Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications.

BACKGROUND: In various surgical cases, effective tissue adhesives are required for both hemostasis (eg, intraoperative bleeding) and air sealing (eg, thoracic surgery). We have designed a chitosan molecule (Az-CH-LA) that can be photocrosslinked by ultraviolet (UV) light irradiation, thereby forming a hydrogel. The purpose of this work was to evaluate the effectiveness and safety of the photocrosslinkable chitosan hydrogel as an adhesive with surgical applications. METHODS: The sealing ability of the chitosan hydrogel, determined as a bursting pressure, was assessed with removed thoracic aorta, trachea, and lung of farm pigs and in a rabbit model. The carotid artery and lung of rabbits were punctured with a needle, and the chitosan hydrogel was applied to, respectively, stop the bleeding and the air leakage. In vivo chitosan degradability and biologic responses were histologically assessed in animal models. RESULTS: The bursting pressure of chitosan hydrogel (30 mg/mL) and fibrin glue, respectively, was 225 +/- 25 mm Hg (mean +/- SD) and 80 +/- 20 mm Hg in the thoracic aorta; 77 +/- 29 mm Hg and 48 +/- 21 mm Hg in the trachea; and in the lung, 51 +/- 11 mm Hg (chitosan hydrogel), 62 +/- 4 mm Hg (fibrin glue, rubbing method), and 12 +/- 2 mm Hg (fibrin glue, layer method). The sealing ability of the chitosan hydrogel was stronger than that of fibrin glue. All rabbits with a carotid artery (n = 8) or lung (n = 8) that was punctured with a needle and then sealed with chitosan hydrogel survived the 1-month observation period without any bleeding or air leakage from the puncture sites. Histologic examinations demonstrated that 30 days after application, a fraction of the chitosan hydrogel was phagocytosed by macrophages, had partially degraded, and had induced the formation of fibrous tissues around the hydrogel. CONCLUSIONS: A newly developed photocrosslinkable chitosan has demonstrated strong sealing ability and a great potential for use as an adhesive in surgical operations.     

羧甲基壳聚糖在大鼠创伤出血模型的止血效果的观察

目的:建立SD大鼠创伤出血动物模型,观察羧甲基壳聚糖粉的止血效果及组织相容性和生物降解率。方法:①SD大鼠60只,30只用于建立肝脏出血创面,30只用于建立股静脉出血创面;2种模型的大鼠各分3组(羧甲基壳聚糖组、速即纱组、空白对照组),每组10只,并将材料置于大鼠的创面,观察各组的止血时间及出血量。②肝脏出血模型的大鼠1周后剖腹探查,切取肝脏创面组织,行病理组织检查,观察光镜下组织反应。结果:对于肝脏渗血和股静脉出血创面,羧甲基壳聚糖组、速即纱组及空白对照组均可止血,羧甲基壳聚糖组与速即纱组间止血时间及失血量无差异(P0.05);而羧甲基壳聚糖组及速即纱组与空白组比较,在止血时间、失血量上都有统计学差异(P0.01)。1周后羧甲基壳聚糖组大鼠肝脏创面组织在光镜下可见周围组织炎症反应较轻,且羧甲基壳聚糖已吸收。结论:羧甲基壳聚糖粉对大鼠肝脏渗血创面及静脉出血止血效果明显,组织相容性好,生物降解快。     

Stoma-related variceal bleeding: an under-recognized complication of biliary atresia

The medical records of 52 children with biliary atresia treated by portoenterostomy and evaluated for liver transplantation were reviewed to determine the frequency of stoma variceal bleeding and the optimal strategies for prevention and treatment. Eighteen patients had had prior stoma closure, four by preperitoneal closure without takedown from the abdominal wall. Three of the four developed occult variceal bleeding from the stoma closure site. Twenty-two patients had a stoma present at evaluation. All 22 patients with stomas (100%) had at least one bleeding episode requiring transfusion. Treatment included transfusion and local pressure (9), suture ligation of the bleeding site (5), and stoma closure and/or takedown (11). Local treatment led to recurrences in eight of 14 (57%) of the cases. To reduce the high mortality in patients with biliary atresia awaiting liver transplantation, multiple variceal bleeding episodes should be prevented. To eliminate one source, stoma variceal bleeding, the stoma, whether functioning or nonfunctioning should be taken down and closed. Preperitoneal closure alone does not prevent stoma bleeding.     

