European Initial Hands-On Experience with

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Surgical Overview SURGICAL TECHNOLOGY INTERNATIONAL XXV

European Initial Hands-On Experience with HEMOPATCH, a Novel Sealing Hemostatic Patch: Application in General, Gastrointestinal, Biliopancreatic, Cardiac, and Urologic Surgery ABE FINGERHUT, MD, DSC (HON), FACS, FRCPS (G), FRCS (ED) PROFESSOR SECTION FOR SURGICAL RESEARCH, DEPARTMENT OF SURGERY MEDICAL UNIVERSITY OF GRAZ GRAZ, AUSTRIA

SELMAN URANUES, MD, FACS PROFESSOR AND HEAD SECTION FOR SURGICAL RESEARCH CLINICAL DIVISION OF GENERAL SURGERY, DEPARTMENT OF SURGERY MEDICAL UNIVERSITY OF GRAZ GRAZ, AUSTRIA GIUSEPPE MARIA ETTORRE, MD PROFESSOR DEPARTMENT OF HPB SURGERY AND LIVER TRANSPLANTATION SAN CAMILLO HOSPITAL ROME, ITALY EMANUELE FELLI, MD SURGEON DEPARTMENT OF HPB SURGERY AND LIVER TRANSPLANTATION SAN CAMILLO HOSPITAL ROME, ITALY MARCO COLASANTI, MD SURGEON DEPARTMENT OF HPB SURGERY AND LIVER TRANSPLANTATION SAN CAMILLO HOSPITAL ROME, ITALY

GREGORIO SCERRINO, MD, PHD SURGEON UNIT OF GENERAL AND EMERGENCY SURGERY, DEPARTMENT OF GENERAL, EMERGENCY AND TRANSPLANT SURGERY UNIVERSITY OF PALERMO, SCHOOL OF MEDICINE PALERMO, ITALY GIUSEPINA IRENE MELFA, MD SURGEON UNIT OF GENERAL AND EMERGENCY SURGERY, DEPARTMENT OF GENERAL, EMERGENCY AND TRANSPLANT SURGERY UNIVERSITY OF PALERMO, SCHOOL OF MEDICINE PALERMO, ITALY

CRISTINA RASPANTI, MD SURGEON UNIT OF GENERAL AND EMERGENCY SURGERY, DEPARTMENT OF GENERAL, EMERGENCY AND TRANSPLANT SURGERY UNIVERSITY OF PALERMO, SCHOOL OF MEDICINE PALERMO, ITALY GASPARE GULOTTA, MD PROFESSOR, CHIEF OF DEPARTMENT. UNIT OF GENERAL AND EMERGENCY SURGERY, DEPARTMENT OF GENERAL, EMERGENCY AND TRANSPLANT SURGERY UNIVERSITY OF PALERMO, SCHOOL OF MEDICINE PALERMO, ITALY

ALEXANDER MEYER, DR.MED HEAD OF DEPARTMENT DEPARTMENT OF VISCERAL AND VASCULAR SURGERY JOHANNITER HOSPITAL RHEINHAUSEN DUISBURG, GERMANY MARTIN OBERHOFFER, MD CONSULTANT DEPARTMENT OF CARDIAC SURGERY ASKLEPIOS HOSPITAL ST. GEORG HAMBURG, GERMANY MICHAEL SCHMOECKEL, MD, PHD PROFESSOR HEAD OF DEPARTMENT DEPARTMENT OF CARDIAC SURGERY ASKLEPIOS HOSPITAL ST. GEORG HAMBURG, GERMANY LUCA PAOLO WELTERT, MD SURGEON DEPARTMENT OF CARDIAC SURGERY EUROPEAN HOSPITAL ROME, ITALY

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GRAZIANO VIGNOLINI, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY MATTEO SALVI, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY LORENZO MASIERI, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY GUIDO VITTORI, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY GIAMPAOLO SIENA, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY ANDREA MINERVINI, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY SERGIO SERNI, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY MARCO CARINI, MD SURGEON DEPARTMENT OF UROLOGY CAREGGI HOSPITAL, UNIVERSITY OF FLORENCE FLORENCE, ITALY

#590 Fingerhut FINAL European initial hands-on experience with HEMOPATCH, a novel sealing hemostatic patch: Application in general, gastrointestinal, biliopancreatic, cardiac and urologic surgery FINGERHUT/URANUES/ETTORRE/FELLI/COLASANTI/SCERRINO/MELFA/RASPANTI/GULOTTA/MEYER/OBERHOFFER /SCHMOECKEL/ WELTERT/VIGNOLINI/SALVI/MASIERI/VITTORI/SIENA/MINERVINI/SERNI/CARINI

ABSTRACT

T

opical hemostatic agents that can seal tissues and assist in the coagulation cascade of patients undergo-

ing surgery have been readily available for several decades. Using either synthetic or animal/plant-

derived materials, these agents represent a powerful tool to reduce postoperative bleeding

complications in cases where mechanical or energy-driven hemostasis is not possible or insufficient.

