Paris P. Tekkis

Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients.

Objective:To identify risk factors associated with cancer-specific survival and develop a predictive model for patients undergoing primary hepatic resection for metastatic colorectal cancer. Background:No published studies investigated collectively the inter-relation of factors related to patient cancer-specific survival after hepatectomy for metastatic colorectal cancer. Methods:Clinical, pathologic, and complete follow-up data were prospectively collected from 929 consecutive patients undergoing primary (n = 925) or repeat hepatic resection (n = 80) for colorectal liver metastases at a tertiary referral center from 1987 to 2005. Parametric survival analysis was used to identify predictors of cancer-specific survival and develop a predictive model. The model was validated using measures of discrimination and calibration. Results:Postoperative mortality and morbidity were 1.5% and 25.9%, respectively. 5-year and 10-year cancer-specific survival were 36% and 23%. On multivariate analysis, 7 risk factors were found to be independent predictors of poor survival: number of hepatic metastases >3, node positive primary, poorly differentiated primary, extrahepatic disease, tumor diameter ≥5 cm, carcinoembyonic antigen level >60 ng/mL, and positive resection margin. The first 6 of these criteria were used in a preoperative scoring system and the last 6 in the postoperative setting. Patients with the worst postoperative prognostic criteria had an expected median cancer-specific survival of 0.7 years and a 5-year cancer-specific survival of 2%. Conversely, patients with the best prognostic postoperative criteria had an expected median cancer-specific survival of 7.4 years and a 5-year cancer-specific survival of 64%. When tested both predictive models fitted the data well with no significant differences between observed and predicted outcomes (P > 0.05). Conclusion:Resection of liver metastases provides good long-term cancer-specific survival benefit, which can be quantified pre- or postoperatively using the criteria described. The “Basingstoke Predictive Index” may be used for risk-stratifying patients who may benefit from intensive surveillance and selection for adjuvant therapy and trials.

Evaluation of the Learning Curve in Laparoscopic Colorectal Surgery: Comparison of Right-Sided and Left-Sided Resections

Objective:To provide a multidimensional analysis of the learning curve in major laparoscopic colonic and rectal surgery and compare outcomes between right-sided versus left-sided resections. Summary Background Data:The laparoscopic learning curve is known to vary between surgeons, may be influenced by the patient selection and operative complexity, and requires appropriate case-mix adjustment. Methods:This is a descriptive single-center study using routinely collected clinical data from 900 patients undergoing laparoscopic surgery between November 1991 and April 2003. Outcome measures included operation time, conversion rate (CR), and readmission and postoperative complication rates. Multifactorial logistic regression analysis was used to identify patient-, surgeon-, and procedure-related factors associated with conversion of laparoscopic to open surgery. A risk-adjusted Cumulative Sum (CUSUM) model was used for evaluating the learning curve for right and left-sided resections. Results:The conversion rate for right-sided colonic resections was 8.1% (n = 457) compared with 15.3% for left-sided colorectal resections (n = 443). Independent predictors of conversion of laparoscopic to open surgery were the body mass index (BMI) (odds ratio [OR] = 1.07 per unit increase), ASA grade (OR = 1.63 per unit increase), type of resection (left colorectal versus right colonic procedures, OR = 1.5), presence of intra-abdominal abscess (OR = 5.0) or enteric fistula (OR = 4.6), and surgeons experience (OR 0.9 per 10 additional cases performed). Having adjusted for case-mix, the CUSUM analysis demonstrated a learning curve of 55 cases for right-sided colonic resections versus 62 cases for left-sided resections. Median operative time declined with operative experience (P<0.001). Readmission rates and postoperative complications remained unchanged throughout the series and were not dependent on operative experience. Conclusions:Conversion rates for laparoscopic colectomy are dependent on a multitude of factors that require appropriate adjustment including the learning curve (operative experience) for individual surgeons. The laparoscopic model described can be used as the basis for performance monitoring between or within institutions.