In vivo Evaluation of the Chitosan-Based Haemostatic Agent Omni-stat® in Porcine Liver Resection and in Liver Injury

Background: Omni-stat?, a polysaccharide made by de-acetylation of chitin, is currently in use as a battlefield topical haemostat. This experimental study undertakes the first evaluation of Omni-stat in an in vivo porcine hepatectomy and liver trauma model. Methods: A model of sequential liver resection was employed: following liver resection, further resections were undertaken in the same animal provided that there was cessation of bleeding from the earlier resection and that haemodynamic stability was maintained. An additional liver trauma injury was undertaken after completion of all resections. Data were collected on heart rate, blood pressure, haematocrit, resection volumes, blood loss and the efficacy of Omni-stat in haemostasis. Results: Eight minor resections and 12 major resections were undertaken. Topical application of Omni-stat to raw post-transection surfaces immediately upon completion of resection achieved complete haemostasis with a single application in 14 of 15 (93%) resections. There was no recurrence of bleeding during the 5-hour protocol. The median time for cessation of bleeding after resection in the Omni-stat group was 3 min (range 3-6). This was not significantly different from time to cessation of bleeding in 5 control resections. There was no difference in blood loss or haemodynamic parameters. Respiratory rate was significantly faster after application of Omni-stat. In 2 liver lacerations, Omni-stat was effective in achieving cessation of haemorrhage. Conclusion: Omni-stat is an effective haemostat in experimental in vivo porcine liver resection and liver trauma. Further evaluation is required to assess its physiological absorption profile in man and its comparative efficacy against commercially established agents.     

Use of a modified chitosan dressing in a hypothermic Coagulopathic grade V liver injury model

Background

Exsanguination from hepatic trauma is exacerbated by the lethal triad of acidosis, coagulopathy, and hypothermia. We evaluated the application of a modified chitosan dressing in a hypothermic coagulopathic model of grade V liver injury.

Methods

Subject swine underwent induced hypothermic coagulopathy followed by standardized grade V liver injuries. A modified chitosan dressing was applied and compared with standard packing.

Results

Pretreatment temperature, activated clotting time, and blood loss were similar between groups. Post treatment blood loss was significantly less and resuscitation mean arterial pressure were significantly greater in the modified chitosan group (P < .0001 and P < .018, respectively). Mean fluid resuscitative volume was significantly less in the modified chitosan group (P < .0056). Hemostasis was achieved on average 5.2 minutes following modified chitosan and never achieved with standard packing. At 1 hour post injury, all treatment animals survived compared with half of controls.

Conclusions

Modified chitosan dressings provide simple rapid treatment of life-threatening liver injuries.     

腹腔镜肝切除术中预防和控制出血的策略

近年来,腹腔镜微创技术发展迅速,腹腔镜肝切除术被逐渐运用于各种肝脏疾病的治疗,但由于创面出血难以控制的特点,腹腔镜下肝切除术仍具有一定难度。只有有效预防和控制术中出血,腹腔镜肝切除术才能顺利完成。目前预防和控制术中出血的方式主要有:肝血流阻断的方式、各种腹腔镜断肝器械的运用、腹腔镜超声技术、低中心静脉压技术、肝实质断面的处理等。笔者对以上几种方式做一个综述。     

The efficacy and safety of chitosan dextran gel in a burr hole neurosurgical sheep model

Background

Achieving and maintaining haemostasis is of paramount importance in neurosurgery. Chitosan has been shown in both animal and human models to be significantly effective in haemostasis as well as in reducing adhesion formation.

Objectives

To evaluate the haemostatic potential and to study histopathological changes caused by novel chitosan dextran gel in a neurosurgical sheep model.

