PAPER
OF THE
22ND ANNUAL ESA MEETING
Early and Long-term Oncological Outcomes After Laparoscopic Resection for Colorectal Liver Metastases A Propensity Score-based Analysis Marc-Antoine Allard, MD, Antonio Sa Cunha, MD, Brice Gayet, MD, PhD,y Rene´ Adam, MD, PhD, Diane Goere, MD, PhD,z Philippe Bachellier, MD,§ Daniel Azoulay, MD, PhD,ô Ahmet Ayav, MD, PhD,jj Francis Navarro, MD, and Patrick Pessaux, MD, PhDyy; on behalf of the Colorectal Liver Metastases-French Study Group
Objective: To compare early and long-term outcomes in patients undergoing resection for colorectal liver metastases (CLM) by either a laparoscopic (LA) or an open (OA) approach. Background: The LA is still a matter of debate regarding the surgical management of CLM. Methods: Data of all patients from 32 French surgical centers who underwent liver resection for CLM from January 2006 to December 2013 were collected. Aiming to obtain 2 well-balanced cohorts for available variables influencing early outcome and survival, the LA group was matched 1:1 with the OA group by using a propensity score (PS)-based method. Results: The unmatched initial cohort consisted of 2620 patients (LA: 176, OA: 2444). In the matched cohort for operative risk factors (LA: 153, OA: 153), the LA group had shorter hospitalization stays [11.1 (9) days vs 13.9 (10) days; P ¼ 0.01] and was associated with lower rates of grade III to V complications [odds ratio (OR): 0.27, 95% confidence interval (CI) 0.14– 0.51; P ¼ 0.0002] and inhospital transfusions (OR: 0.33 95% CI 0.18–0.59; P < 0.0001). On a prognostic factors well-balanced population (LA: 73, OA: 73), the LA group and the OA group experienced similar overall (OS) and disease-free (DFS) survival rates [OS rates of 88% and 78% vs 84% and 75% at 3 and 5 years, respectively (P ¼ 0.72) and DFS rates of 40% and 32% vs 52% and 36% at 3 and 5 years, respectively (P ¼ 0.60)]. Conclusions: In the patients who are suitable for LA, laparoscopy yields better operative outcomes without impairing long-term survival. Keywords: colorectal liver metastases, early outcome, laparoscopic liver resection, oncological outcome
(Ann Surg 2015;262:794–802)
L
aparoscopy has been adopted worldwide as the approach of choice for a large number of abdominal procedures in elective or emergency settings, and in benign or malignant disease.1,2 The first series of hepatectomies performed by laparoscopy were reported almost 2 decades ago.3,4 Since then, numerous studies have demonstrated the From the Hoˆpital Paul Brousse, Villejuif, France; yInstitut Mutualiste Montsouris, Paris, France; zGustave Roussy, Villejuif, France; §Hoˆpital Hautepierre, Strasbourg, France; ôHoˆpital Henri Mondor, Cre´teil, France; jjCenter Hospitalier Universitaire, Nancy, France; Center Hospitalier Re´gional Universitaire, Montpellier, France; and yyNouvel Hoˆpital Civil, Institut HospitaloUniversitaire de Strasbourg, Strasbourg, France. Disclosure: The authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.annalsofsurgery.com). Reprints: Antonio Sa Cunha, MD, Center Hepato-Biliaire, Hoˆpital Paul Brousse, Assistance Publique-Hoˆpitaux de Paris (AP-HP), 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France. E-mail: [email protected]. Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0003-4932/14/26105-0821 DOI: 10.1097/SLA.0000000000001475
794 | www.annalsofsurgery.com
safety and feasibility of laparoscopic liver resections.5–7 Some recent reports even suggest that there are no more technical boundaries for laparoscopy.8–10 In western countries, colorectal liver metastases (CLM) remain by far the first indication for hepatectomy.11 Moreover, thanks to major improvements in chemotherapy over the past decade, the number of patients eligible for CLM resection continues to increase. Surgical treatment relies on 2 principles: (1) complete resection of the totality of tumors and (2) margin-free achievement. Theoretical concerns have been raised regarding the ability of laparoscopy to meet these oncological objectives. In 2009, an international panel of expert surgeons investigated the place of laparoscopy in liver surgery and stated that the LA could be used in CLM.12 However, the place of laparoscopy in CLM resection is still debated.13 To date, there is no randomized trial comparing the 2 approaches, and retrospective studies comparing laparoscopic approach (LA) and open approach (OA) are missing. Hence, this study aimed to compare early and long-term outcomes of patients who underwent CLM resection by either OA or LA after matching with a propensity score-based method.
