Prospective Clinical Trial of Factors Predicting the Early Development of Incisional Hernia after Midline Laparotomy

Radovan Veljkovic, MD, PhD, Mladjan Protic, MD, Aleksandar Gluhovic, MD, Zoran Potic, MS, Zoran Milosevic, MD, PhD, Alexander Stojadinovic, MD, FACS
Information-based scoring systems predictive of outcomes of midline laparotomy are needed; these systems can support surgical decisions with the aim of improving patient outcomes and quality of life, and reducing the risk of secondary surgical procedures. STUDY DESIGN: All study subjects were followed for a minimum of 6 months after operation. Numerous demographic, clinical, treatment, and outcomes-related perioperative factors were recorded to determine statistical association with the primary end point: incisional hernia development. The first analysis was designed to establish the statistical model (scoring system) for estimating the risk of incisional hernia within 6 months of midline laparotomy. Univariate and multivariate analyses were performed. A simple additive model was constructed using stepwise logistic and linear regression. The second part of the study analysis was validation of the scoring systems developed initially. RESULTS: A logistic linear minimum regression model was developed based on four covariates independently predictive of incisional hernia: Body mass index (BMI) 24.4kg/m2; fascial suture to incision ratio (SIR) 4.2; deep surgical site, deep space, or organ infection (SSI); and time to suture removal or complete epithelialization 16 days (TIME). The hernia risk scoring system equation [p(%) 32(SIR) 30(SSI) 9(TIME) 2(BMI)] provided accurate estimates of incisional hernia according to stratified risk groups based on total score: low (0 to 5 points), 1.0%; moderate (6 to 15 points), 9.7%; increased (16 to 50 points), 30.2%; and markedly increased (50 points), 73.1%. CONCLUSIONS: A statistically valid, straightforward, and clinically useful predictive model was developed for estimating the risk of incisional hernia within 6 months of midline laparotomy. Prospective independent validation of this model appears indicated. (J Am Coll Surg 2010;210:210219. Published by Elsevier Inc. on behalf of the American College of Surgeons)
BACKGROUND:

Disclosure Information: Nothing to disclose. Our team includes military service members and employees of the US Government. This work was prepared as part of our official duties. Title 17 USC 105 provides that Copyright protection under this title is not available for any work of the United States Government. Title 17 USC 101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that persons official duties. The views expressed in this presentation are those of the authors and do not reflect the official policy of the Department of the Army, the Department of Defense or the US Government. Received August 6, 2009; Revised October 22, 2009; Accepted October 23, 2009. From the Clinic of Abdominal, Endocrine and Transplantation Surgery, Clinical Center Vojvodina, Novi Sad (Veljkovic, Protic, Gluhovic, Milosevic) and Potic Consulting, Agency for consulting and management (Protic), Novi Sad, Serbia; the Department of Surgery, Division of Surgical Oncology, Walter Reed Army Medical Center (Stojadinovic); and the United States Military Cancer Institute, Clinical Trials Group (Stojadinovic), Washington, DC. Correspondence address: Colonel Alexander Stojadinovic, MD, United States Military Cancer Institute, Walter Reed Army Medical Center, 6900 Georgia Ave, Room 5C27A, NW, Washington, DC 20307.

Ventral hernia, a well established complication of midline laparotomy, is defined as a protrusion of intraperitoneal structures through a defect in the anterior abdominal wall fascia.1-4 Despite important technologic advances in surgery, incisional hernias remain a frequent secondary surgical event, complicating approximately 10% to 15% of abdominal incisional closures5 and accounting for nearly 100,000 of the 700,000 abdominal wall hernia repairs conducted annually in the US.6 Incisional hernias of the anterior abdominal wall are multifactorial in origin, reflecting predisposing patient, disease, and surgical technique-specific factors. In spite of extensive reporting of this often unsightly, complicated, and lifestyle-limiting problem to date, the surgical community has struggled to identify predisposing factors that can be modified to reduce the likelihood of incisional hernia development. In particular, clinical development and application of a scoring system for predicting outcomes of midline laparotomy incisions remain to be

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ISSN 1072-7515/10/$36.00 doi:10.1016/j.jamcollsurg.2009.10.013

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Abbreviations and Acronyms

enrolled into the study voluntarily agreed to participate and gave written, signed informed consent.
Study interventions

body mass index logistic and linear regression model LOG LIN MIN Model logistic linear minimal regression model LOG Model logistic regression model ROC receiver operating characteristic SIR suture to incision ratio SSI surgical site infection BMI LOG LIN Model

realized. The opportunity for meaningful clinical change lies in the development of an intuitive information-based scoring system that is clinically useful and that can support surgical decisions with the ultimate aim of improving patient outcomes and quality of life, and reducing the risk of secondary surgical procedures. This prospective observational cohort trial was conducted to define a scoring system to estimate risk of early hernia development in patients undergoing midline laparotomy for diverse urgent and elective surgical indications.

