Does Arterialization of Portal Vein Have Any Effects in Large-for-Size Liver Transplantation? Hemodynamic, Histological, and Biomolecular Experimental Studies.

BACKGROUND: In pediatric liver transplantation, the optimal size of the transplanted liver ranges between 0.8% and 4.0% of the recipient's weight. Sometimes, the graft weight exceeds this upper limit, characterizing the large-for-size condition potentially associated with reduced blood flow and worsening of ischemia-reperfusion injury. Therefore, it would be beneficial to increase the portal flow through arterialization of the portal vein. Materials and methods: Fifteen pigs underwent large-for-size liver transplants. They were divided into two groups: control (CTRL 6 animals - conventional technique) and arterialization - a shunt was established between the portal vein and the splenic artery (ART 9 animals). Hemodynamic, biochemical, histological, and molecular variables were compared. Results: Arterialization resulted in a significant increase in portal vein pressure but no changes in other hemodynamic variables, as shown in the analysis of variance. It was observed lower ALT values (p = 0.007), with no differences regarding the values of blood pH and lactate (p = 0.54 and p = 0.699 respectively) or histological variables (edema, steatosis, inflammation, necrosis, and IRI - p = 1.0, p = 0.943, p = 0.174, p = 0.832, p = 0.662, respectively). The molecular studies showed significantly increased expression of IL6 after 3 hours of reperfusion (p = 0.048) and decreased expression of ICAM immediately after reperfusion (p = 0.03). The regression analysis suggested a positive influence of portal flow and pressure on biochemical parameters. Conclusion: Arterialization of the portal vein showed no histological, biochemical, or molecular benefits in large-for-size transplantation.

Pediatric living donor left lateral segment liver transplantation for biliary atresia: Doppler ultrasound findings in early postoperative period.

PURPOSE: To analyze hepatic hemodynamic parameters detected by Doppler ultrasound (DU) of uncomplicated children with biliary atresia who underwent left lateral segment living donor liver transplantation (LLS-LDLT), explore its normal change trend over time and determine the normal reference interval. METHODS: We retrospectively involved the data from 227 biliary atresia patients (100 Males,127 Females). Hemodynamic parameters include peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI), and pulsation index (PI) of the hepatic artery (HA), portal vein velocity (PVV), portal vein flow (PVF) and hepatic vein velocity (HVV) during intra-operative and on the 1st, 3rd, 5th and 7th day after operation were collected. Repeated measures analysis of the variance and Friedman test were used to analyze the changing trend of hemodynamic parameters over time in the first week after the operation. RESULTS: PSVHA and EDVHA showed a similar changing tendency at one week after surgery, with an overall decrease-rise trend; RIHA and PIHA also changed similarly with an overall rise-decrease trend. The HVV and PVV at surgery were lower than at all time points after surgery. As for PVF, the value of POD5 was the highest and then decreased. Additionally, this study provided the normal reference interval of hemodynamic parameters for LLS-LDLT patients, which were PSVHA: 18.4-98.3 cm/s, EDVHA: 0-43.3 cm/s, RIHA: 0.41-1.0, PIHA: 0.51-2.0, PVV: 19.0-83.7 cm/s, HVV: 19.4-68.0 cm/s, and PVF:99.5-500.0 ml/min/100 g at intraoperation. Within the first postoperative week: PSVHA: 21.0-97.7 cm/s, EDVHA: 0-32.7 cm/s, RIHA: 0.47-1.0, PIHA: 0.62-2.0, PVV: 23.0-92.0 cm/s, HVV: 19.7-86.0 cm/s, and PVF: 100.0-513.0 ml/min/100 g. CONCLUSION: The hepatic hemodynamic of post-transplanted children detected by DU had specific changing trends and normal ranges, which provides valuable reference values for ultrasonologists and pediatric transplant clinicians.

Influence of interapplicator distance on multibipolar radiofrequency ablation during physiological and interrupted liver perfusion in an in vivo porcine model.

