"Mesh versus suture repair for umbilical hernias a prospective"
Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Table of Contents Chapter Titel Page Amendments 3 Confidentiality statement 4 Investigators signature of agreement 5 Investigators signature of agreement – 6 Primary investigator copy Study Committee 7 Study participants 8 Summary 9 1.0 INTRODUCTION 10 1.1 Anatomy and Pathofysiology 12 1.2 Complications 13 1.3 Risk Factors for hernia recurrence 13 2.0 PATIENTS AND METHOD 14 2.1 Statistical analysis 14 2.2 Practical implication of trial 15 2.3 Method of repair and per-operative procedure 16 2.3.1 Method of mesh repair 17 2.3.2 Method of suture repair 18 2.4 Post-operative procedure 18 3.0 FOLLOW-UP 21 BIBLIOGRAPHY 22 TABLES 23 Appendix 1: Patient Information and Informed Consent Form 2 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Amendments Please note the following revisions have been made to the protocol. Page AMENDMENT Date Inserted 3 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Confidentiality statement Investigators signature of confidentiality The information contained within this document is the intellectual property of the studies writing committee. This document is provided to you in confidence as an investigator or potential investigator. Furthermore this document may be provided to consultants, staff, sponsors and applicable independent ethics committees by (potential) investigators. It is to be understood that no part of this document may be disclosed to others without the explicit written consent of the study coordinator prof. dr. J. Jeekel except to the extent necessary to obtain informed consent. Signature: Date: - - 200 Name: Centre: 4 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Clinical study protocol Investigators signature of agreement I, the investigator, agree to conduct the clinical study as described in this protocol. I will adhere to national and local guidelines and will conduct this study in accordance with current Good Clinical Practice (GCP) guidelines. I have examined the study protocol in full and discussed the contents and objectives of this protocol with the primary investigator. No modifications to the protocol shall be made without prior agreement of both the primary investigator and myself. All modifications must be documented in writing in the amendment section on page 2. I agree to cooperate fully with monitoring and audits by the study committee and health authorities in allowing full access to all relevant source data and documents. Personal copy INVESTIGATOR Signature: Date: - - 200 Name: Centre: PRIMARY INVESTIGATOR Signature: Date: - - 200 Name: 5 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Clinical study protocol Investigators signature of agreement Please remove this copy Please remove this copy I, the investigator, agree to conduct the clinical study as described in this protocol. I will adhere to national and local guidelines and will conduct this study in accordance with current Good Clinical Practice (GCP) guidelines. I have examined the study protocol in full and discussed the contents and objectives of this protocol with the primary investigator. No modifications to the protocol shall be made without prior agreement of both the primary investigator and myself. All modifications must be documented in writing. I agree to cooperate fully with monitoring and audits by the study committee and health authorities in allowing full access to all relevant source data and documents. Primary investigator copy INVESTIGATOR Signature: Date: - - 200 Name: Centre: PRIMARY INVESTIGATOR Signature: Date: - - 200 Name: Please remove this copy and return to: Erasmus MC, Department of Surgery, H.H. Eker, ‘s Gravendijkwal 230, 3015 CE, Rotterdam 6 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Study Committee Study coordinator: H.H. Eker, MD Department of Surgery, Erasmus MC, Rotterdam Principal Investigators: J. Jeekel, MD, PhD. Professor of Surgery Department of Surgery Erasmus MC, Rotterdam Writing committee: H.H. Eker, MD Department of Surgery Erasmus MC, Rotterdam J.F. Lange, MD, PhD. Professor of Surgery Department of Surgery, Erasmus MC, Rotterdam J. Jeekel, MD, PhD. Professor of Surgery Department of Surgery Erasmus MC, Rotterdam W.C.J. Hop, PhD. Statistician Department of Epidemiology & Biostatistics Erasmus MC, Rotterdam 7 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Study participants Rules regarding publication Participating investigators that include 10% or more of the required patients will be asked to co-author publications regarding the study. Vancouver