Sequential changes in the metabolic response to orthotopic liver transplantation during the first year after surgery.

OBJECTIVE: To quantify the sequential changes in the metabolic response occurring in patients with end-stage liver disease after orthotopic liver transplantation (OLT). SUMMARY BACKGROUND DATA: Detailed quantification of the changes in energy expenditure, body composition, and physiologic function that occur in patients after OLT has not been performed. Understanding these changes is essential for the optimal management of these patients. METHODS: Fourteen patients who underwent OLT for end-stage liver disease had measurements of resting energy expenditure, body composition, and physiologic function immediately before surgery and 5, 10, 15, 30, 90, 180, and 360 days later. RESULTS: Resting energy expenditure was significantly elevated after surgery (24% above predicted), peaking around day 10 after OLT, when it averaged 42% above predicted. A significant degree of hypermetabolism was still present at 6 months, but at 12 months measured resting energy expenditure was close to predicted values. Before surgery, measured total body protein was 82% of estimated preillness total body protein. During the first 10 days after OLT, a further 1.0 kg (10%) of total body protein was lost, mostly from skeletal muscle. Only 54% of this loss was restored by 12 months. Significant overhydration of the fat-free body was seen before OLT, and it was still present 12 months later. Although significant losses of body fat and bone mineral occurred during the early postoperative period, only body fat stores were restored at 12 months. Both subjective fatigue score and voluntary hand grip strength improved rapidly after OLT to exceed preoperative levels at 3 months. At 12 months grip strength was close to values predicted for these patients when well. Respiratory muscle strength improved less markedly and was significantly lower than predicted normal levels at 12 months. CONCLUSIONS: Before surgery, these patients were significantly protein-depleted, overhydrated, and hypermetabolic. After surgery, the period of hypermetabolism was prolonged, restoration of body protein stores was gradual and incomplete, and respiratory muscle strength failed to reach expected normal values. Our measurements indicate that OLT does not normalize body composition and function and imply that a continuing metabolic stress persists for at least 12 months after surgery.

Global impact of human immunodeficiency virus and AIDS.

This review provides information on the epidemiology, economic impact, and intervention strategies for the human immunodeficiency virus (HIV)/AIDS pandemic in developing countries. According to the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) at the end of 1999, an estimated 34.3 million people were living with HIV/AIDS. Most of the people living with HIV, 95% of the global total, live in developing countries. Examples of the impact of HIV/AIDS in Africa, Asia, Latin America, the Caribbean, and the Newly Independent States provide insight into the demographics, modes of exposure, treatment and prevention options, and the economic effect of the epidemic on the global community. The epidemic in each region of the world is influenced by the specific risk factors that are associated with the spread of HIV/AIDS and the responses that have evolved to address it. These influences are important in developing HIV/AIDS policies and programs to effectively address the global pandemic.

Identification of the fascia propria by magnetic resonance imaging and its relevance to preoperative assessment of rectal cancer.

UNLABELLED: If rectal cancer does not penetrate the fascia propria of the rectum and the rectum is removed with the fascial envelope intact (extrafascial excision), then local recurrence of the cancer will be minimal. Modern imaging techniques have identified a fascial plane surrounding the rectum and mesorectum, and it has been suggested that this is the fascia propria. The aim of this study was to identify whether this plane is the rectal fascia propria and whether tumor invasion through this fascia can be identified preoperatively. METHODS: Two separate experiments were performed: 1) pelvic magnetic resonance imaging was performed before and after dissection and marking of the plane of extrafascial dissection of the rectum of a cadaver; and 2) magnetic resonance imaging was performed in 43 rectal cancer patients preoperatively. Two radiologists independently reported the depth of tumor invasion in relation to the fascia propria. The tumors were resected by extrafascial excision, and a pathologist independently reported the relation of the tumor to the fascia propria. RESULTS: The marker inserted in the extrafascial plane showed that the plane visualized on pelvic magnetic resonance imaging was the fascia propria dissected in extrafascial excision of the rectum. The magnetic resonance imaging detected tumor penetration through the fascia propria with a sensitivity of 67 percent, a specificity of 100 percent, and an accuracy of 95 percent. CONCLUSION: The surgical fascia propria can be identified on preoperative magnetic resonance imaging in patients with rectal cancer. Tumor invasion through this fascia can be detected on magnetic resonance imaging. This method of assessment offers a new way to select those patients who require preoperative radiotherapy.

Results of extrafascial excision and conventional surgery for rectal cancer at Auckland Hospital.

