Effects of a caspase and a calpain inhibitor on resting energy expenditures in normal and hypermetabolic rats: a pilot study.

Several diseases induce hypermetabolism, which is characterized by increases in resting energy expenditures (REE) and whole body protein loss. Exaggerated protein degradation is thought to be the driving force underlying this response. The effects of caspase and calpain inhibitors on REE in physiological and hypermetabolic conditions, however, are unknown. Thus, we studied whether MDL28170 (calpain inhibitor) or z-VAD-fmk (caspase inhibitor) affect REE under physiological conditions and during hypermetabolism post-burn. Rats were treated five times weekly and observed for 6 weeks. Treatment was started 2 h (early) or 48 h (late) after burn. In normal rats, MDL28170 transiently increased REE to 130 % of normal during week 2-4. z-VAD-fmk reduced REE by 20-25 % throughout the observation period. Within 14 days after burns, REE increased to 130+/-5 %. Whereas MDL28170/early treatment did not affect REE, MDL28170/late transiently increased REE to 180+/-10 % of normal by week 4 post-burn. In contrast, with z-VAD-fmk/early REE remained between 90-110 % of normal post-burn. z-VAD-fmk/late did not affect burn-induced increases in REE. These data suggest that caspase cascades contribute to the development of hypermetabolism and that burn-induced hypermetabolism can be pharmacologically modulated. Our data point towards caspase cascades as possible therapeutic targets to attenuate hypermetabolism after burns, and possibly in other catabolic disease processes.

Requirement for postoperative imaging in an enhanced recovery programme.

AIM: Enhanced recovery after surgery (ERAS) produces benefits to patients by reducing the length of hospital stay and morbidity. Its effect on nursing and physiotherapy workload has been studied, but the demand upon radiology is unclear. We aimed to determine radiology use to understand possible hidden expenditure not included in existing ERAS cost-effectiveness analyses. METHOD: Two-hundred and sixty-five patients from a prospective multidimensional ERAS database were retrospectively assessed for postoperative radiology use. All had undergone colorectal surgery within an established ERAS programme from 2008 to 2009, with all data prospectively recorded. Laparoscopy was offered for all primary colon and rectal resections. All adverse events, including gut dysfunction, surgical site infection and reoperation, were assessed. All radiology within 30 days of surgery was recorded. RESULTS: Radiology data were absent in 12 patients, leaving 253 for analysis. Postoperative radiology was used in 71 (28%) patients, and 41 (16%) had CT of the abdomen and pelvis (A/P) within 30 days of surgery. In 33 (13%) patients this was required during the primary admission, including 30% of patients with any postoperative adverse event. Nine (27%; 3.6% of the whole cohort) of the 33 patients required reoperation. No patient required interventional radiology. The median time to CT (A/P) during primary admission was 5 (interquartile range, 3-8) days. Eight (3%) patients had CT (A/P) after readmission with one reoperation. Forty (16%) patients underwent plain radiology (chest or abdominal) and six (2%) had abdominal ultrasound. Using general estimates of CT and plain radiology total costs, these data suggest an overall radiology cost of over £22,000, amounting to a radiology cost of £90 per ERAS patient. CONCLUSION: Postoperative radiology is required in a significant proportion of ERAS patients, potentially reflecting a low threshold to investigate in the presence of an adverse event. Very few require subsequent intervention. Radiology costs incurred with ERAS should be considered in future economic analyses.

The influence of an enhanced recovery programme on clinical outcomes, costs and quality of life after surgery for colorectal cancer.

OBJECTIVE: Optimizing peri-operative care using an enhanced recovery programme improves short-term outcomes following colonic resection. This study compared a prospective group of patients undergoing resection of colorectal cancer within an enhanced recovery programme, with a prospectively studied historic cohort receiving conventional care. PATIENTS AND METHODS: Sixty patients underwent elective resection within an enhanced recovery programme (ERP). This incorporated pre-operative counselling, epidural analgesia, early feeding and mobilization. Clinical outcomes were compared with 86 prospectively studied historic control patients receiving conventional care (CC). All patients completed EORTC QLQ-C30, QLQ-CR38 and health economics questionnaires up to three months after surgery. RESULTS: Baseline clinical data were similar in both groups. Postoperative hospital stay was significantly reduced in the ERP, with patients staying 49% as long as those in the CC group including convalescent hospital stay (95% CI 39% to 61%P < 0.001). There were no differences in the number of complications, readmissions or re-operations. There were no significant differences in quality of life or health economic outcomes. CONCLUSION: Patients undergoing colorectal resection within an ERP stay in hospital half as long as those receiving conventional care, with no increased morbidity, deterioration in quality of life or increased cost.