guidelines will be adhered to. Erasmus Medisch Centrum Rotterdam Ikazia Ziekenhuis dr. Molewaterplein 40/50 Montessoriweg 1 3015 GD Rotterdam 3083 AN Rotterdam Telephone: 010-4639222 Telephone: 010-2975000 Fax: 010-4635307 Fax: 010-4865900 W.F. Weidema, MD, PhD. MCRZ Medisch Centrum Rijnmond Zuid Reinier de Graaf Groep, lokatie Reinier de Olympiaweg 350 Graaf Gasthuis 3078 HT Rotterdam Postbus 5011 Telephone: 010-2911911 2600 GA Delft Fax: 010-4323481 Telephone: 015-2604025 Fax: 015-2603599 Groene Hilledijk 315 H. Oei, MD, PhD. 3075 EA Rotterdam (L.P.S. Stassen, MD, PhD.) Telephone: 010-2903000 Fax: 010-2903805 E. vd Harst, MD, PhD. Sint Franciscus Gasthuis IJsselland Ziekenhuis Kleiweg 500 Postbus 690 3045 PM Rotterdam 2900 AR Capelle aan de IJssel Telephone: 010-4616161 Telephone: 010-2585000 Fax: 010-418644 I. Dawson, MD, PhD. C.H.A. Wittens, MD, PhD. Onze Lieve Vrouwe Gasthuis Isala Kliniek Postbus 95500 Postbus 10500 1090 HM Amsterdam 8000 GM Zwolle Telephone: 020-5999111 Telephone: 038 - 424 20 00 Fax: 020-5993840 D. van Geldere, MD, PhD. M.P. Simons, MD, PhD. 8 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Summary Purpose The purpose of the present study is to investigate whether or not the use of mesh is indicated in the repair of all size umbilical hernias as to reduce the rate of recurrence. This method is regularly used in umbilical hernia reconstruction although most surgeons repair small hernias using suture repair (fascia adaptation). Especially risk factors for hernia recurrence such as hernia size and BMI > 30 kg/m2 need to be evaluated and correlated to the method of hernia repair. Study design Randomised controlled, double blinded, multi-centre trial. 300 consecutive patients with an umbilical hernia will be included in the study. Patients will be randomised in one of two groups of 150 patients each. Group 1 will include patients that will undergo primary (suture) repair; group 2 umbilical hernias will be repaired using a pre-peritoneal, flat polypropylene mesh in a tension free fashion. Stratification will be utilized for the size of the hernia (<2 cm or ≥2 cm) and the participating centre. Patients will visit the outpatient clinic after 2-3 weeks and after 3, 12 and 24 months. The cumulative hernia recurrence rate during the 2-years follow-up period will be the primary outcome of the study. Complications, pain and QOL are secondary endpoints. Statistical analysis All analyses will be performed according to the intention to treat principle and as specified in the protocol. Financial support None. 9 Mesh versus suture repair for umbilical hernias: a double blinded, randomised controlled trial Protocol 1.0 INTRODUCTION In 2003, 4518 umbilical hernias were repaired in the Netherlands (www.prismant.nl). Recurrence of umbilical hernia is a common problem in the adult population. Recently recurrence rates of 1% have been reported through the use of mesh prosthetics in all size umbilical hernias and pre- peritoneal mesh is thought to become the standard in inguinal, incisional and umbilical hernia repair (see table 1) [1, 2]. The Mayo technique and its modifications could not stand the test of time: a recurrence rate of 20% and higher is not acceptable for any surgical procedure . Evidence from one retrospective study suggests that the repair of umbilical hernias larger than 3 cm should be performed using prosthetic mesh in order to avoid the high recurrence rates of primary repair of larger hernias. The same study reported an overall recurrence rate of 13% after a mean follow up of 30 months . Our previous experience in Rotterdam (as of yet unpublished data, IKAZIA hospital) has yielded results similar to those published. In a retrospective analysis, 110 patients were seen in the outpatient clinic. Suture repair was shown to have a recurrence rate of 14% (n=98) after a mean follow up of 32 months. No recurrences were seen in patients with mesh repair (n=12). The favourable results of primary herniorraphy (in the study of Schumacher et al) in umbilical hernias smaller than 2 cm (measured by ultrasound)  led us to the question whether or not primary repair is still acceptable practice for small hernias (table 2). Luijendijk et al have previously described the beneficial effect of mesh repair in incisional hernias . Nyhus critically comments that the use of prosthetic materials, regardless of hernia type or size has reached worrying levels. He and others propose individually tailored hernia repair [6, 7]. One might furthermore argue that the 10 use of mesh in small hernias is time consuming, in general more difficult and that the placement of mesh