A prospective study of peri-diagnostic and surgical wait times for patients with presumptive colorectal, lung, or prostate cancer.

The objective of this study was to prospectively measure peri-diagnostic and surgical time intervals for patients with suspected colorectal, lung, or prostate cancer. Prospective eligible patients were referred to a regional hospital in Ottawa, Canada between February 2004 and February 2005 for diagnostic assessment of presumptive colorectal, lung, or prostate cancer. Chart abstractions were used to measure nine time intervals; the primary interval was the date of referral for diagnostic assessment to the date the patient was informed of the diagnosis. Health-related quality-of-life (HRQL) was assessed 5 days following the patient being informed of their diagnosis. The median (IQR) time for the primary interval was 71 (30-110), 37 (29-49), and 81 (56-100) days for colorectal, lung, and prostate patients, respectively (Kruskal-Wallis P=0.0001). This interval was significantly less for colorectal patients diagnosed with cancer than for those without cancer (median difference=59.0 days; Wilcoxon P=0.003). No differences in HRQL existed for patients with cancer and those without. Colorectal and prostate patients wait longer between referral for suspected cancer and being informed of their diagnosis than current recommendations. The shorter diagnostic intervals for colorectal patients with cancer suggest clinicians have an effective process for triaging patients referred for diagnostic assessment.

Endogenous glucose production following injury increases with age.

To evaluate the influence of aging on the increase in endogenous glucose production that follows injury, we studied 22 fully resuscitated, clinically stable, previously healthy patients aged < or = 30 yr or > or = 60 yr admitted to hospital following injury, and 11 healthy volunteers in the same age groups. Endogenous glucose production was determined using a primed constant infusion of D-glucose-6,6-2d2. Urine cortisol and C-peptide were markedly higher in patients than volunteers (both P < 0.01), and urine C-peptide was lower in older than in younger patients (P < 0.05). Urine cortisol increased as a function of the interaction of age and Injury Severity Score (ISS) (r2 = 0.40, P < 0.001). Intracellular water was markedly lower and extracellular water greater in patients compared with volunteers (both P < 0.001), reflecting the loss of body cell mass and expansion of the extracellular space following injury. Endogenous glucose production (milligrams per minute per liter intracellular water) was best described as a function of ISS and age-ISS interaction (r2 = 0.35, all P < 0.05), and was increased 56% and 78% in younger and older patients, respectively, in comparison with the respective volunteer groups. Endogenous glucose production following injury increases in relation to the severity of injury and patient age. Greater cortisol elaboration and diminished insulin secretion in older patients may contribute to this age effect.

The induction of interleukin-1 in humans and its metabolic effects.

To investigate the metabolic effects of interleukin-1 and its role as a mediator of host responses to trauma and sepsis, we injected seven healthy male subjects with etiocholanolone, an inflammatory agent that stimulates systemic responses thought to be mediated by interleukin-1. The subjects were fed a constant diet during each 4-day study and received three daily intramuscular injections of etiocholanolone, 0.10 mg/kg. Etiocholanolone injection resulted in inflammation, fever, leukocytosis, increased serum C-reactive protein, hypoferremia, and increased plasma activity of interleukin-1/lymphocyte-activating factor. Plasma concentrations of the counterregulatory hormones were normal. Protein metabolism, as reflected in nitrogen balance, 15N turnover, and forearm flux of alanine and glutamine, was unaltered. Serum glucose and insulin levels and tissue responsiveness to insulin were normal. This dissociation of acute-phase and catabolic responses may reflect the magnitude of the stimulus; higher levels of interleukin-1 may initiate catabolic responses. Alternatively, other mediators such as the counterregulatory hormones may direct the catabolic responses that occur after injury and sepsis.

Both inflammatory and endocrine mediators stimulate host responses to sepsis.