METHODS Data Collection Data were obtained from a questionnaire-based survey of patients who underwent surgery for CLM in 32 French surgical centers from January 2006 to December 2013. This study was performed under the direction of The French National Surgical Association (Association Franc¸aise de Chirurgie) after institutional approval. Files were submitted by surgeons of each institution. The following items were evaluated: (1) demographic data, (2) disease characteristics, (3) preoperative management, (4) intraoperative data, (5) postoperative course, (6) histological findings, (7) postoperative oncological management, and (8) follow-up. Details of query are provided in supplementary data, http://links.lww.com/SLA/A859. Subsequently, data were made anonymous and all questionnaires were merged into a single file. Patients were identified by the first 3 letters of their first and last name, their date of birth, and their institution. The quality of information was checked. In case of missing data (>10% per variable), questionnaires were sent back to centers and missing information was completed. Finally, patients without follow-up information or with outliers were excluded.
Study Population All patients who underwent CLM resection with histologically proven diagnosis on the surgical specimen were included. Only first-time hepatectomies were considered. Patients who underwent Annals of Surgery Volume 262, Number 5, November 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Surgery Volume 262, Number 5, November 2015
Oncological Outcomes After Laparoscopic Resection
re-hepatectomy or any potentially noncurative procedure [macroscopically incomplete (R2) resection or surgical biopsy, for example] were excluded.
rank test and survival curves were plotted with the Kaplan Meier method. After matching, survival comparisons were performed by using the Cox proportional hazard model. The statistical analysis was performed with R3.0.0 (www.cran.r-project.com) and the nonrandom, ggplot2 survival pack ages.
Definition of LA In this study, the term LA includes pure laparoscopic hepatectomy, hand-assisted hepatectomy, or robotic hepatectomy. On an intention to treat basis, conversions to open surgery were considered as belonging to the LA group.
RESULTS Baselines of the Study Population
Statistical Analysis In the unmatched cohort, categorical data were compared using x2 test or Fisher exact test as appropriate. T test was used to compare continuous data. We calculated the linear correlation coefficient (r) to assess a potential relationship between 2 continuous variables. To ensure comparability between the 2 groups, a matching method using a propensity score (PS) was used. Patients of the LA group were matched to patients of the OA group (matching ratio 1:1), with the closest estimated PS within 0.2 of the standard deviation of the logit of the PS.14 Unpaired patients of the LA group were excluded. For matching, we selected variables (having less than 15% of missing data) that are known, in the literature, to potentially affect the outcome of interest. Indeed, previous studies15,16 investigating the selection of variables for PS have shown that including variables affecting the treatment assignment, but without effect on outcome, will not reduce the risk of bias but instead, increase the variance of the estimated effect of a treatment. On the contrary, variables that do not affect the treatment assignment, but that impact outcome, must be carefully balanced in the matched groups. As recommended, posttreatment variables were not included.17 For early outcome analysis, PS was estimated by using factors with a potential impact on morbidity: age of the patient >70 years, the American Society of Anaesthesiology (ASA) score, body mass index (BMI) >30 kg/m2, type of hepatectomy (ie, limited hepatectomy, sectionectomy, left hepatectomy, right hepatectomy, extended right hepatectomy, and extended left hepatectomy), preoperative portal vein embolization, use of vascular exclusion, simultaneous digestive anastomosis, combined radiofrequency ablation, number of resected specimen per patient (unique vs multiple), and use of preoperative chemotherapy. Early outcome was assessed by using the 90-day mortality, length of hospital stay, and occurrence of severe complications defined by Grade III to V Clavien-Dindo classification.18 In the matched samples, proportions and mean were compared by using the McNemar test and the t test, respectively. Matching was taken into account for calculations of odd ratio (OR) and 95% confidence interval (CI). The following prognostic factors of CLM were used for PS estimation: sex, age (>70 years), primary tumor lymph node (Nþ vs N0), location of primary tumor (rectum vs colon), histological tumor number, maximum histological tumor size, location of CLM (unilobar vs bilobar), portal vein embolization, preoperative chemotherapy, number of resected specimen per patient (unique vs multiple), combined use of radiofrequency ablation, presence of concomitant extrahepatic disease, and time of occurrence (synchronous vs metachronous). The carcinoembryonic antigen level was not included because of missing data. Because adjuvant therapy is a posttreatment variable, it has not been selected. The 2 endpoints for survival evaluation were overall survival (OS) and disease-free survival (DFS). Time of survival was calculated from the date of hepatectomy until the date of event of interest (death for OS, and death or first recurrence for DFS) or the date of last follow-up. For survival analysis, we excluded from the initial cohort all patients alive with a follow-up shorter than 6 months. Before matching, survival probability was compared by using the log ß