Radiofrequency ablation (RFA) is a curative treatment option for early stage hepatocellular carcinoma (HCC). Vascular inflow occlusion to the liver (Pringle manoeuvre) and multibipolar RFA (mbRFA) represent possibilities to generate large ablations. This study evaluated the impact of different interapplicator distances and a Pringle manoeuvre on ablation area and geometry of mbRFA. 24 mbRFA were planned in porcine livers in vivo. Test series with continuous blood flow had an interapplicator distance of 20 mm and 15 mm, respectively. For a Pringle manoeuvre, interapplicator distance was predefined at 20 mm. After liver dissection, ablation area and geometry were analysed macroscopically and histologically. Confluent and homogenous ablations could be achieved with a Pringle manoeuvre and an interapplicator distance of 15 mm with sustained hepatic blood flow. Ablation geometry was inhomogeneous with an applicator distance of 20 mm with physiological liver perfusion. A Pringle manoeuvre led to a fourfold increase in ablation area in comparison to sustained hepatic blood flow (p < 0.001). Interapplicator distance affects ablation geometry of mbRFA. Strict adherence to the planned applicator distance is advisable under continuous blood flow. The application of a Pringle manoeuvre should be considered when compliance with the interapplicator distance cannot be guaranteed.

Partial orthotopic liver transplantation in combination with two-stage hepatectomy: A proof-of-concept explained by mathematical modeling.

BACKGROUND: Resection And Partial Liver Segment 2/3 Transplantation with Delayed total hepatectomy (RAPID) includes total hepatectomy in 2 steps with small graft transplantation at first stage. To avoid graft portal hyperperfusion, portal vein pressure monitoring is required after revascularization and right portal vein clamping. To date, portal flow modulation has not been reported but simulating hemodynamics in RAPID patients would be useful to anticipate these procedures. Our team developed hemodynamic 0D modeling; we aimed to assess if this mathematical model could be accurately used in the RAPID setting. METHODS: The modified 0D model was retrospectively tested on 3 patients. We compared our estimated portal vein pressures and portocaval gradients to those intraoperatively measured, as indication to modulate portal flow relies on these measures. FINDINGS: Portal pressures measured after right portal vein clamping (end of RAPID procedure) in patients 1, 2 and 3 were respectively of 14, 16 and 12 mmHg while the simulated pressures were of 13.1, 14.8 and 11.5 mmHg (p = 0.25). Portocaval gradients measured after right portal vein clamping in the 3 patients were respectively of 10, 11 and 7 mmHg while the simulated gradients were of 9.9, 11.6 and 8.3 mmHg (p = 0.5). INTERPRETATION: We succeeded to predict portal vein pressures and portocaval gradients after RAPID. This promising report demonstrates that 0D simulation could be a useful tool for human decision-making. Moreover, such a patient-specific model could be of importance if we transpose RAPID experience to hepatocellular carcinoma bearing cirrhotics, a population with high probability of portal hypertension after RAPID.

Allogeneic Venous Grafts of Different Origin Used for Portal Vein Reconstruction After Pancreaticoduodenectomy - Experimental Study.

BACKGROUND: In clinical medicine, little is known about the use of allografts for portal vein (PV) reconstruction after pancreaticoduodenectomy (PD). Portal and caval systems are physiologically different, therefore the properties of allografts from caval and portal systems were studied here in a pig model. MATERIALS AND METHODS: PD with PV reconstruction with allogeneic venous graft from PV or inferior vena cava (IVC) was performed in 26 pigs. Biochemical analysis and ultrasonography measurements were performed during a 4-week monitoring period. Computer simulations were used to evaluate haemodynamics in reconstructed PV and explanted allografts were histologically examined. RESULTS: The native PV and IVC grafts varied in histological structure but were able to adapt morphologically after transplantation. Computer simulation suggested PV grafts to be more susceptible to thrombosis development. Thrombosis of reconstructed PV occurred in four out of five cases in PV group. CONCLUSION: This study supports the use of allografts from caval system for PV reconstruction in clinical medicine when needed.

