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Incisional hernia after open resections for colorectal liver metastases – incidence and risk factors
HPB
http://dx.doi.org/10.1016/j.hpb.2016.02.001
ORIGINAL ARTICLE
Incisional hernia after open resections for colorectal liver metastases – incidence and risk factors Jan H. Nilsson1, Peter Strandberg Holka1 & Christian Sturesson1 1
Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
Abstract Background: Incisional hernia is one of the most common complications after laparotomy. The aim of this retrospective study was to investigate incidence, location and risk factors for incisional hernia after open resection for colorectal liver metastases including the use of perioperative chemotherapy and targeted therapy evaluated by computed tomography. Methods: Patients operated for colorectal liver metastases between 2010 and 2013 were included. Incisional hernia was defined as a discontinuity in the abdominal fascia observed on computed tomography. Results: A total of 256 patients were analyzed in regard to incisional hernia. Seventy-eight patients (30.5%) developed incisional hernia. Hernia locations were midline alone in 66 patients (84.6%) and involving the midline in another 8 patients (10.3%). In multivariate analysis, preoperative chemotherapy >6 cycles (hazard ratio 2.12, 95% confidence interval 1.14–3.94), preoperative bevacizumab (hazard ratio 3.63, 95% confidence interval 1.86–7.08) and incisional hernia from previous surgery (hazard ratio 3.50, 95% confidence interval 1.98–6.18) were found to be independent risk factors. Conclusions: Prolonged preoperative chemotherapy and also preoperative bevacizumab were strong predictors for developing an incisional hernia. After an extended right subcostal incision, the hernia location was almost exclusively in the midline. Received 28 December 2015; accepted 14 February 2016
Correspondence Department of Surgery, Skåne University Hospital, S-221 85 Lund, Sweden. Tel: +46 46 172347. Fax: +46 46 172335. E-mail: [email protected]
Introduction Incisional hernia is one of the most common complications after laparotomy. The reported incidence is highly variable depending on underlying disease, type of incision used, length of follow up and method for hernia detection.1 Numerous risk factors associated with an increased incisional hernia incidence have been reported, including gender (both male and female), age, surgical site infection, obesity and aortic aneurysm.1–4 The incisional hernia incidence after liver resections has been studied only to a limited extent2,5,6. No study including only patients with liver metastases from colorectal cancer has previously been made. Liver metastases are a common consequence of colorectal cancer where the only available potential curative treatment is surgery.7,8 Although laparoscopic liver resections are feasible and increasingly being used, open resection is still the most common
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procedure.9 Before liver resection of colorectal metastases a majority of patients receive preoperative chemotherapy9,10 which has been shown to be an independent risk factor for incisional hernia.11 Non-midline incisions give lesser incisional hernias and in liver resections an extended right subcostal incision is recommended.1,2 Medical imaging diagnostics increases the ability to detect incisional hernias as compared to physical examination.1,4,12 Computed tomography (CT) has been suggested as the “gold standard” because of its high reliability for diagnosing incisional hernia.4 Still, few studies exist that have used CT in a consequent manner to analyze incisional hernia incidence. The aim of this retrospective study was to investigate incidence, location and risk factors for incisional hernia after open liver resection for colorectal liver metastases including the use of perioperative chemotherapy and targeted therapy evaluated by CT.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Table 1 Patient characteristics for the two groups with and without
Table 1 (continued )
incisional hernia Incisional hernia No incisional hernia
P
Number of patients
78
178
–
Gender (male:female)
48:30
110:68
0.969
Age (years)
68 (37–82)
68 (35–85)
0.880
Current smoking
13
36
0.505
Diabetes mellitus
11
19
0.432
Body mass index (kg/m2)
26.0 (18.4–41.1)
25.0 (17.7–38.2)
0.076
Total muscle area (mm2)
13,360 (6391–20,599)
13,350 (5460–21,906)
0.802
Skeletal muscle depletion
27
76
0.225
Subcutaneous fat (mm)
12 (3–34)
12 (2–35)
0.415
Body fat percentage (%)
39.1 (19.2–57.2)
38.0 (8.6–66.6)
0.531
Preoperative chemotherapy
44
96
0.656
5 (1–16)
5 (1–13)
0.552
Preoperative chemotherapy > 6 cycles
13
19
0.169
Preoperative bevacizumab
11
8
0.009
Previous liver resection
15
18
0.045
Incisional hernia before surgery
23
13
<0.0001
ASA grade (1/2:3/4)
54:24
129:49
0.597
Preoperative albumin (g/l)
38 (25–46)
38 (24–47)
0.522
Preoperative creatinine (mmol/l)
73.5 (36–132)
73.0 (31–150)
0.645
Operating time (hours)
4.76 (1.0–9.8)
4.75 (1.1–13.0)
0.955
Operative bleeding (ml)
350 (25–2000)
300 (25–8000)
0.683
Incision type (ERSI:Mercedes)
60:16
138:36
0.948
Major resection
26
68
0.457
Hospital stay (days)
7 (3–34)
7 (2–76)
0.804
Incisional surgical site infection
8
15
0.638
Remote infection
3
9
0.673
Number of chemotherapy cycles
(continued on next page)
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Incisional hernia No incisional hernia
P
Morbidity 9 (Clavien-Dindo 3)
18
0.732
Postoperative chemotherapy
104
0.774
45
Data are presented as number or median (range). ASA, American Society of Anesthesiologists; ERSI, extended right subcostal incision.
