GUARDIX Sol 5gAdvanced Adhesion BarrierTaufik Akbar, Apt.Scientific CommunicationMedical Affairs DepartmentDexa GroupRSUD Prof. Dr. Margono SoekarjoPurwokerto, 19 Oktober 2011

MinophagenMeijiAstellasDaiwaTanabeSanten Strategic Alliance PartnersDexa Medica GroupUCBCobiosa*

Export DestinationsDexa Operations:Our Distributors:*

Awareness of Postoperative Adhesion*

Postoperative Adhesion DefinitionAdhesions are a type of scar tissue that may form an abnormal connection between organs and tissues aftermany types ofsurgical procedures.

These injuries are normally caused by suturing, cauterization, and abrading tissues and organs during surgery.

Guardix Slide. Korea. 2010

**Postoperative AdhesionEpidemiologyIntraperitoneal adhesions ranges from 67 to 93% after general surgical abdominal operations and up to 97% following open gynaecological pelvic proceduresAdhesions form between the wound and the omentum in over 80% of patients and these adhesions may involve the intestines in 50% of patients United States, up to 70% of small bowel obstructions are due to adhesionsThe incidence of small bowel obstruction has been reported to be as high as 10% after appendectomy, 6.4% after open cholecystectomy, and 10 to 25% after intestinal surgeryCheung JPY, et al. ASIAN JOURNAL OF SURGERY ; 2009 32 (3):180-6

***Postoperative AdhesionEpidemiology Abdomen and pelvis 90% of abdominal surgery, 55-94% of pelvic surgery 55% of ovary surgery, 36% of fimbrae surgery Spine 24% of failed back surgery syndrome caused by peridural scar Endometrium (D&C) 20~50% of endometrial synechiae occurred after D&CGuardix Slide. Korea. 2010

Postoperative AdhesionThe American Journal of Surgery (2011) 201, 111-21

Postoperative AdhesionCardiothoracic surgeryAdhesion development in cardithoracic surgery causes increased bleeding & cardiac injuryResternotomy result in cardiac injury in 2-6%Massive bleeding & mortality 37-50%Orthopedic SurgeryAdhesion development in the digital canal after repair of an injured digital flexor tendon is wellknown complication of procedure

*Diamond MP, etal. Human Reproduction Update 2001;7(6):567-76

**Postoperative AdhesionRay NF, Denton WG, Thamer M, Henderson SC, Perry S. Abdominal adhesiolysis: inpatient care and expenditures in the U.S. in 1994. J. Am. Coll. Surg. 1998;186(1): 1-9.Van Goor H, Morbidity and mortality of inadvertent enterotomy during an adhesiotomy. British Journal of Surgery 2000; 87: 467-471Complications caused by adhesion at abdomen & pelvis

ComplicationsPatients (operation) casesRatio caused by adhesionSmall intestine atresia5 Million cases (Digestive organ)1 Million cases (Urinary organ)4974 %Stomach rupture19 %Infertility6 Millions of people1520 %Chronic pelvis pain2050 %

1. Abdomen (intestine, peritoneum)2. Pelvis (uterus, ovary, fallopian tubes, fimbria, endometrium etc)3. Spine (nerve root)4. Thoracic cavity (lung, heart, pleura)Feasible Adhesive OrgansPostoperative AdhesionGuardix Slide. Korea. 2010

Mechanism of Postoperative AdhesionThe American Journal of Surgery (2011) 201, 111-21

* Adhesion MechanismWhen tissue is injured, Macrophages, fibroblast and Fibrin matrix gather to the injured surface by inflammatory responseMacrophages make the basement of adhesion, fibrin matrix is developed, and fibroblast grows up, and then the formation of the blood vessel starts.As the adhesion developed, it is increased blood vessel and systematized With the progress of existed adhesion, The separation with the tissue became indefinite, and formed the densely bandsPostoperative AdhesionGuardix Slide. Korea. 2010

How to Prevents Postoperative Adhesion?*

Anti-adhesion methods Meticulous surgical techniques Pharmaceutical agents: corticosteroids, NSAIDs Fluid instillations: dextran, carboxymethylcellulose, HA gel PEO (polyethylene oxide) solution, lactated Ringer's solution Physical barriers: Oxidized-regenerated cellulose Expanded PTFE (polytetrafluoro ethylene) HA+CMC membrane Collagen spongeAdhesion BarrierGuardix Slide. Korea. 2010