Recently, a novel sealing hemostatic patch, HEMOPATCH (Baxter International, Deerfield, IL), was

developed. The device is a thin and flexible patch consisting of a specifically-formulated porous collagen

matrix, coated on one side with a thin protein-binding layer. This gives the patch a dual mechanism of action, in which the two components interact to achieve hemostasis by sealing off the bleeding surface and initiating the body’s own clotting mechanisms.

Here we present a series of case reports that outline the quick, effective hemostatic sealing of HEMOPATCH

in a variety of clinical applications, including solid organ, gastrointestinal, biliopancreatic, endocrine,

cardiovascular, and urologic surgeries.

Essentially a feasibility study, these reports demonstrate how HEMOPATCH can be applied to seal almost any

bleeding surface encountered during a range of procedures. Our results show that the device is eminently

capable in both via laparotomy and laparoscopic approaches, and in patients with impaired coagulation or highly variable anatomies.

In conclusion, our cases document the ease-of-use, application, and immediate hemostatic effect of the patch across a broad range of surgical settings and paves the way for future randomized clinical trials with more extensive follow-up.

INTRODUCTION The use of topical agents to seal tissues or intervene in the coagulation cascade of patients undergoing surgery have been used widely in Europe since the 1970s.1 The active agents are either synthetic or derived from animals or plants. Synthetic agents are better for sealing but do not intervene in the coagulation cascade.2,3 In contrast, collagen-based sealants are pro-coagulants, triggering or accelerating the cascade, but are not suited for tissue fixation.4 The use of topical agents to promote these two actions has given rise to a large number of experimental and clinical publications. However, the results in these publications have been somewhat

contradictory.5-8 Nevertheless, hemostatic agents are useful agents for reducing postoperative bleeding complications, particularly in specific areas such as sutures lines, whether anastomotic or not, and they are especially helpful when these sites are difficult to access.3 The majority of recent evaluations of such agents have focused on the effect of these agents on the requirement for blood transfusion.9 A novel sealing hemostatic patch, HEMOPATCH, recently became available. This hemostatic adjunct is a soft, thin, and flexible patch consisting of a porous collagen matrix, which facilitates clotting, coated on one side with a thin protein-binding layer known as pentaerythritol polyethylene glycol ether tetra-succinimidyl glutarate (NHS- 30 -

PEG). This coating allows rapid adhesion (within two minutes) to lesions via electrophilic crosslinking. The patch consequently has a dual-method mechanism of action, in which the two components interact to achieve hemostasis by sealing off the bleeding surface and initiating the body’s own clotting mechanisms (Fig. 1). The patch, which is suitable for surgery via laparotomy or a minimal access route, is resorbed into the body within six to eight weeks. Significant preclinical testing has been conducted to confirm the hemostatic performance, biocompatibility and safety profile of the patch.4,10,11 Furthermore, feasibility and reliability of application was demonstrated in a preliminary study of seven patients with confirmed renal masses undergoing zero-ischemia laparo-



scopic partial nephrectomy. 12 In all patients, the patch was applied to the tumor resection site after suturing of the renal parenchyma, perfecting hemostasis and fixation within two to three minutes. For the current case series, we gathered a series of 17 individual procedural reports in which the sealing hemostatic patch was used as an adjunctive hemostatic procedure. The cases cover several surgical specialties (in some circumstances, more than one per case), falling broadly into the following categories: Solid

organ: One partial splenic resection, two sectionectomies, one resection for metastases, one for liver abrasion, and one liver trauma Gastrointestinal: Two cases of colonic and rectal anastomoses Bilio-pancreatic: Two cholecystectomies—one for acute cholecystitis—and four pancreatic resections, including two Whipple procedures and two distal pancreatectomies Endocrine: One total thyroidectomy Cardiovascular: Bleeding from one bypass suture line and tissues after dissection of epicardial fat, one from an aortocoronary bypass at the anastomosis of the saphenous vein to the right coronary artery, and one distal suture-line of an aortic prosthesis combined with an aortic valve and ascending aorta replacement (Wheat procedure) Urological: one partial nephrectomy, one robotic-assisted kidney tumor resection, and one robotic-assisted nerve-sparing prostatectomy

