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Figure 1.
Complicated hernia presentation by acuity and race. *Black individuals were significantly more likely than white individuals to present with acute hernia complications requiring emergent surgery.

Complicated hernia presentation by acuity and race. *Black individuals were significantly more likely than white individuals to present with acute hernia complications requiring emergent surgery.

Figure 2.
Complicated presentation by acuity and patient insurance.

Complicated presentation by acuity and patient insurance.

Table 1. 
Patient Diagnosis on Hospital Readmission Less Than 30 Days From Operative Procedure
Patient Diagnosis on Hospital Readmission Less Than 30 Days From Operative Procedure
Table 2. 
Postoperative Morbidity, 30-Day Readmission, and 6-Month Recurrence Rate by Patient Race and Socioeconomic Status
Postoperative Morbidity, 30-Day Readmission, and 6-Month Recurrence Rate by Patient Race and Socioeconomic Status
Table 3. 
Socioeconomic Status by Race
Socioeconomic Status by Race
1.
Regnard  JFHay  JMRea  SFingerhut  AFlamant  YMaillard  JN Ventral incisional hernias: incidence, date of recurrence, localization and risk factors.  Ital J Surg Sci 1988;18 (3) 259- 265PubMed
2.
Deveney Karen  E Hernias and other lesions of the abdominal wall GM  DohertyLW  Way Current Surgical Diagnosis and Treatment New York, NY: McGraw-Hill; 2005: 724736
3.
Polite  BNDignam  JJOlopade  OI Colorectal cancer model of health disparities: understanding mortality differences in minority populations.  J Clin Oncol 2006;24 (14) 2179- 2187PubMedArticle
4.
Smink  DSFishman  SJKleinman  KFinkelstein  JA Effects of race, insurance status, and hospital volume on perforated appendicitis in children.  Pediatrics 2005;115 (4) 920- 925PubMedArticle
5.
Memtsoudis  SGBesculides  MCSwamidoss  CP Do race, gender, and source of payment impact on anesthetic technique for inguinal hernia repair?  J Clin Anesth 2006;18 (5) 328- 333PubMedArticle
6.
Asolati  MHuerta  SSarosi  GHarmon  RBell  CAnthony  T Predictors of recurrence in veteran patients with umbilical hernia: single center experience.  Am J Surg 2006;192 (5) 627- 630PubMedArticle
7.
 Social Security Death Index.  Washington, DC: US Social Security Administration; 2008
8.
 US Census Bureau Zip Code Tabulation Fact Sheet.  Washington, DC: US Census Bureau; 2000
9.
Birkmeyer  NJGu  NBaser  OMorris  AMBirkmeyer  JD Socioeconomic status and surgical mortality in the elderly.  Med Care 2008;46 (9) 893- 899PubMedArticle
10.
Fiscella  KFranks  PMeldrum  SBarnett  S Racial disparity in surgical complications in New York State.  Ann Surg 2005;242 (2) 151- 155PubMedArticle
11.
Askew  GWilliams  GTBrown  SC Delay in presentation and misdiagnosis of strangulated hernia: prospective study.  J R Coll Surg Edinb 1992;37 (1) 37- 38PubMed
12.
Mort  EAWeissman  JSEpstein  AM Physician discretion and racial variation in the use of surgical procedures.  Arch Intern Med 1994;154 (7) 761- 767PubMedArticle
13.
Gittelsohn  AMHalpern  JSanchez  RL Income, race, and surgery in Maryland.  Am J Public Health 1991;81 (11) 1435- 1441PubMedArticle
14.
 Black-white disparities in health care.  JAMA 1990;263 (17) 2344- 2346PubMedArticle
15.
Society for Surgery of the Alimentary Tract, SSAT patient care guidelines: surgical repair of incisional hernias.  J Gastrointest Surg 2007;11 (9) 1231- 1232PubMedArticle
16.
Weissman  JSStern  RFielding  SLEpstein  AM Delayed access to health care: risk factors, reasons, and consequences.  Ann Intern Med 1991;114 (4) 325- 331PubMedArticle
17.
Diette  GBRand  C The contributing role of health-care communication to health disparities for minority patients with asthma.  Chest 2007;132 (5) (suppl)802S- 809SPubMedArticle
18.
Levinson  WHudak  PLFeldman  JJ  et al.  “It's not what you say . . . ”: racial disparities in communication between orthopedic surgeons and patients.  Med Care 2008;46 (4) 410- 416PubMedArticle
19.
Gornick  MEEggers  PWReilly  TW  et al.  Effects of race and income on mortality and use of services among Medicare beneficiaries.  N Engl J Med 1996;335 (11) 791- 799PubMedArticle
20.
Friedman  E Money isn't everything: nonfinancial barriers to access.  JAMA 1994;271 (19) 1535- 1538PubMedArticle
21.
Cunningham  PJ Mounting pressures: physicians serving Medicaid patients and the uninsured, 1997-2001.  Track Rep 2002; (6) 1- 4PubMed
22.
Schulman  KABerlin  JAHarless  W  et al.  The effect of race and sex on physicians' recommendations for cardiac catheterization.  N Engl J Med 1999;340 (8) 618- 626PubMedArticle
23.
Andrulis  DP Access to care is the centerpiece in the elimination of socioeconomic disparities in health.  Ann Intern Med 1998;129 (5) 412- 416PubMedArticle
24.
Groeneveld  PWLaufer  SBGarber  AM Technology diffusion, hospital variation, and racial disparities among elderly Medicare beneficiaries: 1989-2000.  Med Care 2005;43 (4) 320- 329PubMedArticle
25.
Ricciardi  RSelker  HPBaxter  NNMarcello  PWRoberts  PLVirnig  BA Disparate use of minimally invasive surgery in benign surgical conditions.  Surg Endosc 2008;22 (9) 1977- 1986PubMedArticle
26.
Nguyen  NTZainabadi  KMavandadi  S  et al.  Trends in utilization and outcomes of laparoscopic versus open appendectomy.  Am J Surg 2004;188 (6) 813- 820PubMedArticle
Original Article
August 2010