Patients and methods Patients operated for colorectal liver metastases by laparotomy were included. Data were obtained retrospectively from patient records and radiological imaging examinations. Extracted data consisted of age, gender, length, weight, body mass index, current smoking, diabetes mellitus, preoperative chemotherapy (defined as chemotherapy administration within 90 days before surgery), preoperative blood samples, American Society of Anesthesiologists (ASA) grade, operative procedure, 30-day morbidity classified according to ClavienDindo13 and postoperative chemotherapy (defined as chemotherapy administration within 90 days after surgery). Prolonged preoperative chemotherapy was defined as more than 6 cycles. The most recent preoperative CT scan and all CT images from the normal patient follow-up program, typically consisting of one CT scan every six month the first three years followed by one CT scan yearly, were analyzed by one investigator (JHN). Incisional hernia was defined as a discontinuity in the abdominal fascia observed on CT scan.3,11 On preoperative CT, the existence of an incisional hernia from previous colorectal resection or previous liver resection was recorded. The localization of incisional hernia after liver operation was determined to midline, mid-subcostal or lateral, where the midline was unaffected by the hernia in the latter two groups. Subcutaneous fat thickness was measured 2 cm caudal from the xiphoid process on preoperative CT images. Total preoperative muscle area (TMA) was manually traced on the CT transversal plane image on the third lumbar level where vertebral spinae were clearly visible and then automatically calculated.14,15 From TMA, a skeletal muscle index (SMI) was calculated by correcting for height. Skeletal muscle depletion, previously often referred to as sarcopenia, was defined as SMI <41.1 cm2/ m2 for women and <43.75 cm2/m2 for men.15,16 Body fat percentage was calculated as body weight (kg) – (0.3 × TMA (cm2))/body weight (kg).17,18 If a liver re-resection was made on a patient the incisional hernia incidence follow-up was ceased and the patient was analyzed as a new patient with a new incisional hernia follow-up. The study protocol was approved by the regional ethics committee.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Surgical procedure The liver was normally accessed through a right subcostal incision typically 4–5 cm caudal of the costal margin with a midline cranial extension to the xiphoid process typically measuring 4–8 cm, signifying an extended right subcostal incision. If necessary, the incision was extended to the left resulting in a bilateral subcostal incision with a cranial midline extension (Mercedes incision). Liver resection was performed according to standard technique.19 A major resection was defined as resection of 3 Couinaud’s segments. The abdominal wall fascia was closed in two layers with running no. 0 PDS suture (Johnsson & Johnsson, Diegem, Belgium) and the skin was stapled. No drains were used. Statistical analysis All results are expressed as median (range). Mann–Whitney Utest was used to compare continuous data and c2 test for categorical data. Kaplan–Meier was used to estimate incisional hernia incidence and the log-rank test was used to compare risk factors. To analyze the effect of risk factors on incisional hernia incidence Cox regression analysis was used to calculate hazard ratios and 95 per cent confidence intervals. Factors with a p < 0.1 on univariate Cox regression analysis were included in further multivariate analysis. A p < 0.05 was considered statistically significant. Statistical analysis was performed using IBM SPSS Statistics version 22 (IBM, Armonk, NY, USA).
Results A total of 262 consecutive patients were operated with laparotomy for colorectal liver metastases between 2010 and 2013. Six patients
were excluded because of no follow-up radiology was made before the patients died (n = 4) or no available images (n = 2), leaving 256 patients to be analyzed in regard to incisional hernia. In total, 78 patients (30.5%) were found to develop incisional hernia, with a Kaplan–Meier estimated rate of incidental hernia of 34.9% at 60 months. The median follow-up period was 13 (range 2–59) months. Patient characteristics and perioperative data for the hernia and non-hernia groups are shown in Table 1. Incisions were extended right subcostal (198 patients, 77.3%), Mercedes (52 patients, 20.3%) and midline (3 patients, 1.2%). Hernia locations were midline alone in 66 patients (84.6%), midline plus mid-subcostal or lateral in 8 patients (10.3%) and lateral in 3 patients (3.8%). The median length of follow-up until a hernia was identified on CT was 7 (range 1–27) months. The majority of the hernias were small, typically on the order of one cm (results not shown). Among patients with incisional hernia prior to current liver surgery (n = 36), 24 had hernia after colorectal resection and 12 had hernia after previous liver resection, 23 developed incisional hernia (log-rank p < 0.0001, Fig. 1). Preoperative chemotherapy was oxaliplatin-based in 75 (54%) patients and irinotecan-based in 34 (24%) patients. Twenty-four (17%) patients were treated with multiple chemotherapy regimens. Patients with prolonged preoperative chemotherapy (>6 cycles) were more prone to develop incisional hernia (log-rank p = 0.025, Fig. 2). Fig. 3 shows the Kaplan–Meier plot of incisional hernia incidence for patients receiving preoperative bevacizumab, where 11 out of 19 (58%) patients developed incisional hernia (log-rank p < 0.0001). Eight out of 23 patients with surgical site infection developed incisional hernia without statistical difference as compared to patients without infection (log-rank p = 0.313). Obesity (BMI > 30 kg/m2) (n = 32) was not found to have any impact on incisional hernia incidence (logrank p = 0.340). Univariate and multivariate hazard ratio analysis of risk factors for incisional hernia development are shown in Table 2.
