Orthotopic allotransplantation of the canine liver; a simplified technic with hypothermia

A simplified technique of the liver transplantation under hypothermia has been studied in dog. An immersion hypothermia was used in both the donor and the recipient. The temperature of the graft at excision was lowered to 20 degrees C with supplemental use of topical cooling. The temperature of the recipient was lowered at 27 degrees C when the transplantation was attempted. Chlorpromazine and dopamine were employed beneficially in hypothermia. No perfusion or irrigation of the graft was performed. The use of heparin was avoided. Anastomoses were carried out in turn of the proximal vena cava, portal vein, distal vena cava and the hepatic artery with a stem shaped aorta. Reperfusion was established after the completion of anastomosis between the proximal vena cava and portal vein. The anhepatic phase of the recipient was uneventfully lasted without heparinization. All dogs, 5 out of 11 without early surgical troubles survived more than 5 days. Immunosuppressive therapy was not employed except one which died of pneumonia on the 19th postoperative day. Histologically, these dogs were free from ischemic injury and/or thrombotic lesion throughout transplantation procedure.     

Segmental liver transplantation from living donors. Report of the technique and preliminary results in dogs

A technique of orthotopic liver transplantation using a segmental graft from living donors was developed in the dog. Male mongrel dogs weighing 25-30 kg were used as donors and 10-15 kg as recipients. The donor operation consists of harvesting the left lobe of the liver (left medial and left lateral segments) with the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The grafts are perfused in situ through the left protal branch to prevent warm ischemia. The recipient operation consists of two phases: total hepatectomy with preservation of the inferior vena cava using total vascular exclusion of the liver and veno-venous bypass, implantation of the graft in the orthotopic position with anastomosis of the left hepatic vein to the inferior vena cava and portal, arterial and biliary reconstruction. Preliminary experiments consisted of four autologous left lobe transplants and nine non survival allogenic left lobe transplants. Ten survival experiments were conducted. There were no intraoperative deaths in the donors and none required transfusions. One donor died of sepsis, but all the other donor dogs survived without complication. Among the 10 grafts harvested, one was not used because of insufficient bile duct and artery. Two recipients died intraoperatively of air embolus and cardiac arrest at the time of reperfusion. Three dogs survived, two for 24 hours and one for 48 hours. They were awake and alert a few hours after surgery, but eventually died of pulmonary edema in 2 cases and of an unknown reason in the other. Four dogs died 2-12 hours postoperatively as a result of hemorrhage for the graft's transected surface. An outflow block after reperfusion was deemed to be the cause of hemorrhage in these cases. On histologic examination of the grafts, there were no signs of ischemic necrosis or preservation damage. This study demonstrates the technical feasibility of living hepatic allograft donation. It shows that it is possible, in the dog, to safely harvest non ischemic segmental grafts with adequate pedicles without altering the vascularization and the biliary drainage of the remaining liver. We propose that this technique is applicable to human anatomy.     

Intraoperative physiologic monitoring and management during hepatic lobectomy using the liver isolation-perfusion technic.

The high operative mortality of major hepatic resection for tumor can be improved by a technic of resection using complete vascular isolation and hypothermic perfusion of the liver. Complete clamping of the portal vein, vena cava, and hepatic artery was necessary and well tolerated. Major physiologic, biochemical, and coagulation changes, however, can occur with this technic that requires close monitoring by the anesthesiologist. With astute observation and prompt corrective measures when indicated, these changes can be minimized to enable a safe and smooth resection to be carried out.     

Orthotopic transplantation of a partial hepatic autograft in dogs

The purpose of this study was to investigate the availability of an orthotopic transplantation of partial hepatic autograft in dogs as a means of surgical training. Male momgrel dogs weighting 10–15kg were used. The left lobe of the liver was harvested while preserving the left branches of the portal vein, hepatic artery and bile duct, and the left hepatic vein. The remnant liver was removed while preserving the inferior vena cava using a veno-venous bypass. Orthotopic transplantation of the autograft was performed while anastomosing the left hepativ vein to the inferior vena cava, portal and arterial reconstruction, and external biliary drainage. Thirteen out of 29 dogs survived more than 48 h after transplantation. However, 6 out of 13 dogs were sacrificed after developing bile peritonitis due to a dislodgement of the biliary catheter, and only two dogs were able to survive for 7 days after transplantation. The arterial ketone body ratio recovered to 1.0 within 1 h after reperfusion, and the ratio of the dogs that survived for more than 48 h remained above 1.0 until sacrifice. Orthotopic transplantation of a partial hepatic autograft is a useful and simple procedure to train surgeons for partial liver transplantation.     