Method

Ten sheep underwent neurosurgical burr hole procedure. Bleeding control was tested at the level of bone, dura and brain separately with both chitosan gel and Gelfoam paste on separate burr holes. Baseline bleeding was measured at the time of injury using the Boezaart scale, and then every 2 min after the application of each agent until complete haemostasis or 10 min, whichever was earlier. Safety was assessed through MRI scans and histopathological analysis.

Results

Mixed modeling showed no statistical difference in time to haemostasis between chitosan gel and Gelfoam paste (means of log-normalized areas under the curve were 1.3688 and 1.3196 respectively) for each burr hole (p?=?0.7768). Logistic regression modeling showed that Chitosan significantly decreased the incidence of bleeding beyond the first time point measured after application of the treatment when compared to Gelfoam (OR?=?2.7, p?=?0.04). Average edema volume (cm³) on post-operative MRI was 0.97 for Gelfoam and 1.11 for (p?=?0.49) while average histology scores were 2.5 for Gelfoam versus 3.3 for chitosan (p?=?0.32).

Conclusion

Chitosan dextran gel is an effective haemostatic agent to control bleeding in brain tissue. It is safe and nontoxic to neural tissue.     

门静脉高压症食管胃曲张静脉破裂出血治疗技术规范专家共识（2013版）

门静脉高压症是指由各种原因导致的门静脉系统压力升高所引起的一组临床综合征.门静脉高压症导致的食管胃曲张静脉破裂出血病死率较高.目前针对门静脉高压症食管胃曲张静脉破裂出血的治疗方法很多,包括药物、内镜、经颈静脉肝内门体分流术、分流术、断流术、肝移植等.为进一步合理选择门静脉高压症治疗方法并推广应用,卫生和计划生育委员会卫生公益性行业科研专项“门静脉高压症治疗方法的合理选择和推广应用”专家组,针对门静脉高压症食管胃曲张静脉破裂出血治疗技术规范等相关问题进行充分研讨,并参照国内外有关资料,结合我国具体情况,制订了我国门静脉高压症食管胃曲张静脉破裂出血治疗技术规范专家共识,供广大临床医师参考.     

Chitosan arrests bleeding in major hepatic injuries with clotting dysfunction: an in vivo experimental study in a model of hepatic injury in the presence of moderate systemic heparinisation

INTRODUCTION

The purpose of this study was to explore the effectiveness of two chitosan formulations, Omni-Stat® granules and Celox Gauze®, in a model of major hepatic injury in the presence of clotting dysfunction.

MATERIALS AND METHODS

Major hepatic injuries in moderately heparinised swine were treated with either Omni-Stat® granules or Celox Gauze® as compared to control plain gauze.

RESULTS

Plain gauze control failed to stop the bleeding in 13 of 14 attempts. Omni-Stat® arrested the bleeding in 18 of 18 attempts, providing it was in contact with the bleeding surface. Celox Gauze® arrested bleeding in 5 out of 6 attempts initially, and with further pressure in the sixth.

CONCLUSIONS

The results support the evidence that chitosan-derived products act independently of classical clotting pathways and should be effective in patients who suffer major liver injury even in the presence of clotting dysfunctions.     

肝移植手术出血特点及其对术后呼吸功能恢复的影响

目的研究肝移植手术中出血特点以及失血/输血量对术后呼吸功能恢复的影响。方法回顾性分析我科于2001年月2～2006年月948例几种不同病因肝移植患者手术过程出血特点以及失血、输血量对呼吸功能恢复的影响。结果病肝切除阶段是主要的出血时间段,广泛渗血为主要特点;不同疾病病因手术出血量明显不同。出血量最多为肝癌合并肝硬化、其它依次为肝硬化、急性重症肝炎、无肝硬化肝癌(P<0.05)。术中出血量大于5000ml明显影响患者术后呼吸功能的恢复,并且造成较高的围手术期并发症及死亡率(P<0.05)。结论肝移植术中大出血与术后呼吸功能恢复和术后并发症关系密切,是影响肝移植成败的重发因素之一。因此,尽量减少手术中出血是非常重要的。     

Induction of controlled cardiac tamponade in the management of massive unexplained postcardiotomy bleeding. Case report and review of the literature