Mortality and morbidity in gastro-oesophageal cancer surgery: initial results of ASCOT multicentre prospective cohort study

Abstract Objective To evaluate the effect of comorbidity and other risk factors on postoperative mortality and morbidity in patients undergoing major oesophageal and gastric surgery. Design Multicentre cohort study with data on postoperative mortality and morbidity in hospital. Data source and methods The ASCOT prospective database, comprising 2087 patients with newly diagnosed oesophageal and gastric cancer in 24 hospitals in England and Wales between 1 January 1999 and 31 December 2002. Multivariate logistic regression analysis was used to model the risk of death and postoperative complications. Results 955 patients underwent oesophagectomy or gastrectomy. Of these, 253 (27%) were graded ASA III or IV, and 187 (20%) had a high physiological POSSUM score (≥ 20). Operative mortality was 12% (111/955). Physiological POSSUM score, surgeons assessment, type of operation, hospital case volume, and tumour stage independently predicted operative mortality. Medical complications were associated with higher physiological POSSUM scores and ASA grade, oesophagectomy or total gastrectomy, thoracotomy, and radical nodal dissection. Stage and additional organ resection predicted surgical (technical) complications. Conclusions Many patients undergoing surgery for gastro-oesophageal cancer have major comorbid disease, which strongly influences their risk of postoperative death. Technical complications do not seem to be influenced by preoperative factors but reflect the extent of surgery and perhaps surgical judgment. Detailed prospective multicentre cooperative audit, with appropriate risk adjustment, is fundamental in the evaluation of cancer care and must be properly resourced.

Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study.

Objective:To assess local recurrence, disease-free survival, and overall survival in magnetic resonance imaging (MRI)–predicted good prognosis tumors treated by surgery alone. Background:The MERCURY study reported that high-resolution MRI can accurately stage rectal cancer. The routine policy in most centers involved in the MERCURY study was primary surgery alone in MRI-predicted stage II or less and in MRI “good prognosis” stage III with selective avoidance of neoadjuvant therapy. Patients and Methods:Data were collected prospectively on all patients included in the MERCURY study who were staged as MRI-defined “good” prognosis tumors. “Good” prognosis included MRI-predicted safe circumferential resection margins, with MRI-predicted T2/T3a/T3b (less than 5 mm spread from muscularis propria), regardless of MRI N stage. None received preoperative or postoperative radiotherapy. Overall survival, disease-free survival, and local recurrence were calculated. Results:Of 374 patients followed up in the MERCURY study, 122 (33%) were defined as “good prognosis” stage III or less on MRI. Overall and disease-free survival for all patients with MRI “good prognosis” stage I, II and III disease at 5 years was 68% and 85%, respectively. The local recurrence rate for this series of patients predicted to have a good prognosis tumor on MRI was 3%. Conclusions:The preoperative identification of good prognosis tumors using MRI will allow stratification of patients and better targeting of preoperative therapy. This study confirms the ability of MRI to select patients who are likely to have a good outcome with primary surgery alone.

A Meta-analysis on the Influence of Inflammatory Bowel Disease on Pregnancy

Background: Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management. Aim: To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD. Design: The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls. Patients and setting: A total of 3907 patients with IBD (Crohn’s disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria. Results: For women with IBD, there was a 1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52 to 2.31; p<0.001) compared with controls. The incidence of low birth weight (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). Conclusion: The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group.

Magnetic Resonance Imaging–Detected Tumor Response for Locally Advanced Rectal Cancer Predicts Survival Outcomes: MERCURY Experience

PURPOSE To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. METHODS In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. RESULTS On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. CONCLUSION MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

Diagnostic Precision of Fecal Calprotectin for Inflammatory Bowel Disease and Colorectal Malignancy

OBJECTIVES:Fecal calprotectin (FC) is a relatively new marker of intraluminal intestinal inflammation. Using meta-analytical techniques, the study aimed to evaluate the diagnostic precision of FC for inflammatory bowel disease (IBD) and colorectal cancer (CRC) in adults and children.METHODS:Quantitative meta-analysis was performed on prospective studies, comparing FC levels against the histological diagnosis. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver-operating characteristic (sROC) curves and subgroup analysis were undertaken. Study quality and heterogeneity were evaluated.RESULTS:Thirty studies of 5,983 patients were included. FC levels in patients with IBD were higher by 219.2 micrograms per gram (μg/g) compared with normal patients (P < 0.001). sROC curve analysis showed a sensitivity of 0.95 (95% CI 0.93–0.97), specificity of 0.91 (95% CI 0.86–0.91), and an area under the curve (AUC) of 0.95 for the diagnosis of IBD. Patients with colorectal neoplasia had nonsignificantly higher FC levels by 132.2 μg/g compared with noncancer controls (P = 0.18). Sensitivity and specificity of FC for the diagnosis of CRC were 0.36 and 0.71, respectively, with an AUC of 0.66. The diagnostic precision of FC for IBD was higher in children than adults with better accuracy at a cutoff level of 100 μg/g versus 50 μg/g. Sensitivity analysis and metaregression analysis did not significantly alter the results.CONCLUSIONS:FC cannot be recommended as a screening test for CRC in the general population. FC appeared to offer a good diagnostic precision in distinguishing IBD from non-IBD diagnoses, with higher precision at a cutoff of 100 μg/g.