Impact of Race and Socioeconomic Status on Presentation and Management of Ventral Hernias

Author Affiliations

Author Affiliations: Division of General Surgery, Department of Surgery, The Mount Sinai Hospital, New York, New York.

Arch Surg. 2010;145(8):776-780. doi:10.1001/archsurg.2010.141
Abstract

Objective  To assess for disparity in presentation and management of ventral hernias.

Design  Retrospective review.

Setting  Academic center.

Patients  Three hundred twenty-one patients who underwent ventral hernia repair from 2005 to 2008.

Main Outcome Measures  Disparity in ventral hernia presentation, management, and outcome. Univariate analysis was conducted by unpaired t test and χ2 test.

Results  Black individuals were more likely than white individuals to present with acute hernia complications requiring emergent surgery (11% vs 4%; P < .01). This finding persisted after controlling for socioeconomic status (SES). Assessment by SES demonstrated patients with Medicaid were more likely to present with incarcerated or strangulated hernias (39% vs 25%; P < .001) and had longer hospital stays (4.7 vs 3 days; P < .05) as compared with patients with private insurance. Patients classified as low income had increased 30-day readmission rates as compared with average- or high-income patients (32% vs 9% vs 7%, respectively; P < .01). No difference in use of minimally invasive technique, performance of primary vs mesh repair, or postoperative morbidity or mortality was demonstrated. Twelve-month follow-up demonstrated no difference in recurrence rate by race or SES.

Conclusions  Our study demonstrates the existence of disparity in patient presentation with complicated ventral hernia. Despite clear disparity by race and SES, at our institution, disparate presentation did not equate to disparate treatment or postoperative complications. No difference was demonstrated by use of operative technique, perioperative outcome, or 12-month recurrence rate. This study illustrates the need for long-term measures directed at reevaluation of organizational and institutional factors that perpetuate inequality.

The rate of ventral hernia formation following laparotomy ranges from 2% to 15%, with an estimated 100 000 ventral hernia repairs performed annually in the United States.1 While many remain asymptomatic, patients may present with complications of ventral hernia including small-bowel obstruction or ischemia secondary to incarcerated or strangulated bowel.1 Such complex presentations often confer worse patient morbidity and mortality and are avoidable by early operative repair.2

Health disparity based on race and socioeconomic status influences the presentation and treatment of many operative conditions, with hernias being no exception.3,4 Studies demonstrate that black individuals with inguinal hernias are more likely than white individuals to receive general anesthesia during herniorrhaphy and have prolonged hospital stays and greater postoperative pain.5 A study focusing on umbilical hernias demonstrated that black individuals are at increased risk of hernia recurrence as compared with white individuals.6 To our knowledge, no studies investigating health disparity and ventral hernia currently exist. The purpose of this study was to establish the impact of race and socioeconomic status on clinical presentation, management, and operative outcome of patients with ventral hernia.

