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PubMed2005

Differences of perioperative liver function, transfusion, and complications according to the type of hepatectomy in living donors.

Numerous living donor hepatectomy are being performed safely. However, donors are still exposed to various complications including hepatic failure. We examined the donor's potential risk and morbidity depending on the type of hepatectomy: left lateral segmentectomy (group LLS, n = 30), left lobectomy (group LL, n = 15), and right lobectomy (group RL, n = 128). The charts and computerized hospital data of 173 donors from March 2000 to September 2003 were retrospectively reviewed. We analyzed liver function tests (LFT), RBC transfusion, and complications. Although the graft weight was greatest, and surgical and anesthetic times were longest in the group RL, there were no significant differences in postoperative hospital stay, RBC transfusion, and major complications among the groups. However, minor complications were significantly higher in group RL than group LLS. Postoperative prothrombin time and total bilirubin were significantly higher in the group RL than the other groups (P < 0.05). Living donor hepatectomy is relatively safe, and it is evidenced by rapid recovery of LFT and low occurrence of major complications. However, noticeable depression of LFT and frequent minor complications occur after hepatectomy, especially RL.

Adult↗
PubMed2005

Restoration of hepatic mast cells and expression of a different mast cell protease phenotype in regenerating rat liver after 70%-hepatectomy.

Mast cells (MC) can undergo significant changes in number and phenotype; these alterations result in the differential expression of growth factors and cytokines. Kit ligand (KL; stem cell factor) is produced by mesenchymal cells, and in the liver by biliary epithelial cells. Recent studies suggest that KL, and its receptor c-kit, may be involved in liver regeneration after loss of liver mass. However, KL is also the major growth, differentiating, chemotactic, and activating factor for MC. The aim of our study was to elucidate the dynamics and phenotype of hepatic MC and KL/c-kit expression during liver regeneration after partial (70%) hepatectomy in the rat. Regenerating livers were harvested after 1, 3, 7, and 14 days, respectively (n = 6 each day). MC were stained for naphthol-AS/D-chloroacetate esterase and counted as MC per bile ductule. MC phenotype was assessed by rat MC protease (RMCP)-1 and -2 immunofluorescence staining, in order to distinguish RMCP-1 positive connective tissue MC (CTMC) from RMCP-2 positive mucosa MC (MMC). mRNA expression of RMCP, c-kit, and the differentially spliced variants of KL was quantified by RT-PCR. MC counts per bile ductule decreased in regenerating rat liver tissue at day 3, compared with native livers, and became normal thereafter. Hepatic MC were predominantly of a CTMC phenotype expressing RMCP-1, as previously published; after hepatectomy, between 76 and 99% of all MC double-expressed RMCP-1 and -2, compatible with an MMC phenotype. The ratio of the two alternatively spliced mRNAs for KL (KL-1 : KL-2), and c-kit mRNA expression did not differ significantly between regenerating livers and the livers of sham operated animals. These results suggest that hepatic mast cells are restored during liver regeneration after partial hepatectomy in the rat. Restored MC express an MMC phenotype, suggesting migration from outside into the regenerating liver. Alternative splicing of KL is affected by the surgical procedure in general, and, together with its receptor c-kit, doesn't seem to be involved in liver regeneration after partial hepatectomy in the rat. Further functional studies, and studies in regenerating human livers might offer the possibility of elucidating the role of the hepatic mast cell, and its different protease phenotypes during liver regeneration after surgical loss of liver mass.

Animals↗
PubMedDate not supplied

Choice of treatments for small hepatocellular carcinoma: hepatectomy, embolization or ethanol injection.

The results of hepatectomy, percutaneous ethanol injection therapy and transcatheter arterial embolization for small hepatocellular carcinoma (HCC) of 3 cm or less in diameter from the published literature were compared with the authors' experiences with surgical treatment. The survival rates for those treated by hepatectomy and ethanol injection were almost the same, being more than 90% at 1 year and 70% at 3 years. The overall results achieved by embolization were inferior to those achieved by the other two therapeutic modalities, although the 1 year survival rate was not worse. The cancer-free survival rates after hepatectomy and ethanol injection were also similar. Most of the patients with small HCC had associated liver cirrhosis or chronic active hepatitis, but the degree of liver dysfunction and the level of hepatic reserve varied. Anatomically, the number, size, and location of the cancer also varies. Choice of treatment for small HCC should be made based upon the degree of liver function and the anatomic status of the cancer. For example, a patient with multiple (more than four) cancer nodules is a good candidate for embolization. Ethanol injection is indicated for a small HCC, deeply seated in a severely diseased liver. Hepatectomy is the first choice for a small HCC situated near the surface of a liver with relatively good liver function.

