Effect of respiration, exercise, and food intake on hepatic vein circulation

Since the effects of respiration, nutrition, and exercise on blood flow in the hepatic vein are not well understood, the objective of this study was to determine the hemodynamic influence of these factors on hepatic venous circulation using Doppler ultrasonographic tracings. The venous blood flow of the middle hepatic vein was determined during arrested full inspiration, midinspiration, and expiration in 25 healthy subjects. The maximum velocity and the systolic-to-diastolic ratio of the blood flow were measured. The portal vein blood flow velocity was measured in 20 volunteers before and after food intake. The portal vein blood flow and the hepatic vein flow velocity were examined in eight volunteers after exercise. During inspiration, maximum blood flow velocity of the hepatic veins decreased compared to midinspiration (P < 0.001). With expiration the maximum velocity increased (P < 0.001). After food consumption, there was no change in the velocity of the hepatic veins, but the portal vein blood flow increased (P = 0.041). After physical exercises, the maximum velocity of the hepatic venous flow increased, on average, about 148% (P = 0.01), and the portal vein blood flow decreased about 44% (P = 0.027). To achieve standard measurements of hepatic venous blood flow, the state of respiration and physical exertion should be established. The nutritional status had only a minor influence on hepatic vein measurements.     

Surgical intervention for patients with stage IV-A hepatocellular carcinoma without lymph node metastasis: proposal as a standard therapy

OBJECTIVE: The aim of this study was to evaluate the effects of surgical treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly advanced HCC patients has yielded poor long-term survival. Surgical intervention has been initiated in an effort to improve survival. METHODS: The outcome of 150 patients who underwent hepatic resection was studied. Survival analysis was made by stratifying stage IV-A HCC patients into two groups-those with and those without involvement of a major branch of the portal or hepatic veins. Those with involvement were further divided into subgroups according to major vascular invasions. RESULTS: Patients who had multiple tumors in more than one lobe without vascular invasion had a significantly better 5-year survival rate (20%) than those with vascular invasion (8%) (p < 0.01). The survival rate of patients with hepatic vein tumor thrombi (10%) was better than the rate for those with tumor thrombi in the inferior vena cava (0%), in whom no patients survived more than 2 years, although the survival rate for those with portal vein tumor thrombi in the first branch (11%) was no different from the rate for that in the portal trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to 1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A HCC patients brought longer survival rates for some patients. We recommend surgical intervention as an effective therapeutic modality for patients with advanced HCC.     

Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2

To determine the relationship between quantitative Doppler parameters of portal, hepatic, and splanchnic circulation and hepatic venous pressure gradient (HVPG), variceal size, and Child-Pugh class in patients with alcoholic cirrhosis, we studied forty patients with proved alcoholic cirrhosis who underwent Doppler ultrasonography, hepatic vein catheterization, and esophagoscopy. The following Doppler parameters were recorded: time-averaged mean blood velocity, volume flow of the main portal vein flow, and resistance index (RI) of the hepatic and of the superior mesenteric artery. Doppler findings were compared with HVPG, presence and size of esophageal varices, and Child-Pugh class. There was a significant inverse correlation between portal velocity and HVPG (r = -.69), as well as between portal vein flow and HVPG (r = -.58). No correlation was found between RI in the hepatic artery or superior mesenteric artery and HVPG. No correlation was found between portal vein measurements and presence and size of varices. Severe liver failure was associated with lower portal velocity and flow. In patients with alcoholic cirrhosis, only portal vein blood velocity and flow, but neither hepatic nor mesenteric artery RI, are correlated to the severity of portal hypertension and to the severity of liver failure.     