Methods

Following approval by the Mount Sinai School of Medicine institutional review board, a retrospective medical record review was performed of 321 patients who underwent ventral hernia repair at The Mount Sinai Medical Center from 2005 to 2008. Patients were identified from an administrative database by International Classification of Diseases, Ninth Revision codes (551.2, 551.21, 551.29, 552.2, 552.21, 552.29, 553.2, and 553.21) for ventral hernia repair. Minors, patients with hernia recurrence in the immediate perioperative period following ventral hernia repair, and patients with umbilical, inguinal, and Spigelian hernias were excluded from the study. A ventral hernia was defined as a defect of the anterior abdominal wall not involving the umbilicus or a hernia resulting from a previous laparotomy incision. Emergent surgery was defined as operative intervention for an acutely irreducible hernia or clinical suspicion of ischemic bowel. Timing of operative procedure, laparoscopic vs open operative technique, and method of repair were at the discretion of the individual surgeon.

Electronic medical records were reviewed for patient demographics, comorbidity, patient medical and social history, and hospital presentation. Operative and anesthesia records, hospital course, and postoperative morbidity and mortality were assessed. Outcome at a mean of 12 months assessing hernia recurrence and postoperative mortality was obtained. Recurrence was determined by review of patient medical records. Mortality was determined by cross-referencing patient social security number with the online social security death index database.7

Race categorization was based on self-recorded information within the medical record. Socioeconomic status was assessed using income and insurance measures. Income classification was determined based on patient zip code at time of hospital admission and correlated with the 2000 US Census Bureau data for median household income by zip code.8 Low income was defined as median annual household income less than $20 997; average income, $20 998 to $62 991; and high income, greater than $62 991. Privately insured patients were those with nongovernment-subsidized insurance or patients with Medicare and a supplemental private insurance carrier. Publicly insured patients were classified as those with Medicare or Medicaid. All patients in this study were insured.

Statistical analysis was conducted by unpaired t test with 2-tail distribution for quantitative values and χ2 test for categorical values. P values less than .05 for associations were considered to confer significance. Prism 4.0 software (GraphPad Software, San Diego, California) was used for all analyses.

Results
Population characteristics

Of the 321 patients who underwent ventral hernia repair since 2005, 186 patients (58%) were white; 62 (19%), black; 59 (18%), Hispanic; 6 (2%), Asian; and 8 (3%), race not specified. Mean patient age was 52.9 years. By sex, 199 patients (62%) were female and 122 (38%), male. Income analysis demonstrated 7% of patients were low income; 67%, average income; and 26%, high income. The majority of patients (81%) had private insurance, while 19% were publicly insured (P < .01). Ninety-two patients (29%) had a complicated hernia presentation. Sixty-nine patients (75%) had a chronically incarcerated hernia and 23 patients (25%) presented with an acutely incarcerated or obstructing hernia, of which 17 (74%) required emergent surgery. Mean preoperative American Society of Anesthesiologists score was 2.1. Fifty-four percent of operations were via an open approach and 46%, laparoscopic, with 5 cases (3%) requiring open conversion secondary to adhesions. Mean intraoperative blood loss was 80 mL and mesh was used in 267 repairs (83%). Mean length of stay was 3 days (median, 2 days). No mortalities occurred and no patient required intensive care unit stay. The postoperative morbidity rate was 8%. The 30-day readmission rate was 10% and mean length of stay after readmission was 1.5 days. Reasons for readmission are demonstrated in Table 1. Follow-up at a mean of 12 months demonstrated an 8% recurrence rate. Table 2 illustrates postoperative morbidity, readmission, and recurrence by patient demographic.