Protagonism of the arterial circulation in the preservation of the pig's liver by simple perfusion and hypothermic storage

A modified technique to perform the successive perfusions of the liver that are necessary for its preservation by the simple perfusion method and hypothermic storage is presented. This technical variety has been tested on Large White pig's livers and consists in doing the successive perfusions of cooling, preservation and washout, first through the hepatic artery and there after through the portal vein. The macroscopic and biochemical characteristics of the effluents obtained through the infrahepatic inferior vena cava during the perfusion-washout of the livers at the end of the period cold ischemia shows its effectiveness. Likewise, the hepatic perfusion-washout begun via the arterial vein and finished via the portal one avoids post-revascularization hyperpotassemia in the receptor animals. It is hypothesized that the arterial protoganism of perfusions, when the simple perfusion and hypothermic storage method of hepatic preservation is used, could be a prophylaxis against complications of a post-transplant biliary origin.     

Washout of the pig liver with Haemaccel after hypothermic preservation

In hepatic preservation by simple perfusion and hypothermic storage, a portal and hepatic washout before revascularization would avoid receptor hyperkaliema. In this report we study the effectiveness of this washout with Haemaccel at room temperature. Large-White pigs were used and eight livers were perfused "in situ" via the portal wein with Hartmann's solution containing 10,000 IU of heparin at 4 degrees C, and afterwards, via portal and arterial routes with C2 solution at 4 degrees C. After a cold ischemia time of less than 31/2 hours a liver washout via the portal vein and hepatic artery with Haemaccel before portal revascularization was done. The high concentrations of glucose, K+, GOT, GPT and LDH in the effluents obtained during the washout are attributed to Haemaccel hyperosmolarity. A portal and arterial hepatic washout associated with free drainage of the first 50-100 ml of portal venous blood after hepatic portal revascularization through the infrahepatic inferior vena cava (IH-IVC), prevents hyperkaliemia from occurring after a portal and arterial revascularization in the orthotopic liver transplant (OLT) in pigs.     

Usefulness and problems of total hepatic vascular exclusion in liver surgery]

Total hepatic vascular exclusion (THVE) is an useful method enabling safe and sure hepatic resection in patients with liver tumors adjacent to the large hepatic veins or inferior vena cava (IVC), tumor thrombi, invasion of the IVC, etc. To avoid serious hypotension during THVE, test clamping of the IVC prior to the procedure is indispensable. Hemodynamics should be carefully maintained by blood transfusion and sufficient infusion of colloidal and electrolyte solutions during THVE. The veno-venous bypass method which shunts blood from the IVC and portal vein to the superior vena cava enables prolongation of the period of THVE and is useful to avoid postoperative renal dysfunction. In situ liver perfusion with cold solution during THVE is an additional modality by which the liver is protected from warm ischemic injury and the duration of THVE can be further prolonged. However, the maximum duration of THVE is still controversial, especially in patients with chronic liver damage. The most appropriate method for THVE should be carefully chosen in each case by considering the type of lesion, liver function, and the goal of the surgery.     

Orthotopic transplantation of segmental hepatic graft from living donors in the dog. Technic and results

The authors describe new technic of non-auxiliary orthotopic transplantation of segmental liver harvested from living dogs. 32 dogs were utilized. In the donor dogs, the left medial and lateral lobes were mibilized. The left portal branch, left hepatic artery, left biliary branch and the left hepatic vein were dissected free. The segmental liver graft was perfused and cooled in-situ through the left portal vein. The recipient dogs underwent two steps total hepatectomy: First the segments I, II, III, IV and V were resected. The segments VI and VII were maintained as well as the right portal vein and the retro-hepatic inferior vena cava order to keep the splanchnic and caval flux and to avoid the spleno-cavo-jugular by-pass. The segmental liver graft was then transplanted in an orthotopic position. Termino-lateral hepatico-caval anastomosis and left porto-portal anastomosis as well as arterial and biliary reconstruction were executed. All the donors survived more than 30 days. Nine recipient dogs died during the first three post-operative days from hemorrhage (3 dogs), fibrinolysis (2 dogs), primary non function of the graft (2 dogs) and hepatic artery thrombosis (1 dog). Seven recipients survived more than 30 days.     