Carcinoma↗
PubMedDate not supplied

Rat peripheral mononuclear cell thymidine kinase activity increases during liver regenerative processes after partial hepatectomy.

Deoxythymidine kinase (TK; EC 2.7.1.21) activity in the liver has been used as a marker of liver regeneration after partial hepatectomy. In this study we examined TK activity of various organs, plasma and peripheral blood mononuclear cells (PMNC) in 70% partially hepatectomized rats. TK activity of lymph nodes, small intestine, heart, lung, kidney and thymus did not increase significantly during the course of the study, except for spleen at 72 h. On the other hand, PMNC-TK and liver cystosolic TK activity increased in a parallel fashion at all times after partial hepatectomy; they began to increase 12 h after surgery and peaked 48 h post-surgery. Fractionation of PMNC into T cells and B cells revealed that both populations increased and peaked 48 h post-surgery. Plasma TK peaked 12-24 h after surgery, then declined at 36, 48 and 72 h after partial hepatectomy. This change paralleled plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PMNC-TK activity correlated significantly with liver cystosolic TK activity 24 h (r = 0.743; P < 0.05) and 48 h (r = 0.708; P < 0.05) after partial hepatectomy. However, it did not correlate with plasma levels of TK, AST and ALT. The results indicate that in the early stage of liver regeneration PMNC-TK may provide a marker of liver regenerative processes.

Alanine Transaminase↗
PubMed1996

Treatment with a novel lipid A analogue, FS-112, and partial hepatectomy causes submassive liver necrosis and impaired liver regeneration in mice.

A novel experimental model of submassive liver necrosis with impaired regeneration has been established. A novel lipid A analogue, FS-112, was injected intravenously into male BALB/c mice, followed 2 days later by a 70% partial hepatectomy. Over the next 9 days, mice became severely jaundiced, with a peak total bilirubin (TBil) concentration of (mean +/- s.d.) 12.9 +/- 2.1 mg/dL 7 days postoperatively. In contrast, the TBil concentration in vehicle-treated mice remained less than 2 mg/dL. Significant elevations of L-alanine:2-oxoglutarate aminotransferase (ALT) were also observed 3-7 days after the operation in mice pretreated with FS-112, compared with mice pretreated with the vehicle. Submassive liver necrosis was observed with extensive mononuclear cell infiltration in mice treated with FS-112 and subjected to partial hepatectomy. Furthermore, both the BrdU and the proliferating cell nuclear antigen (PCNA) labelling index (LI) 1 day following partial hepatectomy in mice pretreated with FS-112 (8.6 +/- 4.3 and 7.9 +/- 4.2%, respectively) were significantly lower than levels in vehicle-treated mice (25.8 +/- 3.8 and 26.5 +/- 10.5%, respectively). The time course of changes in the BrdU LI in liver specimens from mice treated with both FS-112 and partial hepatectomy did not increase, even 3, 5, and 7 days postoperatively. Excellent liver regeneration with a PCNA LI 10-fold higher than the resting level was observed in mice treated with D-galactosamine hydrochloride. These results strongly suggest that this animal model of submassive liver necrosis may be suitable for clarifying the mechanisms of impaired liver cell regeneration often seen in fulminant hepatitis.

Animals↗
PubMed1981

Metabolism of acetate to amino acids in brains of rats after complete hepatectomy.

The concentration of glutamine increases in the brain after hepatectomy. In the present studies the conversion of intravenously given [14C]acetate to [14C]glutamate and [14C]glutamine was studied in control rats and in rats at 6 h after complete hepatectomy. The incorporation of label into glutamate was only slightly inhibited, but the further incorporation into glutamine was greatly inhibited, after hepatectomy. These data, and previous data using [14C]glucose as precursor, indicate that synthesis of glutamine in brain is inhibited after hepatectomy, and suggest that its concentration must increase because degradation is inhibited to an even greater extent.