Host responses to sepsis and trauma are complex and their mediators are not well understood. To examine the roles of "endocrine" and "inflammatory" mediators, we studied healthy volunteers in four experimental groups: continuous 72-hour infusion of normal saline; continuous 72-hour infusion of hydrocortisone, glucagon, and epinephrine; daily intramuscular injection of the inflammatory agent etiocholanolone; and combined etiocholanolone injection--hormone infusion. In this model hypermetabolism, hyperglycemia, hyper-insulinemia, insulin resistance, negative nitrogen balance, and accelerated protein flux were mediated predominantly by infusion of the counterregulatory hormones. Etiocholanolone injection resulted in fever, acute-phase--protein synthesis, and hypoferremia. Leukocyte, temperature, and C-reactive--protein responses reflected major interactions between these stimuli. Both inflammatory and endocrine mediators are necessary for the complete manifestation of host responses to critical illness.

Inhibition of cyclo-oxygenase attenuates the metabolic response to endotoxin in humans.

Acute infection initiates fever, acute-phase changes, and catabolic responses in the host, resulting in weight loss, hypermetabolism, and accelerated proteolysis. To test the hypothesis that cyclo-oxygenase inhibition might attenuate these responses, we administered Escherichia coli endotoxin intravenously to seven normal volunteers and to seven additional subjects pretreated with a cyclo-oxygenase inhibitor (ibuprofen). Control studies were also performed following administration of saline and ibuprofen alone. Vital signs, metabolic rate, and concentrations of pituitary and stress hormones, as well as those of other substrates, were serially measured. Endotoxin administration produced a response similar to an acute illness, with flulike symptoms, fever, tachycardia, increased metabolic rate, and stimulation of stress hormone release. These changes were markedly attenuated by cyclo-oxygenase inhibition. The leukocytosis, hypoferremia, and elevation of the C-reactive protein level induced by endotoxin were unaffected by cyclo-oxygenase inhibition. These data indicate that activation of the cyclooxygenase pathway is necessary to produce many of the metabolic changes observed during critical illness.

Parenteral nutrition by peripheral vein.

Peripheral parenteral nutrition can provide perioperative nutritional support to patients with inadequate oral intake in whom total parenteral nutrition with hypertonic dextrose administered by a central vein cannot be undertaken because of sepsis, subclavian vein thrombosis, or lack of expertise and familiarity. Peripheral parenteral nutrition may be indicated in patients with marginal nutritional status whose postoperative course and period of starvation are unpredictable and in patients being started on a total enteral nutrition regimen. In patients with increased requirements because of stress or malnutrition who need full nutritional support by a peripheral method, the lipid system is indicated. In certain instances, large enough volumes can be infused to provide sufficient calories and protein for nutritional repletion. Protein-sparing therapy is indicated for nutritional maintenance in patients who do not clearly require full support by total parenteral nutrition but who are taking insufficient calories and protein orally. Peripheral parenteral nutrition avoids the risks of subclavian vein catheterization but requires that adequate peripheral veins are available. The metabolic complications are minimal compared with those of total parenteral nutrition, and the nutritional management of the diabetic patient is greatly simplified. Several techniques of preserving peripheral veins and prolonging their use have been discussed.

Critical care for the elderly patient.

Elderly individuals will continue to make up a major portion of patients requiring critical care. Age and chronic disease-related factors blunt the reserves with which the elderly can meet the demands of critical surgical illness. The clinician must remain vigilant to subtle changes in the patient's course which may indicate a developing complication and must pay attention to all the details of comprehensive critical care management. With careful attention and timely physiologic support, the elderly patient has as good a chance of surviving as a similarly ill younger patient, although his or her course may be more prolonged. The priorities are the same. Thus, the primary disease must be addressed: necrotic tissue débrided, pus drained, wounds closed, fractures set. Cardiopulmonary performance (oxygen delivery) must be maintained sufficiently to meet the heightened oxygen needs associated with critical illness. This may require invasive hemodynamic monitoring and pharmacologic support. Gas exchange in the lungs must be maintained without compromising cardiovascular function or exhausting the patient. Patients should be kept warm, pain free, and calm. Intravascular volume and the composition of the extracellular fluid must be maintained. Nutritional support should be provided early in amounts sufficient to meet the patient's basal nutritional requirements and increased needs associated with the critical illness. If at all possible, some or all of this nutritional support should be provided via the gastrointestinal tract. The use of specialized nutrients or of agents designed to minimize the catabolism of critical illness or to enhance anabolism is an area of active investigation. The indications for these therapeutic strategies in the elderly should become clearer in the years ahead.

Preventive measures in the elderly surgical patient.

