Continuous hepatic artery infusion with an implantable pump: problems with hepatic artery anomalies

The implantable pump for continuous hepatic artery chemotherapy requires even distribution of the chemotherapy to the whole liver for maximum efficacy. The hepatic arterial supply and its anomalies must be understood to achieve this. We reviewed the arteriograms of 100 patients who were potentially arterial perfusion candidates. Fifty percent had normal hepatic arterial anatomy. Twenty percent had a replaced or accessory right hepatic artery and 17% had an accessory or replaced left hepatic artery. The methods used to implant the pump catheters in these anomalous situations were reviewed. The use of dual catheter pumps for arterial anomalies has necessitated extended operative time and increased the risk of uneven hepatic perfusion. Catheterization of the portal vein, which is technically simpler, deserves consideration as an alternative in the presence of an aberrant arterial system.     

Total hepatic arterial perfusion after occlusion of variant lobar vessels: implications for hepatic arterial chemotherapy

The surgical placement of hepatic arterial cannulas, followed by intra-arterial chemotherapy, is a promising technique for the treatment of unresectable hepatic malignancies. Complete perfusion of the liver with drugs is essential, but may be difficult to achieve in some patients with variant arterial anatomy. In 79 patients, we encountered 15 with variant anatomy that precluded standard single or dual cannulation techniques. In 12 patients variant lobar arteries were ligated at surgery. Postoperative transarterial coil occlusion was used in three patients. In each case, the remaining hepatic lobar artery was perfused with a single catheter. Complete bilobar hepatic perfusion was documented by a technetium 99m macroaggregated albumin scan in 13 of 15 (87%) patients. Of patients scanned more than 5 days after occlusion, six of six (100%) had full perfusion of the region supplied by the variant lobar vessels. Postocclusion hepatic arteriography demonstrated translobar collateral vessels that provided perfusion of the region of the occluded variant artery. There was no added morbidity from lobar arterial occlusion and no disparity in tumor response between perfusion by direct cannulation and perfusion by collateral flow. Occlusion of variant hepatic lobar arteries in conjunction with single catheter cannulation to infuse the remaining lobar vessels is a useful technique to provide total hepatic arterial perfusion in patients with variant hepatic arterial anatomy.     

A method for hepatic arterial perfusion studies in the rat

The current model for selective hepatic arterial infusion therapy was evaluated for its suitability for short-term pharmacokinetic experiments. This preparation consists of selective cannulation of the common hepatic artery via the gastroduodenal artery of the rat. Radioactive microspheres were injected to determine hepatic or extrahepatic sites of perfusion. Radioactive microsphere determination of hepatic arterial flow and cardiac output were also performed. Our data indicate that at high flow rates (2 ml/min), significant loss of drug would occur due to retrograde flow. Modification of the model to include temporary proximal hepatic artery occlusion ensures hepatic delivery of greater than 95% of drug. Furthermore, temporary hepatic artery occlusion does not alter cardiac output or hepatic arterial blood flow. Selective hepatic arterial infusion in rats with synchronous temporary hepatic artery occlusion is an adequate model for short-term pharmacokinetic studies.     

Effectivity of laser-induced thermotherapy: in vivo comparison of arterial microembolization and complete hepatic inflow occlusion

BACKGROUND AND OBJECTIVES: Laser-induced thermotherapy (LITT) is a promising method for local treatment of liver metastases. The aim of this study was to compare the effect of LITT on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. STUDY DESIGN/MATERIALS AND METHODS: In a porcine liver model, LITT (30 W 15 minutes) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle's maneuver, n = 12). LITT lesions were macro- and microscopically assessed after liver dissection. RESULTS: Hepatic inflow occlusion led to a fourfold increase in lesion volume after arterial microembolization and a ninefold increase after complete interruption (6.3. cm3 vs. 27.1 cm3 vs. 58.8 cm3, P < 0.01). CONCLUSIONS: Interrupting hepatic perfusion significantly increases lesion volumes in LITT. This beneficial effect can also be achieved in the percutaneous application mode by LITT combined with arterial microembolization via a hepatic artery catheter.     