GUARDIX Sol 5gAdvanced Adhesion Barrier

Product Information Ingredient : Sodium Hyaluronate Sodium Carboxymethyl Cellulose Sterilization : EO (ethylene oxide) Specification : 5 g 150-200 cm2 Storage : Room temperature Expiry Date : 24 months Guardix Slide. Korea. 2010

Mechanism of ActionGuardix sticks to the internal tissues and separates the organs to help prevent them from attaching to one another as they healOnce placed inside the body Guardix is reabsorbed within seven days, so it does not remain and does not need to be removed*Without GuardixWith GuardixGuardix Slide. Korea. 2010

Safety Profile*Biorane Co., Ltd, Safety Test Report Guardix-sol; No. 2003-1

Application of GuardixObstetrics & Gynecology1. Indication Uterus and related surgery, Laparoscopic surgery, Cesarian section.

2. How to use Apply Guardix to part of doubted adhesion area. Apply Guardix after intrauterine surgery.

Guardix Slide. Korea. 2010

Application of Guardix*Neuro Surgery/Orthopedic Surgery: Spine1. Indication Laminectomy, discectomy etc. for using in every vertebra operation

2. How to use Even distribute to Dura area after vertebra surgery or after spinal nerve surgeryGuardix Slide. Korea. 2010

Application of GuardixIntraabdominal Surgery

1. IndicationViscous and lubricant coating on operated sites after operationTo minimize tissue adhesion on operated sites after operation (laparatomy, laparascopy)

2. How to useApply Guardix to part of doubted adhesion area

*Guardix Slide. Korea. 2010

Clinical Trial*

Intrauterine Surgery*

*Objective : The prospective, double blind study was performed to assess the efficacy of Hyaluronic acid + Sodium Carboxymethyl Cellulose (HA + CMC) gel in preventing the development of intrauterine adhesions (IUAs) following intrauterine surgery.

Method : A total of 64 patients with abortion, submucosal myoma, septate uterus were underwent intrauterine surgery. Patients: Group A, 10ml of Hyaluronic acid + Sodium Carboxymethyl Cellulose (HA + CMC) intrauterine cavity, Group B, 10ml of saline was applied

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*Result

INTRAABDOMINAL SURGERY*

Comparison of intraperitoneal honey and sodium hyaluronate-carboxymethylcellulose for the prevention of postoperative intra-abdominal adhesionsBackground: This study compares the use of honey with a standard bioresorba-ble membrane (HA-CMC) to prevent the formation of posoperative intraabdominal adhesionMethode:Laparotomy divided into three groups :Group 1 (control) represented the cecal abrasion group, with no intraperitone-al administration of any substance. Group 2 (honey group) underwent cecal abrasion and intraperitoneal adminis-tration of honey. Group 3 (hyaluronate-carboxymethylcellulose group) underwent cecal abrasio-n and intraperitoneal hyaluronate-carboxymethylcellulose application*Emre A. CLINICS 2009;64(4):363-8

Comparison of intraperitoneal honey and sodium hyaluronate-carboxymethylcellulose for the prevention of postoperative intra-abdominal adhesions*Emre A. CLINICS 2009;64(4):363-8

Comparison of intraperitoneal honey and sodium hyaluronate-carboxymethylcellulose for the prevention of postoperative intra-abdominal adhesions*P

BACKGROUND: Postoperative abdominal adhesions are associated with numerous complications, including small bowel obstruction, difficult and dangerous reoperations, and infertility. A sodium hyaluronate and carboxymethylcellulose was developed to reduce formation of postoperative adhesions. The objectives of our prospective study were to assess the incidence of adhesions that recurred after a standardized major abdominal operation using direct laparoscopic peritoneal imaging an-d to determine the safety and effectiveness of HA+CMC in preventing postoperative adhesions.

STUDY DESIGN: Eleven centers enrolled 183 patients with ulcerative colitis or fa-milial polyposis who were scheduled for colectomy and ileal pouch-anal anastomosis with diverting-loop ileostomy. Before abdominal closure, patients were randomly assigned to receive or not receive HA+CMC placed under the midline incision. At ileostomy closure eight to 12 weeks later, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision. *Becker JM, et al. J Am Coll Surg. 1996 Oct;183(4):297-306

*ResultBecker JM, et al. J Am Coll Surg. 1996 Oct;183(4):297-306Percentage of Patients (%)