Effect of Remote Ischemic Preconditioning in Patients Undergoing Hepatectomy With Portal Triad Clamping: A Randomized Controlled Trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce liver injury in patients undergoing hepatectomy for colorectal liver metastasis, but its role is unclear in hepatocellular carcinoma patients with portal triad clamping during hepatectomy. METHODS: In this prospective, randomized trial, 140 patients with hepatocellular carcinoma undergoing liver resection requiring portal triad clamping were randomized to a RIPC group or a control group. Patients in the RIPC group received RIPC (3 cycles of 5-minute ischemia and 5-minute reperfusion in right upper limb with cuff pressure at 30 kPa [225 mm Hg]) approximately 10 minutes after induction of anesthesia. In the control group, patients received sham RIPC (the cuff was not inflated). The primary outcome was the postoperative peak level of total bilirubin (TBIL) and was analyzed with the independent t test. Secondary outcomes were liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. RESULTS: Data from 136 patients (69 in the RIPC group and 67 in the control group) were analyzed. The RIPC group had on average a 5.9 µmol lower peak level of TBIL than the control group; the mean difference is -5.9, and the 95% confidence interval (CI) reverses to -17.9 to 6.1. There were no significant differences between the 2 groups in liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. CONCLUSIONS: We found no evidence that RIPC can reduce postoperative liver injury after hepatectomy.

Microvascular proliferation of the portal vein branches in the liver of biliary atresia patients at Kasai operation is associated with a better long-term clinical outcome.

AIM OF THE STUDY: We previously showed an increased number of smaller portal vein (PV) branches in the portal areas of liver biopsy specimens of biliary atresia (BA) patients. We evaluated the correlation between this histopathological feature and the prognosis. PATIENTS AND METHODS: Twenty-five consecutive patients with BA encountered between 2000 and 2012 were classified into three prognostic groups based on their postoperative outcomes: Excellent (n = 11) for native-liver survivors with a normal liver function, Good (n = 6) for native-liver survivors with liver dysfunction, and Poor (n = 8) for survivors after liver transplant or on a waiting list. Data from morphometrical analyses, including the fibrotic portal area, numbers of PVs, diameter and total area of PV branches, were statistically compared among the three groups. MAIN RESULTS: The number of PV branches per unit area of the whole-liver specimen in the poor prognostic group was significantly lower than that in the excellent group (3.1 ± 0.6 vs. 5.2 ± 2.0/mm2, p = 0.03). There were no significant differences in the other parameters. CONCLUSIONS: This is the first report on the relationships between morphometrically analyzed PV branches and the postoperative course in BA patients. The portal venous system is involved as the primary lesion in BA.

Effect of Portal Venous Pressure on Liver Function of Donors in Living Donor Liver Transplantation.

BACKGROUND We assessed the alterations in portal hemodynamics associated with donor right hepatectomy and its effects on functional regeneration of the remnant liver. MATERIAL AND METHODS This prospective study included 30 adult living donors who underwent right hepatectomy in the Liver Transplantation Unit, Faculty of Medicine, Cairo University from June 2015 to October 2016. During donor surgery, portal venous pressure (PVP) was measured using an antithrombotic catheter inserted into the main portal vein, and was measured before and after clamping of the right portal vein. Postoperatively, liver function tests were done daily until normalization. The outcome measures were the time to normalization of liver function tests and effect of residual volume and steatosis on PVP. RESULTS All donors had normal PVP before clamping and changed significantly after clamping (p<0.001). After clamping, 25 donors (83%) had a PVP above 12 mmHg; i.e. had high portal pressure. The median percentage of change was 55%. There were obvious increases in liver enzymes and bilirubin after surgery, but albumin and international normalized ratio showed progressive decreases postoperatively. The percent change in PVP was positively correlated with the levels of liver enzymes, time to normalization of liver enzymes, albumin, and bilirubin, and with the degree of steatosis, bit it was negatively correlated with residual liver volume. CONCLUSIONS During living donor liver transplantation, PVP increases by over 50% after clamping of the right portal vein of the donor's liver. This increase is associated with temporary delay of normalization of liver function of the donors.