Laparoscopic colonic surgery--mission accomplished or work in progress?

Laparoscopic colonic resection may facilitate early postoperative recovery due to reduced surgical stress, pain and ileus. However, large randomised studies have only shown marginal improvements in outcome compared with open surgery, reporting a median hospital stay of about 5-7 days. Concomitant with these developments multimodal rehabilitation, which involves a revision of general postoperative care principles, improved pain relief with epidural analgesia and early oral nutrition and mobilization, has demonstrated greater improvements in recovery after open surgery, resulting in a median hospital stay of about 2-4 days. Recent single centre, randomised studies where laparoscopic and open colonic resection are combined with multimodal rehabilitation have not resolved the debate regarding which is the optimal operative technique. Therefore, new strategies are required to integrate laparoscopy with multimodal rehabilitation in order to establish its advantages, cost effectiveness and indications in specific groups of patients or colorectal procedures, thus justifying widespread application of the laparoscopic technique.

Randomized clinical trial comparing laparoscopic and open surgery for colorectal cancer within an enhanced recovery programme.

BACKGROUND: Laparoscopic resection of colorectal cancer may improve short-term outcome without compromising long-term survival or disease control. Recent evidence suggests that the difference between laparoscopic and open surgery may be less significant when perioperative care is optimized within an enhanced recovery programme. This study compared short-term outcomes of laparoscopic and open resection of colorectal cancer within such a programme. METHODS: Between January 2002 and March 2004, 62 patients were randomized on a 2 : 1 basis to receive laparoscopic (n = 43) or open (n = 19) surgery. All were entered into an enhanced recovery programme. Length of hospital stay was the primary endpoint. Secondary outcomes of functional recovery, quality of life and cost were assessed for 3 months after surgery. RESULTS: Demographics of the two groups were similar. Length of hospital stay after laparoscopic resection was 32 (95 per cent confidence interval (c.i.) 7 to 51) per cent shorter than for open resection (P = 0.018). Combined hospital, convalescent and readmission stay was 37 (95 per cent c.i. 10 to 56) per cent shorter (P = 0.012). The relative risk of complications, quality of life results and cost data were similar in the two groups. CONCLUSION: Despite perioperative optimization of open surgery for colorectal cancer, short-term outcomes were better following laparoscopic surgery. There was no deterioration in quality of life or increased cost associated with the laparoscopic approach.

Endonasal dacryocystorhinostomy: a report by the American Academy of Ophthalmology.

OBJECTIVE: This document describes endonasal dacryocystorhinostomy (DCR) and examines the evidence to answer key questions about the effectiveness of the procedure compared with external DCR; the relative indications, contraindications, advantages, and limitations of the procedure; and patient selection, surgical technique, postoperative care, and complications. METHODS: A literature search conducted for the years 1968 to 2000 retrieved 93 citations. The panel members reviewed 71 of these articles and selected 64 for the panel methodologist to review and rate according to the strength of evidence. A level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a level II rating is assigned to well-designed cohort and case-control studies; and a level III rating is assigned to case series and poorly designed prospective and retrospective studies, including case-control studies. RESULTS: The published literature includes two reports that describe clinical trials comparing endonasal with external DCR with a 1-year follow-up. The success rate was 91% for the external DCR group in both reports and 63% and 75% for the endonasal DCR groups, defined by patency to irrigation. A longitudinal cohort study included a control group of age-matched external DCR patients who were compared with a study group of endonasal DCR patients. The reported success rate at 9 months following surgery for the endonasal cohort was 90% and was not statistically significantly different from the 94% success rate noted in the external DCR control group. Remaining data on reported success rates of primary and revision endonasal DCR were obtained from a collection of uncontrolled observational case studies with varying periods of follow-up and success rates ranging from 59% to 100%. CONCLUSIONS: It is difficult to make definite evidence-based determinations about the relative efficacy of endonasal and external DCR because of the deficiencies in the reported literature. Based on level III evidence, the available data suggest that endonasal DCR may be a viable option for the correction of acquired nasolacrimal duct obstruction and complex forms of congenital dacryostenosis in selected patients. This procedure may be indicated on a primary basis or as revisional surgery following failed external or endonasal DCR. Some studies comparing endonasal DCR with external DCR suggested lower success rates in the endonasal group; other studies yielded success rates comparable with or exceeding those of external surgery. Reported complications of endonasal DCR do not generally appear to be greater in frequency or magnitude than those associated with external DCR. Disadvantages of endonasal DCR include the preferred use of general anesthesia by many surgeons, the high cost of expensive equipment and instrumentation, and the relatively steep learning curve for this procedure. Depending on the preference of the surgeon, more postoperative care may be required for patients undergoing endonasal DCR than external DCR. Both the advantages and the limitations of endonasal DCR relative to external DCR should be carefully discussed with patients who are contemplating endonasal surgery.