BACKGROUND: Recent studies have suggested that local recurrence rates following rectal cancer surgery are reduced if the mesorectum is removed intact within its fascia propria. The present study aims to compare the outcomes of conventional surgery for rectal cancer and surgery in which the rectum and mesorectum are removed by the technique of extrafascial excision (EFE). METHODS: All patients undergoing surgery for rectal cancer at Auckland Hospital from 1980 to 1996 were identified. Demographic, tumour, operation, outcome, survival and follow-up data were obtained from patient charts, New Zealand (NZ) Death Registry, death certificates and the NZ Electoral Roll. Complication rates, recurrence rates, overall and cancer-free survival and treatment costs were calculated for each group. RESULTS: A total of 262 patients had curative surgery (138 had conventional surgery, 124 had EFE). The groups were similar with respect to age, sex, operation performed and Dukes' stage. There was no difference in complication rates between the groups. Mean follow-up was 7 years in survivors. Twenty-nine conventional-surgery (21%) and eight EFE (6%) patients developed local pelvic recurrence. The 5-year actuarial local recurrence rates were 30% and 10%, respectively (P = 0.0006). The 5-year overall survival was 54% for conventional surgery and 60% for EFE (P = 0.23). The 5-year cancer-free survival was 63% for conventional surgery and 74% for EFE (P = 0.02). Average initial costs were NZ$15,717 and NZ$15,158 for conventional surgery and EFE, respectively. The average cost of local recurrence was an additional NZ$10,471. CONCLUSIONS: The present study adds further support to the growing evidence that excision of the mesorectum within an intact fascial envelope reduces local recurrence rates after surgery for rectal cancer. There appears to be an associated improvement in cancer-free survival. Complication rates and cost were not increased in the patients having EFE.

Extrafascial excision of the rectum: surgical anatomy of the fascia propria.

PURPOSE: It is now agreed that it is of vital importance to maintain the fascia propria as an intact envelope around the mesorectum to prevent tumor spillage while performing rectal excision for cancer. There are several surgical techniques described to achieve an intact fascial envelope, each arising from differing descriptions of the fascia propria of the rectum. The aim of this study was to describe the detailed surgical anatomy of the fascia propria. METHODS: Thirteen rectal specimens surgically removed by the technique of extrafascial excision were subjected to gross inspection, dissection, and histologic and electron microscopic examination. The attachments, thickness, and composition of the fascia propria were determined. RESULTS: The fascia propria is a continuous fascial sleeve surrounding the rectum and mesorectum that can be dissected as a complete "sock" off a fresh extrafascial specimen. It is 154 (+/- 1 standard deviation = 61-391) microm thick, is thinner anteriorly than posteriorly (P < 0.05), and is composed predominantly of collagen. It can be identified surgically at the pelvic brim as a shiny membrane and lies inside the hypogastric nerves and the pelvic plexuses. CONCLUSION: The fascia propria forms a sleeve around the mesorectum, offering a surface against which to dissect, enabling safe removal of the rectum with its intact mesorectum while preserving the autonomic nerves of the pelvis. The term "extrafascial excision" highlights the importance of the fascia propria in this operation.

Similarity of changes in body composition in intensive care patients following severe sepsis or major blunt injury.

Critically ill patients admitted to the intensive care unit with severe sepsis or major blunt injury undergo massive changes in body composition. We compared these changes in 12 patients with generalized peritonitis, and in 18 patients with major blunt injury over a 21-day period soon after their admission. Body composition was measured as soon as the patients were hemodynamically stable, and again 5, 10, and 21 days later. In both groups, losses in total body protein (TBP) were greatest over the first 10 days. TBP lost over the study period averaged 13.1 +/- 1.3 (SEM)% for the sepsis group, and 14.6 +/- 1.3% for the trauma group. Total body water (TBW) lost postresuscitation averaged 11.1 +/- 1.3 L and 6.7 +/- 1.1 L for the two groups, respectively, these changes largely being accounted for by changes in extracellular water (ECW). Our results demonstrate a striking similarity in the changes in total body protein for these two groups of critically ill patients. The sepsis patients retained approximately twice the volume of fluid of those with major trauma.

Surgery in New Zealand.

Surgery in New Zealand is performed by more than 500 surgeons who serve a population of 3.8 million people. Most of the surgeons are trained in New Zealand under the auspices of the Royal Australasian College of Surgeons. Surgical services are consistent with the highest standards of Western countries.

Extrafascial excision of the rectum for cancer: a technique for the avoidance of the complications of rectal mobilization.