Quantitative study of liver hemodynamic changes in rats with small-for-size syndrome by the 4D-CT perfusion technique.

OBJECTIVE: The microcirculatory hemodynamic changes of small-for-size syndrome (SFSS) are still unclear. In this study, they were investigated by four-dimensional CT perfusion (4D-CTP) technique. METHODS: The sham group, 50, 60, 70 and 80 % partial hepatectomy (PH) rat groups were established. At 1 hour (1 h), 1 day (1 d), 3 days (3 d) and 7 days (7 d) post-operation, serological examination, 4D-CTP scan and histopathological examination were performed. One-way analysis of variance and the Kruskal-Wallis test were used for the comparison. RESULTS: Based on the diagnostic criteria of SFSS, the 80 % group was considered to be a successful model. In all the PH groups, portal vein perfusion and total liver perfusion peaked at 1 h and declined at 1d and 3d. Both portal vein perfusion and total liver perfusion were significantly higher in the 80 % group than the sham group, 50 and 60% groups at 1 h (p < 0.05), and 80 % group at 3d and 7d (p < 0.05). In the 50 and 60 % groups, hepatic artery perfusion decreased at 1 h and maintained at a lower level until at 7 d; whereas, in the 70 and 80% groups, it increased at 1 h, then decreased and reached the lowest level at 7 d. No significant difference appeared in hepatic artery perfusion between any two groups at any time points. At all time points, hepatic perfusion index was lower in all the PH groups than the sham group. Significant differences in hepatic perfusion index appeared between the 80% group and the sham group at 1 h and 1 d (p < 0.05). CONCLUSIONS: The CTP parameters quantitatively revealed the microcirculatory hemodynamic changes in SFSS, which were further confirmed to be associated with histopathological injury. It is suggested that the hemodynamic changes in SFSS remnant liver can provide useful information for further revealing the mechanism of SFSS and may help for guiding the treatments. ADVANCES IN KNOWLEDGE: By using the 4D-CTP technique, the hepatic microcirculatory hemodynamic changes could be quantitatively measured in vivo for small animal research.

Portal Vein Flow by Doppler Ultrasonography and Liver Volume by Computed Tomography in Living Donor Candidates: Correlation with Indocyanine Green Test.

OBJECTIVES: Our goal was to investigate the correlation between indocyanine green test results and imaging parameters in living liver donor candidates. MATERIALS AND METHODS: Our study included 219 healthy donor candidates who were evaluated with Doppler ultrasonography (portal vein time average flow), computed tomography (liver volume), liver biopsy (fat fraction), and indocyanine green retention rate at 15 minutes. RESULTS: Portal vein time average flow (r= -0.375), fat-free liver volume/body weight ratio (r = -0.239), and portal vein time average flow × fat-free liver volume/body weight ratio (r = -0.424) showed significant correlations with indocyanine green retention rate at 15 minutes (all P < .001). CONCLUSIONS: Imaging parameters were significantly correlated with indocyanine green retention rate at 15 minutes in living liver donor candidates.

Unusual spontaneous porto-systemic shunt: The importance of diagnosing non-anatomical porto-systemic shunts to improve portal flow in pediatric living-related liver transplantation. Case report.

Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of "steal flow syndrome" cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation. We present a 12-month-old female who received an uneventful LDLT from her mother, and the GRWR was 4.8. During the early post-operative period, she became hemodynamically unstable, developed ascites, and altered LFT. The post-operative ultrasound identified reversed portal flow, finding a non-anatomical PSS. A 3D CT scan confirmed the presence of a mesocaval shunt through the territory of the right gonadal vein, draining into the right iliac vein, with no portal inflow into the liver. The patient was re-operated, and the shunt was ligated. An intraoperative Doppler ultrasound showed adequate portal inflow after the procedure; the patient evolved satisfactorily and was discharged home on day number 49. The aim was to report a case of post-operative steal syndrome in a pediatric recipient due to a mesocaval shunt not diagnosed during the pretransplant evaluation.