Population assessment by race

Evaluation by race demonstrated that black individuals were significantly younger than white individuals at the time of operative intervention (48 vs 56 years; P < .001). Figure 1 demonstrates complicated presentation by race. Black individuals were more likely to require emergent surgery (11% vs 4%; P < .01) and had significantly increased 30-day readmission rates (18% vs 8%; P = .02) as compared with white individuals. No difference between black individuals vs white individuals in intraoperative course, use of laparoscopic modality (52% vs 54%, respectively), performance of primary (25% vs 20%, respectively) vs mesh (75% vs 80%, respectively) repair, postoperative complication, or necessity of reoperation was demonstrated. Twelve-month follow-up demonstrated no difference in recurrence rate by race.

Population assessment by income and insurance measures

Two hundred sixty-four patients had private insurance and 57, public. Assessment by insurance parameters demonstrated patients with public insurance had significantly increased complicated presentations (39% vs 25%; P < .001) and longer length of stay (4.7 vs 3 days; P < .05) as compared with patients with private insurance. Figure 2 demonstrates complicated presentation by insurance carrier. A trend toward increased 30-day readmission was also demonstrated in patients with public vs private insurance (14% vs 9%; P = .11). No difference by patient insurance was demonstrated in requirement for emergent surgery, intraoperative course, operative approach, performance of primary vs mesh repair, postoperative complication, 30-day reoperation, or 12-month recurrence rate.

Analysis by income demonstrated patients classified as low income were significantly more likely to be readmitted within 30 days of surgery than patients classified as average or high income (32% vs 9% vs 7%, respectively; P < .01). No significant difference in any other parameter was demonstrated.

Population assessment by race and socioeconomic parameters

Evaluation by race and socioeconomic parameters demonstrated that both black and Hispanic individuals were less likely to have private insurance and be in lower income brackets than white individuals. Table 3 demonstrates socioeconomic status by race. Assessment of patients with private insurance demonstrated that black individuals were more likely to present acutely and require emergent operative intervention than white individuals (13% vs 3%; P = .004). Assessment by race of patients with public insurance demonstrated no difference in presentation.

Black individuals classified as low income had increased 30-day readmission as compared with white individuals (29% vs 0%; P = .03). No difference by race and socioeconomic status was demonstrated by intraoperative course, laparoscopic approach, primary vs mesh repair, postoperative complication, 30-day reoperation, or 6-month recurrence rate.

Comment

Our study demonstrates the existence of both racial and socioeconomic health disparity in patients with ventral hernia. Overall, black individuals were more likely to require emergent surgery and had increased 30-day readmission rates as compared with white individuals. In addition, this finding persisted after controlling for socioeconomic status. Assessment of insurance and income parameters demonstrated that black individuals with private insurance were more likely than white individuals with private insurance to require emergent surgery. Black individuals classified as low income also had increased 30-day readmission rates as compared with white individuals.

Socioeconomic status, however, had the most substantial impact on health disparity. Patients with public insurance were at a significantly increased risk for acute and chronic complicated presentations and had longer hospital stays and a trend toward increased 30-day readmission rates as compared with patients with private insurance. Public insurance remained an independent risk factor for complicated hernia presentation requiring emergent operative intervention, even after controlling for race. Assessment by income demonstrated that patients classified as low income had increased 30-day readmission rates as compared with patients in average- or high-income brackets.

The disparity in patient presentation with ventral hernia demonstrated by this study is likely attributable to inequitable access to health care. Many studies demonstrate disparate medical care in minorities and patients of low socioeconomic status and attribute this finding to financial barriers and patient health beliefs.916 Weissman et al16 reported that black individuals, uninsured patients, and patients without a primary physician were 40% to 80% more likely to delay seeking or obtaining health care and accredited this, in part, to patient perceptions regarding medical care. Patients who delayed their care mainly did so under the premise that most health care issues resolve without medical intervention. Such perceptions likely represent a deficiency in patient education and understanding of disease processes.17,18 Because the greatest risk factor for patient presentation with strangulated or incarcerated ventral hernia is delay of operative repair, any patient belief system preventing timely medical attention potentially increases the incidence of complicated presentation.11,15 Surgeons must ensure that patients are well informed and understand potential operative complications prior to procedures, as well as give explicit instructions as to when medical attention cannot be delayed. Improving patient education on clinical signs warranting medical attention may decrease presentation with advanced disease.