Development of a dedicated risk-adjustment scoring system for colorectal surgery (colorectal POSSUM).

The aim of the study was to develop a dedicated colorectal Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (CR‐POSSUM) equation for predicting operative mortality, and to compare its performance with the Portsmouth (P)‐POSSUM model.

Laparoscopic versus open appendectomy in children: a meta-analysis

Objective:This study aims to use meta-analysis to compare laparoscopic and open appendectomy in a pediatric population. Summary Background Data:Meta-analysis is a statistical tool that can be used to evaluate the literature in both qualitative and quantitative ways, accounting for variations in characteristics that can influence overall estimate of outcomes of interest. Meta-analysis of laparoscopic versus open appendectomy in a pediatric population has not previously been performed. Methods:Comparative studies published between 1992 and 2004 of laparoscopic versus open appendectomy in children were included. Endpoints were postoperative pyrexia, ileus, wound infection, intra-abdominal abscess formation, operative time, and postoperative hospital stay. Results:Twenty-three studies including 6477 children (43% laparoscopic, 57% open) were included. Wound infection was significantly reduced with laparoscopic versus open appendectomy (1.5% versus 5%; odds ratio [OR] = 0.45, 95% confidence interval [CI], 0.27–0.75), as was ileus (1.3% versus 2.8%; OR = 0.5, 95% CI, 0.29–0.86). Intra-abdominal abscess formation was more common following laparoscopic surgery, although this was not statistically significant. Subgroup analysis of randomized trials did not reveal significant difference between the 2 techniques in any of the 4 complications. Operative time was not significantly longer in the laparoscopic group, and postoperative stay was significantly shorter (weighted mean difference, −0.48; 95% CI, −0.65 to −0.31). Sensitivity analysis identified lowest heterogeneity when only randomized studies were considered, followed by prospective, recent, and finally large studies. Conclusions:The results of this meta-analysis suggest that laparoscopic appendectomy in children reduces complications. However, we also see the need for further high-quality randomized trials comparing the 2 techniques, matched not only for age and sex but also for obesity and severity of appendicitis.

A Comparison of Hand-Sewn Versus Stapled Ileal Pouch Anal Anastomosis (IPAA) Following Proctocolectomy: A Meta-Analysis of 4183 Patients

Objective:Using meta-analytical techniques, the study compared postoperative adverse events and functional outcomes of stapled versus hand-sewn ileal pouch-anal anastomosis (IPAA) following restorative proctocolectomy. Background:The choice of mucosectomy and hand-sewn versus stapled pouch-anal anastomosis has been a subject of debate with no clear consensus as to which method provides better functional results and long-term outcomes. Methods:Comparative studies published between 1988 and 2003, of hand-sewn versus stapled IPAA were included. Endpoints were classified into postoperative complications and functional and physiologic outcomes measured at least 3 months following closure of ileostomy or surgery if no proximal diversion was used, quality of life following surgery, and neoplastic transformation within the anal transition zone. Results:Twenty-one studies, consisting of 4183 patients (2699 hand-sewn and 1484 stapled IPAA) were included. There was no significant difference in the incidence of postoperative complications between the 2 groups. The incidence of nocturnal seepage and pad usage favored the stapled IPAA (odds ratio [OR] = 2.78, P < 0.001 and OR = 4.12, P = 0.007, respectively). The frequency of defecation was not significantly different between the 2 groups (P = 0.562), nor was the use of antidiarrheal medication (OR = 1.27, P = 0.422). Anorectal physiologic measurements demonstrated a significant reduction in the resting and squeeze pressure in the hand-sewn IPAA group by 13.4 and 14.4 mm Hg, respectively (P < 0.018). The stapled IPAA group showed a higher incidence of dysplasia in the anal transition zone that did not reach statistical significance (OR = 0.42, P = 0.080). Conclusions:Both techniques had similar early postoperative outcomes; however, stapled IPAA offered improved nocturnal continence, which was reflected in higher anorectal physiologic measurements. A risk of increased incidence of dysplasia in the ATZ may exist in the stapled group that cannot be quantified by this study. We describe a decision algorithm for the choice of IPAA, based on the relative risk of long-term neoplastic transformation.