Haemodynamic alterations and their morphological basis in biliary obstruction

Abstract: The relationship between the haemodynamic alterations and morphological changes in the liver caused by biliary obstruction was investigated in rats after ligation of the common bile duct. In these rats, the portal vein pressure was markedly elevated, and the differences in blood pressure between the portal vein and the terminal portal venule and between the terminal portal venule and the terminal hepatic venule were greater than in the sham-operated rat. The livers showed narrowing of the most peripheral branches of the portal vein due to compression by proliferated bile ductules and sinusoidal stenosis due to enlarged liver cells, but there was no perceptible change in the hepatic vein branches. These data suggest that hepatic circulatory disturbance in biliary obstruction is caused by deformation of the peripheral portal vein branches and sinusoidal stenosis.     

Trichinella spiralis: Intestinal expression of systemic stage-specific immunity to newborn larvae

Rats immunized with newborn Trichinella spiralis larvae i.v. were found to confer a specific anti-newborn larvae immunity in the small intestine. In rats immunized with newborn larvae i.v. and then challenged with adult worms intraintestinally, total newborn larvae recovery was reduced by 75-90% in thoracic duct lymph and in hepatic portal vein blood. No newborn larvae were found in the peritoneal fluid of immunized rats. In addition to an absolute reduction in number, larval migration from the small intestine to the thoracic duct was delayed by 6-12 h and migration to the portal vein was inhibited for at least 8 h. The establishment of adult worms in the small intestine and female worm fecundity were not affected by anti-newborn larvae immunity. Identical quantitative effects on newborn larvae migration from the small intestine were achieved by homologous transfer of anti-newborn larvae immune serum i.v. into naive recipient rats.     

Comparison of pre-operative exams and per-operative findings in living donor liver transplantation

BACKGROUND: Success in living donor liver transplantation is associated to donor vascular and biliar anatomy. AIM: Compare pre-operative and per-operative findings in living liver donors related to portal vein, hepatic artery, bile duct and hepatic venous drainage anatomy. METHODS: Donors charts of living donor liver transplants done at Clinics Hospital of the Federal University of Paraná, Curitiba, PR, Brazil, were reviewed between March 1998 and August 2005. On the pre-operative period the anatomy was analysed through: celiac and mesenteric arteriography of the hepatic artery and portal vein (venous phase); magnetic resonance imaging of the venous drainage, portal vein and bile duct. Normality was determined based on data of the literature. Pre-operative findings were compared to per-operative findings. RESULTS: Portal vein and hepatic artery were studied in 44 patients, 16 females and 28 males, mean age of 33 years old. In 8 cases the left liver lobe was used to pediatric receptor, in 36 cases the right liver lobe was used to adult receptor. Bile duct anatomy was studied in 37 cases and venous drainage in 32. Over all, the findings related to pre-operative and per-operative anatomy were not coincident in 36.36% of the cases. In the case of hepatic artery, they were not coincident in 11.36%, in the case of the portal vein in 9.1%, in the case of the venous drainage in 9.37% and in the case of the bile duct in 21.6%. CONCLUSION: The pre-operative and per-operative findings related to vascular and bile duct donor anatomy are frequently different in living donor liver transplantation.     

Long-term survival of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement

We report the case of a very rare 6-year disease-free survivor of intrahepatic cholangiocarcinoma with hilar lymph node metastasis and portal vein involvement. A 76-year-old female with liver dysfunction was referred to our institution. Contrast-enhanced computed tomography showed a 5-cm low-density tumor with irregular marginal enhancement in the left and caudate lobes of the liver. Cholangiography revealed complete obstruction of the left hepatic bile duct. Angiography showed obstruction of the left branch of the portal vein. Metastasis to the hilar lymph nodes was disclosed at surgery. The patient underwent left hepatectomy with caudate lobectomy, resection of the extrahepatic bile duct, and lymphadenectomy. The total vascular exclusion of the liver was used for hepatectomy and reconstruction of the portal vein. Microscopically, the tumor was a poorly differentiated adenocarcinoma with many infiltrating lymphocytes, and extensive necrosis was present within the tumor. The experience gained in the present case suggests that aggressive surgery may be a potential approach to provide a hope of long-term survival for patients with intrahepatic cholangiocarcinoma despite the presence of regional lymph node metastasis and vascular invasion.     