Organizational and financial barriers also contribute to disparity. Insurance coverage alone does not ensure adequate access to health care.19,20 Studies demonstrate that the proportion of physicians accepting Medicaid is declining and such practices often have quotas as to the number of publicly insured patients they accept.2124 As a result, Medicaid patients often have difficulty gaining access to already limited practices. Financial and space limitations impeding access to health care for patients of low socioeconomic status may prevent timely diagnosis and intervention in patients with ventral hernia. Increased provisions for Medicaid patients and assurance of sufficient postoperative follow-up, regardless of insurance or economic status, are necessary to prevent complicated hernia presentation.

Despite clear disparity in ventral hernia presentation by race and socioeconomic status, no difference was demonstrated in use of laparoscopic vs open operative technique. This finding contrasts with other studies demonstrating disparate use of minimally invasive modalities in patients of low socioeconomic status.25,26 The Mount Sinai Medical Center is a tertiary care institution specializing in minimally invasive surgery where the vast majority of surgeons favor the laparoscopic over open operative approach. This likely accounts for the demonstrated equivalent use of minimally invasive modalities. Additionally, no difference in primary vs mesh repair, postoperative morbidity and mortality, necessity for reoperation, or 12-month recurrence rate was demonstrated. Overall, at our institution, disparate presentation did not equate with disparate treatment or increased rates of postoperative complication, mortality, or short-term recurrence. While health care costs inevitably factor into decision making, they should not dictate care. Every effort should be made to ensure that patients receive equivalent care and that operative decisions are based on optimal intervention rather than racial or socioeconomic factors.

This study did, however, identify that minorities and patients categorized as low income had increased 30-day hospital readmission rates as well as increased hospital stay for patients with public insurance. This difference is likely attributable to access barriers rather than increased operative morbidity, because no increase in 30-day postoperative complication was demonstrated by race or socioeconomic status. Patients without regular physicians are more likely to use acute care facilities as their primary medical source.23 Without assurance of appropriate follow-up, health care providers may admit patients with diagnoses typically amenable to outpatient care to ensure appropriate initial therapy. This theory is supported by our finding that the majority of readmissions were for surgical site infections and postoperative pain control. Increased readmission rates and longer lengths of stay may negatively impact patients by increasing time away from work and family. In addition, readmission and longer hospital stays pose the financial burden of hospitalization to both patient and institution.

The major strength of this study is that all patients presented to a single tertiary care institution with access to comparable surgical management and operative technologies. While this study did identify clear racial and economic disparity, the cause of such discrepant presentation with ventral hernia remains speculative. Prospective studies accounting for patient belief systems and documenting preoperative and postoperative health care access are necessary. Such studies will help formulate long-term measures directed at patient education and reevaluation of organizational and institutional factors that perpetuate inequality.

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Article Information

Correspondence: Celia M. Divino, MD, Division of General Surgery, The Mount Sinai Medical Center, 5 E 98th St, Box 1259, 15th Floor, New York, NY 10029 (celia.divino@mountsinai.org).

Accepted for Publication: May 13, 2009.

Author Contributions: Ms Bowman had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of analysis. Study concept and design: Bowman, Telem, and Divino. Acquisition of data: Bowman, Hernandez-Rosa, Stein, and Williams. Analysis and interpretation of data: Bowman and Telem. Drafting of the manuscript: Bowman, Telem, Hernandez-Rosa, Stein, and Williams. Critical revision of the manuscript for important intellectual content: Bowman, Telem, and Divino. Statistical analysis: Telem. Administrative, technical, and material support: Bowman, Hernandez-Rosa, Stein, Williams, and Divino. Study supervision: Divino.

Financial Disclosure: None reported.