Major Hepatic Resection Using Vascular Isolation and Hypothermic Perfusion

The technique and results of 29 major hepatic resections using the method of complete vascular isolation and hypothermic perfusion of the liver are reported. The method enables the surgeon to perform otherwise difficult or impossible resections through chilled bloodless hepatic parenchyma. Major intrahepatic vascular structures can thus be recognized and controlled readily under clear vision. Direct neoplastic involvement of, or tumor thrombi in the portal vein, hepatic vein or vena cava, can be successfully dealt with by appropriate surgical measures. The operative mortality was 10.3% for this series which included many tumors previously deemed unresectable. The technical detail and intraoperative physiologic monitoring crucial to success in the use of the method are described. It is hoped that with the widened scope of resectability afforded by this technique, and the use of adjuvant chemotherapy, the currently experienced low cure rates for hepatic cancer can be improved.     

Liver resection using total vascular exclusion of the liver preserving the caval flow,in situ hypothermic portal perfusion and temporary porta-caval shunt: a new technique for central tumors

Standard total vascular exclusion (TVE) of the liver is indicated for resection of tumors involving or adjacent to the vena cava and/or the confluence of the hepatic veins. The duration of liver ischemia can be prolonged by combined portal hypothermic perfusion of the liver (in or ex situ). The use of a venovenous bypass (VVB) during standard TVE maintains stable hemodynamics as well as optimal renal and splanchnic venous drainage. When the hepatic veins can be controlled, TVE preserving the caval flow negates the need for VVB. However this technique remains limited in duration as it is performed under warm ischemia (so-called normothermia) of the liver. To prolong the ischemia time, we have designed a modification of TVE with preservation of the caval flow including the use of temporary porta-caval shunt (PCS) and hypothermic perfusion of the liver. We describe here the first two cases of this new technique. Two patients underwent left hepatectomy extended to segments 5 and 8 (also called extended left hepatectomy) for large centrally located tumors. TVE lasted seventy-two and seventy-nine minutes, respectively. The postoperative course was uneventful and both patients were discharged on day ten and day twenty-five respectively. Both are alive without recurrence at ten and seven months following surgery. Provided the roots of the hepatic veins can be controlled, this technique combines the advantages of standard TVE with in situ hypothermic perfusion and VVB and obviates the need and the subsequent risks of the latter.     

A simple method of orthotopic liver transplantation in dogs.

Orthotopic liver transplantations were performed by one team in 18 dogs using a cuff method to anastomose the portal vein, the suprahepatic vena cava and the infrahepatic vena cava without external or internal shunts. Total and warm ischemic times of donor liver averaged 124 and 32 minutes, respectively. The average occlusion time of the portal vein and the infrahepatic vena cava were 9.7 and 13.9 minutes, respectively. During this time, uncontrolled hypotension, petechiae or hemorrhagic enterogastritis did not develop. Sixteen of 18 dogs survived more than five days, and five dogs lived more than three weeks. The cause of death was not related to the cuff method in any instance. This approach proved to be a technically simple and satisfactory procedure.     

自体原位肝移植逆行灌注法对大鼠急性肾损伤的影响

目的探讨自体原位肝移植术中经下腔静脉逆行灌注对大鼠肾功能的影响,为临床肝移植应用经下腔静脉逆行灌注法提供实验依据。方法 60只自体原位肝移植大鼠随机分为逆行灌注组、门静脉灌注组与假手术组各20只。前两组建立自体肝移植模型,其中逆行灌注组采用经下腔静脉逆行灌注法,先开放下腔静脉,再开放门静脉,最后开放肝动脉。门静脉灌注组采用常规经门静脉正向灌注法,先开放门静脉,再开放下腔静脉,最后开放肝动脉。假手术组开腹后游离肝门处门静脉、肝动脉及肝上、下下腔静脉,不予阻断,17min后关腹。分别检测3组术前1h、术后1h、8h及术后1d、5d的血清肌酐(Scr)、血尿素氮(BUN)水平;无肝期结束后1h、8h、1d取左肾组织行光镜检查观察肾组织病理形态学变化。结果术前1h,各组肾功能指标比较差异均无统计学意义(均为P>0.05);与假手术组比较,逆行灌注组、门静脉灌注组术后1h、8h及1d的Scr、BUN水平显著增高,而且逆行灌注组上述两指标明显低于门静脉灌注组(均为P<0.05),但术后5d3组比较差异均无统计学意义(均为P>0.05)。无肝期结束后1h,逆行灌注组和门静脉灌注组肾组织病理学检查发现肾间质充血,8h出现明显的肾小管上皮细胞水肿及肾间质充血,逆行灌注组明显轻于门静脉灌注组;无肝期结束后1d两组肾组织损伤呈现好转趋势,且逆行灌注组明显优于门静脉灌注组。结论自体原位肝移植术中实施逆行灌注可减轻大鼠急性肾损伤,改善大鼠早期肾功能。     