Serious complications can occur following mobilization of the rectum for cancer including: ureteric injury, rectal perforation, hemorrhage, autonomic nerve damage, and local recurrence of the tumor in the pelvis. Each of these complications can be minimized by careful dissection in correct tissue planes in the pelvis. The rectum and mesorectum are surrounded by the fascia propria, a thin fascial envelope. This envelope offers a surface for dissection that leads the surgeon to a safe plane lying inside the autonomic nerves, the ureter, and the presacral vessels, and lying outside of the mesorectum and its associated vessels and lymphatics. The surgical anatomy of the pelvis is presented, with emphasis on the rectal fascia propria, as a basis for a detailed description of the technique of extrafascial excision of the rectum.

Preoperative staging of rectal cancer.

With the widespread introduction of preoperative radiotherapy for rectal cancer and the development of transanal endoscopic microsurgery for selected early lesions, preoperative radiological staging of these tumours has taken on increasing importance. This study is a systematic review to evaluate computed tomography (CT), endorectal sonography (ES) and magnetic resonance imaging (MRI) as preoperative staging modalities in rectal cancer. A Medline-based search identifying studies using CT, ES, or MRI in preoperative staging of rectal cancer between 1980 and 1998 was undertaken. The list of papers was supplemented by extensive cross-checking of citation lists. Studies were included if they met predetermined criteria. Data from the accepted studies were entered into pooled tables comparing radiological and pathological staging results for each modality both in determining bowel wall penetration and involvement of lymph nodes. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were determined for the pooled results. Eighty-three studies from 78 papers including 4,897 patients met the inclusion criteria. In determining the wall penetration of the tumour the values for sensitivity for CT, ES, MRI and MRI with endorectal coil were 78%, 93%, 86% and 89%; for specificity 63%, 78%, 77% and 79%; and for accuracy 73%, 87%, 82% and 84%, respectively. In determining the nodal involvement by tumour the sensitivity values for CT, ES, MRI and MRI with endorectal coil 52%, 71%, 65% and 82%; for specificity 78%, 76%, 80% and 83%; and for accuracy 66%, 74%, 74% and 82%, respectively. MRI with an endorectal coil is the single investigation that most accurately predicts pathological stage in rectal cancer.

Sequential metabolic changes following induction of systemic inflammatory response in patients with severe sepsis or major blunt trauma.

We have recently completed studies in critically ill patients with severe sepsis or major trauma that investigated sequential changes in the metabolic response following admission to the intensive care unit. Protein, water, and energy metabolism were measured using in vivo neutron activation analysis, tracer dilution, dual-energy x-ray absorptiometry, and indirect calorimetry. Over the 3-week study period both groups of patients lost 13% of their total body protein. The severe sepsis patients retained twice the volume of fluid of those with major trauma, and the return to normal hydration in the sepsis group was correspondingly prolonged, especially for those in the elderly age group. In both groups of patients resting energy expenditure increased progressively over the first week to around 40% above normal and was still elevated 3 weeks from onset of illness. A twofold increase in total energy expenditure occurred in both groups of patients between the first and second weeks of critical care admission. The prolonged hypermetabolism throughout the study period was not reflected in the concentrations of circulating proinflammatory cytokines, which fell rapidly over the first week. The pattern of changes seen in plasma proinflammatory and antiinflammatory cytokine concentrations is similar for sepsis and trauma. The remarkably similar metabolic sequelae seen in critically ill patients following the onset of severe sepsis or major trauma may constitute a universal response to the induction of the systemic inflammatory response syndrome.

Wound healing associated with severe surgical illness.

Severe injury or infection is associated with a hypermetabolic response that, when excessive, results in impaired wound healing and as a consequence increased morbidity and mortality. The objective examination of wound healing in humans is difficult and generally requires the use of models. Evidence is accumulating that nutritional and growth factors play important roles in improving the wound healing response, particularly after thermal injury and uncomplicated major surgery. The septic patient represents the biggest challenge to those seeking to optimize wound healing capacity. Advances in molecular biology have provided promising therapies in experimental studies of wound healing that await clinical investigation.

Overview of modern management of patients with critical injury and severe sepsis.

Over the last 10 years there have been substantial changes in the issues confronting intensivists and surgeons caring for critically ill patients. A substantial increase in the number of elderly patients with surgical illness and complex co-morbidity has accompanied the increase in the proportion of elderly in populations in the developed world. This phenomenon has been seen particularly with sepsis. Incidence rates for blunt trauma have declined overall, but the problems of the elderly trauma patient have become more evident. Major elective surgery remains a common indication for short-term intensive care in many countries, but the need for cost-containment has led to increased use of high-dependency care for many such patients. Expectations of both society and clinicians have increased, and this has been reflected in the increased demand for complex procedures (e.g., liver transplantation, cerebral artery aneurysm clipping, aortic aneurysm repair) in patients previously considered at too high risk. Along with these expectations have come pressures on clinicians to reduce costs at the same time as improving clinical outcomes. Despite many advances in the care of critically ill patients with injury or sepsis, mortality, morbidity, and cost remain high; and nutritional support is frequently required. The duration and extent of the metabolic changes seen in response to critical surgical illness and intensive care treatments have become better characterized. Although some of the changes in body water and fat are modifiable, loss of large amounts of (functional) protein has been resistant to various strategies so far studied.