2015 Wolters Kluwer Health, Inc. All rights reserved.
A total of 2620 patients were included. The OA group consisted of 2444 patients (93.3%) and the LA group contained 176 patients (6.7%). From the total, 1,527 were men, 1,093 women, and the mean age was 62.1 (11) years. The proportion of patients with a BMI >30 kg/m2 was 9.8%. Roughly 38.4% (1007 patients) underwent major liver resections and a portal vein embolization was performed in 418 (15.9%) patients. A mean maximal tumor size of 36.4 (31) mm was obtained and the mean tumor number found was 3.1 (3). Concomitant extrahepatic disease was present in 414 (9.3%) patients. The 90-day mortality was 1.4%.
Rate of LA When considering the study population over the entire study period, the rate of LA was 6.7%. Although the global number of patients operated for CLM increased over time, the rate of LA remained stable (Fig. 1). A total of 19 centers (48.7%) performed laparoscopic liver resection for CLM. Of them, the mean rate of LA was 15.3%, ranging from 1.4% to 100%. A tendency of relationship between the volume (total number of cases reported over the study period) per center and the proportion of cases performed by laparoscopy (P ¼ 0.06, r ¼ 0.26) was observed. Eighty-three percent of centers performing at least 12 resections for CLM per year reported laparoscopic liver resections versus 37.5% of the centers performing less than 12 resections for CLM per year (P ¼ 0.03).
Comparison of OA Versus LA Before Matching Early Outcome The LA group included 168 pure laparoscopic procedures, 3 hand-assisted hepatectomies, and 5 robotic hepatectomies.
FIGURE 1. Rate of laparoscopic approach during the study period. www.annalsofsurgery.com | 795
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Surgery Volume 262, Number 5, November 2015
Allard et al
TABLE 1. Characteristics of Patients, Disease, and Outcomes Before Matching According to the Type of Approach OA Group
LA Group
N ¼ 2444 Variables Patient characteristics Sex Female Male Mean age (SD), years Age 70 yrs >70 yrs BMI 30 kg/m2 >30 kg/m2 ASA classification 1 2 3 Operative data Type of hepatectomy Limited Sectionectomy Right hepatectomy Extended right hepatectomy Left hepatectomy Extended left hepatectomy Portal vein embolization N Y Pedicle clamping N Y Combined digestive anastomosis N Y Total vascular exclusion N Y Combined RFA N Y Number of resected specimen Single Multiple Disease characteristics Primary location Colon Rectum Primary tumor node N0 Nþ Preoperative chemotherapy N Y Time of occurrence Metachronous Synchronous Concomitant extrahepatic disease N Y Tumor distribution Unilobar Bilobar Mean maximum tumor size (SD), mm 36
796 | www.annalsofsurgery.com
N ¼ 176
No.
%
No.