Neuro Surgery*

Clinical trial target & classificationAge between 20 to 60Patients who are going to have the first operation related to neuromuscular disease such as unilateral herniated, lumbar intervertebral disk removalClassification : Randomly allocate experiment group with adhesion barrier and control group with not using adhesion barrier according to table of random numbers, n=64Clinical trials on effectiveness evaluation variationMajor evaluation deviation : 6 weeks after operation define 5 levels according to scar grade by MRI. Comparison between control and experiment groupsSupplement evaluation deviation : 1 and 6 weeks after operation, check clinical symptoms (Weber evaluation method, Mixed markeing method, Walking evaluation, Major symptoms evaluation, Normal activity evaluation) in comparison to control and experiment groups.Neuro Surgery Clinical Trials ProtocolBioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

Effectiveness evaluation method (1) Major evaluation variation MRI scar grade (2) Supplement evaluation variation Symptom evaluation methodNeuro Surgery Clinical Trials ProtocolBioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

GradeScar formation0No/trace scar10% < scar 25%225% < scar 50%350% < scar 75%475% < scar 100%

Weber methodVery goodPatients are very much satisfiedGoodPatients are satisfied and pain is decreasedModeratePatients are dissatisfied, partly difficult to workPoorPatients are not able to work due to chronic lumbago & sciatica

(2) Effectiveness Evaluation Major evaluation deviation - Classify by scar grade after 6 weeksNeuro Surgery Clinical Trials ResultBioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

(2) Effectiveness Evaluation (General) Comparison on average points of scar grade after 6 weeks (t-test) Comparison scar grade distribution after 6 weeksNeuro Surgery Clinical Trials ResultScar grade average (6 weeks later)Control groupGuardix groupGuardixControlBioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

(N)MRI Scar score(6 weeks after operation)p-valueAverageStandard deviationControl group(28)2.170.8890.000Guardix group(30)0.970.795

MRI Scar score(6 weeks after operation, N/%)Tot01234Control group1/3.45/17.211/41.49/34.51/3.428Guardix group9/2914/48.46/19.41/3.2030Tot10191710158

Scar grade(0,1,2=Effective, 3,4=No effective)When scar grade is high, scar presses nerve and causes higher risk of pain(Fishers exact test p=0.002) (2) Effectiveness Evaluation (General)Neuro Surgery Clinical Trials ResultBioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

MRI scar grade(6 weeks after operation, N/%)TotalEffectiveNo effectiveControl group18/64.310/35.728Guardix group29/96.71/3.330Total471158

(2) Effectiveness Evaluation (General) - Weber evaluation method (chi-square test)Neuro Surgery Clinical Trials ResultBioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

1 week after operation (p=0.116)6 weeks after operation (p=0.007)ItemsExplanationControl groupExperiment groupTotalControl groupExperiment groupTotalPoorPatients are not able towork due to chroniclumbago and sciatica0/00/000/00/00ModeratePatients aredissatisfied, difficultto work18/(64.3%)15/(50%)3315/(53.6%)10/(33.3%)25GoodPatients are satisfied,decreased pain7/(25.0%)5/(16.7%)126/(21.4%)1/(3.3%)7Very goodPatients re very muchsatisfied3/(10.7%)10/(33.3%)137/(25%)19/(63.3%)26Tot283058283058

(1) EffectivenessControl and Guardix group shows differences on 6 weeks after operation scar grade which is major evaluation deviation.Control and Guardix group shows differences according to Supplement evaluation deviation clinical symptom point & Weber evaluation method. Effectiveness was approved by general effectiveness evaluation

(2) SafetyNo severe side effects detected from Yongdong Severance Hospital and Hanyang University Medical CenterGuardixsol is claimed that safe according to safety evaluation

CONCLUSION NEURO SURGERYBioraine, A clinical study to evaluate the efficacy and safety of GUARDIX-SL for prevention of adhesion following Spinal Surgery; 2006, 36 39

Cardio Thoracic Surgery*

Methods:A comparative, evaluator-masked, randomized, multicenter study design was used. Before chest closure, infants undergoing initial sternotomy for eventual staged palliative cardiac operations were randomized to barrier film placement (n 54) or control (no treatment, n 49) at 15 centers. At repeat sternotomy 2 to 13 months later, the extent and severity of adhesions at the investigational surgical site (ISS) were assessed. A four-grade adhesion severity scoring system was standardized as follows: none, mild (filmy, noncohesive, requiring blunt dissection), moderate (filmy, noncohesive, requiring sharp and blunt dissection), and severe (dense, cohesive, requiring extensive sharp dissection).*

