MRI in predicting curative resection of rectal cancer: new dilemma in multidisciplinary team management.
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Humans↗
Biomedical subjects
Ara W Darzi
Publications and source records attributed to Ara W Darzi.
Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease.
AIMS: The aim of this study was to assess the diagnostic precision of antiSaccharomyces cerevisiae (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) in inflammatory bowel disease (IBD) and evaluate their discriminative ability between ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Meta-analysis of studies reporting on ASCA and pANCA in IBD was performed. Sensitivity, specificity, and likelihood ratios (LR+, LR-) were calculated for different test combinations for CD, UC, and for IBD compared with controls. Meta-regression was used to analyze the effect of age, DNAse, colonic CD, and assay type. RESULTS: Sixty studies comprising 3,841 UC and 4,019 CD patients were included. The ASCA+ with pANCA- test offered the best sensitivity for CD (54.6%) with 92.8% specificity and an area under the ROC (receiver operating characteristic) curve (AUC) of 0.85 (LR+ = 6.5, LR- = 0.5). Sensitivity and specificity of pANCA+ tests for UC were 55.3% and 88.5%, respectively (AUC of 0.82; LR+ = 4.5, LR- = 0.5). Sensitivity and specificity were improved to 70.3% and 93.4% in a pediatric subgroup when combined with an ASCA- test. Meta-regression analysis showed decreased diagnostic precision of ASCA for isolated colonic CD (RDOR = 0.3). CONCLUSIONS: ASCA and pANCA testing are specific but not sensitive for CD and UC. It may be particularly useful for differentiating between CD and UC in the pediatric population.
Adult↗
Laparoscopic versus open surgery for rectal cancer: a meta-analysis.
BACKGROUND: Laparoscopic rectal cancer surgery aims to provide patients with curative resection while minimizing postoperative morbidity and mortality. This study used meta-analytical techniques to compare laparoscopic and open surgery as the primary treatment for patients with rectal cancer with regard to short-term and long-term outcomes. METHODS: A literature search was performed on all studies between 1993 and 2004 comparing laparoscopic and open surgery for rectal cancer. Subgroup analysis was performed on patients undergoing abdominoperineal excision of the rectum. The following end points were evaluated: operative outcomes, postoperative recovery, and early and late adverse events. RESULTS: Twenty studies matched the selection criteria and reported on 2071 subjects, of whom 909 (44%) underwent laparoscopic and 1162 (56%) underwent open surgery for rectal cancer. Time to stomal function (weighted mean difference [WMD], -1.52; 95% confidence interval [95% CI], -2.20, -1.01), first bowel movement (WMD, -.72; 95% CI, -1.21, -.22), feeding solids (WMD, -.92; 95% CI, -1.35, -.50), and length of hospital stay (WMD, -2.67; 95% CI, -3.81, -1.54) were all significantly reduced after laparoscopic surgery. In patients who underwent abdominoperineal excision of the rectum, wound infection (odds ratio, .15; 95% CI, .03, .73) and requirement for postoperative parenteral analgesia (WMD, -.63; 95% CI, -1.22, -.04) were also significantly reduced. There was no difference between groups in the extent of oncological clearance. CONCLUSIONS: Laparoscopic rectal cancer surgery results in an earlier postoperative recovery and a resected specimen that is oncologically comparable to open surgery. Results from randomized trials reporting long-term outcomes such as cancer recurrence (local and metastatic) and 5-year survival are eagerly awaited.
Clinical Trials as Topic↗
Outcomes following laparoscopic versus open repair of incisional hernia.