Massive unexplained bleeding is a catastrophic complication of open heart surgery. The following paper describes a successful attempt to terminate such a hemorrhage by induction of controlled cardiac tamponade which caused augmentation of mediastinal pressure without hemodynamic decompensation, thereby aiding in hemostasis. This modality has not previously reported. Few events in clinical medicine are so ominous as the major unexplained hemorrhage. Diffuse bleeding from multiple transected small vessels may be controlled by mechanical techniques which apply pressure directly over the bleeding area. However, where the mediastinum is the source of bleeding, application of such a direct pressure with a closed chest, is both technically difficult and potentially risky. Reported attempts to stop bleeding by increasing the mediastinal pressure included the induction of pneumothorax, and the increase of positive end expiratory pressure (PEEP) has been published. To the best of our knowledge, a deliberate induction of controlled cardiac tamponade in order to terminate prolonged unexplained massive postcardiotomy hemorrhage has not been reported so far.     

Evaluation of FloSeal as a potential intracavitary hemostatic agent

BACKGROUND: Noncompressible hemorrhage is a major cause of death in combat and civilian trauma. When surgery is unavailable, one potential solution to such hemorrhage might be the introduction of an agent into the closed body cavity to provide hemostasis via a combination of coagulative and tamponade effects. FloSeal is an agent containing collagen and thrombin with proven hemostatic efficacy when applied with manual pressure to a bleeding site. The current studies were conducted to analyze the ability of FloSeal to reduce blood loss and increase survival time when applied directly, immediately, and without additional pressure to a severe liver injury in rats. METHODS: Male rats were anesthetized and catheters were placed in the carotid artery (for measurement of blood pressure) and jugular vein (for resuscitation with lactated Ringers, 3.3 mL/min/kg BW). After midventral laparotomy, the liver was exposed and caudal portions of both medial lobes ( approximately 1% of body weight) were rapidly excised. FloSeal (5 mL, 800 units Thrombin/mL) or vehicle (5 mL, 0.9% NaCl) was directly and immediately applied to the cut liver surface. The abdominal cavity was closed and resuscitation initiated. After hemorrhage-induced death, or after euthanasia at 90 minutes, fluid loss (blood + resuscitation fluid) was measured. RESULTS: Compared with the control group, direct and immediate application of FloSeal was associated with a reduction in the amounts of fluid lost into the abdominal cavity (p < 0.01) (19.2 +/- 1.5 versus 25.1 +/- 1.5 g) and enhanced mean arterial pressure at 5, 20, and 30 minutes after injury (p = 0.02), but neither survival time (p = 0.12) nor percent survival (p = 0.17) differed between treated and control groups. CONCLUSIONS: Reductions in fluid loss after liver injury and hemorrhage in FloSeal-treated rats in the absence of additional applied pressure are encouraging, and provide evidence for the ability of FloSeal to reduce blood loss when applied immediately and directly to a bleeding tissue.     

Variceal bleeding, hypersplenism, and systemic mastocytosis. Pathophysiology and management

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Though rarely a surgical disease, it occasionally presents as variceal bleeding secondary to portal hypertension. Ultrastructural studies of the liver and spleen and portal pressure measurements support the hypothesis that a perisinusoidal intrahepatic fibrosis is responsible for the increased portal pressure. When variceal bleeding complicates systemic mastocytosis, shunt surgery is indicated, with the type of shunt dictated by both hematologic and hemodynamic issues. Satisfactory blockade of histamine release can be achieved preoperatively by disodium cromoglycate and/or histamine antagonists to obviate any systemic effects precipitated by shunting of mast cell-rich splenic blood into the systemic circulation.     