References
1.
Regnard  JFHay  JMRea  SFingerhut  AFlamant  YMaillard  JN Ventral incisional hernias: incidence, date of recurrence, localization and risk factors.  Ital J Surg Sci 1988;18 (3) 259- 265PubMed
2.
Deveney Karen  E Hernias and other lesions of the abdominal wall GM  DohertyLW  Way Current Surgical Diagnosis and Treatment New York, NY: McGraw-Hill; 2005: 724736
3.
Polite  BNDignam  JJOlopade  OI Colorectal cancer model of health disparities: understanding mortality differences in minority populations.  J Clin Oncol 2006;24 (14) 2179- 2187PubMedArticle
4.
Smink  DSFishman  SJKleinman  KFinkelstein  JA Effects of race, insurance status, and hospital volume on perforated appendicitis in children.  Pediatrics 2005;115 (4) 920- 925PubMedArticle
5.
Memtsoudis  SGBesculides  MCSwamidoss  CP Do race, gender, and source of payment impact on anesthetic technique for inguinal hernia repair?  J Clin Anesth 2006;18 (5) 328- 333PubMedArticle
6.
Asolati  MHuerta  SSarosi  GHarmon  RBell  CAnthony  T Predictors of recurrence in veteran patients with umbilical hernia: single center experience.  Am J Surg 2006;192 (5) 627- 630PubMedArticle
7.
 Social Security Death Index.  Washington, DC: US Social Security Administration; 2008
8.
 US Census Bureau Zip Code Tabulation Fact Sheet.  Washington, DC: US Census Bureau; 2000
9.
Birkmeyer  NJGu  NBaser  OMorris  AMBirkmeyer  JD Socioeconomic status and surgical mortality in the elderly.  Med Care 2008;46 (9) 893- 899PubMedArticle
10.
Fiscella  KFranks  PMeldrum  SBarnett  S Racial disparity in surgical complications in New York State.  Ann Surg 2005;242 (2) 151- 155PubMedArticle
11.
Askew  GWilliams  GTBrown  SC Delay in presentation and misdiagnosis of strangulated hernia: prospective study.  J R Coll Surg Edinb 1992;37 (1) 37- 38PubMed
12.
Mort  EAWeissman  JSEpstein  AM Physician discretion and racial variation in the use of surgical procedures.  Arch Intern Med 1994;154 (7) 761- 767PubMedArticle
13.
Gittelsohn  AMHalpern  JSanchez  RL Income, race, and surgery in Maryland.  Am J Public Health 1991;81 (11) 1435- 1441PubMedArticle
14.
 Black-white disparities in health care.  JAMA 1990;263 (17) 2344- 2346PubMedArticle
15.
Society for Surgery of the Alimentary Tract, SSAT patient care guidelines: surgical repair of incisional hernias.  J Gastrointest Surg 2007;11 (9) 1231- 1232PubMedArticle
16.
Weissman  JSStern  RFielding  SLEpstein  AM Delayed access to health care: risk factors, reasons, and consequences.  Ann Intern Med 1991;114 (4) 325- 331PubMedArticle
17.
Diette  GBRand  C The contributing role of health-care communication to health disparities for minority patients with asthma.  Chest 2007;132 (5) (suppl)802S- 809SPubMedArticle
18.
Levinson  WHudak  PLFeldman  JJ  et al.  “It's not what you say . . . ”: racial disparities in communication between orthopedic surgeons and patients.  Med Care 2008;46 (4) 410- 416PubMedArticle
19.
Gornick  MEEggers  PWReilly  TW  et al.  Effects of race and income on mortality and use of services among Medicare beneficiaries.  N Engl J Med 1996;335 (11) 791- 799PubMedArticle
20.
Friedman  E Money isn't everything: nonfinancial barriers to access.  JAMA 1994;271 (19) 1535- 1538PubMedArticle
21.
Cunningham  PJ Mounting pressures: physicians serving Medicaid patients and the uninsured, 1997-2001.  Track Rep 2002; (6) 1- 4PubMed
22.
Schulman  KABerlin  JAHarless  W  et al.  The effect of race and sex on physicians' recommendations for cardiac catheterization.  N Engl J Med 1999;340 (8) 618- 626PubMedArticle
23.
Andrulis  DP Access to care is the centerpiece in the elimination of socioeconomic disparities in health.  Ann Intern Med 1998;129 (5) 412- 416PubMedArticle
24.
Groeneveld  PWLaufer  SBGarber  AM Technology diffusion, hospital variation, and racial disparities among elderly Medicare beneficiaries: 1989-2000.  Med Care 2005;43 (4) 320- 329PubMedArticle
25.
Ricciardi  RSelker  HPBaxter  NNMarcello  PWRoberts  PLVirnig  BA Disparate use of minimally invasive surgery in benign surgical conditions.  Surg Endosc 2008;22 (9) 1977- 1986PubMedArticle
26.
Nguyen  NTZainabadi  KMavandadi  S  et al.  Trends in utilization and outcomes of laparoscopic versus open appendectomy.  Am J Surg 2004;188 (6) 813- 820PubMedArticle
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