Among these, there were several laparoscopic applications, including two cholecystectomies, a distal pancreatectomy, a partial splenectomy, a partial nephrectomy, a nerve-sparing prostatectomy, and a kidney tumor enucleation (the last two of these also being roboticassisted procedures). SELECTED DETAILS Selected CaseCASE Details Liver resection A 63-year-old obese (body mass index [BMI]=31), hypertensive man with hepatitis B virus-related liver cirrhosis (Child-Pugh class A) presented with a 5 cm hepatocellular carcinoma. An open 6–7-segment sectionectomy was performed. The liver parenchymal

Figure 1. Mechanism of action of the sealing hemostatic patch.

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#590 Fingerhut FINAL European Initial Hands-On Experience with HEMOPATCH, a Novel Sealing Hemostatic Patch: Application in General, Gastrointestinal, Biliopancreatic, Cardiac, and Urologic Surgery FINGERHUT/URANUES/ETTORRE/FELLI/COLASANTI/SCERRINO/MELFA/RASPANTI/GULOTTA/MEYER/OBERHOFFER /SCHMOECKEL/ WELTERT/VIGNOLINI/SALVI/MASIERI/VITTORI/SIENA/MINERVINI/SERNI/CARINI

Figure 2. Placement (left) and subsequent sealing and hemostasis (right) of the liver surface using HEMOPATCH.

division border was sealed off with HEMOPATCH after elective, traditional, but incomplete, hemostasis and biliostasis (Fig. 2). As shown in the figure, the sealing hemostatic patch achieved good adherence to the heavily electrocoagulated liver surface. Importantly, the patch stopped the residual oozing from the electrocoagulated area. Total blood loss was 200 cc without any need for transfusion. Similarly, in another case example of segment 6–7 sectionectomy, performed on a 31-year-old female with a 7 cm adenoma, HEMOPATCH was used to complete hemostasis of the liver surface with satisfactory outcome.

Figure 3. Application of HEMOPATCH (outlined) to the transection line on the pancreatic stump.

Bilio-pancreatic surgery In one case, a 54-year-old man with diabetes and chronic pancreatitis underwent a Whipple procedure. HEMOPATCH was used to prevent bleeding following difficult and intraadventitial dissection of the major vessels (portal vein, superior mesenteric artery, and vein). As such, no postoperative complications were observed. Use of HEMOPATCH in distal pancreatectomy involved two patients. The first, who underwent laparoscopy, was a 49-year-old female with a pancreatic tumor, and the second was a 60-yearold woman with pancreatic tail metastasis originating from kidney carcinoma.

Figure 4a. Active bleeding following laparoscopic stapled transection of the lower splenic pole.

HEMOPATCH was applied to the proximal stump (Fig. 3), and no postoperative bleeding or pancreatic fistula were observed in either case.

Gallbladder Two patients (one taking antiplatelet treatment) undergoing laparoscopic cholecystectomy for acute cholecystitis had diffuse bleeding from the liver bed at the end of the procedure. HEMOPATCH was easily inser ted through one of the 10 mm trocars, deployed, and applied to the liver bed correctly without difficulty. Both patients had an uneventful post-operative recovery.

Figure 4b. HEMOPATCH hemostatic patches were used to seal the wound and prevent further bleeding.

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Figure 5. Reinforcement of the jejuno-transverse anastomosis with HEMOPATCH.

Spleen A 64-year-old woman presented with a four-year history of thrombocytopenia and splenomegaly. As hematologic work-up was inconclusive, diagnostic partial splenectomy was deemed necessary. After laparoscopic transection of the lower pole with an endostapler, active bleeding from a 1.5 cm capsule injury occurred. Several HEMOPATCH patches were applied to cover both the injury site and the stapler line and were successful in stemming the bleeding (Figs. 4a and 4b). Colon and rectum A 70-year-old male who had under-

Figure 6. Hemostatic sealing of HEMOPATCH following thyroidectomy.

gone several previous surgeries associated with chemoradiation for rectal cancer presented with anastomotic leakage after an operation for intestinal obstruction requiring a repeat laparotomy. During dissection, severe liver abrasions occurred and the difficult and unsure hemostatic status of the end-to-side jejunotransversostomy led the surgeon to apply HEMOPATCH on both the liver and the anastomotic site (Fig. 5). The patient was discharged four weeks after the final laparotomy—the late discharge being essentially due to surgical site healing problems. There were no further bleeding or anastomotic complications reported.

Figure 7a. HEMOPATCH applied to the bleeding sites of an anastomosis and dissected epicardial fat.