%
P
1021 1423 61.9
41.8 58.2 11
72 104 65.1
40.9 59.1 11
0.88
1798 646
73.6 26.4
109 67
61.9 38.1
0.001
2132 231
90.2 9.8
158 18
89.7 10.3
0.95
254 1750 370
10.7 73.7 15.6
21 131 24
11.9 74.4 13.7
0.72
1030 401 489 125 177 15
46.0 17.9 21.9 5.6 7.9 0.7
66 30 63 3 14 0
37.5 17.0 35.8 1.7 8.0 0.0
OF THE
22ND ANNUAL ESA MEETING
Early and Long-term Oncological Outcomes After Laparoscopic Resection for Colorectal Liver Metastases A Propensity Score-based Analysis Marc-Antoine Allard, MD, Antonio Sa Cunha, MD, Brice Gayet, MD, PhD,y Rene´ Adam, MD, PhD, Diane Goere, MD, PhD,z Philippe Bachellier, MD,§ Daniel Azoulay, MD, PhD,ô Ahmet Ayav, MD, PhD,jj Francis Navarro, MD, and Patrick Pessaux, MD, PhDyy; on behalf of the Colorectal Liver Metastases-French Study Group
Objective: To compare early and long-term outcomes in patients undergoing resection for colorectal liver metastases (CLM) by either a laparoscopic (LA) or an open (OA) approach. Background: The LA is still a matter of debate regarding the surgical management of CLM. Methods: Data of all patients from 32 French surgical centers who underwent liver resection for CLM from January 2006 to December 2013 were collected. Aiming to obtain 2 well-balanced cohorts for available variables influencing early outcome and survival, the LA group was matched 1:1 with the OA group by using a propensity score (PS)-based method. Results: The unmatched initial cohort consisted of 2620 patients (LA: 176, OA: 2444). In the matched cohort for operative risk factors (LA: 153, OA: 153), the LA group had shorter hospitalization stays [11.1 (9) days vs 13.9 (10) days; P ¼ 0.01] and was associated with lower rates of grade III to V complications [odds ratio (OR): 0.27, 95% confidence interval (CI) 0.14– 0.51; P ¼ 0.0002] and inhospital transfusions (OR: 0.33 95% CI 0.18–0.59; P < 0.0001). On a prognostic factors well-balanced population (LA: 73, OA: 73), the LA group and the OA group experienced similar overall (OS) and disease-free (DFS) survival rates [OS rates of 88% and 78% vs 84% and 75% at 3 and 5 years, respectively (P ¼ 0.72) and DFS rates of 40% and 32% vs 52% and 36% at 3 and 5 years, respectively (P ¼ 0.60)]. Conclusions: In the patients who are suitable for LA, laparoscopy yields better operative outcomes without impairing long-term survival. Keywords: colorectal liver metastases, early outcome, laparoscopic liver resection, oncological outcome
(Ann Surg 2015;262:794–802)
L
aparoscopy has been adopted worldwide as the approach of choice for a large number of abdominal procedures in elective or emergency settings, and in benign or malignant disease.1,2 The first series of hepatectomies performed by laparoscopy were reported almost 2 decades ago.3,4 Since then, numerous studies have demonstrated the From the Hoˆpital Paul Brousse, Villejuif, France; yInstitut Mutualiste Montsouris, Paris, France; zGustave Roussy, Villejuif, France; §Hoˆpital Hautepierre, Strasbourg, France; ôHoˆpital Henri Mondor, Cre´teil, France; jjCenter Hospitalier Universitaire, Nancy, France; Center Hospitalier Re´gional Universitaire, Montpellier, France; and yyNouvel Hoˆpital Civil, Institut HospitaloUniversitaire de Strasbourg, Strasbourg, France. Disclosure: The authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.annalsofsurgery.com). Reprints: Antonio Sa Cunha, MD, Center Hepato-Biliaire, Hoˆpital Paul Brousse, Assistance Publique-Hoˆpitaux de Paris (AP-HP), 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France. E-mail: [email protected]. Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0003-4932/14/26105-0821 DOI: 10.1097/SLA.0000000000001475
794 | www.annalsofsurgery.com
safety and feasibility of laparoscopic liver resections.5–7 Some recent reports even suggest that there are no more technical boundaries for laparoscopy.8–10 In western countries, colorectal liver metastases (CLM) remain by far the first indication for hepatectomy.11 Moreover, thanks to major improvements in chemotherapy over the past decade, the number of patients eligible for CLM resection continues to increase. Surgical treatment relies on 2 principles: (1) complete resection of the totality of tumors and (2) margin-free achievement. Theoretical concerns have been raised regarding the ability of laparoscopy to meet these oncological objectives. In 2009, an international panel of expert surgeons investigated the place of laparoscopy in liver surgery and stated that the LA could be used in CLM.12 However, the place of laparoscopy in CLM resection is still debated.13 To date, there is no randomized trial comparing the 2 approaches, and retrospective studies comparing laparoscopic approach (LA) and open approach (OA) are missing. Hence, this study aimed to compare early and long-term outcomes of patients who underwent CLM resection by either OA or LA after matching with a propensity score-based method.