Intestinal metabolism of Polygonum cuspidatum in vitro and in vivo.

Rhizoma et Radix Polygoni Cuspidati (RRPC) is commonly prescribed for the treatment of amenorrhea, arthralgia, jaundice and abscess in traditional Chinese medicine. Previous pharmacological studies have indicated that polyphenols are the main pharmacological active ingredients in RRPC. Meanwhile, the poor bioavailability of polyphenols in RRPC implies that those components are probably metabolized by intestinal bacteria before absorption. However, there is rather limited information about RRPC''s metabolites produced by intestinal bacteria and the intestinal absorbed constituents. In the present study, the metabolites were characterized after the aqueous extract of RRPC was incubated with the crude enzyme of human intestinal bacteria in vitro. The metabolic characteristics of glycosides in RRPC were figured out by comparing the metabolic profiles of emodin-8-O-ß-d-glucopyranoside and polydatin between aqueous extract of RRPC and equivalent amounts of these two glycosides. The transitional constituents absorbed into blood were investigated in rats via intraduodental administration and portal vein intubation. A total of 38 prototype components and 43 metabolites were detected and characterized in vivo. The overall results demonstrated that the intestinal bacteria played an important role in the metabolism of RRPC, and the main metabolic pathways were hydrolysis in vitro, glucuronidation and sulfation in vivo.

Portal Inflow Modulation by Somatostatin After Major Liver Resection: A Pilot Study.

: Major hepatectomy (MH) can lead to an increasing portal vein pressure (PVP) and to lesions of the hepatic parenchyma. Several reports have assessed the deleterious effect of a high posthepatectomy PVP on the postoperative course of MH. Thus, several surgical modalities of portal inflow modulation (PIM) have been described. As for pharmacological modalities, experimental studies showed a potential efficiency of Somatostatin to reduce PVP and flow. To our knowledge, no previous clinical reports of PIM using somatostatin are available. Herein, we report the results of PIM using somatostatin in 10 patients who underwent MH with post-hepatectomy PVP > 20 mmHg. Our results suggest Somatostatin could be considered as an efficient reversible PIM when PVP decrease is above 2.5 mmHg.

Changes in liver perfusion and function before and after percutaneous occlusion of spontaneous portosystemic shunt.

PURPOSE: To evaluate changes in liver perfusion after occlusion of spontaneous portosystemic shunt and to analyze mechanisms of liver profile improvement. MATERIALS AND METHODS: Liver function changes and portal venous and hepatic arterial blood flow were evaluated using perfusion CT before and after shunt occlusion in 23 patients who underwent percutaneous occlusion of spontaneous portosystemic shunt because of gastric varices (n = 15) or hepatic encephalopathy (n = 8). RESULTS: Portal venous blood flow was significantly higher at 1 week (278.7 ml/min, 92.7-636.7, p = 0.012), 1 month (290.0 ml/min, 110.1-560.1, p < 0.001) and 3 months (299.6 ml/min, 156.7-618.5, p = 0.033) after shunt occlusion than the baseline (220.9 ml/min, 49.5-566.7). Hepatic arterial liver blood flow became lower than the baseline (132.3 ml/min, 47.9-622.3) after shunt occlusion, but a significant decrease was observed only at 1 month later (107.9 ml/min, 45.8-263.6 p = 0.027). Serum albumin concentration became significantly higher than the baseline (3.4 mg/dl, 1.9-4.5) at 1 month (3.8 mg/dl, 2.3-4.3, p = 0.018) and 3 months (3.9 mg/dl, 2.6-4.3, p = 0.024) after shunt occlusion. CONCLUSION: Shunt occlusion increases portal venous blood flow and decreases hepatic arterial blood flow, thereby improving the liver profile.

The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.

Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP). The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05). Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.

Partial hepatectomy hemodynamics changes: Experimental data explained by closed-loop lumped modeling.

The liver function may be degraded after partial liver ablation surgery. Adverse liver hemodynamics have been shown to be associated to liver failure. The link between these hemodynamics changes and ablation size is however poorly understood. This article proposes to explain with a closed-loop lumped model the hemodynamics changes observed during twelve surgeries in pigs. The portal venous tree is modeled with a pressure-dependent variable resistor. The variables measured, before liver ablation, are used to tune the model parameters. Then, the liver partial ablation is simulated with the model and the simulated pressures and flows are compared with post-operative measurements. Fluid infusion and blood losses occur during the surgery. The closed-loop model presented accounts for these blood volume changes. Moreover, the impact of blood volume changes and the liver lobe mass estimations on the simulated variables is studied. The typical increase of portal pressure, increase of liver pressure loss, slight decrease of portal flow and major decrease in arterial flow are quantitatively captured by the model for a 75% hepatectomy. It appears that the 75% decrease in hepatic arterial flow can be explained by the resistance increase induced by the surgery, and that no hepatic arterial buffer response (HABR) mechanism is needed to account for this change. The different post-operative states, observed in experiments, are reproduced with the proposed model. Thus, an explanation for inter-subjects post-operative variability is proposed. The presented framework can easily be adapted to other species circulations and to different pathologies for clinical hepatic applications.

Postoperative pneumatosis intestinalis (PI) and portal venous gas (PVG) may indicate bowel necrosis: a 52-case study.

BACKGROUND: The significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) is controversial. This retrospective study evaluated the risk factors for bowel necrosis in patients with PI and/or PVG. METHODS: Between 2002 and 2015, 52 patients were diagnosed with PI and/or PVG and were included in this study. The patients were classified according to the presence or absence of bowel necrosis in surgical findings or at autopsy. Patient characteristics and clinical findings related to bowel necrosis were investigated. RESULTS: Bowel necrosis was diagnosed in 17 (32.7 %) patients. Amongst these 17, 10 patients received salvage surgical intervention, and seven of those diagnosed with bowel necrosis survived after the operation. The remaining 35 patients received conservative treatment with or without exploratory laparotomy. Between patients with and without bowel necrosis, laboratory data revealed significant differences in the levels of C-reactive protein (P = 0.0038), creatinine (P = 0.0054), and lactate (P = 0.045); clinical findings showed differences in abdominal pain (P = 0.019) and peritoneal irritation signs (P = 0.016); computed tomography detected ascites (P = 0.011) and changes of bowel wall enhancement (P = 0.03) that were significantly higher in patients with bowel necrosis. The rate of PI and/or PVG detected in patients postoperatively was significantly higher in patients with bowel necrosis (P < 0.0001). Multivariate analysis showed that bowel necrosis was significantly more likely when PI or PVG was detected in postoperative patients than in patients who had not had surgery (P = 0.003). CONCLUSIONS: PI and/or PVG, alone, are not automatically indicative of bowel necrosis. However, when these conditions occur postoperatively, they indicate bowel necrosis requiring reoperation.

Successful modulation of portal inflow by somatostatin in a porcine model of small-for-size syndrome.

BACKGROUND: Somatostatin may prevent the small-for-size syndrome in subjects undergoing extended hepatectomy by decreasing portal pressure. METHODS: Twenty pigs underwent 70% hepatectomy (H70 group, n = 7), 90% hepatectomy (H90 group, n = 7), or sham laparotomy (control group, n = 6). Splanchnic hemodynamics was measured before and after an intraoperative infusion of somatostatin. RESULTS: The portal vein flow normalized to liver weight increased in both H70 and H90 groups (from 125 ± 42 to 342 ± 82 mL/min/100g, P = .031 and from 140 ± 46 to 530 ± 241, P = .016, respectively). The hepatic venous pressure gradient (HVPG) increased in the H90 group only (from 5.5 ± 5.8 to 13 ± 4.9 mm Hg, P = .004). Somatostatin decreased portal vein flow normalized to liver weight in both H70 and H90 groups (from 408 ± 224 to 360 ± 227 mL/min/100g, P = .031 and from 560 ± 190 to 466 ± 189 mL/min/100g, P = .016), and restored a normal HVPG in the H90 group (from 14.3 ± 4.8 to 7.7 ± 6.1 mm Hg, P = .047). CONCLUSIONS: Somatostatin restores a normal HVPG in the setting of small-for-size syndrome and can be considered as an effective pharmaceutical modality of portal inflow modulation after extended hepatectomy.