Acetates↗
PubMed2005

The influence of spleen size on liver regeneration after major hepatectomy in normal and early cirrhotic liver.

BACKGROUND/PURPOSE: The relationship between liver regeneration and spleen size after major hepatectomy in normal and cirrhotic liver was studied by single photon emission computed tomography (SPECT). MATERIALS AND METHODS: Twenty-six patients, 18 patients with normal liver and eight patients with cirrhotic liver, receiving major hepatectomy were included. Liver and spleen volumes were measured by SPECT before major hepatectomy, 6 months, 1 year and 2 years after operation. The correlation of liver and spleen volume during liver regeneration was analyzed. RESULTS: In both groups, the residual liver volume increased within the first year and decreased in the second year. No difference in regeneration ability was found. The spleen volume in cirrhotic liver was increased, with a trend similar to normal liver during the first year. In contrast, the increased spleen volume persisted up to the second year in cirrhotic patients. Age per year, the female sex, and body surface index had a positive correlation with increased percentage of liver volume. The spleen volume per 100 ml with time played a significantly negative role in increasing percentage of liver volume, confidence interval: -2.16 to -27.92, P=0.011. CONCLUSION: In early cirrhotic liver within normal functional limits, the liver still could regenerate as a normal liver after major hepatectomy in 1 year. Age, the female sex, and body surface index had positive correlation but the size of spleen volume played a negative role to regenerative liver volume.

Adult↗
PubMed1991

Streaming liver. VIII: Cell production rates following partial hepatectomy.

Twenty-four young, female, random-bred rats weighing 250 g were partially hepatectomized and killed in groups of four animals at the following times: 1 h and 1, 2, 3, 7 and 14 days. One hour before killing, each rat was injected i.p. with 0.5 microCi [3H]-thymidine, specific activity 5 Ci/mmol/g body weight. Livers were processed histologically and dipped into liquid emulsion for autoradiography. Twenty-four hours after partial hepatectomy, hepatocyte and littoral labelling indices rose, reaching on the third day respective peak values of 3.7%, and 15.4%, whereupon they declined, remaining slightly above pre-treatment level. Labelling indices served for cell production estimates. On day 3 the hepatocyte labelling index rose 26-fold. At the same time hepatocytes doubled their ploidy, indicating that half of the observed L.I. increase was directed to DNA accumulation and not to cell division. The hepatocyte production rate therefore increased 13-fold (or 1300%). The acinus diameter increased 15%, and cell density declined 5%, so that the acinus capacity to retain cells increased only 5%. Since the acinus did not enlarge proportionally to cell production, it is concluded that 95% of newly formed cells were eliminated. Partial hepatectomy thus triggers two processes: an acute process lasting about a week marked by massive and rapid cell turnover during which most newly formed cells are eliminated; and a second, more protracted process which serves for liver mass restoration. It is proposed that partial hepatectomy induces an acute shortage of a hitherto unknown metabolite that is produced by newly formed cells immediately after hepatectomy.

Animals↗
PubMed1994

Changes in receptor-mediated endocytosis in liver sinusoidal cells after partial hepatectomy in the rat.

Liver sinusoidal cells play an important role in host defense by clearing particulate matter and macromolecules from the circulation. In this study, receptor-mediated endocytosis in sinusoidal cells was examined in two-thirds hepatectomized rats using 125I-labeled formaldehyde-treated bovine serum albumin (fBSA) as an endocytable macromolecule. The liver-weight to body-weight ratio in hepatectomized rats returned to the control value 10 days after hepatectomy. The endocytotic index for fBSA in sinusoidal cells decreased significantly to 0.0210 +/- 0.0017 (controls, 0.0598 +/- 0.0019) on the first day, then returned to the control level at 5 days (0.0554 +/- 0.0030). The changes in hepatic uptake for fBSA showed a similar time course of the endocytotic index. A transient increase in the uptake of fBSA per unit weight of liver of 22-39% above control occurred 2 to 3 days after hepatectomy. In contrast to fBSA, the endocytotic index in hepatocytes evaluated with 125I-labeled asialofetuin reached the minimum level on the second day, and then recovered to the control level 10 days after hepatectomy. These results suggest that endocytosis of fBSA by sinusoidal cells decreases after hepatectomy and rapidly recovers to normal before the completion of liver regeneration, whereas endocytosis of asialofetuin by hepatocytes decreases following hepatic resection and returns to normal when regeneration is substantially complete.