灵芝壳聚糖促进轻医美项目导致的创面修复研究进展

轻医美项目后形成创面、伤口愈合过程的生理机制复杂,涉及不同成分之间的相互作用,表现为 出血、疼痛、红斑等。炎症因子介入、细菌数量的控制等相关因素均可影响创面修复进程。灵芝壳聚糖是 具有正电荷的天然多糖,具有高生物相容性和低免疫原性,不会引起排异反应或过度免疫反应,还具有抗 炎、抗氧化、抗菌、促进伤口愈合等作用,是创面修复的天然生物材料。近几年来灵芝壳聚糖在轻医美项 目导致的创面中展示出良好的修复效果,本文主要综述了医疗美容分类、轻医美后创面表现及灵芝壳聚糖 在轻医美创面修复中的应用优势,以期为灵芝壳聚糖生物材料在医疗美容领域的发展提供一定参考。     

Epidural anesthesia and analgesia in liver resection and living donor hepatectomy

Parenteral analgesics are still diffusely administered for postoperative pain after major liver resection, while epidural analgesia is widely criticized because of possible changes in the postoperative coagulation profile. The safety of regional anesthesia in liver resections is based on appropriate timing of needle placement and catheter removal and on the individual's skill in performing both the puncture and the catheterization. In the absence of liver failure or in cases of only moderate hepatic dysfunction, the risk of neurologic complications and spinal hematomas does not appear greater than when an epidural is performed for routine abdominal or thoracic surgery. Various anesthetic strategies have been adopted to prevent bleeding during liver resection, such as fluid restriction, diuretic administration, and vasodilator drugs. Lowering central venous pressure (CVP) seems to play a prominent role in prevention of bleeding since an elevated CVP may be associated with increased blood loss at various phases of liver resection. However, a low CVP may not be tolerated by all patients: intraoperative hemodynamic instability may, in fact, easily ensue because of the cardiovascular depressant effects of anesthetics, surgical blood losses, and manipulation of the inferior vena cava. We suggest combining intraoperative epidural anesthesia with general (light) anesthesia as a useful strategy to keep the CVP low during liver resection without vasodilators or diuretics. Epidural anesthesia does not lead to changes in intravascular volume, but only promotes redistribution of blood, decreasing both venous return and portal vein pressure, thus contributing to reduced hepatic congestion and surgical blood loss.     

Liver metastases, a rare cause of portal hypertension and stoma bleeding. Brief review of literature

INTRODUCTIONPortal hypertension is an unusual complication of liver metastases, which is frequently occurring in malignant disease. Portal hypertension may cause oesophageal varices and also stoma varices (colostomy and ileostomy). Oesophageal varices and bleeding from these varices have been frequently reported in literature. Stomal varices have also been reported in literature mostly associated with liver cirrhosis. These stomal varices lead to the massive bleeding causing morbidity and mortality.Portal hypertension is a pathological increase in portal pressure gradient (the difference between pressure in the portal and inferior vena cava veins). It is either due to an increase in portal blood flow or an increase in vascular resistance or combination of both. In liver cirrhosis, the primary factor leading to portal hypertension is increase in portal blood flow resistance and later on development of increased portal blood flow. It has been postulated that in liver metastasis the increase in portal flow resistance occurs at any site within portal venous system as a consequence of mechanical architectural disturbance.PRESENTATION OF CASEWe report a case of a 64 year old gentleman who developed portal hypertension due to secondary metastases from colorectal cancer. He subsequently developed bleeding varices in his end colostomy.DISCUSSIONWe believe that the combination of extensive metastases and chemotherapy induced portal hypertension in our patient.CONCLUSIONOur case and other literature review highlight that the recurrent bleeding stoma associated with colorectal cancer should be investigated for portal hypertension.     

Combined sclerotherapy and operation for the treatment of bleeding oesophageal varices.

OBJECTIVE--To identify prognostic factors in a consecutive series of patients with bleeding oesophageal varices and develop an optimum regimen of treatment. DESIGN--Retrospective review. SETTING--I Department of Surgery, University Hospital, Vienna, Austria. PATIENTS--301 consecutive patients with bleeding oesophageal varices. OUTCOME MEASURES--Median survival and survival at one year after sclerotherapy alone (n = 213), or sclerotherapy with portosystemic shunt (n = 54), Hassab's devascularisation (n = 29), or liver transplantation (n = 5). RESULTS--Prognosis was dependent on the severity of liver damage at the start of treatment. Median survival for Child's class A was 47 months, for Child's class B 54 months, and for Child's class C 2 months. The overall one year survival for patients in Child's class C was 33%, for sclerotherapy alone 28%, and for sclerotherapy and portosystemic shunt 42%, Hassab's devascularisation 50%, and liver transplantation 80%. CONCLUSION--Despite the small number of patients who underwent liver transplantation and their poor initial prognosis (Child's class C, n = 4; class B, n = 1) our results suggest that liver transplantation should be considered for the treatment of patients with end stage cirrhosis and bleeding varices.     