Discussion
Figure 1 Kaplan–Meier plot of incisional hernia (IH) incidence for pa-
tients with IH before surgery and patients without IH before surgery. P < 0.0001 (log rank test)
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In the present study, the first to include only patients with colorectal liver metastases, an incisional hernia incidence of 30.5% was found even though abdominal wall closure was made in two layers with a running, slowly absorbable monofilament suture in accordance with current evidence to prevent incisional hernias.1 Some previous studies of hernia incidence after liver resection have reported much lower figures, about 5%.2,5 The difference can most likely be attributed to the routine use of CT for diagnosis in the present study. In recent studies, using CT for diagnosis of incisional hernias, an incidence of 31.3% and 31.5% was reported after resection of hepatocellular carcinoma6 and colorectal resections,20 respectively. Because of the high incidence of incisional hernias, implantation of prophylactic mesh has been tried in mid-line incisions
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 2 Kaplan–Meier plot of incisional hernia (IH) incidence for pa-
tients with more than 6 cycles of pre-operative chemotherapy and patients receiving 6 or less cycles of pre-operative chemotherapy. P = 0.025 (log rank test)
with promising results in terms of efficacy20 and safety.21 No trials on prophylactic mesh implantation have to date been conducted for subcostal incisions after liver resections. Prolonged preoperative chemotherapy (>6 cycles) was independently associated with an increased incidence of incisional hernia with a hazard ratio of 2.12. The subject is little investigated with only one previous study, including different types of abdominal procedures, which also showed an association between preoperative chemotherapy and incisional hernia incidence.11 Prolonged preoperative chemotherapy has previously been shown to reduce the liver regenerative capacity after portal vein occlusion22 and liver resection.23 When used in the neoadjuvant setting for colorectal liver metastases, the number of chemotherapy cycles is normally limited to 6,24 with little impact on the incidence of incisional hernia according to the present study. Postoperative chemotherapy did not increase the hernia incidence. Bevacizumab is a monoclonal anti-vascular endothelial growth factor antibody, which has been shown to have the potential to impair wound healing25 although not previously described as a risk factor for incisional hernia occurrence. With a hazard ratio of 3.63 it was the most powerful independent risk factor for incisional hernia. However, the number of patients treated with bevacizumab was small and the result needs to be corroborated in larger studies. The presence of incisional hernia before liver surgery was another strong independent predictor for incisional hernia. The majority of these patients had an incisional hernia after previous colorectal resection located at a certain distance from the incision for liver resection. The Kaplan–Meier estimate for incisional hernia occurrence at 60 months was as high as 78.0%, thereby identifying a previously not described high-risk group. HPB 2016, 18, 436–441
The vast majority of incisional hernias occurred in the midline of the cranial extension of the subcostal incision, in accordance with evidence that midline incisions are more prone to incisional hernias than transverse incisions.1 To reduce the incidence of incisional hernias, a rational deduction of this finding would be to minimize or abandon this extension whenever possible. No association between body composition and incisional hernia incidence was found, investigating body mass index, skeletal muscle depletion, body fat percentage and thickness of subcutaneous fat, although a body mass index >26 kg/m2 resulted in a pvalue of 0.054 in univariate analysis. A high body mass index has been demonstrated as a risk factor in several previous studies.5,11 Body composition has been suggested to influence surgical outcome after liver resection for colorectal metastases, including both short-term morbidity26 and long-term survival.15 Another factor without significance for development of incisional hernia was surgical site infection, previously shown to be of importance.11 However, the number of patients included may well have been too small to detect this influence. In addition, information about the occurrence of infection was sought retrospectively in patient records with the risk of underestimating the incidence of at least subcutaneous infections. The weaknesses of the study are mostly due to the retrospective design and the relatively few patients with risk factors such as preoperative bevacizumab. In addition, the clinical significance of the occurrence of incisional hernia was not evaluated and the sizes of the hernias were not consistently measured, although the majority of hernias were small, on the order of one cm. However, it has been reported that patients with incisional hernia experience a lower health-related quality of life on physical components and worse body image.27 In liver transplantation, it has been shown that patients with incisional hernia experience