Components of energy expenditure in patients with severe sepsis and major trauma: a basis for clinical care.

OBJECTIVE: To obtain accurate values for the components of energy expenditure in critically ill patients with sepsis or trauma during the first 2 wks after admission to the intensive care unit. DESIGN: Prospective study. SETTING: Critical care unit and university department of surgery in a single tertiary care center. PATIENTS: Twelve severely septic (median Acute Physiology and Chronic Health Evaluation II Score, 23; range, 15 to 34) and 12 major trauma patients (median Injury Severity Score, 33.5; range, 26 to 50). INTERVENTIONS: Total body fat, total body protein, and total body glycogen were measured as soon as hemodynamic stability had been reached and repeated 5 and 10 days later. Resting energy expenditure (REE) was measured daily by indirect calorimetry. MEASUREMENTS AND MAIN RESULTS: Changes in total body fat, total body protein, and total body glycogen in critically ill patients provide data for the accurate construction of an energy balance. Energy intake minus energy balance gives a direct measurement of total energy expenditure (TEE) and, when combined with measurements of REE, activity energy expenditure can be obtained. TEE, REE, and activity energy expenditure were calculated for two sequential 5-day study periods. REE progressively increased during the first week after the onset of severe sepsis or major trauma, peaking during the second week at 37 +/- 6% (SEM) and 60 +/- 13% greater than predicted, respectively. For both the sepsis and trauma patients, TEE was significantly higher during the second week than during the first week (3257 +/- 370 vs. 1927 +/- 370 kcal/day, p < .05, in sepsis; 4123 +/- 518 vs. 2380 +/- 422 kcal/day, p < .05, in trauma). During the first week after admission to the hospital, TEE in sepsis and trauma patients, respectively, averaged 25 +/- 5 and 31 +/- 6 kcal/kg of body weight/day, and during the second week, 47 +/- 6 and 59 +/- 7 kcal/kg/day (p < .03, for comparison of first and second weeks). For the first week, the ratio of TEE to REE was 1.0 +/- 0.2 and 1.1 +/- 0.2 but during the second week rose to 1.7 +/- 0.2 and 1.8 +/- 0.2 in patients with sepsis (p < .05, for comparison of weeks) and trauma (p = .09), respectively. CONCLUSIONS: Total energy expenditure is maximal during the second week after admission to the critical care unit, reaching 50 to 60 kcal/kg/day.

Restorative proctocolectomy with ileal pouch-anal anastomosis in 203 patients: the Auckland experience.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become an established operation for patients with ulcerative colitis and familial adenomatous polyposis (FAP). The results of a 15-year experience with IPAA are reported. METHODS: Between September 1982 and June 1997, 203 patients had IPAA surgery. From a review of the charts, data were collected on the surgical procedure, the diagnosis and early and late complications. Pouch function was assessed by means of a postal questionnaire. RESULTS: Of the 201 patients (median age of 32 years; 89 women) with complete records, 122 had J pouches, 65 had W pouches and 14 S pouches were constructed. The pre-operative diagnosis in 88% was ulcerative colitis and in 10% it was FAP. During a median follow-up time of 6.1 years the diagnoses were changed for 8% of the patients; in 4% the diagnosis was changed to Crohn's disease. The overall mortality was 1.5% (early = 2, late = 1). The overall morbidity was 62% (early = 17%, late = 52%). The pouch was removed or was non-functional in 9%. All patients with a final diagnosis of Crohn's disease have had their pouch excised. The median stool frequency was 4.0 (range 1.3-8.7) during the day, and 0.7 (range 0-2.1) during the night. The fewer night-time stools (J = 1.0+/-0.6; W = 0.4+/-0.5 P < 0.0001) and the reduced requirement of the W-pouch patients for anti-diarrhoeals (P = 0.004) were offset by the need for two W-pouch patients to pass a catheter to empty their pouches. CONCLUSIONS: The type of patients who present for IPAA surgery and the outcomes observed in this series of Auckland patients are similar to those reported from major centres elsewhere.