Role of hepatic artery in haemodynamics in normal and cirrhotic livers in rats

To examine the degree of influence of the hepatic artery on microcirculation in the liver, microscopic observation of blood flow in the hepatic minute blood vessels and the sinusoids and pressure measurements at key points in hepatic vascular pathways in vivo were performed before and after hepatic artery ligation in normal and cirrhotic rats. In normal rats, portal vein pressure (109 mmH2O) fell 10 mmH2O after hepatic artery ligation, but the pressures of the terminal portal venule, the terminal hepatic venule and the inferior vena cava did not change. In cirrhotic rats, portal vein pressure (206 mmH2O) and terminal portal venule pressure (106 mmH2O) fell 23 and 10 mmH2O after hepatic artery ligation respectively: the pressures in the terminal hepatic venule and the inferior vena cava did not change. These results suggests that the pressure transmitted from the hepatic artery was mostly supplied to the intrahepatic portal vein in normal rats and both to the intrahepatic portal vein and to the sinusoids in cirrhotic rats. In both normal and cirrhotic rats, however, the pressure transmitted from the hepatic artery was about 10 per cent of the initial portal vein pressure, and the blood flow in minute vessels and sinusoids did not change after hepatic artery ligation. Accordingly, it is believed that the hepatic artery plays only a small role in the haemodynamics of the liver in both normal and cirrhotic rats, irrespective of the distribution and manner of the hepatic arterial termination.     

Laparoscopic findings of congenital hepatic fibrosis: A case report and review of the published work

A 33‐year‐old man visited a hospital after vomiting blood. Emergent esophagogastroduodenoscopy revealed the presence of varices in the lower esophagus. The patient did not have a past history of alcohol consumption and was negative for hepatitis B and C viruses. He was referred to our hospital for closer examination. Portal hypertension was detected by conventional imaging modalities, but signs of liver cirrhosis, thrombosis, stenosis, malformation of the portal vein and bile duct abnormalities were not observed. We performed laparoscopy‐guided liver biopsy to examine the cause of portal hypertension. In addition to prominent development of collateral vessels on hepatic ligaments and the omenta, marbled whitish markings with black‐green spots were dispersed over the liver surface, but nodular formation and lymphatic vesicles were not found. Biopsied specimen demonstrated severe dense fibrosis in portal areas and von Meyenburg complexes (vMC). Based on these findings, the diagnosis of congenital hepatic fibrosis (CHF) was made. Post‐biopsy hemostasis was confirmed under laparoscopy and no major complications occurred after biopsy. We reviewed 11 cases of CHF which had undergone laparoscopy in Japan, including our case. Marbled whitish markings, black‐green spots and collateral vessels were seen in 11, five and seven cases, respectively. When we encounter the patients having portal hypertension of unknown etiology, laparoscopy‐guided liver biopsy should be considered as a safe and useful diagnostic procedure. Black‐green spots in marbled whitish markings, which reflect vMC in broad fibrotic areas, are laparoscopic characteristics of CHF.     

Pathogenesis of hepatic atrophy in canine model of hepatolithiasis

The pathogenesis of the hepatic atrophy that accompanies hepatolithiasis was investigated pathomorphologically using a canine model. Two groups were evaluated: infected and noninfected. In the infected group, inflammation in Glisson’s capsule caused by cholangitis involved the portal vein at the region of the large bile duct. At this region, the periportal fibrosis ratio was significantly greater in the infected group than in the noninfected group both at 1 and 3 months. At the regions of the septal and interlobular bile ducts, the caliber ratio of the portal vein in the two experimental groups was less than in the normal liver both at 1 and 3 months. At both regions, the caliber ratio of the portal vein in the infected group was less than in the noninfected group at 3 months. The rate of atrophy was significantly greater in the infected group than in the noninfected group at 3 months. These results suggest that disturbance of the portal venous blood flow attributed to cholangitis of the large bile ducts is one of the most important factors leading to hepatic atrophy in hepatolithiasis.     