The death rates associated with all forms of surgical illness increase consistently with age but appear more closely related to physiologic and medical status than to age per se. Changes in physiologic function with advancing age are marked by a decreased sensitivity to perturbations and a decreased efficiency of homeostatic mechanisms. Recognition of the heterogeneity of the aging process is fundamental to appropriate decision-making in the elderly surgical patient and thus to avoiding complications. Careful preoperative assessment of medical problems and potential age-related changes in physiologic function, preoperative orientation and teaching, consideration of deep venous thrombosis prophylaxis, effective pain management, early postoperative mobilization and careful attention to drug and fluid and electrolyte therapy are essential in management of the elderly surgical patient.

Retroperitoneal perforation of the rectum during barium enema examination.

Colorectal perforation during barium enema examination is rare. The authors report the case of an 84-year-old woman in whom retroperitoneal perforation of the rectum occurred during barium enema examination. Potential mechanisms of injury include trauma, overinflation of the balloon, recent instrumentation and associated disease of the rectal mucosa. When the colon has been well prepared before examination, and air alone, not barium, has been insufflated into the retroperitoneum, then such injuries may be managed successfully without operation, as in this case.

Pancreatic abscess.

Pancreatic abscess, although an uncommon complication of pancreatitis, is a serious cause of morbidity and death. During the 5-year period beginning in March 1976, 19 patients with pancreatic abscess were seen at the Ottawa Civic Hospital. Abdominal pain, mass, fever and leukocytosis were common; the serum amylase value was usually normal. twelve patients underwent external drainage; in 6 the abscess was drained internally through the posterior wall of the stomach. The overall mortality was 16%. Morbidity was high; 7 (37%) of the 19 patients required reoperation for recurrent sepsis. Differentiation of pancreatic abscess from phlegmonous pancreatitis or pseudocyst can be difficult. Ultrasonography may be useful but computerized axial tomography is the the diagnostic method of choice. Prompt débridement and external drainage are the mainstays of surgical treatment but internal drainage may be appropriate in selected patients.

Role of catabolic hormones in the hypoketonaemia of injury.

Adaptation to fasting results in ketosis, protein conservation, and diminished energy requirements. To determine whether the attenuation of these responses following injury is due to an altered hormonal environment, we infused the catabolic hormones cortisol, glucagon, and adrenaline into seven fasting subjects for 72 h. Saline alone was administered during a comparable control period. Hormone infusion achieved blood levels typical of moderate injury and resulted in hypermetabolism, hyperglycaemia, hyperinsulinaemia, and marked suppression of fasting ketosis. The hypoketonaemia could not be accounted for by decreased precursor availability, accelerated ketone utilization or increased urinary excretion. The altered hormonal environment associated with critical illness attenuates fasting ketosis by limiting hepatic ketogenesis.

Perforated ulcers in critical illness.

Although gastroduodenal ulcers rarely perforate during critical illness, this occurrence causes specific and difficult problems of diagnosis and management. In our review of the records of 19 critically ill patients whose ulcers perforated, we found that classical symptoms were frequently absent. The perforations often were manifested by nonspecific clinical events, such as unexplained ileus or hypotension. Diagnosis was typically delayed and on occasion was first suspected after observing pneumoperitoneum on a routine x-ray. While the ulcers were characteristically very large (greater than 2 cm), minimal inflammation surrounded them. Mortality was 56% in the 16 patients whose perforations were diagnosed before death or discharge. Fifteen patients were treated with simple patching of the ulcer. Perforated ulcers in critically ill patients differ in several important ways from those occurring in otherwise healthy individuals.

An optimized method for cell-based phage display panning.

BACKGROUND: Traditional methods of phage display panning, bind purified antigen to plates or other solid phases to which libraries are then applied, followed by vigorous washings in detergent-supplemented buffers to select for specific phage Fab. These methods are not directly applicable to antigens in their native environment on cell surfaces or in settings where the target antigen is unknown. OBJECTIVES: To develop a model antigen system employing whole cells rather than purified protein immobilized on a substrate; to optimize methods for phage display panning using a cell-based system. RESULTS: Specificity of binding of phage Fab to antigen on cells was demonstrated by output titer and by flow cytometry. Output titers showed a plateau and binding advantage, after four washes, corresponding to removal of most non-specifically bound phage. Enrichment advantage was independent of input phage number. Longer incubation times, to cell tolerance, improved specific binding. Temperature had modes impact as a variable in the panning and washing. An increase in output titers paralleled enrichment for specific phage Fab. CONCLUSION: An optimized method applied to whole cells can productively enrich specific phage Fab in mixtures with large excesses of non-specific phage Fab over several rounds of panning.