Resection and reconstruction of the inferior vena cava for major hepatic resection]

The inferior vena cava (IVC) is partially or segmentally resected in major hepatic resection for malignant hepatic tumors in case of possible direct invasion to the IVC wall or IVC tumor thrombosis. The reconstruction methods of the IVC are divided into three categories depending on the degree of IVC resection: simple suture; patch repair; and segmental replacement. In segmental replacement, a synthetic material such as a cylindrical expanded polytetrafluoroethylene (ePTFE) grafts is widely utilized as a substitute. The total hepatic vascular exclusion technique is usually necessary in concomitant resection of the suprahepatic IVC. When a longer duration of hepatic vascular exclusion is required to resect and reconstruct the suprahepatic IVC and hepatic vein confluence, in situ hypothermic perfusion, the ante situm technique, or ex vivo bench surgery must be applied. When an ePTFE graft is replaced in the resected IVC, a Carrel patch of the IVC is used for the hepatic vein orifice to maintain anastomotic patency. Alternatively, the hepatic vein can be reanastomosed to an inferior vena caval segment transpositioned from the intact infrahepatic IVC portion by replacing the resected infrahepatic IVC with an ePTFE graft.     

彩色多普勒超声评价支架植入术治疗移植肝血管狭窄

目的探讨彩色多普勒血流显像技术（CDFI）在移植肝血管狭窄支架植入术疗效评估中的价值。方法13例肝动脉狭窄,1例门静脉狭窄,2例肝静脉狭窄。于支架植入术前、后行CDFI检查并每隔3～4个月随访复查,取多普勒参数肝内动脉血流阻力指数和加速度、门静脉吻合口管径及其两端血流速度比值、肝静脉狭窄处管径及肝静脉和下腔静脉肝下段血流频谱进行统计学分析。结果肝动脉狭窄者支架植入术后RI升高,SAT缩短,治疗前后差异有显著性意义（P〈0.05）。门静脉和肝静脉狭窄者支架植入术后狭窄段管径增宽,植入的支架呈并行相间的线样强回声,门静脉吻合口两端血流速度梯度下降,肝静脉和下腔静脉肝下段血流频谱由术前的平坦波恢复为两相或三相波。结论CDFI检查是评价移植肝血管狭窄支架植入术疗效的可靠方法。     

Hepatic vascular exclusion as a model for complete and stable hepatic ischemia in dogs.

In order to confirm a complete ischemia model, 1-hour warm hepatic ischemia by hepatic vascular exclusion (HVE) was studied in dogs, in comparison with that by inflow occlusion (IOC) only. The splanchnic venous bed and/or infrahepatic inferior vena cava were decompressed by a centripetal pump-driven venovenous bypass. Indocyanine green retention test revealed no hepatic blood flow in the HVE model during ischemia, while hepatic blood perfusion was still present in the IOC model. All 5 of the IOC dogs survived more than 7 days after revascularization, while 4 of the 5 HVE dogs died within 9 h. After the induction of hepatic ischemia, lactate increased in both HVE and IOC dogs. After revascularization, transaminases and guanase were elevated, the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate) decreased and the serum lactate accumulated more in HVE dogs than in IOC dogs. The hepatic redox state of IOC dogs was significantly decreased by additional clamping of the inferior vena cava. It is concluded that the HVE model with a pump-driven active bypass provides complete and stable hepatic ischemia, resulting in greater deterioration of hepatic cellular functions; hence it is more suitable as a model of complete hepatic ischemia than the IOC one.     

16 肝细胞癌合并脉管系统癌栓的外科治疗

目的:探讨肝细胞癌（HCC）合并脉管系统癌栓的外科治疗效果。方法:回顾性分析1993年1月—2002年1月采用肝切除和癌栓取出术治疗HCC合并脉管系统癌栓68例的临床资料，其中门静脉癌栓63例，肝左静脉癌栓1例，肝中静脉癌栓合并门静脉左支癌栓1例，肝右静脉、下腔静脉合并门静脉右支癌栓1例，下腔静脉癌栓2例。HCC合并门静脉癌栓患者中6例术后行门静脉化疗。结果:6例术后3个月内死于肝肾功能衰竭， HCC合并脉管系统癌栓患者术后1，3，5年生存率分别为41.7%，20.8%，4.1%。结论:肝切除并癌栓取出术是HCC合并脉管系统癌栓有效的治疗方法，术后辅助治疗能提高治疗的效果。     