Significance of septal fibrosis for disturbance of hepatic circulation

Abstract: To examine the significance of fibrous septa of the liver for hepatic circulatory disturbance, haemodynamic changes were investigated in rats with septal fibrosis induced with horse serum injections. The fibrotic liver showed thin fibrous bands originating in the vicinity of the peripheral branches of the hepatic vein connected with each other and partly with the portal triads, without conspicuous periportal, pericentral or perisinusoidal fibrosis. There was no evidence of hepatic cell enlargement, disarrangement of hepatic cell plates or narrowing of the sinusoids in the fibrotic livers. Portal vascular resistance, bile production and hepatic oxygen consumption, which were measured by an isolated liver perfusion method, were much the same in the normal and the fibrotic livers. Moreover, there was no significant difference in in vivo blood pressures of the portal vein, the terminal portal venule, the terminal hepatic venule and the inferior vena cava between the normal and the fibrotic rats. These data suggest that septal fibrosis in itself does not disturb hepatic circulation.     

Transcapillary water and protein flux in the canine intestine with acute and chronic extrahepatic portal hypertension

Intestinal transcapillary water and total protein flux were determined in dogs with chronic extrahepatic portal hypertension after construction of an aortic-portal shunt combined with hilar portal vein constriction and compared to acute portal vein constriction. Measurements were made of thoracic duct lymph flow, portal venous pressure, and total protein concentration in plasma, thoracic duct lymph, intestinal and liver lymph. From these data and calculations based on the dual visceral origin of thoracic duct lymph from liver and intestine, intestinal transcapillary water flux in chronic extrahepatic portal hypertension (portal venous pressure = 21.4 +/- 2 mm Hg; mean +/- SEM), increased 5-fold (93 +/- 12 from 17 +/- 4 microliters/min/kg, P less than 0.001), while intestinal total protein flux expressed as protein clearance (intestinal transcapillary water flux X intestinal lymph/plasma total protein concentration) was unchanged (13 +/- 3 from 10 +/- 2 microliters/min per kg; P greater than 0.4), a finding supported by unaltered whole body plasma albumin "leak rate" (83 +/- 16 from 80 +/- 2 microliters/min per kg; P greater than 0.9). In acute portal vein constriction (portal venous pressure = 26 +/- 1 mm Hg) intestinal transcapillary water flux was similarly increased (58 +/- 16 from 9 +/- 2; P less than 0.014) but intestinal total protein flux was increased 3-fold (16 +/- 4 from 5 +/- 2; P less than 0.032). Calculated permeability surface area product and protein reflection coefficient (cross-point method) increased similarly in both preparations. In accord with earlier findings in patients with hepatic cirrhosis, chronic elevation in portal pressure increased intestinal transcapillary water flux but not total protein flux.     

In vivo assessment of the hepatic microcirculation after mesenterico‐portal bypass (REX‐shunt) using orthogonal polarization spectral imaging

Background: Extrahepatic portal vein thrombosis, not associated with cirrhosis or tumours, is the second most frequent cause of portal hypertension worldwide. Especially in children, anatomic mesenterico‐portal interposition (REX‐shunt) has become an established treatment. The changes in hepatic microcirculation after reperfusion of the shunt have not been investigated so far. Aims: This study investigates the hepatic microcirculation before and after REX‐shunt interposition using orthogonal polarization spectral imaging (OPS). Patients and methods: Since 2004, three consecutive patients with extrahepatic portal vein thrombosis underwent REX‐shunt interposition. We measured the hepatic microcirculation by OPS before and directly after REX‐shunt reperfusion and analysed the capillary vessel diameter, red blood cell velocity, functional capillary density and volumetric blood flow. Furthermore, we compared our values with the physiological values of the hepatic microcirculation defined previously by other investigators. Results: All shunts showed an excellent function in the follow‐up investigations. The intra‐individual microcirculatory analysis revealed a reduction in the red blood cell velocity after shunt reperfusion in particular. Conclusions: Our results provide preliminary evidence for the reversal of the hepatic arterial buffer response following the restoration of the portal venous blood flow. This may be a short‐term effect because of the restored portal venous blood flow.     