in a small (less than 2 cm’s) hernia will lead to enlargement of the fascial defect. In the previous randomised controlled trial Arroyo and co-workers have used surgeon-fabricated mesh-plugs to close fascial defects smaller than 3 cm’s staying in the pre-peritoneal plane . A similar technique has been employed by Kurzer et al to seal umbilical defects smaller than 3 cm’s. A mesh cone was inserted and fixed using non- absorbable sutures (2/0 polypropylene) in the four quadrants . As of yet, as indicated in table 1, only one randomised trial has been conducted to compare the recurrence rates of suture and mesh repair used in umbilical hernia reconstruction. Usher and Wallace introduced the use of polypropylene mesh in hernia repair in 1958 . It is still widely used in abdominal hernia repair, mainly for its mild reactivity in human tissues and the ability to not aggravate abdominal infections [10, 11]. According to the criteria first proposed by Scales  and Cumberland  polypropylene mesh has near ideal properties; it is pliable, flexible and holds sutures well. More recently criteria were redefined by Debodinance et al.  as: “An ideal implant material must: not undergo physical modification by tissue fluids, be chemically inert, not trigger inflammatory or foreign body cell response in body tissues, be noncarcinogenic and nonallergenic, be capable of resisting mechanical stress and sterilization, and be able to be manufactured in the necessary shape. Polyester, polypropylene and expansive polytetrafluoroethylene fulfil these criteria”. 1.1 Anatomy and Pathofysiology Important in the embryology of the umbilical defect is the fusion of ectoderm and embryonic mesoderm to form the fascial margin of the umbilical ring. To allow the passage of the umbilical arteries and the umbilical vein to the umbilical cord, an abdominal wall defect is present from the third week of 11 gestation onwards. After birth, thrombosis of both the arteries and the vein occurs and thus facilitates contraction of the umbilical ring by cicatrisation. Subsequently the weakest area of the umbilical ring is the superior aspect of it, the area between the umbilical vein and the cranial margin of the umbilical ring. The relative lack of elastic fibres in the obliterated umbilical vein is held responsible for this weakness. This is the typical site for herniation in the paediatric population when cicatrisation is impaired or the newly formed scar is subjected to elevated intra abdominal pressures. The anatomical margins of the so-called umbilical canal (in adults) are the umbilical fascia from posterior, the linea alba from anterior and the medial edges of the rectus sheaths. The adult umbilical hernia does not seem to result from the persisting juvenile hernia (Only 10% of adults with an umbilical hernia have a history of childhood herniation ). The adult hernia is an acquired hernia and represents herniation through the umbilical canal probably under influence of increased intra-abdominal pressure. Predisposing factors are obesity, multiple pregnancies, ascites and large intra-abdominal tumours. 1.2 Complications Hernia incarceration is regularly seen in cirrhotic patients with ascites. Hernia repair is associated with high morbidity, mortality and recurrence if attempted without prior management of ascites [16-18]. 1.3 Risk Factors for hernia recurrence As previously described hernia size as measured by ultrasound  seems to be a risk factor for recurrence. Obesity (defined as a BMI over or equal to 30 kg/m2) has been shown to increase the risk of incisional hernia recurrence [19, 20]. A meta-analysis by Sauerland et al. showed that the relative risks (RR) of recurrence in 7 studies looking into the association of obesity and recurrence were homogeneous (p=0.15) . Until recently obesity was still 12 regarded an indirect risk factor leading to recurrence through a higher rate of wound infection. It remains unclear whether obesity leads to hernia recurrence through increased abdominal pressure, difficulty in surgery or if it is an indicator for an inherent structural and healing defect. Further risk factors for incisional hernia were identified by many authors and divided into major and minor by Yahchouchy and colleagues (see table 3) . Major factors Minor factors Chronic lung disease Age Obesity Male gender Steroids Post-operative ventilation Type II diabetes mellitus Renal failure Malnutrition Connective tissue disorders Jaundice Malignancy Radiotherapy Transfusion Chemotherapy Anaemia Oral anticoagulants Table 3: Patient-related risk factors for incisional hernia As of yet there is insufficient evidence to suggest that, except for obesity and hernia size, the risk factors mentioned above are also of influence in the development of the umbilical hernias . In the light of this trial it is therefore useful to at least consider all major risk factors common to the population and the demographic minor risk factors in the analysis (underlined in table 3). Umbilical hernias with a diameter of 4 cm or larger will be excluded from participation for ethical reasons (very high recurrence rate after suture repair, see table 2). 