OBJECTIVE To evaluate the long-term outcome of patients treated in the surgical intensive care unit (SICU) for abdominal sepsis. DESIGN Retrospective study. SETTING University hospital, Sweden. SUBJECTS 210 consecutive patients treated for abdominal sepsis in the SICU at Lund University Hospital during the period January 1983 to December 1995. MAIN OUTCOME MEASURES Background information, morbidity, and mortality. Follow-up of surviving patients with interview and completion of a quality of life (QoL) assessment. Information collected postmortem from the registers of the Swedish National Board of Health and Welfare. RESULTS At follow-up, 45 patients of the 151 who survived the initial hospital stay had died, 41 were lost to follow up and 16 chose not to participate in the study; 49 patients completed the study. Median QoL scores were significantly impaired (p < 0.01) although subjective QoL did not change significantly. In-hospital mortality was 28% (59/210) and total mortality over the time period 50% (104/210). CONCLUSION Most patients who survived after treatment of abdominal sepsis in the SICU regained good health and their functional status was restored. Subjective QoL remained unchanged.
OBJECTIVE:To review the physiology, indications, technical aspects, morbidity, and mortality of damage control surgery.DESIGN:Retrospective study of published papers.SETTING:Teaching hospital, United Arab Emirates.INTERVENTIONS:A MEDLINE search on damage control surgery for the years 1981-2001. Further articles were retrieved from the references of the original articles.RESULTS:The indications for damage control surgery are: the need to terminate a laparotomy rapidly in an exsanguinating, hypothermic patient who had developed a coagulopathy and who is about to die on the operating table; inability to control bleeding by direct haemostasis; and inability to close the abdomen without tension because of massive visceral oedema and a tense abdominal wall. The principles of damage control surgery are: Phase I: laparotomy to control haemorrhage by packing; shunting, or balloon tamponade, or both; control of intestinal spillage by resection or ligation of damaged bowel, or both. Phase II: physiological resuscitation to correct hypothermia, metabolic acidosis, and coagulopathy. Phase III: planned reoperation for definitive repair. Damage control surgery is appropriate in a small number of critically ill patients who are likely to require substantial hospital resources; it has a high mortality (mean 45%, range (10%-69%).CONCLUSION:Damage control surgery offers a simple effective alternative to the traditional surgical management of complex or multiple injuries in critically injured patients. Phases I and II can be done at a rural hospital before transfer to a major trauma centre for definitive repair.
OBJECTIVE:To highlight the in vivo protein markers in human peritoneal mesothelial cells according to their anatomical distribution and their interest in theories of peritoneal repair.DESIGN:Clinical laboratory study.SETTING:University Hospital, France.PATIENTS:Sampling of mesothelial cells during 8 laparotomies by impression smears.MAIN OUTCOME MEASURES:Immunochemical semiquantitative measures of proteins.RESULTS:There were uniform ratios of protein markers among the whole peritoneal mesothelial cell population, whatever their anatomical origin (liver, stomach, omentum, small bowel, and abdominal wall).CONCLUSION:This is consistent with the surrounding uninjured mesothelial cells or the exfoliated mesothelial cells, or both, having a role in postoperative peritoneal mesothelial repair.
OBJECTIVE:To compare the classification of gastric cancer adopted by the American Joint Committee on Cancer and the Union International contre le Cancer (AJCC/UICC) (number of nodes involved) with the Japanese classification (sites of nodes involved).DESIGN:Retrospective study.SETTING:Teaching hospital, Turkey.SUBJECTS:134 consecutive patients whose gastric cancer was treated by D2 resection.INTERVENTIONS:Kaplan-Meier survival analysis and Cox's regression model.MAIN OUTCOME MEASURE:Accuracy of prognosis.RESULTS:There were no significant differences in survival rates when pN1 and pN2 categories of the AJCC/UICC classification were subdivided into the n1 and n2 categories of the Japanese classification. However, when those in the n1 and n2 categories of the Japanese classification were subdivided into the pN1, pN2 and pN3 categories of the AJCC/UICC classification, survival differed significantly (p = 0.00001). When both classifications were combined in a multivariate analysis the pN category of the AJCC/UICC classification was found to be the most significant independent prognostic factor (p = 0.0001).CONCLUSION:Classification of lymph node status by number of nodes (AJCC/UICC) rather than anatomical site (Japanese) gives a more accurate prognosis.