Anatomical basis of hepatic venographic alterations in idiopathic portal hypertension

ABSTRACT— Hepatic venograms made in 40 authentic cases of idiopathic portal hypertension (Banti's syndrome) were compared with 13 normal venograms and venograms obtained in 88 cases of cirrhosis, and analyzed in the light of the pathological changes seen in 16 postmortem liver specimens. There were frequent anastomoses between hepatic vein radicles, approximation of middle-size branches to the liver surface, reduction in the angles between the main hepatic vein and its tributaries, and difficulty in opacifying portal vein branches in wedged retrograde portography. These angiographic alterations were corroborated by gross pathological findings which comprised displacement of middle-size hepatic vein branches closer to the liver surface and their approximation among themselves, and seem to be accounted for by the disappearance of liver parenchyma secondary to the peripheral portal circulatory failure.     

Portal-systemic shunting in a patient with normal portal vein pressures and histological evidence of idiopathic portal hypertension

Although idiopathic portal hypertension (IPH) is clinically characterized by portal hypertension and marked splenomegaly, we have experienced a case of spontaneous portal-systemic shunt without splenomegaly in whom the liver histology resembled IPH but with normal portal pressure. We admitted a 64 year old man who had suffered from hepatic encephalopathy for 2 years. Laparoscopy revealed a dark grey liver with a sharp edge and a concave surface. Examination of a liver biopsy specimen revealed peri-portal fibrosis consistent with IPH. A single, large, portal-systemic shunt was identified by percutaneous transhepatic portography. The shunt arose from the left gastric vein and flowed through the left renal vein into the inferior vena cava. No varices were identified. There were no morphological changes in the hepatic or portal veins. Portal vein pressure was normal. There was a slight difference between the portal pressure and the wedged hepatic vein pressure, suggesting a presinusoidal block. This case raises important questions concerning the aetiology of IPH and the relationship between portal hypertension and the development of collateral venous circulation.     

Reutilization of DNA Breakdown Products from Lymphocytes in Lumen of Intestine

Migration of a very large number of lymphocytes (211.8 x 10⁶ per day)into the intestinal canal of rats, which weighed about 100 Gm., was found.Lymphocytes in the lumen of the intestine were 80.2 per cent small, 15.9 percent medium and 3.9 per cent large. Any recycling of instilling cells intothe intestine could not be observed. Lymphocytes labeled with H³-thymidine,obtained from both thymus and mesenteric lymph nodes of donor rats, werewashed and injected into the intestine of recipient rats. H³ activity of the bloodand thoracic duct lymph plasma after administration of labeled lymphocytesshowed that DNA breakdown products from the lymphocytes in the gut wereabsorbed and transferred by way of both the portal vein and the thoracic duct.Evidence that the activity was actually incorporated into the DNA of proliferating cells of the recipient was demonstrated by autoradiographic means.

Submitted on July 15, 1965 Accepted on October 8, 1966     

Establishment of a new pig model for auxiliary partial orthotopic liver transplantation