AIM: The purpose of this study was to compare short- and long-term outcomes for patients undergoing laparoscopic or open surgery for incisional hernia repair using meta-analytical techniques. METHODS: A literature search was performed to identify comparative studies reporting outcomes on laparoscopic versus open surgery for incisional hernia repair. A random-effect meta-analytical model was used and subgroup analysis performed on high-quality studies, those reporting on more than 30 patients, and those published since 2000. RESULTS: Five studies, with a total of 351 patients, satisfied the inclusion criteria. Laparoscopic surgery was attempted in 148 (42.2%) patients. Overall, in the laparoscopic group, operative time was significantly longer--by 12.0 minutes (P = 0.03) and length of stay reduced by 3.3 days (P < 0.003) although this finding was associated with significant heterogeneity between studies (P < 0.001). There was no difference in the short-term adverse events between the groups, but there were fewer wound infections for laparoscopic patients in high-quality studies [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.05, 0.85, P = 0.03] and those reporting on more than 30 patients (OR = 0.19, 95% CI: 0.04, 0.84, P = 0.03). No difference in hernia recurrence was shown in the overall or subgroup analysis. CONCLUSIONS: Laparoscopic incisional hernia repair was associated with a reduced length of stay and lower wound infection rate. The impact on post-operative quality of life and financial implications needs further prospective, validated evaluation.
Hernia, Ventral↗
Laparoscopic vs. open surgery for diverticular disease: a meta-analysis of nonrandomized studies.
PURPOSE: This study was designed to compare outcomes between laparoscopic and open surgery for patients with diverticular disease by using meta-analytic techniques. METHODS: Comparative studies published between 1996 and 2004 of open vs. laparoscopic surgery for diverticular disease were included. The end points that were evaluated are operative and functional outcomes and adverse events. A random effects model was used during analysis of these outcomes; heterogeneity was assessed and sensitivity analysis was performed to account for bias in patient selection. RESULTS: Twelve nonrandomized studies, incorporating 19,608 patients, were included in the analysis. One study with 18,444 patients accounted for 94.5 percent of the total sample. Laparoscopic surgery resulted in reduced infective (odds ratio, 0.61; P = 0.01), pulmonary (odds ratio, 0.4; P < 0.001), gastrointestinal tract (odds ratio, 0.75; P = 0.03), and cardiovascular complications (odds ratio, 0.28; P = 0.0008) with no significant heterogeneity. Operative time was longer with laparoscopic surgery (weighted mean difference, 67.59; P = 0.04), and length of stay was significantly shorter (weighted mean difference, -3.81; P < 0.0001); however, these outcomes demonstrated significant heterogeneity. These results remained significant throughout all the sensitivity analyses except when evaluating high-quality studies (when the study with 18,444 patients was excluded), in which only blood loss and length of stay were significantly in favor of the laparoscopic group. CONCLUSIONS: The results for patients selected for laparoscopic surgery compared with open surgery for diverticular disease are equivalent with a potential reduction in complications and hospital stay. Laparoscopic surgery for diverticular disease performed by appropriately experienced surgeons in the elective setting may be safe and feasible; because of the potential of significant bias arising from the included studies, a randomized, controlled trial is recommended.
Adult↗
A national study on lymph node retrieval in resectional surgery for colorectal cancer.
PURPOSE: This study was designed to develop a mathematical model for predicting the number of lymph nodes harvested in bowel cancer resection specimens based on the current clinical practice in the United Kingdom. METHODS: Prospective clinical data were collected from 8,409 newly diagnosed bowel cancer patients presenting to 79 hospitals in Great Britain and Ireland during a variable 12-month period from 2000 to 2002. A two-level hierarchical regression model was used to identify predictors for lymph node harvest. The model was internally validated by comparing observed and model predicted lymph node harvest for patient subgroups. RESULTS: Inclusion criteria were satisfied by 5,164 patients. The average lymph node harvest was 11.7 nodes with significant between-center variability in lymph node harvest (range, 5.5-21.3 nodes). Increasing age, American Society of Anesthesiology grade, and preoperative radiotherapy were associated with a reduction of lymph node harvest (P < 0.001). Abdominoperineal resection of the rectum and transverse colectomy were the lowest yield procedures for lymph node harvest. Independent predictors of lymph node harvest were age, American Society of Anesthesiology grade, Dukes stage, operative urgency, type of resection, and preoperative radiotherapy. When tested, the model was found to accurately predict lymph node harvest for group statistics (comparison of observed and model predicted lymph node harvest F(1,5154) = 0.63; P = 0.427). CONCLUSIONS: The results of the study suggest that the minimum number of lymph nodes harvested in colorectal cancer surgery cannot be set at a fixed value. The lymph node harvest model provides a simple tool to the frontline clinician for comparing standards between multidisciplinary bowel cancer teams.