2.0 PATIENTS AND METHODS Inclusion criteria are defined as follows: • Umbilical hernia diagnosed • Age ≥ 18 years • Primary umbilical hernia 13 • Signed Informed consent Exclusion criteria: • Umbilical hernia ≥ 4 cm diameter • Recurrence • Midline laparotomy • Ascites/Cirrhosis • ASAi score IV or above • Incarcerated hernia/emergency procedures “Intention to treat” Patients randomised for mesh hernia repair that for any of reason receive suture repair (or vice versa) will remain in the group randomised for. In this study the hernia recurrence rate during a 24 months follow-up period is the primary study endpoint. Post-operative morbidity and complications are secondary study outcomes . The influence of hernia size will be studied. 2.1 Practical implication of trial All patients eligible to take part in this trial will be informed in depth. The patients will be offered the patient information letter (“Patiënt Informatie Folder”/ PIF) and will be asked to sign the informed consent form (CRF-1.1ii). Patients diagnosed with an umbilical hernia but not eligible to take part in the trial (not willing, exclusion/ inclusion criteria not met) need to be accounted for on the basis of the CONSORT recommendations for improving the quality of reports of parallel-group randomized trials . A separate form is made available for this purpose. Preceding the procedure, risk factors as described on CRF-2 (pre-operative workup) will be assessed by a physician. Further assessment will consist of i American Society of Anaesthesiologists ii Case Record Form 14 physical examination and a quality of life evaluation (MOS SF-36 health surveyi and EQ-5D). Demographics and clinically relevant patient history and relevant other diagnoses, medication, ASA score are also included in the pre-operative evaluation. The patients will be placed into one of the two study groups through the use of computer-generated numbers. Randomisation will take place after the size of the hernia has been established during surgery using either Hegar dilators or a sterile ruler. Therefore two sets of sealed envelopes will be present at the operating theatre. The patient will be kept unaware of the randomisation (for blinding purposes). The investigator in charge will also remain blinded to the method of hernia repair. Ware and Sherbourne have conceptualised the previously mentioned MOS SF-36 health survey for English- speaking patients in 1992. It assesses the general health in patients older than 14 years with an unlimited variety of disease . In 1998 the translations of MOS SF-36 was validated for the Dutch language . The EuroQoL-5D (EQ-5D)  has been validated for the Dutch language as well as for numerous other languages as an efficient non disease specific quality of life measure. 2.2 Method of repair and per- operative procedure All repairs will take place using a method for which consensus was reached by all participating centres. This includes a paraumbilical incision, dissection (avoiding resection) of the hernia sac (figure 1) and restoration of the sac and its contents into the abdominal cavity in both groups. Per-operative resection of the sac must be recorded on the patient’s operation report (part of CRF-3). Closure of the subcutaneous tissue and skin may be achieved using a method chosen by the individual surgeon. i Medical Outcomes Study Short Form 15 Figure 1: pre-reconstruction transverse section of umbilical hernia There are no limitations concerning the method of anaesthesia used in either form of repair. The use of local, general or spinal anaesthesia is permitted in this trial. The use of intravenous antibiotics as prophylaxis is acceptable but not mandatory. Furthermore, routine administration of thrombosis prophylaxis should be considered in the form of bodyweight adjusted LMWH. Case record form 3 (per-operative procedure) asks for completion of all fields noted, such as technical details of procedure (incision, size of the defect and the use of drains), duration of procedure, complications during procedure (including conversion to other procedure), thrombosis prophylaxis, intravenous antibiotics and method of anaesthesia. 