Changes in the hepatic perfusion index during the development of experimental hepatic tumours

A model of microscopic liver tumour has been developed in the Fisher rat by intraportal injection of 1.6 x 10(7) Walker 256 carcinosarcoma cells. Rats were studied at 2, 4 and 6 days after the inoculation of live Walker cells. A control group received dead Walker cells. No tumour was visible in control groups at 2, 4 and 6 days after inoculation. Similarly in rats injected with live cells no tumour was visible at 2 days after inoculation but at 4 and 6 days the percentage hepatic replacement was (mean +/- s.d.) 7.0 +/- 2.3 and 27.9 +/- 6.80 respectively. The hepatic perfusion index was significantly raised at 4 and 6 days after inoculation of live cells compared with control animals and those receiving viable cells after 2 days inoculation. Portal flow and portal venous inflow were significantly reduced when the hepatic perfusion index increased but hepatic arterial flow did not alter. Changes in the hepatic haemodynamics were accompanied by increases in the portal and splanchnic vascular resistance and an increase in the amount of arteriovenous shunting through the liver. These findings confirm studies that the hepatic perfusion index is useful in the detection of occult liver metastases but that the change is not a consequence of an increase in the hepatic arterial flow.     

A prolongation of hepatic vascular exclusion by in situ hypothermic perfusion in dogs.

In situ hypothermic hepatic perfusion was performed in dogs to explore whether the time limit of hepatic vascular exclusion could be prolonged. During hepatic vascular exclusion, hepatic hypothermic perfusion was performed via portal vein using various perfusates under active bypass from the portal vein and infrahepatic inferior vena cava area to the superior vena cava system. Dogs receiving hepatic hypothermic perfusion for 1 hour died when given Ringer's solution but survived more than 7 days when given Euro-Collins' and University of Wisconsin solutions. Although dogs tolerated 2 hours of hepatic hypothermic perfusion when give University of Wisconsin solution, all dogs died by 2 hours of hepatic hypothermic perfusion when given Euro-Collins' solution. The hepatic energy charge and arterial ketone body ratio of dogs that died were significantly lower than for those that survived. This suggests that the regimen of hepatic hypothermic perfusion with University of Wisconsin solution is able to maintain the energy metabolism of the liver under hepatic vascular exclusion for prolonged periods, hence, its possible clinical application.     

Changes in hepatic haemodynamics and hepatic perfusion index during the growth and development of hypovascular HSN sarcoma in rats

Experimental liver tumours were induced in the Hooded Lister rat by the intraportal inoculation of 10(6) HSN sarcoma cells. The hepatic perfusion index was raised 10 days after the inoculation of cells (at the micrometastatic stage) and when overt tumour was present 20 days after inoculation. Overt tumours were hypovascular compared with normal liver. Portal venous flow and portal venous inflow fell significantly when the hepatic perfusion index was increased, but hepatic arterial flow did not alter. Portal vascular resistance and splanchnic vascular resistance were both increased in tumour-bearing animals but portal pressure, arteriosystemic shunting and portosystemic shunting did not increase significantly at any stage during the growth of hepatic tumour. These findings confirm that the hepatic perfusion index can be elevated in the presence of both micrometastic and overt hepatic tumour and that the changes are not due to either arteriosystemic shunting or mechanical portal venous obstruction.     