Animals↗
PubMed1982

The control of liver regeneration after partial hepatectomy in the rat.

1. Normal rat liver slices were incubated for 24 h in culture medium to which had been added freeze-dried plasma, prepared from the blood of rats which had undergone partial hepatectomy (60-70% of liver removed) 10 min, 4 or 24 h previously. No changes in the dry weight of the slices were observed. 2. Similarly, there were no changes in the dry weight or protein content of incubated liver slices when freeze-dried plasma prepared from the blood of rats unilaterally nephrectomized 10 min, 4 or 24 h previously was added to the culture medium. 3. Slices from the remaining liver stump, taken 4 h after partial hepatectomy (60-70% of liver removed) and incubated for 4 h in culture medium, did not release a factor capable of increasing the dry weight of normal liver slices incubated in the same medium. 4. After partial hepatectomy (60-70% of liver removed), there was no increase of guanosine 3':5'-cyclic monophosphate in the remaining part of the liver. 5. No measurable amount of esterase activity was found in normal liver or in the remaining liver stump after partial hepatectomy (60-70% of liver removed). 6. It is suggested that the stimulatory mechanism for liver regeneration is of a different nature from that involved in compensatory renal hypertrophy.

Animals↗
PubMed1992

Effect of in vivo administration of an antibody to epidermal growth factor on the rapid increase in DNA synthesis induced by partial hepatectomy in the rat.

Recent reports indicate that transforming growth factor alpha (TGF-alpha) is produced within the liver and acts as the natural ligand of the epidermal growth factor (EGF) receptor causing the EGF receptor down regulation and the hepatocyte proliferation observed after partial hepatectomy. The reported phenomenon that an antibody to EGF inhibits the regenerative response to partial hepatectomy was therefore re-investigated. The IgG fraction of an anti-rat EGF antibody was injected intravenously at the time of partial hepatectomy, and its effects on regenerative DNA synthesis were compared with those of non-immune IgG. Injection of IgG reduced the DNA synthetic response to partial hepatectomy, assessed 24 hours after resection by 3H-thymidine incorporation, but the effects of normal and anti-EGF IgG were not statistically different, despite the presence of excess anti-EGF IgG in the circulation throughout the experimental period. However, anti-EGF IgG could completely block the proliferative response of hepatocytes in culture to EGF. These results support the suggestion that EGF is not the major mediator of hepatocyte DNA synthesis in the early stages of liver regeneration (less than 24 hours).

Animals↗
PubMed1991

Results of hepatectomy for hepatocellular carcinoma at the National Cancer Center Hospital.

The number of hepatectomies has increased greatly in recent years. Surgery for hepatocellular carcinoma (HCC) in the normal liver has not increased. However, the increase in numbers of hepatectomies for HCC associated with liver cirrhosis is remarkable. More than 80% of our hepatectomy cases were cirrhotic and about 80% of these cirrhotic cases had HCCs 5cm or less in diameter. The operative mortality rate has improved in the latter half of this series, from 10.1% (9/89) to 1.5% (5/338), in spite of an increase in cases with poor liver function. This corresponds to a decrease in the mean value of the annual operative blood loss. The survival rates after hepatectomy for all cases (n = 378) were 40.6% +/- 6.6 (% +/- SE) for 5 year and 22.7% +/- 5.3 for 10 year at the end of 1988. A difference of the 5-year survival rate between the patients operated on before 1981 (n = 78, 25.6% +/- 4.9) and after 1982 (n = 300, 46.1% +/- 4.8) was observed (p less than 0.05). Because the cancer-free survival rates of the patients operated on in the two periods, before 1981 and after 1982, were almost the same, the recent improvement of the survival rates seems to be due to a prolongation of survival time after recurrence.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Effects of doxorubicin and/or cilostazol on cancer cells during liver regeneration after two-thirds hepatectomy in rats.