OBJECTIVE:To evaluate the prognosis of papillary microcarcinoma (PMC) of the thyroid.DESIGN:Prospective study.SETTING:Teaching hospital, Italy.SUBJECTS:89 patients treated for papillary micro carcinoma of thyroid and followed up for at least 6 years (range 6-12).INTERVENTION:Total thyroidectomy and, for lymph node metastases, laterocervical lymphadenectomy.MAIN OUTCOME MEASURES:Sex distribution, mode of onset of disease, diameter of tumour, histological type, histological stage, presence of lymph node metastases at the time of operation and type of operation.RESULTS:When the disease presented with laterocervical lymph nodes it was histologically more aggressive and included follicular (n = 3) and sclerosing (n = 4) types.CONCLUSION:Papillary microcarcinoma has an excellent prognosis if managed initially by total thyroidectomy.
OBJECTIVE:To evaluate the long-term outcome of patients treated in the surgical intensive care unit (SICU) for abdominal sepsis.DESIGN:Retrospective study.SETTING:University hospital, Sweden.SUBJECTS:210 consecutive patients treated for abdominal sepsis in the SICU at Lund University Hospital during the period January 1983 to December 1995.MAIN OUTCOME MEASURES:Background information, morbidity, and mortality. Follow-up of surviving patients with interview and completion of a quality of life (QoL) assessment. Information collected postmortem from the registers of the Swedish National Board of Health and Welfare.RESULTS:At follow-up, 45 patients of the 151 who survived the initial hospital stay had died, 41 were lost to follow up and 16 chose not to participate in the study; 49 patients completed the study. Median QoL scores were significantly impaired (p < 0.01) although subjective QoL did not change significantly. In-hospital mortality was 28% (59/210) and total mortality over the time period 50% (104/210).CONCLUSION:Most patients who survived after treatment of abdominal sepsis in the SICU regained good health and their functional status was restored. Subjective QoL remained unchanged.
OBJECTIVETo study the effect of rectopexy and sigmoid resection (resection rectopexy) on symptoms in patients with internal rectal intussusception.DESIGNRetrospective and prospective study.SETTINGUniversity hospital, Norway.PATIENTS22 patients with internal rectal intussusception.INTERVENTIONSResection rectopexy by an open (n = 13) or laparoscopically-assisted (n = 9) technique.MAIN OUTCOME MEASURESSymptomatic outcome, patients' satisfaction, and morbidity. Outcome was based mainly on the validated KESS score, which covers 10 symptoms included in the definiton of constipation.RESULTSThere was a significant reduction in all 10 symptoms. Two patients complained of incontinence which improved after operation. The number of patients with constipation was reduced from 20 to 8 (p = 0.000) and none became constipated. Mean (95% CI) colonic transit times before and after operation in 10 patients with constipation were 5.3 (4.1 to 6.4) and 4.0 (2.6 to 5.4) days (p = 0.083). Seven of these 10 patients had a reduction of both transit time and constipation score. Six patients had complications after open operations. These included one damaged ureter, reoperations for bleeding, incomplete intestinal obstruction, and 2 wound infections.CONCLUSIONRectopexy with sigmoid resection resulted in improvement in symptoms, including constipation and feeling of incomplete rectal evacuation, and acceptable morbidity.