The liver as a source of somatomedin

Somatomedin (Sm) activity (measured by [35S] utake in chick embryo cartilage) was determined in serum samples simultaneously drawn from the hepatic vein, portal vein, femoral artery and demoral vein of seventeen anaesthezied normal adult dogs). A pool of human serum was taken as reference (Sm = 1 U/ml). Sm levels in the peripheral vein of dogs were 0.38 +/- 0.03 U/ml). Mean +/- SEM). Sm activity was greater in the hepatic vein (0.48 U/ml) than in the other vessels (0.36, 0.39, 0.38 U/ml), and the paired differences were significant (P less than 0.002 to P less than 0.05). In three dogs which received b-GH (20 IU/day), the Sm levels were significantly increased after nine days in the femoural vein (P less than 0.05) and in the hepatic vein (P less than 0.05). The validity of the assay is discussed; a possible interference of NEFA in the assay is eliminated. The difference of Sm levels between hepatic and portal veins, related to hepatic flow measured in seven of these dogs, indicate an important production of Sm by the liver.     

Hepatic and portal surface veins: a new anatomic variant revealed during abdominal CT

OBJECTIVE: The objective of this paper is to describe a new finding on CT of hepatic and portal vein segments located in a subcapsular location on the surface of the liver. SUBJECTS AND METHODS: From a series of more than 11,000 contrast-enhanced abdominal CT scans performed from 1993 to 1997, 14 patients were identified as having hepatic or portal vein segments or both in a subcapsular location on the surface of the liver. RESULTS: We found seven portal vein surface segments in seven patients and 14 hepatic vein surface segments in 12 patients. Of the 14 patients, five had both portal and hepatic vein surface segments. Therefore, in a cohort that exceeded 11,000 patients, the incidence of this finding was 0.1%. Four patients had cirrhosis, two had small hypervascular liver lesions, and eight had healthy livers. The surface veins were not associated with any other recognized vascular anomalies or with anastomoses to extrahepatic systemic veins. CONCLUSION: Hepatic and portal veins can course to a subcapsular location on the surface of the liver. This anatomy is believed to be a normal variant and can be found in patients with healthy livers and normal hepatic vein hemodynamics and in patients with portal hypertension.     

A new antitumor agent: methyl sulfonium perchlorate of echinomycin

Veno-occlusive disease (VOD) is a serious complication of myeloablative therapy and stem cell transplantation. We here describe a case of VOD in a patient with acute myeloid leukemia (AML), who received an autologous peripheral blood stem cell graft after busulphan/cyclophosphamide conditioning in first complete remission and who developed severe VOD at day 17. Color-flow sonography of the portal and hepatic veins revealed hepatofugal blood flow in the portal vein and an absence of flow in the hepatic vein. Treatment with recombinant tissue plasminogen activator (t-PA) was started at a dose of 10 mg/day and increased to 20 mg/day because color-flow sonography indicated no change of blood flow. Daily sonography was continued to monitor the portal and hepatic blood flow in order to assess the need for continuation of t-PA. Once an objective sonographic improvement was observed, t-PA treatment was tapered and stopped. This case demonstrates that color-flow sonography can be used to confirm the clinical diagnosis of VOD. Furthermore this technique provides a way for easily and reliably evaluating the effect in relation to dose of thrombolytic therapy needed. It improves the quality of clinical monitoring which is needed for effective treatment of VOD while minimizing the risk of serious bleeding complications.     

The airway resistance-lung volume plot as a measurement of the closing volume

Following abdominal surgery, insulin and glucose concentrations in the portal vein, and a peripheral vein are compared in patients during control periods and after oral administration of glucose. During the control period, the glucose concentrations are identical in both veins. After glucose loads with the prompt increase of portal glucose concentration the portal-peripheral difference also increases (p less than 0.01). During the control period the insulin concentration in the portal vein is double as compared to peripheral blood (p less than 0.005). After glucose load the increasing portal insulin as well as the peripheral and portal glucose correlate with the portal-peripheral insulin difference (p less than 0.001). Furthermore, there is a significant positive correlation between the peripheral glucose area as a parameter of glucose tolerance and the portal insulin area as a semiquantitative parameter of insulin secretory capacity (p less than 0.001). It can be concluded that in the early postoperative period in patients with a diminished oral glucose tolerance (large glucose areas) there is an even greater insulin response in comparison to patients with normal oral glucose tolerance. On the other hand, however, in those patients with diminished glucose tolerance, the insulin response is essentially delayed.     