A rat model of liver metastases generated by intraportal injection of syngeneic tumor cells after two-thirds hepatectomy to determine the optimal benefit of doxorubicin and/or cilostazol for early hepatic metastases. Four groups of WKA rats had viable tumor cells injected directly into the portal vein after two-thirds hepatectomy. Group A underwent to further treatment. Group B had doxorubicin injected 24 h post-operatively. Group C had cilostazol administered prior to two-thirds hepatectomy. Group D received cilostazol, and doxorubicin injections. The mean survival period in each group was 22.2, 20.0, 28.8, and 22.8 days, respectively. The mean survival was significantly longer in group C than in groups A, B and D (p < 0.05). Based on these findings, we believe that during the phase of liver regeneration adjuvant chemotherapy is not recommended. Cilostazol exerts an important antiproliferative effect on liver metastases after hepatectomy.

Animals↗
PubMedDate not supplied

Beneficial effect of hyperbaric oxygen therapy on liver regeneration after 90% hepatectomy in rats.

BACKGROUND/AIMS: Hyperbaric oxygen therapy (HBOT) has been reported to augment oxygen delivery to ischemic tissues and improve the liver dysfunction in clinical cases. HBOT was performed after 90% hepatectomy in rats to determine its effect on the regeneration of remnant liver. METHODS: After 90% hepatectomy was performed in 8-week-old male Wistar rats, the animals were subdivided into an HBOT (2 atm abs., 80% O2, 1 h/day, 3 days) group and a non-HBOT group. Members of both groups were sacrificed, usually every 4 h until a maximum of 50 h after hepatectomy, and the liver regeneration rate, the proportion of PCNA-positive cells and the ATP volume in the remnant tissues were examined. RESULTS: In the HBOT group, the liver regeneration rate at 36 h and 50 h after operation and the proportion of PCNA positive cells at 8 h was significantly increased compared with the non-HBOT group. The ATP volume in the remnant livers in the HBOT group was also significantly increased at 12 h. CONCLUSION: HBOT augmented liver regeneration after hepatectomy by stabilization of energy metabolism induced by oxygen delivery in rats.

Animals↗
PubMed1987

Experimental model of extended repeated partial hepatectomy in the dog.

The model of extended repeated partial hepatectomy without vascular shunt in dogs is presented. It consisted of 65% initial hepatectomy and after liver regeneration (6-10 weeks) repeated hepatectomy. Finally, only the papillary process of the caudate lobe (PPC), which constitutes 5% of the initial hepatic mass, was left intact. The most important finding was an ability of PPC to reconstitute the liver mass which enabled survival without the vascular shunt. After repeated hepatectomy the need for artificial hepatic assistance (parenteral nutritional support with frozen plasma) was imperative to offset the effects of acute hepatic failure and to support PPC regeneration.

Animals↗
PubMed1995

Hepatic cholesterol 7 alpha-hydroxylase activity and serum 7 alpha-hydroxy-cholesterol level during liver regeneration after partial hepatectomy in rats.

Hepatic cholesterol 7 alpha-hydroxylase is a rate-limiting enzyme for bile acid synthesis, and we have previously shown that the serum 7 alpha-hydroxycholesterol level reflects the enzyme activity in patients with an intact liver. The purpose of this study was to evaluate the alterations in hepatic cholesterol 7 alpha-hydroxylase activity and the serum 7 alpha-hydroxycholesterol level after hepatectomy and the correlations between these parameters and liver mass. Hepatic cholesterol 7 alpha-hydroxylase activity, the serum 7 alpha-hydroxycholesterol level and the remaining liver weight were determined after 70% hepatectomy in rats. Cholesterol 7 alpha-hydroxylase activity was decreased on days 1 and 2 (from 28.3 +/- 3.7 to 8.5 +/- 2.8 and 13.3 +/- 3.6 pmol/min/mg protein, respectively), returned to the preoperative level on day 3 (24.7 +/- 2.6 pmol/min/mg protein) and further elevated thereafter (71.4 +/- 10.9 on day 7 and 51.3 +/- 6.6 pmol/min/mg protein on day 14). The serum level of 7 alpha-hydroxycholesterol changed simultaneously with the enzyme activity, and a significant correlation between the two parameters was observed (r = 0.915, p < 0.0001). The correlations between the liver weight and hepatic cholesterol 7 alpha-hydroxylase activity and serum 7 alpha-hydroxycholesterol level were significant (p < 0.01), but the significances disappeared for the period of days 3-14 (r = 0.424, p = 0.08; r = 0.299, p = 0.228, respectively). In conclusion, hepatic cholesterol 7 alpha-hydroxylase activity is suppressed by hepatectomy and then activated as the liver regenerates. The serum 7 alpha-hydroxycholesterol level is a good parameter of this enzyme activity after partial hepatectomy.