Figure 3 Kaplan–Meier plot of incisional hernia (IH) incidence for pa-
tients receiving pre-operative bevacizumab and patients not receiving pre-operative bevacizumab. P < 0.0001 (log rank test)
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Table 2 Cox proportional hazard analysis of risk factors for incisional hernia development
Factor
Univariate HR
Multivariate P
Gender (male:female)
1.08 (0.68–1.71)
0.736
Age > 70
1.20 (0.76–1.90)
0.438
Current smoking
0.82 (0.45–1.49)
0.523
Diabetes mellitus
1.23 (0.65–2.33)
0.519
Body mass index > 26 kg/m2
1.55 (0.99–2.41)
0.054
Subcutaneous fat > 20 mm
1.34 (0.74–2.43)
0.334
Body fat percentage > 50%
1.74 (0.96–3.15)
0.070
Skeletal muscle depletion
0.76 (0.48–1.21)
0.242
Preoperative chemotherapy
1.23 (0.78–1.93)
0.380
Preoperative chemotherapy > 6 cycles
1.96 (1.08–3.57)
0.028
HR
P
1.51 (0.91–2.50)
0.111
1.52 (0.81–2.86)
0.194
2.12 (1.14–3.94)
0.017 <0.0001
Preoperative bevacizumab
3.55 (1.85–6.69)
<0.0001
3.63 (1.86–7.08)
Previous liver resection
2.11 (1.20–3.71)
0.010
1.32 (0.71–2.48)
0.382
Incisional hernia before surgery
3.58 (2.20–5.84)
<0.0001
3.50 (1.98–6.18)
<0.0001
ASA grade (1/2:3/4)
1.17 (0.72–1.90)
0.517
Incision type (ERSI:Mercedes)
1.12 (0.66–1.90)
0.677
Incisional surgical site infection
1.45 (0.70–3.02)
0.316
Resection size (minor:major)
1.29 (0.81–2.07)
0.289
Morbidity (Clavien-Dindo 3)
1.10 (0.55–2.20)
0.793
Postoperative chemotherapy
0.87 (0.54–1.42)
0.583
HR, hazard ratio; ASA, American Society of Anesthesiologists; ERSI, extended right subcostal incision.
impaired health-related quality of life compared to those without hernia.28 Another weakness is that the size of the bites for abdominal closure was not standardized among operating surgeons, which has been shown to influence the hernia rate.29 In conclusion, this study on patients operated for colorectal liver metastases showed that prolonged preoperative chemotherapy and also preoperative bevacizumab were strong predictors for developing an incisional hernia. The hernia location was almost exclusively in the midline of an extended right subcostal incision.
4. Claes K, Beckers R, Heindryckx E, Kyle-Leinhase I, Pletinckx P,
Conflicts of interest
7. Pawlik TM, Choti MA. (2007) Surgical therapy for colorectal metastases
Claeys D et al. (2014) Retrospective observational study on the incidence of incisional hernias after colorectal carcinoma resection with follow-up CT scan. Hernia 18:797–802. 5. Togo S, Nagano Y, Masumoto C, Takakura H, Matsuo K, Takeda K et al. (2008) Outcome of and risk factors for incisional hernia after partial hepatectomy. J Gastrointest Surg Off J Soc Surg Aliment Tract 12: 1115–1120. 6. Kayashima H, Maeda T, Harada N, Masuda T, Guntani A, Ito S et al. (2015) Risk factors for incisional hernia after hepatic resection for hepatocellular carcinoma in patients with liver cirrhosis. Surgery 158: 1669–1675. to the liver. J Gastrointest Surg Off J Soc Surg Aliment Tract 11:
None to declare.
1057–1077. 8. Pawlik TM, Schulick RD, Choti MA. (2008) Expanding criteria for
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resectability of colorectal liver metastases. Oncologist 13:51–64. 9. Heinrich S, Lang H. (2013) Liver metastases from colorectal cancer: technique of liver resection. J Surg Oncol 107:579–584. 10. Scoggins CR, Campbell ML, Landry CS, Slomiany BA, Woodall CE,
19:1–24. 2. D’Angelica M, Maddineni S, Fong Y, Martin RC, Cohen MS, Ben-Porat L
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metastases. Ann Surg Oncol 16:35–41. 11. Itatsu K, Yokoyama Y, Sugawara G, Kubota H, Tojima Y, Kurumiya Y et al. (2014) Incidence of and risk factors for incisional hernia after abdominal surgery. Br J Surg 101:1439–1447. 12. Naguib N, Rafique H, Dhruva Rao PK, Longworth T, Soukias JM, Masoud A. (2015) A review of the incidence of iatrogenic hernia in both
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laparoscopic and open colorectal surgery: using CT as the gold standard of detection, cohort study. Int J Surg 19:87–90. 13. Dindo D, Demartines N, Clavien PA. (2004) Classification of surgical
comparing primary suture with primary glued mesh augmentation to prevent incisional hernia. Ann Surg 261:276–281. 22. Sturesson C, Keussen I, Tranberg KG. (2010) Prolonged chemotherapy
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von Meyenfeldt MF et al. (2013) Sarcopenia negatively affects preoper-
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(2012) Body composition and outcome in patients undergoing resection
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versus surgery alone for resectable liver metastases from colorectal
16. Harimoto N, Shirabe K, Yamashita YI, Ikegami T, Yoshizumi T, Soejima Y et al. (2013) Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma. Br J Surg 100:1523–1530. 17. Lodewick TM, van Nijnatten TJ, van Dam RM, van Mierlo K, Dello SA, Neumann UP et al. (2015) Are sarcopenia, obesity and sarcopenic obesity predictive of outcome in patients with colorectal liver metas-