METHODS Data Collection Data were obtained from a questionnaire-based survey of patients who underwent surgery for CLM in 32 French surgical centers from January 2006 to December 2013. This study was performed under the direction of The French National Surgical Association (Association Franc¸aise de Chirurgie) after institutional approval. Files were submitted by surgeons of each institution. The following items were evaluated: (1) demographic data, (2) disease characteristics, (3) preoperative management, (4) intraoperative data, (5) postoperative course, (6) histological findings, (7) postoperative oncological management, and (8) follow-up. Details of query are provided in supplementary data, http://links.lww.com/SLA/A859. Subsequently, data were made anonymous and all questionnaires were merged into a single file. Patients were identified by the first 3 letters of their first and last name, their date of birth, and their institution. The quality of information was checked. In case of missing data (>10% per variable), questionnaires were sent back to centers and missing information was completed. Finally, patients without follow-up information or with outliers were excluded.
Study Population All patients who underwent CLM resection with histologically proven diagnosis on the surgical specimen were included. Only first-time hepatectomies were considered. Patients who underwent Annals of Surgery Volume 262, Number 5, November 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Surgery Volume 262, Number 5, November 2015
Oncological Outcomes After Laparoscopic Resection
re-hepatectomy or any potentially noncurative procedure [macroscopically incomplete (R2) resection or surgical biopsy, for example] were excluded.
rank test and survival curves were plotted with the Kaplan Meier method. After matching, survival comparisons were performed by using the Cox proportional hazard model. The statistical analysis was performed with R3.0.0 (www.cran.r-project.com) and the nonrandom, ggplot2 survival pack ages.
Definition of LA In this study, the term LA includes pure laparoscopic hepatectomy, hand-assisted hepatectomy, or robotic hepatectomy. On an intention to treat basis, conversions to open surgery were considered as belonging to the LA group.
RESULTS Baselines of the Study Population
Statistical Analysis In the unmatched cohort, categorical data were compared using x2 test or Fisher exact test as appropriate. T test was used to compare continuous data. We calculated the linear correlation coefficient (r) to assess a potential relationship between 2 continuous variables. To ensure comparability between the 2 groups, a matching method using a propensity score (PS) was used. Patients of the LA group were matched to patients of the OA group (matching ratio 1:1), with the closest estimated PS within 0.2 of the standard deviation of the logit of the PS.14 Unpaired patients of the LA group were excluded. For matching, we selected variables (having less than 15% of missing data) that are known, in the literature, to potentially affect the outcome of interest. Indeed, previous studies15,16 investigating the selection of variables for PS have shown that including variables affecting the treatment assignment, but without effect on outcome, will not reduce the risk of bias but instead, increase the variance of the estimated effect of a treatment. On the contrary, variables that do not affect the treatment assignment, but that impact outcome, must be carefully balanced in the matched groups. As recommended, posttreatment variables were not included.17 For early outcome analysis, PS was estimated by using factors with a potential impact on morbidity: age of the patient >70 years, the American Society of Anaesthesiology (ASA) score, body mass index (BMI) >30 kg/m2, type of hepatectomy (ie, limited hepatectomy, sectionectomy, left hepatectomy, right hepatectomy, extended right hepatectomy, and extended left hepatectomy), preoperative portal vein embolization, use of vascular exclusion, simultaneous digestive anastomosis, combined radiofrequency ablation, number of resected specimen per patient (unique vs multiple), and use of preoperative chemotherapy. Early outcome was assessed by using the 90-day mortality, length of hospital stay, and occurrence of severe complications defined by Grade III to V Clavien-Dindo classification.18 In the matched samples, proportions and mean were compared by using the McNemar test and the t test, respectively. Matching was taken into account for calculations of odd ratio (OR) and 95% confidence interval (CI). The following prognostic factors of CLM were used for PS estimation: sex, age (>70 years), primary tumor lymph node (Nþ vs N0), location of primary tumor (rectum vs colon), histological tumor number, maximum histological tumor size, location of CLM (unilobar vs bilobar), portal vein embolization, preoperative chemotherapy, number of resected specimen per patient (unique vs multiple), combined use of radiofrequency ablation, presence of concomitant extrahepatic disease, and time of occurrence (synchronous vs metachronous). The carcinoembryonic antigen level was not included because of missing data. Because adjuvant therapy is a posttreatment variable, it has not been selected. The 2 endpoints for survival evaluation were overall survival (OS) and disease-free survival (DFS). Time of survival was calculated from the date of hepatectomy until the date of event of interest (death for OS, and death or first recurrence for DFS) or the date of last follow-up. For survival analysis, we excluded from the initial cohort all patients alive with a follow-up shorter than 6 months. Before matching, survival probability was compared by using the log ß