In another case, antiplatelet therapy could not be discontinued prior to surgery. A 64-year-old woman taking aspirin presented with pain in the left abdomen and, after diagnostic workup, underwent exploratory laparotomy for a suspected tubo-ovarian abscess. An extensive resection, including anterior resection of the rectum, salpingectomy and partial resection of the uterus was necessary for an extremely adherent inflammatory pseudotumor of the lower sigmoid colon. At the end of the operation, diffuse and profuse bleeding was noted in the retroperitoneum. However, aggressive surgery (sutures or energy-driven hemostasis) was considered

Figure 7b. HEMOPATCH applied to the central anastomosis of the aortocoronary vein bypass.

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#590 Fingerhut FINAL European Initial Hands-On Experience with HEMOPATCH, a Novel Sealing Hemostatic Patch: Application in General, Gastrointestinal, Biliopancreatic, Cardiac, and Urologic Surgery FINGERHUT/URANUES/ETTORRE/FELLI/COLASANTI/SCERRINO/MELFA/RASPANTI/GULOTTA/MEYER/OBERHOFFER /SCHMOECKEL/ WELTERT/VIGNOLINI/SALVI/MASIERI/VITTORI/SIENA/MINERVINI/SERNI/CARINI

Figure 8. HEMOPATCH placed on the distal suture line after combined replacement of the ascending aorta and aortic valve.

potentially dangerous for the ureter. A HEMOPATCH was applied to the bleeding area and successfully stopped the bleeding without endangering the ureter.

Thyroid A 71-year-old man presented with progressive enlargement of the infrahyoid neck, which had been developing over the past 10 years. Workup documented two nodules, one hypoechoic, the other semi-liquid. Preoperative fine-needle aspiration led to suspicion of follicular carcinoma. A total bilateral

Figure 9. Application of band-shaped HEMOPATCH hemostatic patch on graftto-aorta suture line.

extracapsular thyroidectomy was therefore perfor med through a typical Kocher incision. At the end of the operation, diffuse bleeding was noted around the left recurrent laryngeal nerve. To avoid damaging the nerve with energy-driven hemostasis or suture, a HEMOPATCH was inserted along the nerve in the bleeding area, and also contralaterally as a preventive measure. After confirmation of effective hemostasis (Fig. 6), sustained even after the Valsalva maneuver, the incision was closed without drainage. The patient

was discharged on the second postoperative day, without any untoward event or concern as to compressive hematoma or nerve palsy. One month later, neither hypocalcemia nor aerodigestive symptoms were observed.

Prostate A 65-year-old male underwent robot-assisted radical nerve sparing prostatectomy for biopsy-confirmed adenocarcinoma. To control mild postoperative oozing in the operative field, HEMOPATCH was easily inser ted through a 10 mm trocar, deployed, placed, and applied without any intraoperative incident along the vascular and neural bundles. One month postoperatively, the patient had normal bladder and erectile function. Cardiac Several cases of postoperative bleeding related to cardiovascular surgery are included. The first two focus on coronary artery bypass grafts (CABG) and involved epicardial bleeds arising from the bypass suture line and tissues after dissection of epicardial fat (Fig. 7a), and bleeding from the CABG anastomosis—saphenous vein to the right of the coronary artery (Fig. 7b). In the aorta, the sealing hemostatic patch was used to reinforce the sutureline to prevent suture-line bleeding from a distal aortic prosthesis. Our case involved combined aortic valve and ascending aor ta replacement, known as the Wheat procedure (Fig. 8). Another case is particularly illustrative. This 65-year-old, otherwise

Figure 10. HEMOPATCH placed at the site of the ventricular pacing wires.

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healthy, man was admitted to hospital for symptomatic aortic valve stenosis and underwent aortic valve replacement by implantation of a 23 mm size Trifecta™ valve (St. Jude Medical, Saint Paul, Minnesota). At the end of the operation, diffuse bleeding at the level of the aortic sutures—persisting after the administration of protamine sulphate and infusion of tranexamic acid—led the surgeon to apply HEMOPATCH, which successfully stopped the bleeding without recourse to surgery. The physical characteristics of the patch allowed for easy cutting and shaping to match the geometry of the bleeding area (Fig. 9). Postoperatively, a total of 260 ml was collected in 24 hours and blood parameters were satisfactory. No blood transfusion was necessary during hospitalization. Finally, HEMOPATCH was used to prevent bleeding from a ventricular pacing wire in a redo case. By the end of the off-pump CABG procedures, the ster nal wires were in place and a HEMOPATCH was easily placed at the site of the ventricular pacing wires (Fig. 10), an otherwise difficult area to access for traditional hemostatic procedures. DiscussionDISCUSSION This case series demonstrates the ease and rapidity with which the sealing hemostatic patch can be applied to almost any type of bleeding surface, and how equally easy it is to apply via laparotomy or laparoscopy. These findings complement those of the three experimental comparative studies on the patch,4,10,11 as well as the recently published preliminary clinical investigation.12 Through these procedures, we were able to show that the patch was effective in several different scenarios. Moreover, the surgeon was able to use it preventively, such as for incomplete or unsatisfactory mechanical or energy-driven hemostasis, or in areas