METHODS
Clinical trial design

A prospective, single arm, observational cohort trial was conducted from May 2004 to July 2005. The Institutional Review Board approved this study in compliance with all applicable federal regulations governing the protection of human subjects. Study participants were recruited from patients undergoing midline laparotomy for urgent and elective surgical indications. Informed consent for this study was obtained from each study subject or legal medical representative.
Eligibility criteria

Adult male patients and nonpregnant female patients (age 18 years or older) admitted and operated on for any elective or urgent surgical procedure requiring midline laparotomy were eligible for this trial. Those with premorbid confounding inflammatory conditions, including immune deficiency and connective tissue disorders, or any medical illness requiring immunosuppressive therapy, were excluded. Patients having access to the peritoneal cavity other than midline laparotomy, those with previous anterior abdominal wall incisional hernia, those who withdrew from the study for any reason before the end of the required 6-month follow-up (including those who died during that period), and those with incomplete data were excluded. Patients emerging from the operating room with open surgical wounds were not included in this study. All subjects

Study participants were scheduled for midline laparotomy before study enrollment. Demographic, medical history, laboratory, perioperative, operative, and surgical outcomes data were collected prospectively over a minimum followup period of 6 months after incident operation. Demographic variables included age, gender, height, weight, body mass index (BMI), and occupation. Medical history data included number of previous abdominal operations, diabetes (including patients with both insulin- and noninsulin-dependent diabetes mellitus), COPD (confirmed obstructive lung physiology by pulmonary function testing), history of earlier malignancy, presence of preoperative anemia (hemoglobin 10 g/dL), jaundice (bilirubin 1.2 mg/dL), hypoproteinemia (total protein 6 g/dL), uremia (blood urea nitrogen 7.5 mmol/L), history of smoking, and total number of pack-years (number of packs per day number of years of use) of tobacco use. Laboratory parameters recorded at time of study entry included hemoglobin, white blood cell count, blood urea nitrogen, bilirubin, and total protein level. Perioperative data collected included type of midline laparotomy (elective or urgent), hospital shift during which the operation began (midnight to 8:00 AM, 8:00 AM to 4:00 PM, 4:00 PM to midnight), and antibiotics and/or anticoagulants administered within 1 hour of operation. The transverse abdominal diameter (distance between midaxillary lines at the umbilical level, cm) and sagittal abdominal diameter (midline distance from xiphoid to pubis, cm) were recorded before laparotomy incision. Operative data collected included ratio of incisional to sagittal abdominal length; diagnosis of malignancy during or after operation; operative time (minutes from time of laparotomy incision to closure); average operative time for a given operative procedure (minutes; procedure-specific data obtained from operative logs); ratio of operative time to average operative time for a given operative procedure in this study (%); intraoperative or postoperative transfusion (mL); length of incision (cm, measured using a sterile ruler over the reapproximated fascial incision); type of suture and length of fascial suture (cm, measured as original length minus remaining suture after fascial closure completed); type of fascial closure (continuous versus interrupted versus both); ratio of fascial suture to incision length; placement of retention sutures; and use and number of incisional and/or peritoneal drains. Surgical outcomes data included hospital and postoperative follow-up time from date of operation to hospital discharge and last follow-up, respectively; number of me-

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chanical ventilation days; reoperation during the incident hospital stay; reoperation for ileus during the incident hospitalization; presence, site (abdominal quadrant; right upper quadrant, left upper quadrant, both upper quadrants, right lower quadrant, left lower quadrant, both lower quadrants, three or all four quadrants), and origin (upper gastrointestinal or hepatobiliary; appendix or colorectal; gynecologic) of intraabdominal infection; and development of nosocomial infection (infection that was a result of treatment in hospital, but secondary to the patients original condition, which appeared 48 hours or more after admission or within 30 days of hospital discharge). A nosocomial infection was considered present when it was supported by positive culture results, based on symptoms and clinical or radiologic signs, and required antibiotic therapy in the opinion of an infectious disease physician consultant. Surgical outcomes assessed included development of surgical site infection (as defined by the Centers for Disease Control and National Nosocomial Infections Surveillance System); presence and severity of postoperative nausea, cough, vomiting, and pain (expressed as the worst severity score during the first 4 postoperative days based on a visual analog scale) score ranging from a minimum value of 0 to a maximum value of 40; duration of analgesic use (days); duration (days) and number of antibiotics used postoperatively; and use of, amount of aspirate from, and duration of postoperative nasogastric tube use. Time to skin suture or staple removal and or complete wound epithelialization was also assessed. In the case of uncomplicated healing of the skin incision, the suture or staple removal date was taken as the date of complete healing. In our series, it typically occurred between 8 and 12 days after operation, and there were rare cases in which skin suture or staple removal occurred before the 8th and after the 14th days. In the case of minimally complicated unopened draining wounds without fistula or obvious dehiscence, we used as a cut-off point the date when the wound discharge ceased and/or the subcutaneous wound drain was removed. In the case of a complicated wound that had to be reopened, we used as a cut-off point the date when, in the opinion of the operating surgeon, the wound was completely reepithelialized. Development and time to development of incisional hernia (palpable incisional fascial defect 2 cm in diameter, or visible bulge in the laparotomy incision) was recorded.
Follow-up