2015 Wolters Kluwer Health, Inc. All rights reserved.
A total of 2620 patients were included. The OA group consisted of 2444 patients (93.3%) and the LA group contained 176 patients (6.7%). From the total, 1,527 were men, 1,093 women, and the mean age was 62.1 (11) years. The proportion of patients with a BMI >30 kg/m2 was 9.8%. Roughly 38.4% (1007 patients) underwent major liver resections and a portal vein embolization was performed in 418 (15.9%) patients. A mean maximal tumor size of 36.4 (31) mm was obtained and the mean tumor number found was 3.1 (3). Concomitant extrahepatic disease was present in 414 (9.3%) patients. The 90-day mortality was 1.4%.
Rate of LA When considering the study population over the entire study period, the rate of LA was 6.7%. Although the global number of patients operated for CLM increased over time, the rate of LA remained stable (Fig. 1). A total of 19 centers (48.7%) performed laparoscopic liver resection for CLM. Of them, the mean rate of LA was 15.3%, ranging from 1.4% to 100%. A tendency of relationship between the volume (total number of cases reported over the study period) per center and the proportion of cases performed by laparoscopy (P ¼ 0.06, r ¼ 0.26) was observed. Eighty-three percent of centers performing at least 12 resections for CLM per year reported laparoscopic liver resections versus 37.5% of the centers performing less than 12 resections for CLM per year (P ¼ 0.03).
Comparison of OA Versus LA Before Matching Early Outcome The LA group included 168 pure laparoscopic procedures, 3 hand-assisted hepatectomies, and 5 robotic hepatectomies.
FIGURE 1. Rate of laparoscopic approach during the study period. www.annalsofsurgery.com | 795
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Surgery Volume 262, Number 5, November 2015
Allard et al
TABLE 1. Characteristics of Patients, Disease, and Outcomes Before Matching According to the Type of Approach OA Group
LA Group
N ¼ 2444 Variables Patient characteristics Sex Female Male Mean age (SD), years Age 70 yrs >70 yrs BMI 30 kg/m2 >30 kg/m2 ASA classification 1 2 3 Operative data Type of hepatectomy Limited Sectionectomy Right hepatectomy Extended right hepatectomy Left hepatectomy Extended left hepatectomy Portal vein embolization N Y Pedicle clamping N Y Combined digestive anastomosis N Y Total vascular exclusion N Y Combined RFA N Y Number of resected specimen Single Multiple Disease characteristics Primary location Colon Rectum Primary tumor node N0 Nþ Preoperative chemotherapy N Y Time of occurrence Metachronous Synchronous Concomitant extrahepatic disease N Y Tumor distribution Unilobar Bilobar Mean maximum tumor size (SD), mm 36
796 | www.annalsofsurgery.com
N ¼ 176
No.
%
No.
%
P
1021 1423 61.9
41.8 58.2 11
72 104 65.1
40.9 59.1 11
0.88
1798 646
73.6 26.4
109 67
61.9 38.1
0.001
2132 231
90.2 9.8
158 18
89.7 10.3
0.95
254 1750 370
10.7 73.7 15.6
21 131 24
11.9 74.4 13.7
0.72
1030 401 489 125 177 15
46.0 17.9 21.9 5.6 7.9 0.7
66 30 63 3 14 0
37.5 17.0 35.8 1.7 8.0 0.0