*

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Results:There were significantly fewer patients with any severe adhesions (29.6% vs 71.4%, p < 0.0001), and a significantly lower percentage of the ISS had severe adhesion involvement (21.1 36.9% vs 49.5 42.7%, p 0.0005) in the barrier group compared with the control group at the second sternotomy. Delayed chest closure (p 0.0101), Norwood procedure (p 0.0449), and cardiopulmonary bypass (p 0.0001) were univariate risk factors for more severe adhesions. Multivariate analysis revealed only control group to be a significant risk factor for more severe adhesions (p 0.003). There were no statistically significant differences in adverse events between the groups. No adverse events were definitely attributed to the study device.Conclusions: Use of a novel bioresorbable film was safe and effective in reducing the extent and severity of postoperative adhesions in infants undergoing repeat median sternotomy*

*THANK YOU

***Dexa Medica merupakan salah satu perusahaan farmasi multinasional terkemuka, dengan aliansi di berbagai negara di dunia termasuk di Amerika, Eropa dan juga Asia**Produk2 yang dipasarkan Dexa Medica tidak diragukan lagi kualitasnya, hal ini bisa dilihat bahwa produk2 Dexa Medica diakui di berbagai negara termasuk Eropa, yang kita tahu untuk masuk ke Eropa regulasinya sangat ketat dengan standar kualitas tinggi***Lit: Slide guardix Korea**Literatur: Cheung JPY, et al. Adjuvant Therapy for the Reduction of Postoperative Intra-abdominal Adhesion Formation. ASIAN JOURNAL OF SURGERY VOL 32 NO 3 JULY 2009Cari untuk bedah saraf**Slide Product Info Guardix, D&C: dilatation & curretage****Volume 170, Issue 5, Pages 1396-1403 (May 1994), 42 of 62 Adhesions after extensive gynecologic surgery: Clinical significance, etiology, and preventionBradley J.Monk, MDa, Michael L.Berman, MDa, F.J.Montz, MDb

AbstractPostoperative adhesions occur in 60% to 90% of patients undergoing major gynecologic surgery and represent one of the most common causes of intestinal obstruction in the industrialized world. The incidence of adhesion-related intestinal obstruction after gynecologic surgery for benign conditions without hysterectomy is approximately 0.3%, increasing to 2% to 3% among patients who undergo hysterectomy, and is as high as 5% if a radical hysterectomy is performed. Other adhesion-related complications include chronic pelvic pain, ureteral obstruction, and voiding dysfunction. Intraperitoneal adhesions also can limit the effectiveness of intraperitoneal therapeutic agents used in cancer treatment. Postoperative adhesions are sequelae of impaired fibrinolysis of the fibrin and cellular exudate after peritoneal injury. Adequate blood supply is essential for normal fibrinolysis. Therefore factors that increase ischemia and potentiate adhesion formation include thermal injury, infection, presence of a foreign body, and radiation-induced endarteritis. Only recently, appropriate animal models have been developed to study the process of adhesion formation and prevention. Until clinical confirmation of findings from these investigations exists, only a meticulous surgical technique can be advocated to minimize these untoward effects of surgery. (AM J OBSTET GYNECOL 1994;170:1396-403.)Keywords: Gynecologic surgery, adhesions, complications, prevention

**fokus sampai pada point 3 saja***Slide PI Guardix

Adhesion MechanismWhen tissue is injured, the area becomes inflamed. The body responds by depositing a substance at the injury site called fibrin. Fibrin can act like glue between the injury site and nearby tissues, causing them to stick together. Normally, as the body heals, the fibrin dissolves and is replaced with normal tissue. In some cases, however, decreased blood flow to the injured tissue prevents the fibrin from dissolving. The result is an internal scar, also called an adhesion***Meticulous surgical: pembedahan scara gentle, hati2, tidak banyak manipulasi organ, bersih, tidak banyak perdarahan, dllPTFE: polytetrafluoro ethylene*******Slide Guardix Korea**Slide Guardix Korea