requiring transfusion, need for mechanical ventilation, reoperation, superficial or deep operative site or deep space infection, nosocomial infection, ileus, presence and severity of postoperative nausea, cough, vomiting, and pain. Patients were also followed to determine duration of analgesic and antibiotic use, and time to suture or staple removal or complete wound epithelialization. The primary end points of this study were early development and time to development of incisional hernia. Of the 646 patients who consented to this study, 43 were excluded: 10 because of incomplete data, 12 because of incomplete follow up of less than 6 months, and 21 because of death within 6 months of operation. There were 603 evaluable patients who served as the study population for this analysis.
Objective

The principal aim of this trial was to develop a prognostic scoring system for the early development of incisional hernia within 6 months of midline laparotomy.
Primary outcomes variable

The primary outcomes variable was the presence of incisional hernia at the midline laparotomy site within 6 months of operation.
Sample size

Sample size calculation was based on expected accrual of 700 subjects per year who were expected to meet study eligibility criteria. The calculation was based on the assumption that the probability of incisional hernia in the study population was 12%. A sample size of 181 would allow the positive predictive value to be estimated to within 10% with 95% confidence.
Statistical methods

Study subjects were admitted, consented to operation, and were operated on through a midline laparotomy incision for any elective or urgent surgical indication. All study subjects were followed for a minimum of 6 months for development of surgical adverse events including bleeding

Differences in baseline characteristics were evaluated using Fishers exact test (2-tailed) for categorical variables and the Wilcoxon rank sum test for continuous or ordinal data. Continuous data were presented as either medians with ranges or means with standard deviations ( SD). Significance was determined at the p 0.05 level (2-tailed). Statistical analyses were carried out using SPSS statistical software (version 10.0, SPSS, Inc). The first part of the study analysis was designed to establish the statistical model (scoring system) for estimating risk of incisional hernia within 6 months of midline laparotomy. Univariate and multivariate analyses were performed. Using a set of preoperative and operative risk factors as independent variables and development of incisional hernia as a dependent variable, logistic regression analyses were conducted, with the primary outcomes de-

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Figure 1. Flow of participants followed for the development of incisional hernia within 6 months of elective or urgent midline laparotomy.

fined as presence of incisional hernia at the midline laparotomy site within 6 months of operation. Hosmer-Lemeshow goodness-of-fit was used to study the calibration of the predictive models. Area under the receiver operating characteristic (ROC) curve was used to study the discrimination ability of the models. Thresholds were defined to distinguish low, moderate, high, and extremely high risk groups for the development of incisional hernia within 6 months of midline laparotomy. A simple additive model was constructed using stepwise logistic and linear regression. Validation of the scoring systems was conducted. Because of the modest sample size, validity was tested in two ways: by comparing regression factors and coefficients from the original model with the validation model derived from another multivariate logistic regression analysis on a random data set representing 80% of the original data set; and by applying the originally created model on two 50% subsets of the random data set and comparing predicted and observed results separately.

work (26.7%), hard physical labor (16.3%), and retired (42.6%). Mean body mass index for the study population was 25.6 13.5 kg/m2. Nearly half of the patients in this study (45.9%) were overweight (BMI 25 kg/m2). The incidences of diabetes mellitus (14.9%) and COPD (11.4%) were similar. Active tobacco use was reported in nearly half of study patients (48.3%). Mean sagittal and transverse abdominal diameters were 33.5 3.8 cm and 46.6 8.1 cm, respectively. Before midline laparotomy, one-quarter of patients (n 149; 24.7%) had at least one earlier abdominal operation, and nearly one-third (31.4%) had a diagnosis of malignancy either before or during the time of this study (Table 1). Medical comorbidities were common in this study population, evident in the frequency of preoperative jaundice (8.8%), anemia (14.3%), uremia (23.7%), and hypoproteinemia (21.7%). Mean serum leukocyte, hematocrit, blood urea nitrogen, total protein, and biliribuin levels were 12.5 7.6 103/L (range 3.6 to 10.0 103/L), 38.7% 6.3% (range 38% to 49%), 6.4 4.8 mmol/L (range 1 to 7.5 mmol/L ), 6.44 0.76 g/dL (range 6.0 to 8.0 g/dL ), and 0.708 0.766 mg/dL (range 0.2 to 1.23 mg/dL), respectively.
Operative and perioperative care