Sequential connective matrix changes in experimental acute pancreatitis. An immunohistochemical and biochemical assessment in the rat.

The effects of acute pancreatitis on the rat pancreatic connective tissue matrix were studied following intraductal pancreatic injection of trypsin solution and serial killing of the animals. Pancreatic tissue was examined using light microscopy, hydroxyproline measurement and indirect immunofluorescence, using antibodies against collagen types I, III, IV, procollagen III, fibronectin and laminin. Light microscopy revealed that acute pancreatitis was present for up to four days after injection and that perilobular and intralobular fibrosis appeared at four days and subsequently regressed. Immunofluorescence studies demonstrated an abnormal fibronectin deposit at one day in acute pancreatitis. At four days this deposit was co-located with fibrosis which was composed of collagen and procollagen type III. By eight days the immunofluorescence and light microscopic changes were minimal. Biochemical analysis confirmed a significant rise in hydroxyproline concentration at four days, which was maximal at eight days, subsequently decreasing. This peak at eight days probably reflects collagen breakdown products.

Cardiac-catheterization and cardiac-surgical facilities: use, trends, and future requirements.

Cardiac catheterizations and cardiac operations were evaluated in the population of Olmsted County, Minnesota, from 1973 through 1980, and trends in this region were compared with nationwide trends based on data from several sources. The rates of coronary arteriography and coronary-artery bypass operations in Olmsted county have increased over time, but overall, the rates of catheterization and operation appeared to be leveling off. For the country as a whole, the data appear to show similar trends, but there are wide differences among regions in the rates of operation and catheterization. In 1980 40 per cent of hospitals with cardiac-catheterization laboratories and 55 per cent of those with facilities for open-heart surgery were doing fewer than the suggested minimum numbers of these procedures necessary to achieve optimum results. The data support the view that further growth in the number of cardiac centers should be avoided. We believe there is a need for continued evaluation of the use of cardiac services if quality is to be protected and costs controlled.

Trends in cardiac surgery. Five-year study of a defined population.

The total number and types of cardiac operations performed on residents of Olmsted County, Minnesota, from 1973 through 1977 were studied through the use of the medical-records linkage system at the Mayo Clinic. During this time, 213 patients underwent 216 operations. The rates of cardiac operations per 10,000 population increased from 4.1 in 1973 to 5.9 in 1977. Operations other than for coronary artery bypass showed no significant trends over time, and the average rate was 2.5 per year. The incidence of coronary artery bypass operations increased from 1.5 in 1973 to 4.0 in 1977. On the basis of the rates for open-heart operations and under conditions similar to those in this community, a population of approximately 380,000 persons less than 15 years of age would be required to ensure 75 cases requiring open-heart operations per year, and a population of approximately 230,000 persons more than 14 years of age would provide 200 adult open-heart cases per year. Thus total populations of approximately 1,380,000 and 310,000 of all ages would be required to meet these minimum standards for pediatric and adult open-heart operations.

Neurologic computed tomography in a defined population group.

A total of 766 residents of Olmsted County, Minnesota, underwent neurologic computed tomography (CT) from June 1973 through 1976; 981 scans were performed. The number of CT scans per 1,000 population increased each year and, during the period studied, the average rate based on the initial scan in each case was 2.4 and the rate based on all scans was 3.1. The age-specific rates were greatest among patients 65 years old or older. If CT use plateaus at about 6 scans per 1,000 population, then under conditions similar to those in this community, a population of approximately 400,000 would be required to assure adequate use of a CT scanner for investigating neurologic disease.