Peripheral elimination of growth hormone in chronic liver disease

Chronic liver disease is associated with raised basal and TRH-stimulated PRL and GH levels. In a recent study we found the kidney to be the main site of prolactin elimination in patients with liver disease. In order to determine whether this is specific for PRL or a more general mechanism for polypeptide removal, we studied the elimination of GH, which resembles PRL in molecular weight and primary amino acid sequence, in 5 patients with portal hypertension and hepatic cirrhosis and 5 patients with noncirrhotic portal hypertension. Plasma GH levels were measured before and after TRH in peripheral, hepatic and renal vein samples, taken during diagnostic hepatic vein catheterization. An excessive paradoxical increase of GH after THR stimulation was found in 4 out of 5 cirrhotic patients but in none of the noncirrhotic individuals (p less than 0.025). After TRH the mean hepatic venous levels were significantly lower than the peripheral venous levels in 4 out of 5 noncirrhotic patients but in only 1 of the 5 cirrhotic patients (p less than 0.05). The mean renal vein GH levels were significantly lower than the peripheral levels in 3 out of 5 noncirrhotic patients and in none of the cirrhotic patients. In 2 patients in whom renal and hepatic plasma flow was measured, renal extraction of GH was found to be 0 to 6.4 micrograms, while liver extraction amounted to 22.1 and 34.7 micrograms of GH during the same 60-min period. Despite the similarity in molecular weight and primary amino acid sequence between PRL and GH, GH appears to be mainly taken up by the liver while PRL is mainly eliminated by the kidney in this group of patients with portal hypertension. This suggests that the renal elimination of prolactin is not solely dependent on glomerular filtration. The selective hepatic removal of growth hormone is probably related to a specific action of growth hormone on liver metabolism.     

Individual bile acids in portal venous and systemic blood serum of fasting man

The serum concentrations of cholic acid (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) were determined in peripheral venous and portal venous blood from 10 otherwise healthy patients undergoing elective cholecystectomy. A highly specific and accurate gas chromatographic-mass spectrometric technique was used. Peripheral venous serum contained 0.49 +/- 0.16 (mean +/- SEM) mumole per liter of C, 1.55 +/- 0.32 mumoles per liter of CD, and 1.44 +/- 0.57 mumoles per liter of D. Arterial serum, obtained from 5 of the subjects, did not show any differences in bile acid concentrations compared to venous serum. In contrast, the portal venous content of each bile acid was several-fold greater, 6.14 +/- 1.20 mumoles per liter of C, 8.40 +/- 1.84 mumoles per liter of CD, and 6.18 +/- 2.27 mumoles per liter of D. The hepatic uptake of C was estimated to be about 90%, whereas that of CD and D was lower, about 70%. This difference in hepatic uptake between the individual bile acids was reflected in the relative composition of the total bile acids, which was 30:39:31 (C:CD:D) in portal venous serum and 13:50:37 in peripheral serum. Compared to common duct bile obtained simultaneously, the portal vein contained a greater proportion of CD. The relevance of the data obtained to our present concept of the enterohepatic circulation of bile acids is discussed, and it is suggested that the higher fasting level of CD compared to C in peripheral serum results from the combination of a lower fractional hepatic extraction and a higher portal venous input to the systemic circulation.     