RESULTS
Patient characteristics

The study was initiated in May 2004. Enrollment ended in July 2005. Six hundred forty-six patients were enrolled in the trial and 43 were excluded because of mortality (n 21), incomplete follow-up (n 12), and incomplete data (n 10). Six hundred three patients were followed a minimum of 6 months for development of incisional hernia at the midline laparotomy site. Statistical analysis included these 603 patients. The flow of participants through each stage of the trial is demonstrated in Figure 1. The study population was composed of slightly more men than women (53.7% versus 46.3%), with a mean age at presentation of 56.6 16.7 years (Table 1). Distribution of subjects according to current employment status and occupation was as follows: unemployed (14.4%), light

Preoperative antibiotics were administered to 45.9% of patients and to an additional 166 (27.5%) of patients intraoperatively (Table 1). Preoperative venous thromboembolism prophylaxis with heparin was infrequent in this study (18.4%). Most (72.8%) operations were conducted for urgent surgical indications, and 39.8% of patients had active intraabdominal infection at time of exploration. Mean operative time was 103.2 60.6 minutes. Nearly half of patients received perioperative transfusion of blood products (mean transfusion volume 1,150 883 mL). Mean midline laparotomy incision and fascial closure suture lengths were 19.6 5.2 cm and 88 28 cm, respectively. Mean ratios of suture length to sagittal abdominal length and to length of laparotomy incision were 0.6 0.2 and 5.4 2.5, respectively. Fascial closure was performed in continuous or in a combination of continuous (60.7%) and interrupted manner (37.8%), with use of inner and outer retention sutures in 38.0% and 1% of cases, respectively. Incisional drains were used infrequently (17.4%). Seventy-three (12.2%) patients required postoperative mechanical ventilatory support for a mean period of 1.8 1.9 days (Table 1).
Surgical outcomes data

Mean follow-up time for the study population was 6.9 2.1 months. During that time 13.4% (n 81) of patients developed incisional hernia at the midline laparotomy wound 12 to 190 days after operation (Table 1). Mean time

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Table 1. Baseline and Perioperative Characteristics and Outcomes Data for 603 Patients
Characteristic Patients (n 603) n Median (range) %

Table 1. Continued
Characteristic n Patients (n 603) Median (range) %

Patient age, y Gender, male Body mass index, kg/m2 19 19 to 25 25 Diabetes, yes COPD , yes Current tobacco use, yes Earlier abdominal operations Sagittal abdominal diameter, cm Transverse abdominal diameter, cm History of earlier malignancy, yes Malignancy during or after operation yes Preoperative jaundice , yes Preoperative anemia, yes Preoperative uremia, yes Preoperative hypoproteinemia, yes Preoperative antibiotic prophylaxis, yes Preoperative heparin prophylaxis, yes Urgent operation, yes Operation conducted during work shift 4:00 PM to midnight Midnight to 8:00 AM Duration of operation, min Perioperative blood product transfusion, yes Intraabdominal infection during operation, yes Mechanical ventilation, d Abdominal incision length, cm Length of fascial suture, cm Ratio of suture length to incision length Type of fascial suture Polysorb (Coviden) Vicryl (Ethicon) PDS (Ethicon) Nylon (Ethicon) Type of laparotomy incision closure Continuous Interrupted Combination

59 (1897) 324 45 281 277 90 69 291 0 (03) 33 (2555) 46 (3086) 133 56 53 86 143 131 277 111 439 22.1 9.3 8.8 14.3 23.7 21.7 45.9 18.4 72.8 53.7 7.5 46.6 45.9 14.9 11.4 48.3

253 48 90 (25390) 294 243 0.2 (015) 18 (1136) 90 (50330) 4.9 (2.415.0) 180 191 210 22