Lancet 371:1007–1016. 25. Thornton AD, Ravn P, Winslet M, Chester K. (2006) Angiogenesis inhibition with bevacizumab and the surgical management of colorectal cancer. Br J Surg 93:1456–1463. 26. Peng PD, van Vledder MG, Tsai S, de Jong MC, Makary M, Ng J et al. (2011) Sarcopenia negatively impacts short-term outcomes in patients
tases? HPB 17:438–446. 18. Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L et al. (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9:629–635. 19. Blind PJ, Andersson B, Tingstedt B, Bergenfeldt M, Andersson R, Lindell G et al. (2014) Fast-track program for liver resection–factors prolonging length of stay. Hepatogastroenterology 61:2340–2344. 20. Garcia-Urena MA, Lopez-Monclus J, Hernando LA, Montes DM, Valle de Lersundi AR, Pavon CC et al. (2015) Randomized controlled trial of the use of a large-pore polypropylene mesh to prevent incisional hernia in colorectal surgery. Ann Surg 261:876–881. 21. Timmermans L, Eker HH, Steyerberg EW, Jairam A, de Jong D, Pierik EG et al. (2015) Short-term results of a randomized controlled trial
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cancer (EORTC Intergroup trial 40983): a randomised controlled trial.
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© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.hpb.2016.02.001
ORIGINAL ARTICLE
Incisional hernia after open resections for colorectal liver metastases – incidence and risk factors Jan H. Nilsson1, Peter Strandberg Holka1 & Christian Sturesson1 1
Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden
Abstract Background: Incisional hernia is one of the most common complications after laparotomy. The aim of this retrospective study was to investigate incidence, location and risk factors for incisional hernia after open resection for colorectal liver metastases including the use of perioperative chemotherapy and targeted therapy evaluated by computed tomography. Methods: Patients operated for colorectal liver metastases between 2010 and 2013 were included. Incisional hernia was defined as a discontinuity in the abdominal fascia observed on computed tomography. Results: A total of 256 patients were analyzed in regard to incisional hernia. Seventy-eight patients (30.5%) developed incisional hernia. Hernia locations were midline alone in 66 patients (84.6%) and involving the midline in another 8 patients (10.3%). In multivariate analysis, preoperative chemotherapy >6 cycles (hazard ratio 2.12, 95% confidence interval 1.14–3.94), preoperative bevacizumab (hazard ratio 3.63, 95% confidence interval 1.86–7.08) and incisional hernia from previous surgery (hazard ratio 3.50, 95% confidence interval 1.98–6.18) were found to be independent risk factors. Conclusions: Prolonged preoperative chemotherapy and also preoperative bevacizumab were strong predictors for developing an incisional hernia. After an extended right subcostal incision, the hernia location was almost exclusively in the midline. Received 28 December 2015; accepted 14 February 2016
Correspondence Department of Surgery, Skåne University Hospital, S-221 85 Lund, Sweden. Tel: +46 46 172347. Fax: +46 46 172335. E-mail: [email protected]
Introduction Incisional hernia is one of the most common complications after laparotomy. The reported incidence is highly variable depending on underlying disease, type of incision used, length of follow up and method for hernia detection.1 Numerous risk factors associated with an increased incisional hernia incidence have been reported, including gender (both male and female), age, surgical site infection, obesity and aortic aneurysm.1–4 The incisional hernia incidence after liver resections has been studied only to a limited extent2,5,6. No study including only patients with liver metastases from colorectal cancer has previously been made. Liver metastases are a common consequence of colorectal cancer where the only available potential curative treatment is surgery.7,8 Although laparoscopic liver resections are feasible and increasingly being used, open resection is still the most common
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procedure.9 Before liver resection of colorectal metastases a majority of patients receive preoperative chemotherapy9,10 which has been shown to be an independent risk factor for incisional hernia.11 Non-midline incisions give lesser incisional hernias and in liver resections an extended right subcostal incision is recommended.1,2 Medical imaging diagnostics increases the ability to detect incisional hernias as compared to physical examination.1,4,12 Computed tomography (CT) has been suggested as the “gold standard” because of its high reliability for diagnosing incisional hernia.4 Still, few studies exist that have used CT in a consequent manner to analyze incisional hernia incidence. The aim of this retrospective study was to investigate incidence, location and risk factors for incisional hernia after open liver resection for colorectal liver metastases including the use of perioperative chemotherapy and targeted therapy evaluated by CT.