OBJECTIVE:To describe our experience of treating recurrent thyroid carcinoma.DESIGN:Retrospective study of casenotes.SETTING:Teaching hospital, Mexico.SUBJECTS:20 patients who developed recurrences of 273 who presented with well-differentiated thyroid carcinoma between 1991 and 1999.MAIN OUTCOME MEASURES:Presentation, management, morbidity, and mortality.RESULTS:There were 18 men and 2 women, median age 51 years (range 28-75). 13 were treated initially by total thyroidectomy and 7 with less than total resection. 16 were given ablative doses of 311I. The median time between initial resection and recurrence was 3 years (range 1-6). The sites of recurrence were cervical lymph nodes (n = 12), thyroid bed (n = 3), or both (n = 5). During a median of 3 years 10 patients were free of disease and 2 had died.CONCLUSIONS:Well-differentiated thyroid cancer usually recurs in the cervical lymph nodes. Further resection offers a high cure rate.
OBJECTIVE To describe the demographics, mechanisms, pattern, and severity of injury, the prehospital and hospital care during the first 24 hours, and the outcome in the most severely injured children in a paediatric intensive care unit (PICU). DESIGN Retrospective review. SETTING Paediatric intensive care unit (PICU), Sweden. SUBJECTS 45 children (0-16 years of age) with multiple injuries admitted to the PICU in Gothenburg from January 1990 to October 2000, inclusive. MAIN OUTCOME MEASURE Mortality within 30 days after injury. RESULTS About 2/100000 children with multiple injuries were admitted to the PICU from the greater Gothenburg area each year from 1990-2000 inclusive. Injuries were more common in boys (n = 29, 64%). The mean age was 7 years (SD 5). Traffic related events (n = 29, 64%) and falls (n = 11, 24%) were the leading causes of injury. Thoracic and abdominal injuries were the most common (17% and 16% respectively). Three children died. CONCLUSION Major trauma with multiple injuries is rare in Swedish children. When they are cared for at a centre with the necessary facilities and trained personnel they have a good chance of survival.
OBJECTIVE:To compare a systemic transdermal therapeutic system with local application of glyceryl trinitrate ointment in the treatment of anal fissure.DESIGN:Prospective, multicentre, randomised trial.SETTING:Three teaching hospitals, Turkey.SUBJECTS:89 outpatients with chronic anal fissure were randomly assigned to be treated with either transdermal (n = 52) or 0.2% glyceryl trinitrate ointment (n = 37).INTERVENTIONS:The patients were assessed at the sixth and the twelfth week after initial evaluation by physical examination, anoscopy, and anal manometry.MAIN OUTCOME MEASURES:Changes in the maximal anal resting pressure, healing rate.RESULTS:Anal fissure was completely healed in 38 (73%) and 24 (64%) of the patients after 6 weeks and 48 (81%) and 27 (79%) of the patients in transdermal group and ointment group, respectively. Maximal anal resting pressure was reduced by 24% and 21% in transdermal and ointment groups, respectively.CONCLUSION:Systemic transdermal application of glyceryl trinitrate gave a satisfactory healing rate, which was comparable to that of local application of ointment.