42.0 8.0

Incisional drain, yes Retention sutures , yes Follow-up time, mo Incisional hernia at midline laparotomy site, yes Reoperation during hospitalization, yes Surgical site infection Superficial Deep Postoperative nausea score (mean, 040) Postoperative emesis score (mean, 040) Postoperative cough score (mean, 040) Postoperative pain score (mean, 040) Incision length, cm Worst pain score (040) 20 20 Duration of postoperative IV analgesic use, d, mean; median (range) Duration of postoperative antibiotic use, d, mean; median (range) Time to suture removal/complete epithelialization, d, mean; median (range)

105 235 6 (6-24) 81 11 120 42 4; 3 (029) 2; 1 (018) 6; 5 (030) 21; 21 (636) 18 (1136) 277 326

17.4 39.0

13.4 1.8 19.9 7.0

45.9 54.1

7; 6 (322)

9; 8 (015)

16; 14 (8125)

48.8 40.3

29.9 31.7 34.8 3.6

to development of the hernia was 89.6 50.0 days. Mean length and width of the hernia at time of first detection were 11.4 5.5 cm and 8.0 4.5 cm, respectively. Reoperation during the initial hospitalization was necessary in 11 (1.8%) cases, 63.6% (n 7) of which resulted in incisional hernia as compared with 12.5% of those not requiring repeat midline laparotomy during the same hospital stay (p 0.001). One hundred sixty-two (26.9%) patients experienced postoperative wound infections, the majority of which were superficial surgical site infections. Postoperative nausea, emesis, cough, and pain scores are shown in Table 1. Mean time to skin wound suture removal and/or complete wound epithelialization was 15.8 8.5 days, and median time was 14 days after operation.
Univariate analysis of factors associated with development of incisional hernia

366 9 228

60.7 1.5 37.8

Univariate comparisons were performed for the primary study end point, development of early incisional hernia

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Table 2. Comparison of Patients With (n 81) and Without (n 522) Early Incisional Hernia Within 6 Months of Midline Laparotomy
Outcomes of midline laparotomy incisional hernia No Yes n % n

Characteristic

p Value*

Total patients n %

Body mass index, kg/m2 19 1925 25 Transverse diameter, cm Mean Preoperative uremia No Yes Mean fascial incision length, cm Mean length of fascial suture, cm Mean ratio: fascial suture length to sagittal abdominal diameter, % Mean ratio: fascial suture length to fascial incision length, cm Reoperation during hospitalization No Yes Surgical site infection None Superficial surgical site Deep surgical site Deep space or organ Mean postoperative nausea score Mean postoperative emesis score Mean postoperative cough score Mean postoperative pain score Mean duration postoperative analgesic, d Mean duration postoperative antibiotic, d Mean time to suture removal or complete epithelialization, d (median 14)

0.008 42 253 227 46 8 407 115 19 5 108 58 58 15 5.6 2.6 518 4 408 94 19 1 45 23 66 21 5 62 84 15 5 87.5 36.4 92.5 78.3 50.0 25.0 88.5 80.4 93.3 90.0 81.9 3 28 50 49 8 0.02 53 28 22 5 88 28 64 15 4.1 0.7 74 7 33 26 19 3 66 44 97 23 5 73 10 7 24 17 12.5 63.6 0.001 7.5 21.7 50.0 75.0 0.003 0.002 0.001 0.001 0.001 0.004 0.001 441 120 38 4 73.1 19.9 6.3 0.7 11.5 19.6 0.001 0.003 0.002 0.001 0.001 592 11 98.2 1.8 460 143 76.3 26.7 6.7 10.0 18.1 0.003 45 281 277 7.5 46.6 45.9

Unless otherwise noted, data are given as mean SD. *Only the significant (p 0.05) univariate comparisons are shown.

within 6 months of midline laparotomy. Significant statistical associations were identified for the primary end point and a range of patient and preoperative factors, listed in Table 2, including BMI, transverse abdominal diameter, and preoperative uremia. With the aim of defining a predictive threshold (optimal sensitivity and specificity) for BMI, ROC analysis was conducted to define the threshold of BMI 24.4 kg/m2, where incidence of hernia for 24.4 kg/m2 versus 24.4 kg/m2 was 7.8% (23 of 272) versus 18.8% (58 of 250), p 0.001. Technical factors significantly associated with early development of incisional hernia included length of fascial incision and fascial suture and the ratio of suture length to both

sagittal abdominal diameter and fascial incision length (Table 2). With the aim of defining a predictive threshold (optimal sensitivity and specificity) ratio of fascial suture to incision length, ROC analysis was conducted to define the threshold of suture to incision length of 4.2, where the incidence of hernia for a ratio of 4.2 versus 4.2 was 40.0% (68 of 102) versus 3% (13 of 420), p 0.001. Postoperative factors significantly associated with early development of incisional hernia included reoperation, surgical site infection, severity of nausea, vomiting, cough, and pain, duration of both analgesic and antibiotic use, and time to wound suture removal and healing.