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Table 1 Patient characteristics for the two groups with and without
Table 1 (continued )
incisional hernia Incisional hernia No incisional hernia
P
Number of patients
78
178
–
Gender (male:female)
48:30
110:68
0.969
Age (years)
68 (37–82)
68 (35–85)
0.880
Current smoking
13
36
0.505
Diabetes mellitus
11
19
0.432
Body mass index (kg/m2)
26.0 (18.4–41.1)
25.0 (17.7–38.2)
0.076
Total muscle area (mm2)
13,360 (6391–20,599)
13,350 (5460–21,906)
0.802
Skeletal muscle depletion
27
76
0.225
Subcutaneous fat (mm)
12 (3–34)
12 (2–35)
0.415
Body fat percentage (%)
39.1 (19.2–57.2)
38.0 (8.6–66.6)
0.531
Preoperative chemotherapy
44
96
0.656
5 (1–16)
5 (1–13)
0.552
Preoperative chemotherapy > 6 cycles
13
19
0.169
Preoperative bevacizumab
11
8
0.009
Previous liver resection
15
18
0.045
Incisional hernia before surgery
23
13
<0.0001
ASA grade (1/2:3/4)
54:24
129:49
0.597
Preoperative albumin (g/l)
38 (25–46)
38 (24–47)
0.522
Preoperative creatinine (mmol/l)
73.5 (36–132)
73.0 (31–150)
0.645
Operating time (hours)
4.76 (1.0–9.8)
4.75 (1.1–13.0)
0.955
Operative bleeding (ml)
350 (25–2000)
300 (25–8000)
0.683
Incision type (ERSI:Mercedes)
60:16
138:36
0.948
Major resection
26
68
0.457
Hospital stay (days)
7 (3–34)
7 (2–76)
0.804
Incisional surgical site infection
8
15
0.638
Remote infection
3
9
0.673
Number of chemotherapy cycles
(continued on next page)
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Incisional hernia No incisional hernia
P
Morbidity 9 (Clavien-Dindo 3)
18
0.732
Postoperative chemotherapy
104
0.774
45
Data are presented as number or median (range). ASA, American Society of Anesthesiologists; ERSI, extended right subcostal incision.
Patients and methods Patients operated for colorectal liver metastases by laparotomy were included. Data were obtained retrospectively from patient records and radiological imaging examinations. Extracted data consisted of age, gender, length, weight, body mass index, current smoking, diabetes mellitus, preoperative chemotherapy (defined as chemotherapy administration within 90 days before surgery), preoperative blood samples, American Society of Anesthesiologists (ASA) grade, operative procedure, 30-day morbidity classified according to ClavienDindo13 and postoperative chemotherapy (defined as chemotherapy administration within 90 days after surgery). Prolonged preoperative chemotherapy was defined as more than 6 cycles. The most recent preoperative CT scan and all CT images from the normal patient follow-up program, typically consisting of one CT scan every six month the first three years followed by one CT scan yearly, were analyzed by one investigator (JHN). Incisional hernia was defined as a discontinuity in the abdominal fascia observed on CT scan.3,11 On preoperative CT, the existence of an incisional hernia from previous colorectal resection or previous liver resection was recorded. The localization of incisional hernia after liver operation was determined to midline, mid-subcostal or lateral, where the midline was unaffected by the hernia in the latter two groups. Subcutaneous fat thickness was measured 2 cm caudal from the xiphoid process on preoperative CT images. Total preoperative muscle area (TMA) was manually traced on the CT transversal plane image on the third lumbar level where vertebral spinae were clearly visible and then automatically calculated.14,15 From TMA, a skeletal muscle index (SMI) was calculated by correcting for height. Skeletal muscle depletion, previously often referred to as sarcopenia, was defined as SMI <41.1 cm2/ m2 for women and <43.75 cm2/m2 for men.15,16 Body fat percentage was calculated as body weight (kg) – (0.3 × TMA (cm2))/body weight (kg).17,18 If a liver re-resection was made on a patient the incisional hernia incidence follow-up was ceased and the patient was analyzed as a new patient with a new incisional hernia follow-up. The study protocol was approved by the regional ethics committee.
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Surgical procedure The liver was normally accessed through a right subcostal incision typically 4–5 cm caudal of the costal margin with a midline cranial extension to the xiphoid process typically measuring 4–8 cm, signifying an extended right subcostal incision. If necessary, the incision was extended to the left resulting in a bilateral subcostal incision with a cranial midline extension (Mercedes incision). Liver resection was performed according to standard technique.19 A major resection was defined as resection of 3 Couinaud’s segments. The abdominal wall fascia was closed in two layers with running no. 0 PDS suture (Johnsson & Johnsson, Diegem, Belgium) and the skin was stapled. No drains were used. Statistical analysis All results are expressed as median (range). Mann–Whitney Utest was used to compare continuous data and c2 test for categorical data. Kaplan–Meier was used to estimate incisional hernia incidence and the log-rank test was used to compare risk factors. To analyze the effect of risk factors on incisional hernia incidence Cox regression analysis was used to calculate hazard ratios and 95 per cent confidence intervals. Factors with a p < 0.1 on univariate Cox regression analysis were included in further multivariate analysis. A p < 0.05 was considered statistically significant. Statistical analysis was performed using IBM SPSS Statistics version 22 (IBM, Armonk, NY, USA).