2.2.1 Method of mesh repair Mesh repair should take place using a flat polypropylene mesh (BardMesh/ Prolene)* placed in the pre-peritoneal plane. Fixation of the mesh should be achieved using 0/0 individual, non-absorbable sutures (monofilament Prolene). For evaluation purposes it is necessary to note the batch number of the mesh used. The overlap achieved in repair should be at least 3 cm’s  in each direction of the circular mesh (see figure 2). * BardMesh is a trademark of C.R. Bard, Inc. Prolene is a trademark of Ethicon, Inc. 16 Figure 2: Exploded view and transverse section of mesh placement in umbilical hernia repair In mesh hernia repair the umbilical defect should not be enlarged during the repair procedure. If the surgeon sees need to enlarge the umbilical defect during the operation (which is not the preferred procedure) the enlargement of the defect must be noted in the operation report. The surgeon is permitted to close the fascia defect (after mesh insertion) using sutures if this is possible in a “tension free fashion” to protect the mesh from contact with umbilical skin. In order to protect the viscera it is possible to place omentum or the remains of the hernia sac between viscera and mesh. The use of drains is permitted. Closure of the subcutaneous tissue and skin may be achieved using a method chosen by the individual surgeon. 2.2.2 Method of suture repair Suture repair of the umbilical defect will consist of adaptation of the fascia (linea alba) by interrupted/continuous, non-absorbable polypropylene (monofilament Prolene) sutures of thickness 0/0 (figure 3) in transverse direction. The suture length to wound length ratio should be 4:1. In this study it is not permissible to perform Mayo (vest-over-pants) reconstruction of the 17 umbilical defect. Figure 3: Transverse section of fascia adaptation in suture repair 2.3 Post-operative procedure Post-operative analgesics may consist of diclofenac three times daily 50 mg and paracetamol three times daily 1000 mg (or equivalent) administered orally for six days after surgery. A visual analogue scale (VAS) will be employed to evaluate post-operative pain. Time points will be pre-operative, directly post-operative, at home day 1 until 6 and after 3, 12 and 24 months. Surgical wounds are examined for signs of haematoma and seroma before the patient is allowed to return home. Definitions: • Haematoma: accumulation of blood in the wound area, which warrants surgical exploration and intervention. • Seroma: accumulation of clear fluid in the surgical field as diagnosed by aspiration of clear fluid. • Criteria for defining a Surgical Site Infection (SSI) : Superficial Incisional SSI Infection occurs within 30 days after the operation 18 and infection involves only skin or subcutaneous tissue of the incision and at least one of the following: 1. Purulent drainage, with or without laboratory confirmation, from the superficial incision. 2. Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision. 3. At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness or heat and superficial incision is deliberately opened by surgeon, unless incision is culture-negative. 4. Diagnosis of superficial incisional SSI by the surgeon or attending physician. Do not report the following conditions as SSI: 1. Stitch abscess (minimal inflammation and discharge confined to the points of suture penetration). 2. Incisional SSI that extends into the fascial and muscle layers (see deep incisional SSI). Deep Incisional SSI Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation and infection involves deep soft tissue (e.g., fascial and muscle tissue) of the incision and at least one of the following: 1. Purulent drainage from the deep incision but not from the organ / space component of the surgical site. 2. A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at least one of the following signs or 19 symptoms: fever (>38°C), localized pain, or tenderness, unless site is culture negative. 3. An abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic examination. 4. Diagnosis of a deep incisional SSI by a surgeon or attending physician. Notes: 1. Report infection that involves both superficial and deep incision sites as deep incisional SSI. 2. Report an organ/space SSI that drains through the incision as a deep incisional SSI. Organ/Space SSI Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is in place and the infection appears to be related to the operation and infection involves any part of the anatomy (e.g., organs or spaces), other than the incision, which was opened or manipulated during an operation and at least one of the following: 1. Purulent drainage from drain that is placed through a stab wound into the organ / space. 2. Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ space. 3. An abscess or other evidence of infection involving the organ / space that is found on direct examination, during reoperation, or by histopathologic or radiologic examination. 4. Diagnosis of a deep organ / space SSI by a surgeon or attending physician. 3.0 FOLLOW-UP Re-herniation rate will be assessed after 2-3 weeks (routine follow-up). In 20 addition 3, 12 and 24 months post-operative follow-up are performed (CRF-5 at 2 weeks, 3, 12, and 24 months). The blinded observer will examine the blinded patient for any signs of recurrent umbilical hernia. The patient will undergo ultrasound imaging at the 24-month follow-up point. An independent radiologist will perform the ultrasound imaging and note possible re-herniation on a sketch. The patient is asked to complete a MOS SF-36 and EQ-5D questionnaire (as part of the quality of life evaluation) at the 12-month follow-up point (see table 5). 3.1 Statistical considerations Randomization of patients will be done in the operation theatre using sealed envelopes in centres outside the Netherlands, and by telephone for Dutch centres, after intra-operative measurement of the defect size. Stratification wil be done by centre and defect size (<=2 vs > 2 cm). Primary endpoint. The primary endpoint in this study is the recurrence rate during a follow-up period of 24 months. Kaplan-Meier curves will be constructed to determine the cumulative recurrence rate of the umbilical hernia in the two study arms Comparison will be done using the stratified Logrank test with stratification by the defect size. P<0.05 (two-sided) will be the limit of significance. Whether there is effect modification, i.e. whether the difference in recurrence rate between both study arms depends on the defect size, will be investigate by Cox-regression. 300 Patients will be randomised in this study ( 2 groups of 150 each). Group sizes are based on Fisher’s exact test with two-sided alpha=0.05 and a power of 80% and are based on an expected lowering of the recurrence rate from 13 to 3% through the use of mesh at 24 months follow-up. Assuming a difference of 10% (13% vs 3%) in recurrence rates at 24 months, 135 patients in each group are required at two-sided alpha of 0.05 and a power of 80% (Fisher’s exact test). The power of the study with these numbers will be greater than 21 80% using the intended logrank test in case the hazard rates for recurrence are proportional. To allow for some dropouts, the sample size is set at 150/group. Secundary endpoints • VAS pain score: the longitudinal measurements of Vas scores will be compared between both groups with repeated measurements Anova using SAS PROC MIXED software. • The two QOL scales (SF-36 and EQ-5D) at 12 months will be compared using Analysis of covariance while allowing for baseline score, age and gender. • Complication rates will be compared using Fisher’s exact test. All data will be analyzed on an intention to treat basis. A per-protocol analysis excluding severe violations of the protocol will also be performed. Pain VAS scores and QOL will be compared using the Mann-Whitney test. 300 consecutive patients with an umbilical hernia will be included in the study. Patients will be randomised in one of two groups of 150 patients each. The use of blocked randomisation is prudent to maintain good balance between groups. Data will be analyzed on an intention to treat basis. 22 BIBLIOGRAPHY 1. Arroyo, A., et al., Randomized clinical trial comparing suture and mesh repair of umbilical hernia in adults. Br J Surg, 2001. 88(10): p. 1321-3. 2. Arroyo Sebastian, A., et al., Is prosthetic umbilical hernia repair bound to replace primary herniorrhaphy in the adult patient? Hernia, 2002. 6(4): p. 175-7. 3. Celdran, A., et al., H-hernioplasty: a tension-free repair for umbilical hernia. Br J Surg, 1995. 82(3): p. 371-2. 4. Schumacher, O.P., et al., [Long-term results after Spitzy's umbilical hernia repair]. Chirurg, 2003. 74(1): p. 50-4. 5. Luijendijk, R.W., et al., A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med, 2000. 343(6): p. 392-8. 6. Nyhus, L.M., Ubiquitous use of prosthetic mesh in inguinal hernia repair: the dilemma. Hernia, 2000(4): p. 184-186. 7. Nyhus, L.M., Individualization of hernia repair: a new era. Surgery, 1993. 114(1): p. 1-2. 8. Kurzer, M., P.A. Belsham, and A.E. Kark, Tension-free mesh repair of umbilical hernia as a day case using local anaesthesia. Hernia, 2004. 