Age Factors↗
Pouch-anal anastomosis vs straight ileoanal anastomosis in pediatric patients: a meta-analysis.
BACKGROUND: Restorative proctocolectomy is the treatment of choice for pediatric patients with refractory colitis, inherited polyposis syndromes, and some with colonic aganglionosis. Evidence concerning the optimal method of reconstruction is, however, sparse. METHODS: Studies comparing outcomes from ileal pouch-anal anastomosis (IPAA) and straight ileoanal anastomosis (SIAA) were identified by searching Medline, Ovid, and Embase. Suitable studies were selected and data extracted for meta-analysis. RESULTS: Of 13 studies identified by literature search, 5 satisfied the inclusion criteria, comprising a total of 306 patients, 86 of whom (28.1%) underwent SIAA, and the remainder, IPAA. Pouch failure was more common in the SIAA group (odds ratio, 3.21; confidence interval, 1.24-8.34), as were abdominal salvage procedures (odds ratio, 9.5; confidence interval, 3.14-28.77). Short-term adverse events were similar between the 2 groups, with the exception of perianal sepsis, the higher frequency of which, in SIAA, just reached statistical significance. Bowel frequency was lower in the IPAA patients, although few studies presented functional data in a comparable form. CONCLUSIONS: There are few good-quality studies that compare the outcomes from SIAA and IPAA, meaning that caution should be exercised in the generalization of the results of this meta-analysis, which suggests pouch procedures to be favorable in terms of reconstruction survival and functional outcome.
Adenomatous Polyposis Coli↗
Technical skills continue to improve beyond surgical training.
BACKGROUND: There is growing focus on surgical technical competence and the means by which we are able to measure it. Ongoing studies have shown a plateau effect with increasing experience of the operator. The aim of this study was to assess the technical competence of five groups of surgeons with increasing experience and validate a new rating tool for use in surgical assessment. METHODS: Fifty surgeons performed a saphenofemoral junction ligation on a synthetic groin model. The procedure was videotaped, blinded, and reviewed independently by three assessors. Performance was assessed using a previously validated global rating scale of generic surgical skill. In addition, each procedure was rated with the procedure-specific Imperial College Evaluation of Procedure-Specific Skill (ICEPS) rating scale to establish the construct validity (ability to differentiate on the basis of skill) and inter-observer reliability. RESULTS: Both rating scales showed improved scores with ascending grades (P < .001) and demonstrated a high inter-observer reliability both for generic and procedure-specific skill (alpha = 0.97 and alpha = 0.96, respectively). Total operative scores demonstrated significant differences between surgeons in postgraduate years 1 and 2 and surgeons in years 3 and 4 and also between newly appointed and experienced consultants (P < .041). Procedure-specific performance showed a plateau effect at the registrar level. Generic skill continued to improve, and significant differences were seen between newly appointed and senior consultants (P < .026). CONCLUSION: This study shows that surgical performance continues to improve significantly beyond consultancy, and the data suggest that generic and procedural performance continue to improve, with significant improvement in the former with increasing experience. The ICEPS rating scale demonstrates construct validity and a high inter-observer reliability supporting its use in formative and summative assessment.
Clinical Competence↗
Diagnostic precision of nanoparticle-enhanced MRI for lymph-node metastases: a meta-analysis.