Results A total of 262 consecutive patients were operated with laparotomy for colorectal liver metastases between 2010 and 2013. Six patients
were excluded because of no follow-up radiology was made before the patients died (n = 4) or no available images (n = 2), leaving 256 patients to be analyzed in regard to incisional hernia. In total, 78 patients (30.5%) were found to develop incisional hernia, with a Kaplan–Meier estimated rate of incidental hernia of 34.9% at 60 months. The median follow-up period was 13 (range 2–59) months. Patient characteristics and perioperative data for the hernia and non-hernia groups are shown in Table 1. Incisions were extended right subcostal (198 patients, 77.3%), Mercedes (52 patients, 20.3%) and midline (3 patients, 1.2%). Hernia locations were midline alone in 66 patients (84.6%), midline plus mid-subcostal or lateral in 8 patients (10.3%) and lateral in 3 patients (3.8%). The median length of follow-up until a hernia was identified on CT was 7 (range 1–27) months. The majority of the hernias were small, typically on the order of one cm (results not shown). Among patients with incisional hernia prior to current liver surgery (n = 36), 24 had hernia after colorectal resection and 12 had hernia after previous liver resection, 23 developed incisional hernia (log-rank p < 0.0001, Fig. 1). Preoperative chemotherapy was oxaliplatin-based in 75 (54%) patients and irinotecan-based in 34 (24%) patients. Twenty-four (17%) patients were treated with multiple chemotherapy regimens. Patients with prolonged preoperative chemotherapy (>6 cycles) were more prone to develop incisional hernia (log-rank p = 0.025, Fig. 2). Fig. 3 shows the Kaplan–Meier plot of incisional hernia incidence for patients receiving preoperative bevacizumab, where 11 out of 19 (58%) patients developed incisional hernia (log-rank p < 0.0001). Eight out of 23 patients with surgical site infection developed incisional hernia without statistical difference as compared to patients without infection (log-rank p = 0.313). Obesity (BMI > 30 kg/m2) (n = 32) was not found to have any impact on incisional hernia incidence (logrank p = 0.340). Univariate and multivariate hazard ratio analysis of risk factors for incisional hernia development are shown in Table 2.
Discussion
Figure 1 Kaplan–Meier plot of incisional hernia (IH) incidence for pa-
tients with IH before surgery and patients without IH before surgery. P < 0.0001 (log rank test)
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In the present study, the first to include only patients with colorectal liver metastases, an incisional hernia incidence of 30.5% was found even though abdominal wall closure was made in two layers with a running, slowly absorbable monofilament suture in accordance with current evidence to prevent incisional hernias.1 Some previous studies of hernia incidence after liver resection have reported much lower figures, about 5%.2,5 The difference can most likely be attributed to the routine use of CT for diagnosis in the present study. In recent studies, using CT for diagnosis of incisional hernias, an incidence of 31.3% and 31.5% was reported after resection of hepatocellular carcinoma6 and colorectal resections,20 respectively. Because of the high incidence of incisional hernias, implantation of prophylactic mesh has been tried in mid-line incisions
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Figure 2 Kaplan–Meier plot of incisional hernia (IH) incidence for pa-
tients with more than 6 cycles of pre-operative chemotherapy and patients receiving 6 or less cycles of pre-operative chemotherapy. P = 0.025 (log rank test)
with promising results in terms of efficacy20 and safety.21 No trials on prophylactic mesh implantation have to date been conducted for subcostal incisions after liver resections. Prolonged preoperative chemotherapy (>6 cycles) was independently associated with an increased incidence of incisional hernia with a hazard ratio of 2.12. The subject is little investigated with only one previous study, including different types of abdominal procedures, which also showed an association between preoperative chemotherapy and incisional hernia incidence.11 Prolonged preoperative chemotherapy has previously been shown to reduce the liver regenerative capacity after portal vein occlusion22 and liver resection.23 When used in the neoadjuvant setting for colorectal liver metastases, the number of chemotherapy cycles is normally limited to 6,24 with little impact on the incidence of incisional hernia according to the present study. Postoperative chemotherapy did not increase the hernia incidence. Bevacizumab is a monoclonal anti-vascular endothelial growth factor antibody, which has been shown to have the potential to impair wound healing25 although not previously described as a risk factor for incisional hernia occurrence. With a hazard ratio of 3.63 it was the most powerful independent risk factor for incisional hernia. However, the number of patients treated with bevacizumab was small and the result needs to be corroborated in larger studies. The presence of incisional hernia before liver surgery was another strong independent predictor for incisional hernia. The majority of these patients had an incisional hernia after previous colorectal resection located at a certain distance from the incision for liver resection. The Kaplan–Meier estimate for incisional hernia occurrence at 60 months was as high as 78.0%, thereby identifying a previously not described high-risk group. HPB 2016, 18, 436–441