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Multivariate analysis of factors associated with development of incisional hernia

LOG Model 100

Six covariates were identified with logistic regression analysis (LOG MODEL), which were independently predictive of early development of incisional hernia within 6 months of midline laparotomy: BMI 24.4 kg/m2 (p 0.03); fascial suture to incision ratio 4.2 (p 0.001); deep surgical site or deep space or organ infection (CDC 2 or 3; p 0.001); postoperative pain score 20 (p 0.008); postoperative emesis score 3 (p 0.001); and time to suture removal or complete epithelialization 16 days (p 0.001). The equation for calculating the probability of incisional hernia development using these six covariates is
p 1 1 e ( b 0 b 1 X 1 . . . b n X n)

80

Sensitivity

60

40

20

(p probability of incisional hernia development; b0 model constant; b1 coefficient of risk factor X1; e
basis of natural logarithm).

0 0 20 40 60 80 100 100-Specificity
Figure 2. Receiver operating characteristics curve of the logistic regression model (LOG) for development of incisional hernia.

On the basis of the distribution of predictive values for the dependent variable of interest, incisional hernia development, risk groups were defined according to the following distribution of risk score points for hernia development: low risk score, 0 to 5 points; moderate risk score, 5 to 15 points; increased risk score, 15 to 50 points; markedly increased risk score, 50 points. The value of the Hosmer and Lemeshow goodness-of-fit test (4.6) was at a level of p 0.80, indicating that the predicted and actual percentages of early development of incisional hernia within the 6-month period after midline laparotomy in the groups above are similar (not statistically significantly different). The sensitivity (percent correctness of prediction estimate for patients with hernia) and specificity (percent correctness of prediction estimate for patients without hernia) for the LOG model were 55.5% and 96.9%, respectively, and overall predictive accuracy was 91.4%. Area under the ROC curve was 0.94 (50% probability threshold [most likely case] for calling a patient likely or unlikely for a hernia to develop), as shown in Figure 2. With the principal aim of creating a straightforward predictive model for early development of incisional hernia, we conducted successive logistic and linear regression analysis (LOG LIN MODEL). In the linear analysis of the dependent variable, development of incisional hernia, we used the logistic regression coefficient of each covariate with independent predictive value. The analysis was conducted using six covariates that satisfied a selection criterion of r 0.91, forming a linear predictive model for incisional hernia. The equation for calculating the probability of incisional hernia using the using the six covariates in a LOG_LIN MODEL is shown in Table 3.

For the purpose of everyday use at the point of care and for the rapid assessment of patient-specific risk factors predictive of the early development of incisional hernia, a simplified linear minimal model (LOG_LIN_MIN MODEL) was developed using the same methodology of successive logistical and linear regression analysis. This model was based on four of the six independent predictive variables (BMI 24.4 kg/m2; suture to incision ratio (SIR) 4.2; deep surgical site or deep space or organ infection (SSI) (CDC 2 or 3); and time to suture removal or complete epithelialization (TIME) 16 days), with the scores for the two subjective variables, postoperative pain and emesis, omitted. The equation for calculating the probability of incisional hernia using the four covariates in a LOG_LIN_MIN MODEL is shown in Table 3. The overall model accuracy is reduced somewhat (area under the curve 0.92) with the subjective variables removed; however, it is straightforward, based on objective measures, and permits rapid calculation of risk of early development of incisional hernia. Comparisons were made between the logistic regression and logistic linear minimal regression models, and successive logistic linear regression and logistic linear minimal regression models with correlation coefficients of r 0.87, and r 0.98, respectively. Results of these model comparisons support the use of the logistic linear minimal (LOG_LIN_MIN) model, which is based on fewer independent predictors (four covariates: BMI 24.4 kg/m2 [p 0.001]; suture to incision ratio 4.2 [p 0.001]; deep surgical site or deep space or organ

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Table 3. Equations for Early Incisional Hernia Risk Calculation and Risk
Method Equation Dened parameters Parameter points

LOG_LIN MODEL

P (%) (-6.225) 3.631(SIR) 2.548(SSI) 1.417(TIME) 0.731(BMI) 0.942(PAIN) 1.134(EMESIS)

SIR, suture to incision ratio

1, if 4.2; 0, otherwise 1, if CDC 2 or 3; 0, otherwise 1, if 16 d; 0, otherwise 1, if BMI 24 kg/m2; 0, otherwise 1, if 20 points; 0, otherwise 1, if 3 points; 0, otherwise 1, if 4.2; 0, otherwise 1, if CDC 2 or 3; 0, otherwise 1, if 16 d; 0, otherwise 1, if BMI 24 kg/m2; 0, otherwise