*****Objective : The prospective, double blind study was performed to assess the efficacy of Hyaluronic acid + Sodium Carboxymethyl Cellulose (HA + CMC) gel in preventing the development of intrauterine adhesions (IUAs) following intrauterine surgery.Method : A total of 64 patients with abortion, submucosal myoma, septate urerus were underwent intrauterine surgery. Patients were randomized to two different group. Group A (32 patients) were randomized to intrauterine surgery plus intrauterine application of normal saline(10mL). Hematologic, chemical, coagulative test, urinalysis was performed to drug toxicity at 4th dayafter surgery. Transvaginal sonography was performed to intrauterine debris and inflammation at two weeks after surgery. Each group underwent a followup diagnostic hysteroscopy 4 weeks after surgery and their adhesion formation, severity.Results : In 64 patients, 62 patients were followed up postoperatively. In Group A (32 patients), 4 patients (13%) had mild IUAs and in group B (30 patients) 4 patients(13%) had mild IUAs, 2 patients(6%) had moderate IUAs, 2 patients (6%) were classified as having severe stage IUAs. A significant lower rate of postsurgical intrauterine adhesions was observed in group A (4 out of 42 patients) in comparison with group B (8 out of 30 patients).Conclusion : HA + CMC gel significantly reduce the development and severity of intrauterine adhesions. The results should be confirmed in further studies

***P-nya ditampilkan******BACKGROUND: Postoperative abdominal adhesions are associated with numerous complications, including small bowel obstruction, difficult and dangerous reoperations, and infertility. A sodium hyaluronate and carboxymethylcellulose bioresorbable membrane (HA membrane) was developed to reduce formation of postoperative adhesions. The objectives of our prospective study were to assess the incidence of adhesions that recurred after a standardized major abdominal operation using direct laparoscopic peritoneal imaging and to determine the safety and effectiveness of HA membrane in preventing postoperative adhesions. STUDY DESIGN: Eleven centers enrolled 183 patients with ulcerative colitis or familial polyposis who were scheduled for colectomy and ileal pouch-anal anastomosis with diverting-loop ileostomy. Before abdominal closure, patients were randomly assigned to receive or not receive HA membrane placed under the midline incision. At ileostomy closure eight to 12 weeks later, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision. RESULTS: Data were analyzed for 175 assessable patients. While only five (6 percent) of 90 control patients had no adhesions, 43 (51 percent) of 85 patients receiving HA membrane were free of adhesions (p < 0.00000000001). The mean percent of the incision length involved was 63 percent in the control group, significantly greater than the 23 percent observed in patients who received HA membrane (p < 0.001). Dense adhesions were observed in 52 (58 percent) of the 90 control patients, but in only 13 (15 percent) of the 85 receiving HA membrane (P < 0.0001). Comparison of the incidence of specific adverse events between the groups did not identify a difference (P > 0.05). CONCLUSIONS: This study represents the first controlled, prospective evaluation of postoperative abdominal adhesion formation and prevention after general abdominal surgery using standardized, direct peritoneal visualization. In this study, HA membrane was safe and significantly reduced the incidence, extent, and severity of postoperative abdominal adhesions.

*************Background. Adhesions encountered in reoperative cardiacsurgery can prolong operating time and increase risk.This study was designed to evaluate the ability of a novelbioresorbable barrier film to reduce adhesions in infants.Methods. A comparative, evaluator-masked, randomized,multicenter study design was used. Before chestclosure, infants undergoing initial sternotomy for eventualstaged palliative cardiac operations were randomizedto barrier film placement (n 54) or control (notreatment, n 49) at 15 centers. At repeat sternotomy 2 to13 months later, the extent and severity of adhesions atthe investigational surgical site (ISS) were assessed. Afour-grade adhesion severity scoring system was standardizedas follows: none, mild (filmy, noncohesive,requiring blunt dissection), moderate (filmy, noncohesive,requiring sharp and blunt dissection), and severe(dense, cohesive, requiring extensive sharp dissection).Results. There were significantly fewer patients withany severe adhesions (29.6% vs 71.4%, p < 0.0001), and asignificantly lower percentage of the ISS had severeadhesion involvement (21.1 36.9% vs 49.5 42.7%, p 0.0005) in the barrier group compared with the controlgroup at the second sternotomy. Delayed chest closure(p 0.0101), Norwood procedure (p 0.0449), andcardiopulmonary bypass (p 0.0001) were univariaterisk factors for more severe adhesions. Multivariate analysisrevealed only control group to be a significant riskfactor for more severe adhesions (p 0.003). There wereno statistically significant differences in adverse eventsbetween the groups. No adverse events were definitelyattributed to the study device.Conclusions. Use of a novel bioresorbable film was safeand effective in reducing the extent and severity ofpostoperative adhesions in infants undergoing repeatmedian sternotomy.

*****Ganti kemasan 5 g aja*