Quantitation and fractionation of nutrient hepatic blood flow in normal persons, in persons with portal hypertensive cirrhosis, and after small-diameter portacaval H grafts

Patients maintaining portal perfusion following small-diameter portacaval H grafts have better survival and lower portasystemic encephalopathy rates than those with reversed flow. To determine why this is so, we measured nutrient hepatic blood flow with the use of 99m-Tc-diisopropyl-IDA (DISIDA) clearance pharmacokinetics fractionated into its hepatic arterial and portal venous components. Patients with cirrhosis and portal hypertension had significantly lower nutrient hepatic blood flow than normal persons; this was due almost entirely to reduced portal flow. In patients with prograde portal flow after small-diameter H grafts nutrient hepatic blood flows were nominally reduced from levels seen in patients with portal hypertensive cirrhosis. Postoperative patients with reversed portal flow had significantly less nutrient hepatic blood than those with prograde flow. There was no evidence of significant hepatic arterial compensation for lost portal flow. Of four hemodynamic variables--portal flow direction, portal flow, arterial flow, and nutrient hepatic blood flow--only nutrient hepatic blood flow showed an independent correlation with clinical outcome. Portal perfusion is a critical factor in maintenance of adequate nutrient hepatic blood flow, primarily because hepatic arterial flow does not compensate chronically for lost portal perfusion.     

In-vivo evaluation of a novel bipolar radiofrequency device for interstitial thermotherapy of liver tumors during normal and interrupted hepatic perfusion

BACKGROUND: Only monopolar systems have thus far been available for radiofrequency ablation of liver tumors, whose application is restricted because of the incalculable energy flow, reduction of electrical tissue conduction, and limited lesion size. The aim of this study was to evaluate a novel internally cooled bipolar radiofrequency application device under in vivo conditions and to compare the effect of this system on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. MATERIALS AND METHODS: In a porcine liver model, RFA (60 W, 12 min) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle's maneuver, n = 12). RFA parameters (impedance, power output, temperature, applied energy) were determined continuously during therapy. RFA lesions were macroscopically assessed after liver dissection. RESULTS: Bipolar RFA induced clinical relevant ellipsoid thermal lesions without complications. Hepatic inflow occlusion led to a 4.3-fold increase in lesion volume after arterial microembolization and a 5.8-fold increase after complete interruption (7.4 cm(3)versus 31.9 cm(3)versus 42.6 cm(3), P < 0.01). CONCLUSIONS: The novel bipolar RFA device is a safe and effective alternative to monopolar RFA-systems. Interrupting hepatic perfusion significantly increases lesion volumes in bipolar RFA. This beneficial effect can also be achieved in the percutaneous application mode by RFA combined with arterial microembolization via a hepatic artery catheter.     

Predicting tumor response in patients with colorectal hepatic metastases.

Until now, there has been no reliable means of predicting tumor response to chemotherapy in patients with metastatic colorectal cancer. Using arterial nuclide flow scans as a determinant of tumor response, the degree of tumor perfusion was evaluated in a blinded prospective study. Seventy-three patients with colorectal hepatic metastases received continuous hepatic arterial (N = 52) or systemic intravenous (N = 21) chemotherapy using an implantable pump. All patients had pretreatment hepatic arteriography and arterial flow scans using 99mTc macroaggregated albumin (99mTc-MAA). An arteriogram was characterized as positive if it showed tumor hypervascularity; the 99mTc-MAA flow scan was considered positive if it showed increased tumor uptake relative to the liver. Of 47 patients with an evaluable 99mTc-MAA flow scan who were treated with arterial infusion, 31 had a positive scan; in this group 16 responded to chemotherapy. The 99mTc-MAA scan was negative in 16 patients, of whom one responded to chemotherapy (p less than 0.006). The 99mTc-MAA scan had the greatest predictive value in previously untreated patients (sensitivity = 91%; specificity = 77%). The arteriogram was positive in 25 of 46 evaluable patients, but this finding had little predictive value for tumor response (sensitivity = 56%; specificity = 46%). Of 21 patients receiving systemic intravenous infusion, the scan was positive in nine patients, of whom seven responded to chemotherapy. The 99mTc-MAA scan was negative in 12 patients, of whom one responded to chemotherapy (sensitivity = 88%; specificity = 85%). When 99mTc-MAA-positive and -negative groups were compared, there were no differences in mean patient age, per cent liver involvement, tumor size, or plasma liver function tests. Hepatic tumor perfusion as determined by MAA arterial flow scan is a reliable predictor of tumor response in patients with metastases from large bowel cancer. The test provides a valuable criterion for selecting individuals for treatment of metastases from large bowel cancer by infusion chemotherapy.     