BACKGROUND: At present, there is no accepted, ideal imaging modality or technique for diagnosis of lymph-node metastases. We aimed to assess the diagnostic precision of MRI with ferumoxtran-10-an ultrasmall superparamagnetic iron-oxide nanoparticle used as a contrast agent for diagnosis of lymph-node metastases, compared with that of unenhanced MRI and final histological diagnosis. METHODS: We did a meta-analysis of prospective studies that compared MRI, with and without ferumoxtran-10, with histological diagnosis after surgery or biopsy. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for every study; summary receiver operating characteristic (ROC) and subgroup analyses were done; and study quality and heterogeneity were assessed. Metaregression analysis was used to analyse the effect of ferumoxtran-10 in diagnostic precision of MRI. FINDINGS: Summary ROC curve analysis for per-lymph-node data showed an overall sensitivity of 0.88 (95% CI 0.85-0.91) and overall specificity of 0.96 (0.95-0.97) for ferumoxtran-10-enhanced MRI. Overall weighted area under the curve for ferumoxtran-10-enhanced MRI was 0.96 (SE 0.01), DOR 123.05 (95% CI 5.93-256.93). Unenhanced MRI had less overall sensitivity (0.63 [0.57-0.69]) and specificity (0.93 [0.91-0.94]), with an overall weighted area under the ROC curve of 0.84 (SE 0.11) and DOR of 26.75 (95% CI 8.48-84.42). Significant heterogeneity was noted for studies reporting enhanced MRI and unenhanced MRI. Metaregression analysis confirmed the significant effect of ferumoxtran-10 in the diagnostic precision of MRI (p=0.001). INTERPRETATION: Ferumoxtran-10-enhanced MRI is sensitive and specific in detection of lymph-node metastases for various tumours. It offers higher diagnostic precision than does unenhanced MRI for detection of lymph-node metastases, and allows functional and anatomical definition when used as an imaging modality.
Contrast Media↗
ICAM-1 mediated peritoneal carcinomatosis, a target for therapeutic intervention.
Development of peritoneal metastasis is a significant issue in the treatment of abdominal cancers. Primary interaction between tumour cells and the mesothelium is a vital step in initiating this process. Our aim was to determine the role of the intercellular adhesion molecule-1 (ICAM-1) in mesothelial-tumour adhesion and the effectiveness of therapeutic intervention. Mesothelial cells were derived from omental tissue. ICAM-1 expression in resting state, in the presence of TNF-alpha or after the application of heparin or hyaluronan was determined by flow cytometry. Functional effects on tumour adhesion to a mesothelial monolayer were determined via a Calcein-AM in vitro adhesion assay. In vivo studies were performed utilising 30 WAG/rij rats, which underwent mini-laparotomy with the injection of 1 x 10(5 )CC 513 tumour cells intraperitoneally. Tumour growth was assessed macroscopically and microscopically by two independent examiners. Mesothelial cells expressed high level of ICAM-1, which was up-regulated by the presence of TNF-alpha. The introduction of heparin caused a decrease in ICAM-1 expression, however hyaluronan did not affect the expression. A significant decrease in tumour-mesothelial cell adhesion in vitro and complete aberration of tumour growth in vivo was observed with heparin application. In vitro studies showed utilisation of high molecular weight hyaluronan, which was more limited in vivo. These data imply that heparin may be used as a potential therapeutic through a defined molecular mechanism both in vitro and in vivo. Hyaluronan appears to function as a barrier and hence may be unreliable in blocking peritoneal recurrence.
Animals↗
Assessing the teaching of technical skills.
BACKGROUND: There is a lack of structured instruments to assess how technical skills are taught. We aimed to develop a practical assessment tool that is easy to use and will assess the teaching of technical skills. METHODS: A 5-point Likert global rating scale was constructed. An experienced surgeon independently assessed each surgery using the assessment tool. Trainees also used the assessment tool after the surgery. RESULTS: Forty-two surgeries were assessed: 26 open and 16 laparoscopic surgeries. Interrater reliability between the independent assessor and trainees was performed using a kappa coefficient of .77 and a P value of less than .05. CONCLUSIONS: Our study shows that our assessment instrument has a potential ability to assess any taught technical task. We will continue and expand the study in surgery, and we aim to expand it further to medical specialties (eg, internal medicine, and so forth) that also teach technical tasks (eg, chest drain insertion, and so forth).