Serial changes in titers of antibody to hepatitis B surface antigen after immunization of infants born to mothers with hepatitis B e antigen

The purpose of this study is to identify the existence of hepatovenous intrahepatic anastomosis in normal men. A total of thirteen livers were investigated during the early autopsies of normal men who died in accidents. Perfusion venography of branches of hepatic veins using meglucamine diatrizoate was done in six cases; this method we used had not been reported in the literature. In one case, portal venography was performed. And in the other six cases, liver substance staining was done by injecting the ink through the middle hepatic vein, and such staining of the liver was observed by light microscope. The results show, (1) there are intrahepatic anastomoses between the hepatic veins within the liver; (2) there are anastomoses between the middle hepatic vein and the accessory hepatic veins; and (3) shunts exist between portal veins and hepatic veins. The above findings provide an anatomical basis for the performance of irregular hepatectomy and the rationale for one or two hepatic veins ligation should such veins were traumatized or invaded by liver cancer.     

Change in hepatic arterial hemodynamics induced by hepatocellular carcinoma detected with Doppler sonography

PURPOSE: To understand the hemodynamic differences between the hepatic arterial branches that supply hepatocellular carcinomas (HCCs) and those that do not, we compared the velocity waveforms of both types of arteries. METHODS: Using duplex color Doppler sonography, we examined 38 patients with HCC localized within a single lobe of the liver and 34 patients with chronic liver disease but without HCC (controls). We measured angle-corrected peak systolic velocity and the pulsatility index (PI) of color-coded hepatic arteries along the right anterior segmental portal branch and the vertical segment of the left portal vein. RESULTS: There was no significant difference in peak systolic velocity and PI between the arterial branches tested in the controls. In contrast, we found a significantly lower PI and a higher peak systolic velocity in the arterial branches supplying the tumor than in those not supplying the tumor in patients with an HCC 3 cm or larger in diameter (p < 0.05). The degree of these hemodynamic changes correlated with the tumor size and the presence or absence of tumor thrombus in the major portal branches. CONCLUSIONS: These results indicate that the hepatic arterial branch supplying an HCC has a lower impedance than the branch not supplying the tumor.     

Doppler sonographic diagnosis of severe portal vein pulsatility in constrictive pericarditis: flow normalization after pericardiectomy

This case report describes the noninvasive assessment of hepatic and portal vein hemodynamics in a patient with constrictive pericarditis before and after pericardiectomy. Doppler sonography of the hepatic veins demonstrated a typical W-shaped pattern with pronounced late diastolic flow reversal that disappeared after surgery. Preoperatively, we observed severe pulsatility of the portal vein with flow reversal in systole; after pericardiectomy, portal venous flow was normal. We concluded that the high right atrial pressure in this patient might have led to increased hepatic venous outflow resistance, with subsequent trans-sinusoidal shunting between the hepatic artery and portal vein causing severe portal vein pulsatility. After pericardiectomy and a decrease in right atrial pressure, portal vein flow normalized.     

Portal vein ligation selectively lowers hepatic cytochrome P450 levels in rats

In rats, surgical creation of a portacaval shunt leads to hepatic atrophy and lowered levels of cytochrome P450, the key component of liver enzymes involved with drug metabolism. These effects are largely attributable to diversion of portal blood away from the liver and not to decreased hepatic blood flow. The present study has established a simpler model of portal blood diversion in order to examine the role of portal blood constituents in the regulation of hepatic cytochrome P450. Portal vein ligation was performed on male Wistar rats in which portasystemic anastomoses had been produced by subcutaneous transposition of the spleen. Portal vein ligation resulted in portal hypertension, as evidenced by splenomegaly, and in hepatic atrophy. In liver of rats with portal vein ligation, microsomal cytochrome P450 levels were significantly less than in sham-operated control rats, but cytochrome b5, NADPH-cytochrome c reductase, and glucose-6-phosphatase were unaltered. The activities of four mixed function oxidases also were reduced significantly in the liver of rats with portal vein ligation, the changes being greatest for ethylmorphine N-demethylase, a prototype substrate for the phenobarbital-inducible isoenzyme of cytochrome P450. In contrast, the activity of microsomal heme oxygenase, the rate-limiting step in catabolism of heme to bilirubin, was enhanced after portal vein ligation. Experiments in pair-fed rats showed that the changes observed in liver from rats with portal vein ligation could not be attributed to caloric deprivation. Administration of phenobarbital increased liver mass, cytochrome P450 levels, and mixed function oxidase activities both in rats with portal vein ligation and in controls, indicating that the liver of the ligated rats retained considerable protein synthetic capacity. It appears that hepatic atrophy and lowering of cytochrome P450 levels that follow portal vein ligation are consequences of altered exposure of the liver to factors normally present in portal blood, and that the same alterations may also enhance heme oxygenase activity.     