The vast majority of incisional hernias occurred in the midline of the cranial extension of the subcostal incision, in accordance with evidence that midline incisions are more prone to incisional hernias than transverse incisions.1 To reduce the incidence of incisional hernias, a rational deduction of this finding would be to minimize or abandon this extension whenever possible. No association between body composition and incisional hernia incidence was found, investigating body mass index, skeletal muscle depletion, body fat percentage and thickness of subcutaneous fat, although a body mass index >26 kg/m2 resulted in a pvalue of 0.054 in univariate analysis. A high body mass index has been demonstrated as a risk factor in several previous studies.5,11 Body composition has been suggested to influence surgical outcome after liver resection for colorectal metastases, including both short-term morbidity26 and long-term survival.15 Another factor without significance for development of incisional hernia was surgical site infection, previously shown to be of importance.11 However, the number of patients included may well have been too small to detect this influence. In addition, information about the occurrence of infection was sought retrospectively in patient records with the risk of underestimating the incidence of at least subcutaneous infections. The weaknesses of the study are mostly due to the retrospective design and the relatively few patients with risk factors such as preoperative bevacizumab. In addition, the clinical significance of the occurrence of incisional hernia was not evaluated and the sizes of the hernias were not consistently measured, although the majority of hernias were small, on the order of one cm. However, it has been reported that patients with incisional hernia experience a lower health-related quality of life on physical components and worse body image.27 In liver transplantation, it has been shown that patients with incisional hernia experience
Figure 3 Kaplan–Meier plot of incisional hernia (IH) incidence for pa-
tients receiving pre-operative bevacizumab and patients not receiving pre-operative bevacizumab. P < 0.0001 (log rank test)
© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Table 2 Cox proportional hazard analysis of risk factors for incisional hernia development
Factor
Univariate HR
Multivariate P
Gender (male:female)
1.08 (0.68–1.71)
0.736
Age > 70
1.20 (0.76–1.90)
0.438
Current smoking
0.82 (0.45–1.49)
0.523
Diabetes mellitus
1.23 (0.65–2.33)
0.519
Body mass index > 26 kg/m2
1.55 (0.99–2.41)
0.054
Subcutaneous fat > 20 mm
1.34 (0.74–2.43)
0.334
Body fat percentage > 50%
1.74 (0.96–3.15)
0.070
Skeletal muscle depletion
0.76 (0.48–1.21)
0.242
Preoperative chemotherapy
1.23 (0.78–1.93)
0.380
Preoperative chemotherapy > 6 cycles
1.96 (1.08–3.57)
0.028
HR
P
1.51 (0.91–2.50)
0.111
1.52 (0.81–2.86)
0.194
2.12 (1.14–3.94)
0.017 <0.0001
Preoperative bevacizumab
3.55 (1.85–6.69)
<0.0001
3.63 (1.86–7.08)
Previous liver resection
2.11 (1.20–3.71)
0.010
1.32 (0.71–2.48)
0.382
Incisional hernia before surgery
3.58 (2.20–5.84)
<0.0001
3.50 (1.98–6.18)
<0.0001
ASA grade (1/2:3/4)
1.17 (0.72–1.90)
0.517
Incision type (ERSI:Mercedes)
1.12 (0.66–1.90)
0.677
Incisional surgical site infection
1.45 (0.70–3.02)
0.316
Resection size (minor:major)
1.29 (0.81–2.07)
0.289
Morbidity (Clavien-Dindo 3)
1.10 (0.55–2.20)
0.793
Postoperative chemotherapy
0.87 (0.54–1.42)
0.583
HR, hazard ratio; ASA, American Society of Anesthesiologists; ERSI, extended right subcostal incision.
impaired health-related quality of life compared to those without hernia.28 Another weakness is that the size of the bites for abdominal closure was not standardized among operating surgeons, which has been shown to influence the hernia rate.29 In conclusion, this study on patients operated for colorectal liver metastases showed that prolonged preoperative chemotherapy and also preoperative bevacizumab were strong predictors for developing an incisional hernia. The hernia location was almost exclusively in the midline of an extended right subcostal incision.
4. Claes K, Beckers R, Heindryckx E, Kyle-Leinhase I, Pletinckx P,
Conflicts of interest
7. Pawlik TM, Choti MA. (2007) Surgical therapy for colorectal metastases
Claeys D et al. (2014) Retrospective observational study on the incidence of incisional hernias after colorectal carcinoma resection with follow-up CT scan. Hernia 18:797–802. 5. Togo S, Nagano Y, Masumoto C, Takakura H, Matsuo K, Takeda K et al. (2008) Outcome of and risk factors for incisional hernia after partial hepatectomy. J Gastrointest Surg Off J Soc Surg Aliment Tract 12: 1115–1120. 6. Kayashima H, Maeda T, Harada N, Masuda T, Guntani A, Ito S et al. (2015) Risk factors for incisional hernia after hepatic resection for hepatocellular carcinoma in patients with liver cirrhosis. Surgery 158: 1669–1675. to the liver. J Gastrointest Surg Off J Soc Surg Aliment Tract 11:
None to declare.
1057–1077. 8. Pawlik TM, Schulick RD, Choti MA. (2008) Expanding criteria for
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© 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.