Adult↗
Hypoxia augments gelatinase activity in a variety of adenocarcinomas in vitro.
BACKGROUND: Hypoxia within solid adenocarcinomas and protease up-regulation has been independently implicated as poor prognostic indicators in a variety of tumor types. The authors hypothesize that Matrix Metalloproteases (MMP) are up-regulated in direct response to a hypoxic environment. MATERIALS AND METHODS: Colonic (SW1222), breast (MDA-MB231), and pancreatic (PSN-1) tumor cell lines were exposed to hypoxia (1% oxygen/94% nitrogen/5% carbon dioxide) for periods of up to 24 h. Reaction to a hypoxic environment was determined via invasion across a Matrigel-coated 8-microm Transwell filter. Activity of MMP 2 and 9 was assessed using gelatin zymography. Expression of tissue inhibitor of metalloproteases 1 (TIMP-1) was quantified using ELISA (Biotrak). Correlation between protease expression and invasive capacity was determined using a specific gelatinase inhibitor (MMPI; Calbiochem). RESULTS: All tumor lines demonstrated augmented invasion over 72 h (P < 0.01 all groups). Concomitant significant increase in MMP 2 and 9 activity was observed in the SW1222 and PSN-1 lines. MDA-MB231s showed increase in MMP 9 expression and in a unidentified 103-kDa gelatinase (P < 0.001). The hypoxia-augmented invasion was attenuated by the addition of a specific gelatinase inhibitor confirming interdependence. CONCLUSIONS: Hypoxia induces an increased invasive capacity via gelatinase up-regulation without loss of cell viability. This suggests a mechanism explaining the poorer prognosis seen in patients with protease-secreting solid adenocarcinomas.
Adenocarcinoma↗
Technical performance: relation between surgical dexterity and technical knowledge.
Technical performance consists of surgical knowledge, judgment, and dexterity. Although assessment of surgical dexterity is now possible, assessing technical knowledge and its relation to dexterity has not been elucidated. Surgeons of varying experience were recruited to the skills laboratory to undertake three assessments: simple surgical dexterity (at 14 stations scored by motion analysis), an operating room equipment examination, and a novel error analysis. The scores were correlated, and p < 0.05 was deemed to be significant. Thirty surgeons were recruited; and construct validity was exhibited in all areas. Correlations were shown to exist between the two knowledge examinations (Spearman's rho = 0.39). Correlations existed between all dexterity task parameters and the equipment examination, whereas they existed for only 15 of the 28 parameters of the error examination and were always weaker. The stronger correlations between dexterity and instrument and operating room (OR) equipment reflect greater surgical experience and time spent in the OR. The weaker correlations between the error analysis and dexterity suggest that these skills are learned at different times. The identification of common surgical errors should be more formally taught to ensure greater uniformity.
Anastomosis, Surgical↗
Surgical education in the new millennium: the European perspective.
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Education, Medical↗
Systems approaches to surgical quality and safety: from concept to measurement.
OBJECTIVE: This approach provides the basis of our research program, which aims to expand operative assessment beyond patient factors and the technical skills of the surgeon; to extend assessment of surgical skills beyond bench models to the operating theater; to provide a basis for assessing interventions; and to provide a deeper understanding of surgical outcomes. SUMMARY BACKGROUND DATA: Research into surgical outcomes has primarily focused on the role of patient pathophysiological risk factors and on the skills of the individual surgeon. However, this approach neglects a wide range of factors that have been found to be of important in achieving safe, high-quality performance in other high-risk environments. The outcome of surgery is also dependent on the quality of care received throughout the patient's stay in hospital and the performance of a considerable number of health professionals, all of whom are influenced by the environment in which they work. METHODS: Drawing on the wider literature on safety and quality in healthcare, and recent papers on surgery, this article argues for a much wider assessment of factors that may be relevant to surgical outcome. In particular, we suggest the development of an "operation profile" to capture all the salient features of a surgical operation, including such factors as equipment design and use, communication, team coordination, factors affecting individual performance, and the working environment. Methods of assessing such factors are outlined, and ethical issues and other potential concerns are discussed.