Gastrointestinal Congestion Dilates the Hepatic Artery Through the P38 MAPK Signal Transduction Pathway During Liver Transplantation.

During the neohepatic stage of liver transplantation, hemodynamics change markedly. The current study aimed to investigate whether gastrointestinal congestion caused by inferior vena cava and hepatic portal vein clamping can dilate the hepatic artery and to determine the associated mechanisms. Ring segments of the hepatic artery were treated with the plasma from gastrointestinal congestion or the superior vena cava. The fractions in gastrointestinal congestion and the superior vena cava plasma were tested, and the effect of these fractions on the tone of the hepatic artery ring was examined. Different signal transduction blockers and different inhibitors were then used to determine the exact signal transduction pathway involved. In addition, endothelial cell structure was observed by transmission electron microscopy after treatment with the gastrointestinal congestion plasma or the superior vena cava plasma. Gastrointestinal congestion plasma contained more inflammatory cytokines than superior vena cava plasma, and these cytokines could cause hepatic artery ring dilatation. A P38 mitogen-activated protein kinase (P38 MAPK) signal transduction pathway blocker and nitric oxide (NO), prostaglandin (PGI2), nuclear factor-κB (NF-κB), and adenosine triphosphate (ATP)-sensitive K (KATP) channel inhibitors were able to significantly reverse the ring tension caused by gastrointestinal congestion plasma. The normal endothelium was also injured by treatment with gastrointestinal congestion plasma. The inflammatory cytokines in gastrointestinal congestion can cause hepatic artery ring dilatation through the P38 MAPK signal transduction pathway, and this phenomenon is also associated with NO, PGI2, NF-κB, and the KATP channel. These inflammatory cytokines can injure endothelial cells in the hepatic artery.

Local and Global Function Model of the Liver.

PURPOSE: To develop a local and global function model in the liver based on regional and organ function measurements to support individualized adaptive radiation therapy (RT). METHODS AND MATERIALS: A local and global model for liver function was developed to include both functional volume and the effect of functional variation of subunits. Adopting the assumption of parallel architecture in the liver, the global function was composed of a sum of local function probabilities of subunits, varying between 0 and 1. The model was fit to 59 datasets of liver regional and organ function measures from 23 patients obtained before, during, and 1 month after RT. The local function probabilities of subunits were modeled by a sigmoid function in relating to MRI-derived portal venous perfusion values. The global function was fitted to a logarithm of an indocyanine green retention rate at 15 minutes (an overall liver function measure). Cross-validation was performed by leave-m-out tests. The model was further evaluated by fitting to the data divided according to whether the patients had hepatocellular carcinoma (HCC) or not. RESULTS: The liver function model showed that (1) a perfusion value of 68.6 mL/(100 g · min) yielded a local function probability of 0.5; (2) the probability reached 0.9 at a perfusion value of 98 mL/(100 g · min); and (3) at a probability of 0.03 [corresponding perfusion of 38 mL/(100 g · min)] or lower, the contribution to global function was lost. Cross-validations showed that the model parameters were stable. The model fitted to the data from the patients with HCC indicated that the same amount of portal venous perfusion was translated into less local function probability than in the patients with non-HCC tumors. CONCLUSIONS: The developed liver function model could provide a means to better assess individual and regional dose-responses of hepatic functions, and provide guidance for individualized treatment planning of RT.