On-the-table colonic lavage.

Single-stage surgery is an acceptable option in the modern management of many acute colonic conditions. Anastomosing unprepared colon is a major concern. A technique is described that allows on-the-table colonic lavage to be performed without contamination of the abdominal cavity.

Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis--a randomized, clinical trial.

OBJECTIVES: Tumor necrosis factor (TNF)-alpha appears central to the pathogenesis of severe sepsis, but aspects of the cytokine cascade and the link to physiologic responses are poorly defined. We hypothesized that a monoclonal antibody to TNF-alpha given early in the course of severe sepsis would modify the pattern of systemic cytokine release and, as a consequence, resuscitation fluid requirements, net proteolysis, and hypermetabolism would be reduced. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Critical Care Unit and University Department of Surgery in a single tertiary care center. PATIENTS: Fifty-six patients (from 92 eligible patients) with severe sepsis. Twenty-eight patients were randomized to treatment, and were comparable with the placebo group for age, gender, race, Acute Physiology and Chronic Health Evaluation II score, and site and type of infection. INTERVENTIONS: A 300-mg single dose of cA2 (a chimeric neutralizing antibody to TNF-alpha) was given intravenously within 12 hrs of the onset of severe sepsis. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of TNF-alpha, interleukin (IL)-1beta IL-6, IL-8, IL-10, soluble 75-kilodalton TNF-alpha receptor (sTNFR-75), and IL-1beta receptor antagonist (IL-1ra) were measured by sandwich enzyme-linked immunosorbent assay before cA2 infusion, 8 hrs later, and then daily for a minimum of 4 days. Sequential changes in total body protein, body water spaces, and resting energy expenditure over 21 days were measured, as soon as patients achieved hemodynamic stability, by in vivo neutron activation analysis, tritium and bromide dilution, and indirect calorimetry, respectively. Twenty-one patients died, ten having received cA2. Suppression of measurable TNF-alpha was observed at 8 hrs with subsequent rebound by 24 hrs after cA2 treatment. The concentrations of other cytokines were high, were not reduced by intervention, and decreased logarithmically over 5 days. Both groups reached hemodynamic stability at similar times (57.5 +/- 11.8 hrs in controls vs. 58.6 +/- 9.2 hrs in the cA2 group) and following similar volumes of infused fluids (29.1 +/- 3.4 L vs. 28.9 +/- 4.4 L). No differences in net proteolysis, resolution of body water expansion, or alteration in resting energy expenditure were demonstrated. CONCLUSION: A single dose of cA2 did not alter the overall pattern of cytokine activation or the profound derangements in physiologic function that accompany severe sepsis.

Optimal protein requirements during the first 2 weeks after the onset of critical illness.

OBJECTIVE: To obtain optimal protein requirements in critically ill sepsis or trauma patients during the first 2 wks after admission to the intensive care unit. DESIGN: Retrospective study. SETTING: Department of critical care medicine at a teaching hospital. PATIENTS: Immediate posttrauma patients or severely septic patients. INTERVENTIONS: In vivo neutron activation analysis was used to measure changes in total body protein over a 10-day period which began as soon as the patients were hemodynamically stable. The patients (trauma, n=18; sepsis, n=5) were divided into three groups according to the average daily protein intakes. Because the patients were overhydrated (approximately 10 L) and had variable amounts of body fat, the protein intakes were indexed to normally hydrated (corrected) fat-free mass (FFMc): Groups A, B, and C received an average of 1.1, 1.5, and 1.9 g/kg FFMc/day protein, respectively. MEASUREMENTS AND MAIN RESULTS: Overall, the average loss of total body protein was 1.2=0.7 (SD) kg. Changes in total body protein were significantly (p=.011) different between the three groups. The loss of body protein was significantly more in group A compared with groups B (p=.013) and C (p=.023). When the protein intake was increased from 1.1 g/kg FFMc/day to 1.5 g/kg FFMc/day, protein loss was halved. Further increase in protein intake up to 1.9 g/kg FFMc/day resulted in no further improvement. An intake of 1.5 g/kg FFMc/day was equivalent to 1.0 g/day/kg of body weight measured at the beginning of the study. CONCLUSIONS: Current recommended protein requirements of 1.2 to 2.0 g/kg of body weight/day are excessive if they are indexed to the body weight measured soon after the onset of critical illness. Because individual patients have varying degrees of overhydration early in the illness onset, we suggest that the intensivist should obtain information on preillness body weight and prescribe 1.2g of protein/kg body weight/day. If information is not available, 1.0g of protein/day/kg of measured body weight will give a fair approximation to optimal protein requirements.