN. In contrast, patients with nutritional depletion from benign disease had a decreased rate of net protein loss compared with volunteers and could be made anabolic with the administration of TPN. All patients studied had an elevated rate of plasma glucose production, impaired glucose oxidation, and an increased rate of Cori cycling in the basal state. After 5 days of TPN, most surgical patients showed improved ability to oxidize glucose, but the high rates of glucose recycling to lactate persisted. Patients suffering from sepsis, trauma, or cancer had an enhanced rate of lipolysis in the basal state associated with an increased rate of whole body-fat oxidation compared with healthy volunteers. After administration of TPN, whole-body fat oxidation was significantly decreased in patients with trauma but increased in patients with sepsis or cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

A possible role for IGE-II: evidence in sheep for in vivo regulation of IGF-I mediated protein anabolism.

Using primed constant infusions of [14C]urea we assessed the effects in castrate male lambs of insulin-like growth factor (IGF) II infusion on protein metabolism during concurrent IGF-I infusion. A 300 minute infusion of IGF-I at 15 micrograms/kg.hour (n = 4) increased (p less than 0.001) the plasma IGF-I concentration from 72.5 +/- 6.4 ng/ml to 213.6 +/- 17.4 ng/ml and decreased (p less than 0.01) the rate of net protein catabolism (NPC) from 1.48 +/- 0.28 g/kg.day to 1.02 +/- 0.18 g/kg.day. Infusion of IGF-II at a dose of 50 micrograms/kg.hour concurrently with IGF-I at 15 micrograms/kg.hour (n = 4) was associated with a similar rise (p less than 0.01) in plasma IGF-I concentration from 79.4 +/- 4.1 ng/ml to 225.2 +/- 32.8 ng/ml. Plasma IGF-II increased (p less than 0.05) from 350.6 +/- 41.6 ng/ml to 746.7 +/- 165.5 ng/ml over the infusion. Coadministration of IGF-II completely blocked (p less than 0.01) the anabolic effect of IGF-I and the rate of NPC remained unchanged throughout the combined IGF-I and IGF-II infusion at a level comparable to saline infused controls (n = 4). This study suggests that IGF-II may play a physiological role as a circulating modulator of the anabolic effects of IGF-I.

The effect of tumor bulk on the metabolic response to cancer.

The derangements in energy/substrate metabolism seen in oncology patients are similar regardless of the tumor's site of origin, and in advanced disease these metabolic derangements can be manifested as cancer cachexia. The relationship between tumor size and the degree of metabolic abnormality, however, remains unclear. Using primed constant infusions of stable and radiolabeled isotopes and indirect calorimetry, the authors have determined the rates of net protein catabolism (NPC), glucose oxidation, Cori cycling of glucose, and oxygen consumption in 85 patients with cancer. They have assessed the association between bulk of tumor and metabolic abnormality using regression analysis. A positive correlation was found between tumor bulk and the rates of NPC (r2 = 0.8), plasma glucose appearance (r2 = 0.72), plasma glucose clearance (r2 = 0.70), the percentage of tissue glucose uptake recycled to lactate (r2 = 0.62), and oxygen consumption (r2 = 0.79). The percentage of tissue glucose uptake oxidized was negatively correlated with tumor bulk (r2 = 0.75). The data indicate that the degree of metabolic abnormality seen in cancer patients is closely related to the quantity of malignant tissue present. Progressive increase in tumor size is associated with an increase in peripheral substrate mobilization, an increase in the rate of hepatic glucose production, an increase in tissue glucose uptake, an increase in energy-expensive glucose cycling to lactate, and an increase in protein loss.

The circulating molecular weight forms of infused recombinant insulin-like growth factor-I and effects on glucose and fat metabolism in lambs.

We have investigated the relationship between the plasma distribution of infused recombinant insulin-like growth factor-I across the insulin-like growth factor binding proteins and the resultant effects on glucose and fat metabolism. The studies were performed in 24-h fasted ram lambs which received primed constant infusions of 3H labelled glucose tracer. When isotopic equilibrium had been reached, the animals received 90-min infusions of human insulin-like growth factor-I at various doses (2.5, 20, 40 and 120 micrograms.kg-1.h-1, n = 3 for each dose). Total plasma insulin-like growth factor-I was significantly elevated by infusion at a rate of 40 micrograms.kg-1.h-1 (from 185 +/- 14 micrograms/l to 442 +/- 41 micrograms/l, p less than 0.05) and 120 micrograms.kg-1.h-1 (from 181 +/- 2 micrograms/l to 953 +/- 39 micrograms/l, p less than 0.005). The plasma concentrations of insulin-like growth factor-I not associated with binding proteins remained undetectable (less than 15 micrograms/l) at the end of the 2.5 and 20 micrograms.kg-1.h-1 doses, but were significantly elevated at the end of the 40 and 120 micrograms.kg-1.h-1 infusions (to 71 +/- 14 micrograms/l, p less than 0.05 and 176 +/- 55 micrograms/l, p less than 0.01 respectively). The infused insulin-like growth factor-I associated primarily with 35-60 kilodalton binding proteins. Glucose kinetics were significantly altered only by the highest dose infusion, during which there was a fall in plasma glucose concentration from 3.5 +/- 0.2 mmol/l to 1.9 +/- 0.2 mmol/l (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)