OBJECTIVE:To identify the risk factors affecting the outcome of operations for differentiated and aggressive thyroid carcinoma which may indicate the need for a more aggressive surgical treatment. DESIGN:Retrospective study. SETTING:University hospital. PATIENTS AND INTERVENTIONS:143 patients underwent total thyroidectomy with or without central neck lymphadenectomy or modified neck dissection. There were 85 papillary, 34 follicular, 6 widely-invasive follicular, 6 insular, five oxyphilic, five tall cell, and two diffuse sclerosing papillary carcinomas. MAIN OUTCOME MEASURE:Disease-related survival. RESULTS:At 12-years, the survival was 96%, being 98% among patients with differentiated and 83% among those with aggressive carcinoma (p = 0.0006). Insular and oxyphilic carcinomas had the worst prognosis (at 10 years, 67% and 60%, respectively, p < 0.0001). The high-risk age, metastases, and extent score (AMES) group had worse survival than the low-risk group (12 years, 84% compared with 98%, p = 0.001). Among patients with differentiated carcinoma, the low-risk AMES group had also better outcome than those in the high-risk AMES group (at 12 years, 100% compared with 86%, p < 0.0001), but there was no such difference among patients with aggressive disease. Multivariate analysis showed that women (RR 14.28, 95% confidence interval (CI) 1.13 to 180.28), patients with tumours > or = 5 cm in size (RR 9.60, 95%CI 1.01 to 91.43) and AMES high-risk patients (RR 30.17, 95% CI 1.57 to 577.48) had the worst outcome. CONCLUSION:In patients with differentiated thyroid carcinoma, total thyroidectomy and, if the AMES score indicates a high risk, central neck lymphadenectomy with or without modified neck dissection, is associated with a favourable outcome. Poorer outcome is expected if the carcinoma is aggressive, and an aggressive surgical approach is advocated as a routine.
OBJECTIVE:To evaluate the effect of locally applied tranexamic acid on postoperative blood loss and measures of fibrinolysis in drained blood.DESIGN:Prospective study.SETTING:University hospital, Norway.PATIENTS:30 patients operated on for low back pain by screw fixation of the lumbar spine, 16 of who were randomised to be given topical tranexamic acid.MAIN OUTCOME MEASURES:Postoperative blood loss after 18 hours. Concentrations of plasmin/alpha2-antiplasmin (PAP) and D-dimer in arterial and drained blood at the time of wound closure and in drained blood after 1 hour.RESULTS:In the tranexamic group median (interquartile) blood loss was reduced by half from 525 (325-750) ml to 252 (127-465) ml, p = 0.02. In drained blood after one hour the increase in the concentration of PAP was 150 (109-170)% and D-dimer 150 (107-272)% in the tranexamic group compared with the control group where the increase in PAP was 320 (140-540)% and D-dimer 260 (161-670)%.CONCLUSION:Tranexamic acid applied in the wound inhibits blood loss by up to a half in major orthopaedic surgery probably because it prevents excessive fibrinolysis.
The use of biomarkers in medicine, and in epidemiology in particular, is not new but recent developments in molecular biology and genetics have increased the opportunities for their use. Epidemiological studies based on biomarkers, which belong to the discipline defined as 'molecular epidemiology', offer new avenues to investigate associations between genetic and environmental factors, diseases, and medical interventions. Important recent contributions of molecular epidemiology to cancer research include the definitive evidence of the carcinogenicity of aflatoxin in humans, and the elucidation of the mechanisms of tobacco-related carcinogenesis. However, molecular epidemiology studies are subject to problems of design and analysis similar to those of 'traditional' epidemiological studies. If biomarkers offer new opportunities to overcome some of the limitations of epidemiology, their added value over traditional approaches should be systematically assessed. Biomarkers should be validated though transitional studies; consideration to sources of bias and confounding in molecular epidemiology studies should be no less stringent than in traditional studies.
Maslow's theory of the structure of basic needs and how unmet needs relate to anxiety and stress can be used as an underlying framework for clinical practice. The application of this theory is particularly pertinent to symptomatic conditions. In this paper patients with gastro-oesophageal reflux disease are used as an illustration of how better understanding of patient needs may promote well-being and improve delivery of health care.