General Surgery↗
Tumour-expressed CD43 (sialophorin) mediates tumourmesothelial cell adhesion.
Mesothelial cell intercellular adhesion molecule-1 (ICAM-1) has recently been shown to play a role in tumour cell adherence to the peritoneum. However, solid tumours poorly express its most ubiquitous ligand, beta2 integrin. The aim of this study was to investigate the role of the beta2 integrin subunit and CD43, a known ligand for ICAM-1, in the development of peritoneal metastases. beta2 Integrin subunit and CD43 expression was assessed on a number of tumour cell lines. Adhesion of SW1222 and PSN-1 cells to human peritoneal mesothelial cells was investigated using a fluorometric assay incorporating an inhibitory antibody to beta2 integrin and CD43. beta2 Integrin expression was not inducible on these tumour cell lines, but Western blotting demonstrated CD43 expression in all the cancer cell lines examined and cell surface expression was confirmed by flow cytometry. The anti-CD43 antibody significantly reduced adhesion of PSN-1 and SW1222 cells to HPMC, however beta2 integrin inhibition did not reduce tumour cell adhesion. CD43 is expressed by a variety of carcinoma cell lines, and plays a role in tumour cell-peritoneal adhesion probably via interactions with its putative ligand ICAM-1.
Antigens, CD↗
Relationship of matrix metalloproteinases and macrophages to embolization during endoluminal carotid interventions.
PURPOSE: To investigate if relationships exist among macrophage infiltration, plasma matrix metalloproteinase (MMP) levels, and the number of emboli generated during endoluminal carotid interventions. METHODS: Carotid endarterectomy specimens excised as intact cylinders (n=27) were subjected to a standardized angioplasty procedure under radiological guidance in an ex vivo pulsatile flow model. Emboli collected in distal filters were counted and sized using microscopy. Preoperative plasma gelatinase activity was determined by gelatin zymography and quantified using image analysis software. Levels of tissue inhibitors of metalloproteinases (TIMP) 1 and 2 were determined by ELISA. Macrophages within postangioplasty plaques were analyzed using immunohistochemical staining for CD68 antigen and graded by a blinded examiner. Statistical analysis was performed using Spearman's rank correlation. RESULTS: The median number of emboli recorded during angioplasty was 104 (interquartile range 33.75-242.5, absolute range 13-1090). Plasma MMP-9 and MMP-2 levels correlated with emboli number (r=0.544 [p=0.003] and r=0.412, [p=0.033], respectively), while TIMP-1 and TIMP-2 levels did not. Macrophage infiltration within the plaques correlated with emboli number (r=0.722, p<0.001) and the plasma MMP-9 level (r=0.489, p=0.010). CONCLUSIONS: These data indicate that plaque macrophage infiltration may play a role in the generation of emboli during endoluminal carotid intervention, possibly via modulation of protease activity.
Angioplasty↗
Measurement of surgical dexterity using motion analysis of simple bench tasks.
The possibility of using quantitative motion analysis for objective assessment of simple surgical dexterity is investigated using the Imperial College Surgical Assessment Device (ICSAD) with qualitative analysis undertaken by inspection. Bench-top knot tying and suturing skills were performed and examined for the ability to discriminate between surgeons of varying experience. These exercises were found to discriminate significantly between junior and senior surgeons in terms of both time taken and the number of movements required. The relation between time and motion was found to be variable depending on what skill was being undertaken: simple suturing, suturing at depth, or knot tying (1.71 vs. 1.86 vs. 2.36; p = 0.002 for 1 vs. 2; p < 0.001 for others). When the number of movements in a minute (standardized movements per minute) were considered, both groups were found to work at a similar rate, depending on the task, implying that the more experienced surgeon is more economical, performing the same exercise with fewer moves rather than with higher speed. Motion analysis exhibits face and construct validity and is a reliable assessment of simple surgical dexterity. Its use for objective assessment of dexterity and competence should be encouraged.
Clinical Competence↗