Animals↗
PubMedDate not supplied

Parenteral monoacetoacetin and liver regeneration interaction after partial hepatectomy in the rat.

Parenteral nutrients can be used to manipulate cell proliferation after partial hepatectomy. The relationship among macronutrients--glucose, monoacetoacetin, amino acids--and liver regeneration after partial hepatectomy was investigated. Male rats were anesthetized, received a 70% hepatectomy, and received a low-dose infusion of (1) glucose or (2) monoacetoacetin and a high-dose infusion of (3) glucose, (4) glycerol-glucose, or (5) monoacetoacetin-glucose beginning 6 hours after surgery. The five nonprotein nutrient combinations were infused with and without amino acids. Rats were killed 48 hours after partial hepatectomy, and the label and mitotic indices were determined. Each of the five treatments had a higher label index with amino acids present than with amino acids absent. Low-dose glucose and monoacetoacetin as well as high-dose glucose and glucose-glycerol had higher mitotic indices with amino acids than without amino acids. High-dose monoacetoacetin-glucose was associated with a greater mitotic index than was any other nonprotein substrate treatment, and this response was independent of amino acids being present or absent. In summary, (1) amino acids were needed for maximal cell proliferation rate; (2) the absence of amino acids and not the presence of glucose resulted in reduction of the label and mitotic indices for regenerating liver; (3) high-dose monoacetoacetin increased mitosis with or without amino acids; and (4) monoacetoacetin activity was dose dependent. The results indicate that the best nutrient for treatment of patients with liver injury is acetoacetate. The second best nutrient would be the combination of high-dose glucose and amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetoacetates↗
PubMedDate not supplied

The accumulation and energy load of exogenous lipids in cirrhotic rat liver after partial hepatectomy.

BACKGROUND: The suitability of three energy substrates, glucose, medium-chain triglycerides (MCT) and long-chain triglycerides (LCT), was studied in cirrhotic rats after a partial hepatectomy. METHODS: Rats with thioacetamide-induced cirrhosis underwent a 70% hepatectomy, and were divided into three groups. Each group was then injected with 14C-labeled glucose, 14C-labeled MCT or 14C-labeled LCT, respectively. The subsequent tissue distribution of 14C and the cumulative amount of expired 14CO2 were determined. In a second experiment, the 70%-hepatectomized cirrhotic rats received total parenteral nutrition (TPN). The source of the nonprotein calories was 100% glucose (glucose group), 60% MCT + 40% glucose (MCT group), and 60% LCT + 40% glucose (LCT group). The adenylate energy charge and the glycogen content in the liver remnant were determined. RESULTS: The tissue distribution of 14C revealed that the fat emulsions accumulated preferentially in the liver. One hour after the partial hepatectomy, the concentration of 14C-labeled MCT in the liver remnants was threefold higher than in sham-operated controls. Similarly, the concentration of 14C-labeled LCT was twofold higher. The adenylate energy charge in the glucose group with TPN recovered to preoperative levels within 1-hour after the partial hepatectomy, whereas the LCT group with TPN showed a 24-hour delay in their recovery. The MCT group with TPN exhibited an intermediate time course. CONCLUSIONS: It is suggested that the specific accumulation of MCT and especially LCT emulsions in the cirrhotic liver remnant acts as an energy load rather than an energy substrate.

Adenine Nucleotides↗