Alterations in respiratory mechanics after laparoscopic and open surgical procedures.

OBJECTIVE: To compare the effects of laparoscopic and open surgical procedures on postoperative strength and respiratory mechanics. DESIGN: Prospective cohort study. SETTING: Adult university hospital. PARTICIPANTS: Fifty-one women aged 21 to 62 years scheduled to undergo elective cholecystectomy or hysterectomy (or related procedures), otherwise in good health. INTERVENTIONS: Open or laparoscopic cholecystectomy or hysterectomy (or related procedures). MAIN OUTCOME MEASURES: Maximum voluntary handgrip strength (HGS), forced vital (VC), forced expiratory volume in 1 second (FEV1), and maximal inspiratory pressure (MIP) were each measured preoperatively and on the first postoperative morning. A visual analogue pain scale score was evaluated in relation to performance of the postoperative strength and respiratory measurements. RESULTS: VC, FEV1, and MIP, but not HGS, were decreased after surgery. Postoperative VC, FEV1, and MIP were lower after open procedures than after laparoscopic procedures and after cholecystectomy than after hysterectomy (all p < 0.001). Pain scores were lower after laparoscopic than after open procedures (p < 0.005) and could account in part for differences in postoperative respiratory mechanics. CONCLUSIONS: Cholecystectomy and hysterectomy do not result in generalized muscle weakness, unlike more major abdominal procedures. Postoperative alterations in respiratory mechanics are related to the site of the surgery, the use of an open versus a laparoscopic approach and postoperative pain.

Hyperglycemia after trauma increases with age.

The metabolic responses to trauma and surgery have been well described and are observed most typically in otherwise healthy young and middle-aged individuals. To investigate the effect of age on blood glucose, insulin, and cortisol responses after mild to moderate trauma, we studied 33 patients (Injury Severity Scores, 5-38, and ages 16 to 81 years) before resuscitation and 24-96 hours postinjury. Age was associated with an increase in serum glucose during both "ebb" and "flow" phases of the injury response, but not with serum insulin. Serum glucose also increased with the degree of injury as reflected in Glasgow Coma Scale on admission and Injury Severity Score subsequently. Serum cortisol responses were increased in older patients and tended to decrease with time following injury. A more detailed knowledge of how age may alter the ability of elderly patients to respond to trauma and critical illness is essential to allow the continued development of rational therapies for such patients.

Combined hormonal infusion simulates the metabolic response to injury.

To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses.

Effects of age and body composition on the metabolic responses to elective colon resection.

Advancing age tends to be accompanied by predictable changes in organ-system function and body composition, as well as an increased prevalence of various diseases. Our knowledge of the metabolic responses to surgical stress is derived largely from studies of young and middle-aged individuals. Whether these responses are altered in the elderly is not well established; the characteristic changes in metabolic function and body composition that occur in the elderly may limit their ability to respond adequately and to survive severe or complicated surgical procedures. To evaluate the effects of age and differences in body composition on the metabolic responses to surgery, we studied 20 active and otherwise healthy men aged 43 to 77 years, before and after elective colon resection. Age was not related to weight or total body water (TBW) in the patients studied. Resting preoperative energy expenditure was strongly dependent on TBW (reflecting lean body mass) and age (r2 = 0.80, p less than 0.001), and to TBW and creatinine excretion (reflecting muscle mass) (r2 = 0.85, p less than 0.001). Energy expenditure increased 18 +/- 2% (range, 4% to 40%) after operation but this response was unrelated to age. Postoperative urine nitrogen was related to body weight or TBW, but not to age. Serum glucose, cortisol, white blood cell count count, and C-reactive protein responses were also independent of patient age. The metabolic responses of generally healthy men to a moderate surgical stress do not vary with age in the range studied. The metabolic responses to more severe or prolonged stress may be altered with advancing age and changes in body composition, and in patients with concomitant diseases.