Nodular regenerative hyperplasia of the liver in hematologic disorders: a possible response to obliterative portal venopathy. A morphometric study of nine cases with an hypothesis on the pathogenesis

Nodular regenerative hyperplasia was found in nine patients who had hematological disease including polycythemia vera, agnogenic myeloid metaplasia, primary thrombocythemia, rheumatoid arthritis with thrombocytosis, multiple myeloma, and erythrocytosis associated with polycystic renal disease. Portal hypertension was suspected in three and features of hypersplenism were present in four. 2. Nodular regenerative hyperplasia occurred in livers which had widespread obliteration of portal vein radicals (obliterative portal venopathy). Morphometric analysis indicated that the portal vein lesions were predominately located in veins up to 0.2 mm in diameter and were significantly more frequent than similar lesions occurring in elderly persons. 3. The following pathogenesis of nodular regenerative hyperplasia is proposed: Thrombi, perhaps largely composed of platelet aggregates formed in the portal venous circulation or spleen, embolize to the liver and results in obliterative vascular lesions. Atrophy and regenerative nodule formation occur in response to the interruption of the portal blood supply.     

Portal and peripheral vein insulin responses to intravenous glucose in the rhesus monkey

Catheterization of the portal vein and bilateral femoral veins were performed under general anesthesia in 6 healthy male rhesus monkeys. Four days later, sequential, simultaneous peripheral and portal plasma samples were obtained for glucose and immunoreactive insulin determinations before and after administration of 0.5 Gm. of glucose per kilogram (over a 1-minute period) via the opposite peripheral catheter. Two phases of insulin secretion were noted in both portal and peripheral plasma samples. An immediate early-phase insulin response was noted with a peak response at 1 minute followed by a rapid decline to a nadir at 5 minutes. A second phase of insulin secretion was evident with a peak response at 10 minutes and a subsequent decline to basal levels by 60 minutes. Simultaneous portal vein and peripheral vein glucose concentrations were not significantly different from each other by paired analysis. Thus, in the rhesus monkey peripheral insulin concentrations following intravenous glucose exhibit a biphasic response closely paralleling pancreatic insulin secretion.     

Sinusitis in the immunocompromised host

Using retrospective studies, we have investigated the possibility of obtaining characteristic findings of inflammatory pseudotumor of the liver by magnetic resonance (MR) imaging. We examined 8 patients (involving 8 masses) who had been histologically diagnosed as having an inflammatory pseudotumor in the liver. The histological studies were performed on an excised specimen of 1 mass, and on aspiration needle biopsy specimens and the clinical courses of the other 7 masses. T1 weighted images (T1WI) and T2 weighted images (T2WI) were obtained on MR imaging. MR imagings were analyzed for visualized patterns, patterns of internal structure and patterns of contrast enhancement of dynamic MR imaging. The 8 masses were visualized as hypointense on T1WI and hyperintense on T2WI by MR imaging. Dynamic MR imaging revealed that 1 mass was markedly enhanced peripherally while another mass was homogeneously enhanced, and that enhancement was most marked immediately after injection of contrast medium and then gradually disappeared. Vessels were observed in 4 masses (the portal vein in 2 masses, the hepatic vein in 1 mass, and portal and hepatic veins in 1 mass), and these vessels were clearly visualized on T1WI. The MR imaging findings from the early stage of an inflammatory pseudotumor showed a pattern similar to that of hepatic tumors with rich blood flow. The portal vein or hepatic vein was found in the tumor in half the patients, suggesting that this characteristic was useful for diagnosis of an inflammatory pseudotumor in the liver.     