8(2): p. 104-7. 9. Usher, F.C. and S.A. Wallace, Tissue reaction to plastics; a comparison of nylon, orlon, dacron, teflon, and marlex. AMA Arch Surg, 1958. 76(6): p. 997-9. 10. Wagner, M., Evaluation of diverse plastic and cutis prostheses in a growing host. Surg Gynecol Obstet, 1970. 130(6): p. 1077-81. 11. Tyrell, J., et al., Absorbable versus permanent mesh in abdominal operations. Surg Gynecol Obstet, 1989. 168(3): p. 227-32. 12. Scales, J.T., Tissue reactions to synthetic material. Proc Roy Soc Med, 1953(46): p. 647-52. 13. Cumberland, V.H., A preliminary report on the use of prefabricated nylon weave in the repair of ventral hernia. Med J Australia, 1953(1): p. 143-4. 14. Debodinance, P., et al., [Development of better tolerated prosthetic materials: applications in gynecological surgery]. J Gynecol Obstet Biol Reprod (Paris), 2002. 31(6): p. 527-40. 15. Jackson, O.J. and L.H. Moglen, Umbilical hernia. A retrospective study. Calif Med, 1970. 113(4): p. 8-11. 16. Leonetti, J.P., et al., Umbilical herniorrhaphy in cirrhotic patients. Arch Surg, 1984. 119(4): p. 442-5. 17. Pescovitz, M.D., Umbilical hernia repair in patients with cirrhosis. No evidence for increased incidence of variceal bleeding. Ann Surg, 1984. 199(3): p. 325-7. 18. Loriau, J., D. Manaouil, and F. Mauvais, [Management of umbilical hernia in cirrhotic patients]. J Chir (Paris), 2002. 139(3): p. 135-40. 19. Luijendijk, R.W., et al., Incisional hernia recurrence following "vest- over-pants" or vertical Mayo repair of primary hernias of the midline. World J Surg, 1997. 21(1): p. 62-5; discussion 66. 20. Sauerland, S., et al., Obesity is a risk factor for recurrence after incisional hernia repair. Hernia, 2003. 21. Yahchouchy-Chouillard, E., et al., Incisional hernias. I. Related risk 23 factors. Dig Surg, 2003. 20(1): p. 3-9. 22. Moher, D., K.F. Schulz, and D. Altman, The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Jama, 2001. 285(15): p. 1987-91. 23. Ware, J.E., Jr. and C.D. Sherbourne, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care, 1992. 30(6): p. 473-83. 24. Razavi, D. and B. Gandek, Testing Dutch and French translations of the SF-36 Health Survey among Belgian angina patients. J Clin Epidemiol, 1998. 51(11): p. 975-81. 25. EuroQol--a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy, 1990. 16(3): p. 199-208. 26. Knook, M.T., et al., Optimal mesh size for endoscopic inguinal hernia repair: a study in a porcine model. Surg Endosc, 2001. 15(12): p. 1471- 7. 27. Mangram, A.J., et al., Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol, 1999. 20(4): p. 250-78; quiz 279-80. 24 Tables Trial Population Intervention Events Complications Follow- up Arroyo 200 Suture hernia Recurrence: Seroma/haematoma, Mean et al. consecutive repair 11/100 wound infection & follow- 2001 patients (11%) other: 11% up: 64 diagnosed months with an Mesh hernia Recurrence: Seroma/haematoma, (range umbilical repair 1/100 wound infection & 21-80) hernia (1%) other: 10% Table 1: Trial comparing suture and mesh repair in umbilical hernia reconstruction Hernia size (cm) Number of patients Recurrence rate 1 16 6.3% 1 - 1.9 49 4.1% 2 - 2.9 28 14.3% 3.0 - 3.9 4 25.0% ≥4 11 54.5% Table 2: Hernia size and recurrence (Schumacher, O.P., et al.)  Page CRF number Contents Parameters number 1- Informed consent 2- Physical examination Description of hernia Pre-operative workup Quality of life MOS SF-36 and EQ-5D (see CRF-6) Age, length/ weight, history, medication, Demographics risk factors, ASA score 3- Technical details of procedure (incision, size of the defect, use of drains), duration of procedure, complications during Per-operative procedure procedure (including conversion to other Randomisation procedure), thrombosis prophylaxis, intravenous antibiotics and method of anaesthesia 4- Wound inspection Haematoma, seroma, infection Pain score/use of Daily VAS score (see CRF-7), use of Post-operative analgesics analgesics procedure Complications Re-operation Drains Drain production 5- 2-3 weeks 3 months Follow-up See follow-up assessments (table 5) 12 months 24 months 6- inclusion MOS SF-36 and EQ-5D Quality of life 12 months 7- Daily assessment (hospital/home) VAS pain score Assesment after 3, 12 and 24 months Table 4: CRF overview 25 Reherniation Reoperation MOS SF-36 Ultrasound VAS pain Follow up point (exact date) (exact date) and EQ-5D imaging score Inclusion Not applicable Not applicable × None × Post-operative (days 1- 6) Not applicable Not applicable None None × 2 weeks × × None None None 3 months × × None None × 12 months × × × None × 24 months × × None × × Table 5: Overview of follow-up assessments 26