SSI, surgical site infection TIME, time to suture removal or complete epithelialization BMI, body mass index PAIN, postoperative pain score (040) EMESIS, postoperative emesis score (040) LOG_LIN_MIN MODEL p(%) 32(SIR) 30(SSI) 9(TIME) 2(BMI) SIR, suture incision ratio SSI, surgical site infection TIME, time to suture removal or complete epithelialization BMI, body mass index

Risk groups: Low, risk group score 0 to 5 points, predicted incisional hernia risk 1.0%; moderate, risk group score 5 to 15 points, predicted incisional hernia risk 9.7%; increased, risk group score 15 to 50 points, predicted incisional hernia risk 30.2%; markedly increased, risk group score 50 points, predicted incisional hernia risk 73.1%. LOG_LIN, logistic and linear regression model; LOG_LIN_MIN, logistic linear minimal regression model.

infection [CDC 2 or 3; p 0.001]; and time to suture removal or complete epithelialization 16 days [p 0.001]) than the LOG model. Based on concordance of predicted and actual hernia incidence, the analysis supports the rapid and simple application of the logistic linear minimal (LOG_LIN_ MIN) model to estimate risk of incisional hernia development at point of care or bedside. Cross-validation indicates reliable estimates of predicted relative to actual incidence of early incisional hernia development in the randomly assigned subgroups analyzed and the study population as a whole (data not shown). An equation was developed based on the LOG_LIN_MIN model (p[%] 32[SIR] 30[SSI] 9[time to suture removal or complete epithelialization] 2[BMI]), permitting straightforward estimates of hernia risk (Table 3). Predicted risk of hernia development according to defined low (1.0%), moderate (9.7%), increased (30.2%), and markedly increased (73.1%) risk groups, is shown in Table 3. To illustrate the clinical utility of the model, we present the same patient with various clinical parameters, a middleaged man admitted and operated on for perforated diverticuilitis. Example 1: Suture to incision ratio 5.0; no surgical site infection; skin sutures removed on postoperative day 11; BMI 24 kg/m2. Total score (0000) 0. Predicted risk of hernia development 0%.

Example 2: Suture to incision ratio 5.0; no surgical site infection; skin sutures removed on postoperative day 18; BMI 29 kg/m2.Total score (0092) 11. Predicted risk of hernia development is approximately 10%. Example 3: Suture to incision ratio 5.0; surgical site infection (CDC 2); skin sutures removed on postoperative day 18; BMI 29 kg/m2. Total score (03092) 41. Predicted risk of hernia development is approximately 30%. Example 4: Suture to incision ratio 4.0; surgical site infection (CDC 2); skin sutures removed on postoperative day 18; BMI 24 kg/m2. Total score (323090) 71. Predicted risk of hernia development is approximately 75%.

DISCUSSION Failure of midline laparotomy wound healing often occurs in the setting of multiple predisposing factors including SSI, malnutrition, diabetes, immunosuppression, and morbid obesity. Incisional hernias can pose treatment challenges because patients typically have had multiple previous operations and comorbid conditions contributing to attenuated abdominal wall musculature.5,6 Incisional hernias are almost universally regarded as technical failures. However, technical

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factors relating to suture selection, type of fascial closure, ratio of suture to incision length and postoperative interventions such as symptomatic control of nausea, vomiting, cough, and pain have been considered in strategies developed to reduce the risk of hernia development. Evidence is lacking to show that these risk-reducing strategies are in fact clinically meaningful; they have proved largely ineffective in reducing the high incidence of incisional hernia.7-11 In fact, the current understanding of modifiable predisposing factors for incisional hernia remains incomplete. This study was undertaken to identify factors independently associated with early development of incisional hernia within 6 months of midline laparotomy in a well characterized cohort. A mathematically complicated scoring system based on intuitive objective parameters was developed, tested, and cross-validated, and shown to be highly reliable in predicting hernia risk according to logistic regression (LOG) and successive logistic and linear regression analysis (LOG_LIN) models. Given their mathematic complexity, these models proved unwieldy for everyday surgical use, so we evaluated the validity of a simplified system using successive logistic linear regression minimal model (LOG_LIN_MIN). The simplified LOG_LIN_MIN model developed is an accurate and clinically useful scoring tool for efficient daily use to estimate risk of early incisional hernia. This model is the most straightforward of the three models tested and is based on only four of the original six variables: BMI, fascial SIR, deep surgical site or deep space or organ infection (CDC 2 or 3) and time to suture removal or complete epithelialization. The ROCs of the simplified LOG_LIN_MIN model are favorable (area under the curve 0.92), and cross-validation of the model demonstrated reliable estimates of predicted versus actual incidence of early incisional hernia development. A number of factors shown to be significant on univariate analysis, but not ultimately included in the multivariate models, appear to have clinical meaning and may be related to the independently predictive variables in the models, or may be related to modest sample size and short follow-up. For example, transverse abdominal diameter likely reflects BMI; preoperative uremia is indicative of overall patient condition and is related to SSI risk, as are reoperation during incident hospitalization and duration of perioperative antibiotic use. These parameters are clinically meaningful and should be considered in patient risk management decisions. The significance of this study is the resulting predictive model that can serve as a simple, clinically useful tool used at the bedside to support individualized treatment decisions. Not all of the four predictive factors in the model are modifiable. However, attention to surgical detail during