Gastrointestinal peptides including mammalian bombesin-like peptides, cholecystokinin (CCK), gastrin, and neurotensin stimulate DNA synthesis and cell proliferation in cultured cells and are implicated as growth factors in a number of fundamental processes including development, inflammation, tissue regeneration, and neoplastic transformation. These agonists bind to G protein-coupled receptors (GPCRs) that promote Galpha q-mediated activation of beta isoforms of phospholipase C to produce two second messengers: Inositol (1,4,5) trisphosphate {Ins (1, 4, 5) P3} that mobilises Ca2+ from internal stores, and diacylglycerol that activates the classic and new isoforms of the protein kinase C (PKC) family. PKCs play a critical part in transducing bombesin/gastrin releasing peptide (GRP) receptor signals into activation of protein kinase cascades. Protein kinase D (PKD), a serine/threonine protein kinase with distinct structural and enzymological properties, is activated by phosphorylation in living cells through a new PKC-dependent signal transduction pathway. GPCR agonists including bombesin/GRP induce a rapid and striking activation of PKD by PKC. These results indicate that PKD functions downstream from PKCs and identify a new phosphorylation cascade that is activated by gastrointestinal peptide agonists. The bombesin/GRP GPCR also promotes rapid Rho-dependent assembly of focal adhesions, formation of actin stress fibres and tyrosine phosphorylation of multiple cellular proteins. We identified p125 focal adhesion kinase (FAK), p130 Crk-associated substrate (CAS) and paxillin as prominent targets of gastrointestinal peptide-stimulated tyrosine phosphorylation and developed a model that envisages a G12/Rho-dependent pathway connecting GPCR activation to the tyrosine phosphorylation of these focal adhesion proteins. Separate pathways mediate gastrointestinal peptide stimulation of additional tyrosine kinase pathways including transactivation of Src and epidermal growth factor receptor (EGFR). Tyrosine phosphorylation has a critical role in gastrointestinal peptide-induced cellular migration and cooperates with Gq-stimulated events to promote mitogenesis. The growth-promoting effects of neuropeptides and the elucidation of the signalling pathways that mediate their effects assume an added importance because these agonists and their receptors are increasingly implicated in sustaining the proliferation of clinically aggressive solid tumours including those from lung, pancreas, and colon.
Genomic techniques offer new approaches to the investigation of the aetiology and pathophysiology of intestinal disorders. An important field that is relevant to treatment is the pharmacogenetic investigation of gene variations that may predict response to certain drugs in order to target these drugs more precisely. For the surgeon the perioperative situation will be here of great interest. To date only about 8000 of the estimated 30,000-50,000 human genes have been characterised, so the use of techniques for global analysis of gene expression may allow the identification of new pathways or molecules. In can be anticipated that genomic methods will profoundly influence the treatment of gastrointestinal disorders and will lead to new insights into both aetiology and pathophysiology of chronic intestinal inflammation.
Cirrhosis, a pathological condition defined by deranged hepatic architecture resulting from progressive fibrosis, is the final common pathway through which nearly all chronic diseases of the liver produce morbidity and mortality. Historically, treatments for hepatic fibrosis have been directed against specific causes of chronic liver injury, and include corticosteroids for autoimmune hepatitis, interferon for hepatitis B and C, and iron depletion for haemochromatosis. However, there is no effective treatment for most causes of chronic liver disease. Fortunately, the past decade has witnessed great advances in our understanding of the fundamental pathophysiological mechanisms underlying fibrosis of the liver. It is now recognised that hepatic stellate cells (myofibroblast-like cells that encircle the sinusoids) are primarily responsible for hepatic fibrosis and subsequent progression to cirrhosis. In response to liver injury stellate cells undergo a phenotypic transformation that is termed activation, and characterised by chemotaxis, proliferation, contraction, fibrogenesis, and extracellular matrix degradation. Under conditions of persistent injury the behavioural responses of these stellate cells act in concert to bring about fibrosis of the liver. Recent investigations elucidating the signal transduction pathways that link hepatic injury to stellate cell function suggest novel targets at which treatment for fibrosis may be directed. For example, antagonism of TGF-beta receptor signaling has been shown to modulate fibrosis in animal models. This work, as well as other studies in both humans and animals, indicates that hepatic fibrosis may be slowed or reversed. These results suggest that a rational approach to treatment can be developed based on our detailed understanding of the molecular and cellular mechanisms underlying cirrhosis, which will have a major impact on the clinical management of patients with chronic liver disease.