Functional status is well maintained in older women during adjuvant chemotherapy for breast cancer.

BACKGROUND: While adjuvant chemotherapy is known to improve survival in older women with breast cancer, there is little information about its effects on physical function and health-related quality of life. PATIENTS AND METHODS: 'Young' (<65 years of age) and 'older' (> or = 65 years of age) postmenopausal women completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core Module (QLQ-C30) and BR23 questionnaires and other measures prior to, during and at the completion of anthracycline-based adjuvant chemotherapy, and then 6 and 12 months later. RESULTS: Physical, role and social function decreased during chemotherapy and emotional function improved (all P <0.01). The decline in physical function was more marked in young (age range 31-64 years; n = 45) than in older women (65-80 years; n = 20) (P <0.05), despite similar baseline values and drug dose intensities. Physical and role function had recovered at 6 months post-chemotherapy. Older patients had consistently better emotional function (P <0.01). CONCLUSIONS: Physical function and other functional domains are impaired in postmenopausal women during adjuvant chemotherapy for breast cancer, but recover subsequently. Physical function appeared to be better maintained in the older women, who tolerated adjuvant chemotherapy well overall. A knowledge of these effects is important for clinical decision-making and when defining social support needs during adjuvant chemotherapy.

Aging exaggerates the blood glucose response to total parenteral nutrition.

OBJECTIVE: To determine the effect of age on the blood glucose and insulin responses to a clinical model of glucose loading (i.e., total parenteral nutrition [TPN] with hypertonic glucose), in patients with a variety of conditions. DESIGN: A prospective cohort study. SETTING: An adult university hospital. PATIENTS: Seventy-one consecutive, clinically stable patients receiving central TPN, excluding those with metabolic disease or receiving relevant medications. INTERVENTION: None. MAIN OUTCOME MEASURES: Serum levels of glucose, insulin, C-peptide and cortisol determined in peripheral venous blood obtained immediately before initiating TPN and again 48 to 96 hours later; acute physiology score (APS) and habitual level of physical activity (HAL). RESULTS: Serum levels of glucose, insulin and C-peptide increased following initiation of TPN (all p < 0.001). The serum glucose level during TPN administration increased as a function of both patient age and severity of illness (APS) (r2 = 0.37, all p < 0.01), whereas the serum insulin level was inversely related to age and increased as a function of serum glucose, glucose rate of infusion and HAL (r2 = 0.57, all p < 0.05). The serum C-peptide: insulin molar ratio did not vary with age. CONCLUSIONS: Aging and severity of illness interact to exaggerate the increases in blood glucose that accompany TPN with hypertonic glucose. Serum insulin responses to TPN decline with aging, likely reflecting reduced insulin secretion. Diminished insulin responses may contribute to hyperglycemia and represent a diminished anabolic signal in such patients. The acutely ill elderly patient is predisposed to hyperglycemia and should be monitored carefully even when pre-TPN blood glucose values are normal.

The influence of age on the severity of peritonitis.

OBJECTIVE: To evaluate the influence of age on the evolution and severity of peritonitis. DESIGN: A chart review. SETTING: An adult university hospital. PATIENTS: One hundred and twenty-two patients with acute appendicitis and 100 patients with acute colonic diverticulitis requiring operation or percutaneous drainage. MAIN OUTCOME MEASURES: Patient age and sex, presence of perforation or gangrene (appendicitis), extent of peritonitis (diverticulitis); duration of symptoms prior to admission; admission leukocyte count; duration of hospitalization before surgery; length of hospital stay; and death rate. RESULTS: Patients with acute appendicitis who were aged 65 years or older were three times more likely than younger patients to have a gangrenous or perforated appendix (odds ratio 3.1, 95% confidence interval 1.1 to 8.4, p < 0.05); older patients with perforated diverticulitis were three times more likely than younger patients to have generalized peritonitis than localized (pericolic or pelvic) peritonitis (odds ratio 2.9, 95% confidence interval 1.2 to 7.5, p < 0.05). CONCLUSION: These findings are consistent with the hypothesis that the biologic features of peritonitis differ in the elderly, who are more likely to present with an advanced or severe process than young patients.