Clinical evaluation of hepatic blood flow and oxygen metabolism during thoracoabdominal aortic surgery using pulse dye-densitometry combined with hepatic venous oxygen saturation

OBJECTIVE: There has been no report that pulse dye-densitometry (PDD), a novel non-invasive modality for monitoring hepatic blood flow (HBF), was applied during cardio-pulmonary bypass (CPB). We investigated weather PDD was useful to measure HBF during thoracoabdominal aortic surgery using partial CPB. Furthermore, HBF and hepatic metabolism were assessed during selective visceral perfusion or shunt using PDD, hepatic venous oxygen saturation (ShO2), and analysis of hepatic metabolic products. METHODS: A prospective study was carried out in eight patients who underwent thoracoabdominal aortic surgery from April 1998 to October 1999. Operative adjuncts were partial CPB with mild hypothermia in six (femoral veno-arterial bypass: FF group) and deep hypothermic circulatory arrest in two (DHCA group). Measurements were performed at following five time points; just before initiating CPB, just after establishing CPB, during selective visceral perfusion, during selective visceral shunt, and just after weaning CPB. RESULTS: Plasma clearance rate of indocyanine green measured by PDD well correlated with that obtained by in vitro spectrophotometry (p < 0.0001, R2 = 0.644). PDD demonstrated that decreased IIBF during selective visceral perfusion or shunt was well compensated by increased hepatic oxygen extraction rate in FF group and reduced oxygen consumption in DHCA group. Lactic acid extraction ratio and arterial ketone body ratio also decreased during this period. ShO2 during selective visceral shunt correlated with systemic systolic arterial pressure (SAP), and it showed a marked decrease under 20% when SAP was below 80 mmHg. Postoperative time course of serum total bilirubin and alanine aminotransferase of almost patients were within acceptable limits except the patient who required large amount of homologous blood transfusion. CONCLUSIONS: PDD proved to be a useful modality that enabled non-invasive monitoring of HBF even during partial CPB. Decreased HBF during selective visceral perfusion or shunt in thoracoabdominal aortic surgery was within physiological compensation, which led us conclude that it might be effective adjuncts, for visceral organ protection.     

A dog model using an implanted system for protracted hepatic arterial chemotherapy

A model for hepatic arterial chemotherapy studies using large dogs and an implantable infusion pump has been developed. Using this technique near complete perfusion (greater than 90%) of the liver can be achieved in vivo as determined by hepatic arterial perfusion scintigraphy with technitium 99m macroaggregated albumin. The system is reliable and has been in use for a total of 1353 days (mean of 104 days, range 52-239) in 13 dogs. Pump implantation causes no apparent acute liver damage based on pre- and post-operative alkaline phosphatase and serum glutamic-pyruvic transaminase determinations and does not affect the general mobility or behavior of the animals. Careful placement of the catheter and attention to the physicochemical properties of the solutions loaded are factors contributing to the success of the model. The model permits comprehensive preclinical pharmacokinetic and toxicologic studies of new or preexistent chemotherapeutic agents in the same device that will be used for later administration in human subjects. By providing the means to examine and develop new treatment modalities, it enables the design of even more potent cytotoxic therapy directed into the tumor vascular bed.     

Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft

Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4 degrees C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37 degrees C) (n = 8) or hypothermic (32 degrees C) (n = 8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37 degrees C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P less than 0.05), and there was lower bile output (P less than 0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P less than 0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P less than 0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation.     