where mechanical or energy-driven hemostasis would have been dangerous or difficult, essentially due to issues of access. There are a number of limitations to the current series. These include the lack of controls, the highly selective nature of the inclusion process, the incomplete medium and long-term follow-up for some patients, and the selective use of the patch based on the individual surgeon’s preferences. Consequently, the external validity of this summary is limited, and generalizations for clinical practice cannot yet be made. Nonetheless, the findings underline the facility of application and the immediate hemostatic effect of the patch. In laparoscopic surgery, it is easy to inser t through a 10 mm trocar, without deformation, flaking or losing any of its active components. 12 The patch does not require any particular preparation before application. Thanks to its rapid and firm tissue adherence, inadvertent dislodging is avoidable, and hemostasis can be obtained on vertical structures, without dropping off due to gravity and, finally, its flexibility allows firm application to a variety of rounded or uneven (spleen, kidney, colonic, liver, and vascular) surfaces. Conclusion CONCLUSION In conclusion, the sealing hemostatic patch, as shown in these cases, is a promising, valuable addition to the range of available topical hemostatic agents, and is recommended for further investigation. STI Acknowledgement ACKNOWLEDGEMENTS Editorial support for this manuscript was provided by Medicalwriters.com (Zurich, Switzerland). Editorial support was funded by Baxter Healthcare SA.

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Conflict of Interest AUTHORS’ DISCLOSURES

Professor Fingerhut has received payments from Baxter Healthcare SA for consulting services. Dr Oberhoffer is a speaker for Baxter Healthcare, St. Jude Medical, and Smith & Nephew. ReferencesREFERENCES 1. Martinowitz U, Saltz R. Fibrin sealant. Curr Opin Hematol 1996;3(5):395–402. 2. Wallace DG, Cruise GM, Rhee WM, et al. A tissue sealant based on reactive multifunctional polyethylene glycol. J Biomed Mater Res B Appl Biomater 2001;58(5):545–55. 3. Lodi D, Iannitti T, Palmieri B. Management of haemostasis in surgery: sealant and glue applications. Blood Coagul Fibrinolysis 2012;23(6):465–72. 4. Lewis KM, Spazierer D, Slezak P, et al. Swelling, sealing, and hemostatic ability of a novel biomaterial: A polyethylene glycol-coated collagen pad. J Biomater Appl. 2014; 29(5):780–8. 5. Orci LA, Oldani G, Berney T, et al. Systematic review and meta-analysis of fibrin sealants for patients undergoing pancreatic resection. HPB 2014;16(1):3–11. 6. Fingerhut A, Veyrie N, Ata T, et al. Use of sealants in pancreatic surgery: critical appraisal of the literature. Digestive Surgery 2009;26(1):7–14. 7. Aubourg R, Putzolu J, Bouche S, et al. Surgical hemostatic agents: assessment of drugs and medical devices. J Visc Surg 2011;148(6): e405–8. 8. Uraneus S, Fingerhut A. Splenic Injuries. In: Oestern H, Trentz O, Uranues S, editors. European Manual of Medicine: Head, Thoracic, Abdominal, and Vascular Injuries. Berlin: Springer; 2011. p. 285–96. 9. Carless PA, Anthony DM, Henry DA. Systematic review of the use of fibrin sealant to minimize perioperative allogeneic blood transfusion. Br J Surg 2002;89(6):695–703. 10.Lewis KM, McKee J, Schiviz A, et al. Randomized, controlled comparison of advanced hemostatic pads in hepatic surgical models. ISRN Surg 2014;2014:930803. 11.Lewis KM, Schiviz A, Hedrich HC, et al. Hemostatic efficacy of a novel, PEG-coated collagen pad in clinically relevant animal models. Int J Surg 2014;12(9):940–4. 12.Imkamp F, Tolkach Y, Wolters M, et al. Initial experiences with the HEMOPATCH as a hemostatic agent in zero-ischemia partial nephrectomy. World J Urol 2014.