Management of Retrohepatic Inferior Vena Cava Injury during Hepatectomy for Neoplasms

The aim of this article is to discuss the management of retrohepatic inferior vena cava injury during hepatectomy for neoplasms. Step-by-step hepatic vascular exclusion, digital compression, finger pinching, and surface-to-surface suturing were used in the management of retrohepatic inferior vena cava injury during hepatic resection in 16 cases: 12 patients underwent exclusion of the hepatic artery and portal vein by portal triad clamping (PTC) only; 3 underwent PTC and exclusion of the infrahepatic inferior vena cava (IVC); and 1 underwent PTC together with exclusion of the suprahepatic and infrahepatic IVC. In all cases, bleeding stopped immediately after the management described, with no intraoperative deaths and no postoperative bleeding. The median follow-up was 42.5 months (range 19–60 months) for all patients, and the 5-year survival rate of all patients with malignant tumors was 28.57%. One died of lung metastasis 19 months after operation, one with spontaneous rupture of a hepatocellular carcinoma 19 months after operation, and eight others from recurrence or metastasis 21, 23, 24, 27, 30, 35, 50, or 54 months after operation, respectively. Two patients had a recurrence 4 years and 4 years 6 months after the initial operation, respectively. The recurrent tumors of the liver were resected. The other patients are currently alive without recurrence or metastasis. The techniques described are safe, simple, practical, time-saving, and effective for controlling massive bleeding arising from injury to the retrohepatic inferior vena cava during hepatic resection.     

Ex situ Resektion und Resektion an der in situ perfundierten Leber – Gibt es noch Indikationen?

Most liver tumors can be removed with conventional resection techniques employing partial or total vascular occlusion when needed. Duration of tolerable warm ischemia has not yet been defined, but it seems to be well tolerated up to 60 min. In a few cases with extended vascular resection and reconstruction liver protection by hypothermic perfusion is advantageous. This can be achieved by in situ perfusion, ante situm resection or ex situ resection. Major reconstruction of hepatic vessels with good technical access should be performed under in situ hypothermic protection using veno-venous bypass. Tumors involving the hepatic venous confluence and/or retrohepatic vena cava should be approached by either the in situ, or preferentially, the ante situm resection technique. The indication for an ex situ liver resection resulting in autotransplantation of the remnant liver exists only in rare cases for oncological reasons.     

Chemotherapy by isolated liver perfusion with endovascular occlusion catheter: preliminary experience in pigs

Very high concentrations of cytotoxic drug may be obtained with chemotherapy performed with vascular exclusion. OBJECTIVE: To study the pharmacokinetics and toxicity of melphalan during in situ isolated liver perfusion, and to test an endovascular occlusion catheter. METHODS: Isolated liver perfusion with melphalan (15 mg bolus) was performed in 6 pigs (50-60 kg) for 30 min, with non-oxygenated Ringer's solution. Hepatic outflow, collected by a double balloon catheter inserted into the retrohepatic inferior vena cava, was pumped into the gastroduodenal artery, while the common hepatic artery and portal vein were clamped. RESULTS: A maximum concentration of 30,000 ng/mL was obtained in the circuit before an exponential decrease, while the concentration in systemic blood was less than 500 ng/mL (n = 3). Before closing the abdomen, melphalan concentrations were about 2,000 ng/mg in the liver, and undetectable in the muscle. Postoperative course (2 weeks, n = 2) was uneventful with minor alterations in blood tests and hepatic histology. CONCLUSION: This method of local chemotherapy with melphalan appears to be safe with minor leakage and minimal toxicity.     

Total pancreas sampling and transplantation

Pancreas removal and transplantation consists in three main steps: sampling, preparation of the transplant with reconstruction of vessels and finally transplantation. Sampling requires good anatomical knowledge and perfect synchronization between hepatic surgeons so as to ensure adequate dissection of liver and pancreas vessels: portal vein, splenic, upper mesenteric and hepatic arteries. Washing and conservation of organs require the use of University of Wisconsin solution. The preparation of the pancreatic graft consists in reconstructing the unique arterial axis using an iliac arterial fork sutured with upper mesenteric and splenic arteries. The portal vein is lengthened step by step, avoiding venous patch source of thrombosis. The transplantation is realized in the right flank, on the aorta and the vena cava near the iliac crossroads. The digestive anastomosis is performed between duodenum of the transplant and first bowel hail of the recipient. It must be done carefully to avoid any risk of pancreas fistula.