Superior hepatic mitochondrial oxidation-reduction state in normothermic cardiopulmonary bypass

OBJECTIVE: This study is the first comparative investigation of hepatic blood flow and oxygen metabolism during normothermic and hypothermic cardiopulmonary bypass. METHODS: Twenty-four patients undergoing coronary bypass operations were randomly divided into 2 groups according to their perfusion temperatures, either normothermia (36 degrees C) or hypothermia (30 degrees C). The clearance of indocyanine green was measured at 3 points. Arterial and hepatic venous ketone body ratios (an index of mitochondrial redox potential) and hepatic venous saturation were measured. RESULTS: Hepatic blood flow in both groups was identical before, during, and after cardiopulmonary bypass (normothermia, 499 +/- 111, 479 +/- 139, and 563 +/- 182 mL/min, respectively; hypothermia, 476 +/- 156, 491 +/- 147, and 560 +/- 202 mL/min, respectively). The hepatic venous saturation levels were significantly lower during cardiopulmonary bypass in the normothermic group (normothermia, 41% +/- 13%; hypothermia, 61% +/- 18%; P <.01), indicating a higher level of oxygen extraction use. The arterial ketone body ratio in the hypothermic group decreased severely after the onset of cardiopulmonary bypass (P <.01) and did not return to its subnormal value (>0.7) until the second postoperative day. However, the reduction in arterial ketone body ratio was less severe in the normothermic group. The difference in hepatic venous ketone body ratios was more obvious, and the hepatic venous ketone body ratios in the normothermic group were statistically superior to those of the hypothermic group throughout the course (P <.05-.01). CONCLUSIONS: Normothermic cardiopulmonary bypass provides adequate liver perfusion and results in a better hepatic mitochondrial redox potential than hypothermic cardiopulmonary bypass. Because arterial ketone body ratios reflect hepatic energy potential, normothermia was considered to be physiologically more advantageous for hepatic function.     

Effect of ligation of variant hepatic arterial structures on the completeness of regional chemotherapy infusion

Twenty-three patients with separate arterial supplies to both sides of the liver underwent unilateral arterial ligation and chemotherapy via the remaining artery. Radionuclide infusion studies revealed only 62 percent complete perfusion after left hepatic ligation and 90 percent after right hepatic artery ligation.     

肝动脉解剖变异影像学研究

目的用数字减影血管造影(DSA)和CT血管造影(CTA)进一步探讨肝动脉解剖变异的种类、发生率及特点。方法回顾分析1000例因肝脏疾病而行DSA检查患者的临床资料、肝动脉的DSA,以及其中的32例肝动脉解剖变异的CTA表现。观察肝动脉的起源、走行、分布情况,并分别统计其变异类型和发生率。结果1000例肝动脉造影中,正常型727例,占72.7%;肝动脉变异273例,占27.3%。273例肝动脉变异中属于Michels分型的148例,占14.8%。Michels分型未包括在内者为125例,占12.5%。其中肝总动脉分叉变异54例,占5.4%,肝动脉起源变异214例,占21.4%,肝总动脉分叉 肝动脉起源变异5例,占0.5%。以上变异合并多种变异共存21例,占2.1%。结论肝动脉解剖变异的种类具有多样性、复杂性。除DSA外,CTA亦可显示肝动脉解剖变异。肝胆外科和影像科医师了解肝动脉解剖变异对于术前制定手术方案、提高诊断准确性等有重要意义。     

Detection of hepatic metastases using duplex/color Doppler sonography.

Current imaging modalities are unable to detect small liver metastases because of limited resolution and contrast differentiation. The association between liver metastases and altered liver blood flow has been demonstrated by dynamic scintigraphy, but the clinical feasibility of this test has been questioned. In this study a novel approach to detecting liver metastases was assessed by measurement of liver blood flow using a duplex/color Doppler System. Hepatic arterial and portal venous blood flows were measured in 16 controls, 50 patients with gastrointestinal cancer, and 6 patients with breast cancer. The ratio of hepatic arterial to total liver blood flow (Doppler perfusion index, DPI) and the ratio of hepatic arterial: portal venous blood flow (Doppler flow ratio, DFR) were calculated. The DPI and DFR values of controls and patients with overt liver metastases were clearly separated (p less than 0.0001). The results suggest that duplex/color Doppler ultrasound measurement of hepatic perfusion changes may be of value in the detection of liver metastases.     