fascial closure to optimize the fascial suture to incision ratio (4.2), taking measures to prevent, identify early, and treat SSI may reduce the risk of early incisional hernia. Calculation of the fascial SIR is simple and can be achieved swiftly. This analysis suggests that parsimonious use of fascial closing suture cannot be justified by a cost-savings argument given the increased risk of operative site morbidity necessitating subsequent operative intervention, ie, incisional hernia repair. Time to skin suture removal can indeed be influenced by the surgeon, and efforts should be taken to facilitate wound healing, particularly in reopened wounds, through adequate wound bed preparation and control of local inflammatory response and infection. Wound healing time, although an independent factor in the model, is influenced significantly by coexisting infection, and can be influenced by antimicrobial prophylaxis for SSI. The severity of postoperative vomiting and pain, found to be significant in multivariate analysis, can be influenced through aggressive prophylactic measures and perioperative multimodal pain management. Undoubtedly the most clinically useful model would be one validated prospectively and composed of factors determined before or during operation, which, in high-risk patients, would influence surgical decision-making through consideration of technical measures or interventions (eg, biological mesh onlay) at time of operation that could reduce the likelihood of incisional hernia. Clearly, the most adequate validation would be undertaken on a larger independent prospective cohort followed over a longer (1 year) period of time, with consideration given to altered collagen biology (eg, aneurysmal disease occurence). In addition to the previously mentioned advantages, particularly the development of the first clinically relevant risk prediction model, there are certain limitations of this study that, in our opinion, do not have a significant impact on the overall results. Minimum follow-up time in our study was 6 months, limiting assessment only to early hernia development according to the original study intent. Additional follow-up of this cohort will allow comparison with results from other studies relying on a follow-up period of more than 1 year, and will provide insights into other predictive factors (such as disease related to altered collagen metabolism) and, perhaps most importantly, provide validation of the proposed hernia risk scoring system.10 The link between postoperative infection and incisional hernia is well recognized, and according to this, all pre- and intraoperative factors that may influence the occurrence and/or intensity of postsurgical infection should be analyzed. In our series, administration of antibiotics was at individual surgeon discretion, so variations in antimicrobial prophylaxis were expectedly evident. One

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Incisional Hernia after Laparotomy

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limiting factor for the lack of uniform administration of antibiotics before operation reflects the unique socioeconomic environment in the country at the time of the study and the concurrent lack of clearly established SSI prophylaxis protocols at our institution. One limiting factor in this study is the lack of uniform administration of antibiotics before operation, which is a reflection of the unique socioeconomic environment in the country at the time of this study and the concurrent lack of clearly established surgical site infection prophylaxis protocols at our institution. In conclusion, this study was conducted with the principal aim of developing a statistically valid, straightforward, and clinically useful predictive model for early development of incisional hernia within 6 months of midline laparotomy. A simplified scoring system derived from a validated LOG_LIN_MIN model, which is based on four predictive variables (BMI 24.4 kg/m2, fascial suture to incision ratio 4.2, deep surgical site or deep space or organ infection [CDC 2 or 3], and time to suture removal or complete epithelialization 16 days), was created, providing rapid and straightforward point-of-care estimation of hernia risk with clinically relevant reliability. Prospective independent validation of this model appears indicated.
Author Contributions Study conception and design: Veljkovic, Protic, Milosevic Acquisition of data: Veljkovic, Protic, Gluhovic, Milosevic Analysis and interpretation of data: Veljkovic, Protic, Stojadinovic Drafting of manuscript: Veljkovic, Stojadinovic

Critical revision: Veljkovic, Protic, Gluhovic, Milosevic, Stojadinovic

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