The introduction of a simple maneuver to reduce the risk of postoperative bleeding after major hepatectomies

Background/Purpose  In major hepatectomies, postoperative increases in central venous pressure (CVP) may cause suture failure and massive bleeding. The aim of our study is to test the application of an intraoperative maneuver to reduce the risk of postoperative bleeding. Methods  Our study included 172 consecutive patients who had major liver resection with selective hepatic vascular exclusion and sharp transection of the liver parenchyma. An intraoperative maneuver (5 s occlusion of the hepatic vein) was applied in an alternating way, and the patients were assigned to two groups: Cohort A (n = 86), that was granted the maneuver, and Cohort B (n = 86), that was used as a control group. Results  In Cohort A, application of the maneuver was successful in demonstrating bleeders under low CVP levels. Cohort A had lower rate of massive bleeding requiring emergency reoperation (2.3 vs 5.8%, P = 0.049), less postoperative blood transfusions (13 vs 24%, P = 0.042), lower morbidity (20 vs 35%, P < 0.045) and shorter hospital stay compared to Cohort B. Conclusions  Hepatectomies conducted under low CVP are prone to postoperative hemorrhage which can be prevented if the final bleeding control is performed under high pressure in the hepatic veins. Application of our testing maneuver effectively unmasked previously undetectable bleeding veins.     

Blood-transfusion requirements and blood salvage in donors undergoing right hepatectomy for living related liver transplantation

Living related liver donation for liver transplantation in adults including its risks is receiving increased attention. We present data from 44 liver donors focusing on transfusion requirements and avoidance of heterologous transfusion. The volume of blood transfused (both autologous from preoperative donation and heterologous) was assessed including that derived from intraoperative isovolemic hemodilution, cell-saver salvaged, and retransfused blood. Hemoglobin concentration and central venous pressure were measured at specified time points before and during surgery. Intraoperative blood loss was calculated and correlated to the duration of parenchymal transsection, liver volume resected, and central venous pressure. There were no specific anesthesia-evoked complications. In 4 donors, major bleeding (>2000 mL) occurred. Blood loss averaged 902 +/- 564 mL (SD), yielding a minimal mean hemoglobin concentration of 8.1 +/- 1.2 g/dL. One donor received 3 U of heterologous blood and 30 donors received autologous blood from their preoperative donation. An average of 592 +/- 112 mL of blood derived from perioperative acute isovolemic hemodilution was retransfused as was 421 +/- 333 mL of washed red cells from the cell-saving system. Avoidance of heterologous blood transfusion, application of blood-saving techniques, and efficient pain management are crucial for adult living liver donors. Transfusion of banked blood can be avoided in most patients when intraoperative cell salvage, preoperative autologous blood donation, and intraoperative hemodilution are combined.     

三维腹腔镜下精准肝脏肿瘤切除应用分析

目的探讨三维腹腔镜精准肝脏肿瘤切除的应用价值。 方法回顾性分析10例肝脏肿瘤患者施行腹腔镜精准解剖性肝切除术的临床资料。 结果10例手术均获成功,其中肝癌8例,肝血管瘤2例;术中出血量平均(216 ± 6) ml,术后住院时间平均(10 ± 3) d;术中出血较少,视野清晰,手术时间也较短。术后无胆漏、出血等并发症发生。术后1～3 d肛门排气,术后5～11 d痊愈出院。 结论三维腹腔镜精准解剖性肝切除对于精确分离肝内管道结构具有一定优势,有助于控制术中出血,适用于肝脏肿瘤解剖性肝切除术,尤其适用于半肝切除术。