AIM: To establish a new pig model for auxiliary partial orthotopic liver transplantation (APOLT). METHODS: The liver of the donor was removed from its body. The left lobe of the liver was resected in vivo and the right lobe was used as a graft. After the left lateral lobe of the recipient was resected, end-to-side anastomoses of suprahepatic inferior vena cava and portal vein were performed between the donor and recipient livers, respectively. End-to-end anastomoses were made between hepatic artery of graft and splenic artery of the host. Outside drainage was placed in donor common bile duct. RESULTS: Models of APOLT were established in 5 pigs with a success rate of 80%. Color ultrasound examination showed an increase of blood flow of graft on 5th d compared to the first day after operation. When animals were killed on the 5th d after operation, thrombosis of hepatic vein (HV) and portal vein (PV) were not found. Histopathological examination of liver samples revealed evidence of damage with mild steatosis and sporadic necrotic hepatocytes and focal hepatic lobules structure disorganized in graft. Infiltration of inflammatory cells was mild in portal or central vein area. Hematologic laboratory values and blood chemical findings revealed that compared with group A (before transplantation), mean arterial pressure (MAP), central venous pressure (CVP), buffer base (BB), standard bicarbonate (SB) and K+ in group B (after portal vein was clamped) decreased (P<0.01). After reperfusion of the graft, MAP, CVP and K+ restored gradually. CONCLUSION: Significant decrease of congestion in portal vein and shortened blocking time were obtained because of the application of in vitro veno-venous bypass during complete vascular clamping. This new procedure, with such advantages as simple vessel processing, quality anastomosis, less postoperative hemorrhage and higher success rate, effectively prevents ischemia reperfusion injury of the host liver and deserves to be spread.     

Intraoperative portal vein blood flow predicts allograft and patient survival following liver transplantation

Background:

We hypothesized that operative variables might predict survival following liver transplantation.

Methods:

We examined perioperative variables from 469 liver transplants carried out at the University of Washington during 2003–2006. Logistic regression determined the variables'' contributions to survival at 30, 90 and 365 days.

Results:

Portal vein blood flow (>1 l/min) was significant to patient survival at 30, 90 and 365 days. Complete reperfusion was only a significant predictor of survival at 30 days. This provided model receiver operating characteristic (ROC) area under the curve (AUC) statistics of 0.93 and 0.87 for 30 and 90 days, respectively. At 365 days, hepatic artery blood flow (>250 ml/min) combined with portal vein blood flow was significantly predictive of survival, with an AUC of 0.74. A subset analysis of 110 transplants demonstrated improved 1-year survival with more aggressive vascular revisions.

Discussion:

Portal vein blood flow is a significant predictor of survival after liver transplantation. Initially, the liver''s survival is based on portal vein blood flow; however, subsequent biliary problems and patient demise result from both poor portal vein and inadequate hepatic artery blood flow.     

Influence of Selective Hepatic Vascular Perfusion on Ammonia Metabolism in Dog

In trying to evaluate the influence of vascular pathways in ammonia clearance by the liver, continuous ammonium chloride perfusions were made separately through the hepatic artery and the portal vein in 20 dogs. Continuous ammonium chloride perfusion (45 mg/kg/hr) through the portal vein results in a highly significant increase in peripheral venous and arterial levels of ammonia, in spite of an ammonia concentration remaining normal in the hepatic vein. On the other hand, continuous ammonium chloride perfusion through the hepatic artery does not significantly change the peripheral ammonia concentration nor the hepatic vein ammonia concentration. From these figures, it must be assumed that during portal perfusion. a fraction of ammonium chloride solution is shunted before reaching the sinusoids. During hepatic artery perfusion, the entire amount of the solution is cleared by the liver and no shunts can be detected. The existence and the level of such shunts are discussed.     

Impact of hepatic lymph node metastasis on survival of patients with synchronous resectable or unresectable liver metastases of colorectal cancer

Background

The goals of this retrospective study were to comprehensively evaluate the impact of hepatic lymph node (HLN) involvement on survival in patients with synchronous resectable or unresectable liver metastases from colorectal cancer and to highlight how to deal with such cases in the light of recent advances in chemotherapy.

Methods

The impact of HLN involvement on survival, along with various clinical, pathological, and therapeutic factors, was retrospectively evaluated in 61 patients with synchronous liver metastases from colorectal cancer (resectable, 26; unresectable, 35), undergoing resection of the primary tumor and histopathological evaluation between July 2000 and April 2008.