Femur fracture with associated soft-tissue injury produces hepatic ischemia. Possible cause of hepatic dysfunction

Clinical studies demonstrate that early débridement and operative fixation of femur fractures in multiply injured patients lowers both the incidence and severity of hepatic failure. Perhaps the single most important determinant of hepatic function is nutrient hepatic perfusion. This study compares systemic and hepatic blood flow in rats that have sustained femur fractures with or without associated soft-tissue injury. Femur fracture without soft-tissue trauma resulted in a hyperdynamic state with normal blood flow distribution at 24 hours after injury and normal hemodynamics at 48 hours. When femur fracture was associated with soft-tissue trauma, the elevated cardiac output at 24 hours was not matched by a proportionately elevated hepatic blood flow. In this latter group, the cardiac output was normal at 48 hours, but the hepatic perfusion defect remained. Retained fracture fragments, hematoma, and injured and necrotic soft tissue may serve as a stimulus leading to a pathologic reduction in hepatic perfusion.     

Massive hepatic artery atherosclerosis of an otherwise suitable donor liver: a case report

Most of the few reports about hepatic artery disease found in the literature describe hepatic artery aneurysms or hepatic artery calcifications. Atherosclerosis of the hepatic artery is not commonly evaluated during deceased donor liver procurement. Herein we present a case of a stable 47-year-old Caucasian female donor whose liver function tests were within normal limits and a liver biopsy showed less than 5% steatosis. The liver when received at our center appeared grossly unremarkable. Back-table evaluation showed a complete occlusion of the trunk of the proper hepatic artery. The pathology report revealed hepatic occlusion due to arterial atherosclerosis. Transplantation was canceled, and the liver was used for isolated hepatocyte perfusion, revealing < 25% hepatocyte viability. Hepatic artery atherosclerosis and patency need to be evaluated at the time of procurement to prevent recipient morbidity due to anesthetic induction, or initiation of a recipient abdominal incision prior to declining the liver graft for this rare finding.     

Early changes in intracranial pressure during haemofiltration treatment in patients with grade 4 hepatic encephalopathy and acute oliguric renal failure

We measured the intracranial pressure (ICP), using a subdural catheter in nine patients admitted with grade 4 hepatic encephalopathy due to fulminant hepatic failure complicated by oliguric renal failure. Six patients received daily machine haemofiltration and four patients were treated with continuous arteriovenous haemofiltration (CAVHF). The mean ICP increased during the first hour of machine haemofiltration from 9 +/- 1.4 mmHg to 13 +/- 1.8 mmHg (P less than 0.05), and there was a reduction in the mean arterial pressure from 92.4 +/- 2.7 mmHg to 81 +/- 3.2 mmHg (P less than 0.05) resulting in a reduction in cerebral perfusion pressure of up to 30%. The group treated by CAVHF, although having a greater mean ICP prior to treatment (19 +/- 4.8 mmHg) and a lower mean arterial pressure (66 +/- 3.6 mmHg) and consequently a lower cerebral perfusion pressure, did not show any increase in ICP or reduction in mean arterial or cerebral perfusion pressure. There was a significant reduction in serum osmolality during the first hour of treatment in the machine haemofiltration group (314 +/- 4 mOsm/kg to 309 +/- 4 mOsm/kg, P less than 0.05), whereas there was no corresponding change in the CAVHF group. This suggests that CAVHF is to be preferred for the treatment of acute renal failure in such patients who are at considerable risk of developing cerebral oedema.