Nasal sinus adenocarcinoma in patients exposed to wood dust in the Community of Cantabria, Spain

OBJECTIVE: To determine whether the hepatovenous intrahepatic anastomoses exist in normal humans. METHODS: A total of 13 livers were isolated during the early autopsies of normal men who died in accidents. Perfusion venography of the branches of hepatic veins using meglucamine diatrizoate was performed in 6 cases. This method of investigation has not been reported in the literature. In one case, a portal venography was done. In the remaining 6 cases, liver substance stainings were done by injecting ink through the middle hepatic vein, and the tissue sections of these livers were observed under light microscope. RESULTS: There were intrahepatic anastomoses between the hepatic veins within the liver. These anastomoses belonged to the 4th or 5th branch of hepatic vein near the capsule. There were also anastomoses between the middle hepatic vein and the hepatic short veins. Shunts existed between the portal veins and hepatic veins. CONCLUSIONS: The detection of anastomoses of intrahepatic veins in normal individuals provide anatomical rationale for the performance of irregular hepatectomy, as well as rationale for the ligation of one or two hepatic veins should such veins be traumatized or invaded by liver cancer.     

Characterization of allergenic fractions from Drechslera monoceras

The present status of hepatic resection for hepatocellular carcinoma (HCC) is reviewed with special reference to the vascular aspects. Hepatic resection combined with portal tumor thrombectomy has been attempted in Japan. This procedure may be effective in the prevention of rupture of esophageal varices and making transcatheter arterial embolization possible. According to the report of Yamaoka and his associates, the 1- and 3-year survival rates of 29 patients treated with this combined procedure were 53% and 12%, respectively. This surgical strategy may thus yield survival benefits. In patients with a tumor near the confluence of the major hepatic vein and inferior vena cava, resection of segments 4b, 7, and 8 combined with hepatic vein reconstruction has been performed, which allows functional preservation of the residual liver. The historical development of hepatic vascular exclusion (HVE) is also reviewed. HVE can be performed safely using a centrifugal active pump, even in patients with cirrhosis. Hepatic resection combined with removal of tumor thrombus in the right atrium has been carried out using extracorporeal circulation. There are reports that at least two patients undergoing this operation survived more than 2 years after surgery. The hepatic warm ischemic time should be less than 60 min. Vascular surgery techniques are being increasingly applied in Japan for the treatment of HCC. Such surgery can be performed safely even in patients with cirrhosis. Improvement of long-term survival in patients undergoing such procedures remains an unresolved problem, however.     

Bromodeoxyuridine uptake by early liver metastases in rats: a comparison of the hepatic artery and portal vein infusion routes

Liver metastases generated by the intraportal inoculation of ascites hepatoma cells in Donryu rats were labeled with bromodeoxyuridine (BrdU) through the hepatic artery, or through the portal vein with or without ligation of the hepatic artery, 3, 6, or 9 days after tumor inoculation. The distribution of BrdU-labeled cells was evaluated in 174 metastases, 110-1640 microm in diameter, by immunohistochemical methods. When a dual blood supply from the portal vein and hepatic artery existed, the BrdU-labeled cells were diffusely found in the metastases regardless of their size and the route of BrdU infusion. When blood supply to metastases larger than 610 microm in diameter was from a single source, namely the portal vein, the BrdU-labeled cells were located within 90-290 microm from the margin of the metastases. These results indicate first, that drug uptake by the inner part of the early metastatic liver tumors is achieved through the hepatic artery, and second, that drug uptake by early liver metastases through the portal vein is limited to within the extent of portal diffusion regardless of the size of the metastases. Thus, we conclude that prophylactic treatment against liver metastases would be more effective when given via the hepatic artery route rather than via the portal vein route.