Results

The proportion with HLN metastasis was 11.5 % in resectable cases and 28.6 % in unresectable cases. On multivariate analysis using the Cox proportional hazards model, HLN metastasis (P < 0.001), along with non-resection of hepatic lesions (P < 0.001), larger metastatic tumor volume (P < 0.001), non-use of oxaliplatin-based chemotherapy (P < 0.001), involvement of 4 or more regional lymph nodes (P < 0.001), and excessive lymphatic invasion (P = 0.02), was identified as an independent risk factor for shorter survival.

Conclusions

To establish a new therapeutic strategy for synchronous liver metastasis of colorectal cancer, the HLNs should be examined histologically in patients undergoing resection of their primary colon and rectal cancer.     

Thoracic duct and hepatic lymph in idiopathic portal hypertension

Lymph dynamics in idiopathic portal hypertension has been studied in two phases. In the first phase thoracic duct lymph transport was studied in 11 patients with idiopathic portal hypertension by cannulating the duct. This revealed altered lymph transport in the form of a distended thoracic duct, raised pressure in the duct, and haemorrhagic lymph with an increased flow rate. The lymph flow rate was analysed in relation to various hepatic haemodynamic and biochemical parameters. In the second phase of the study hepatic lymphatics were studied by percutaneous hepatography in 16 patients with idiopathic portal hypertension. By this technique hepatic lymphatics were opacified in patients with idiopathic portal hypertension and cirrhosis with equal frequency. The significance of this finding in relation to the altered hepatic haemodynamics and thoracic duct lymph transport is discussed.     

New thrombolytic modality — regional administration of tissue plasminogen activator for hepatic artery and portal vein thromboses after liver transplantation: Case report

A 2 1/2-year-old boy with biliary atresia underwent orthotopic living-related liver transplantation. On the 7th postoperative day, he had an episode of hepatic arterial thrombosis following disseminated intravascular coagulation (DIC) due to severe intraabdominal sepsis. Tissue plasminogen activator was administered regionally and the hepatic arterial flow recovered promptly. On postoperative day 33, portal vein thrombosis occurred and direct tissue plasminogen activator injections into the portal vein improved portal blood flow. However, the patient eventually died of poorly controlled DIC. Throughout the course, color Doppler ultrasonogram and arterial ketone body ratio were good indicators of hepatic arterial and portal blood flow. When hepatic arterial thrombosis and portal vein thrombosis occur, retransplantation is often inevitable. Thus, while the patient is awaiting a suitable donor, it could be possible to maintain blood flow to the graft with this new thrombolytic therapy.     

Median liver lobe of woodchuck as a model to study hepatic outflow obstruction: a pilot study

Background: Hepatic vein outflow obstruction represents an important clinical problem in living‐liver transplantation. An animal model is required to study the influence of outflow obstruction on the intrahepatic regulation of liver perfusion and the subsequent effects on liver injury and recovery during liver regeneration. The size of woodchucks enables the use of standard clinical imaging procedures. Aim: This study aims at describing hepatic vascular and territorial anatomy of the woodchuck liver based on a virtual three‐dimensional (3D) visualization of the hepatic vascular tree. Methods: Woodchucks (n=6) were subjected to an all‐in‐one computed tomography (CT) after contrasting the vascular and the biliary tree. CT‐images were used for 3D‐reconstruction of hepatic and portal veins and calculation of the corresponding portal and hepatic vein territories and their respective volume using hepavision (MeVisLab). A virtual resection was performed following the Cantlie‐line and territories at risk were calculated. Results: The median lobe of the woodchuck liver has a similar vascular supply and drainage as the human liver with two portal (right and left median portal vein) and three hepatic veins (left, middle and right median hepatic vein). The corresponding portal and hepatic vein subterritories are of a similar relative size compared with the human liver. Virtual splitting of the median lobe of the woodchuck liver revealed areas at risk of focal outflow obstruction, as observed clinically. Conclusion: The median liver lobe of the woodchuck represents, to a small extent, the hepatic vascular anatomy of the human liver and is therefore a suitable potential model to correlate repeated imaging of impaired liver perfusion with histomorphological findings of liver damage and regeneration.