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Short bowel syndrome in infancy and childhood. Analysis of survival in 60 patients.

This report concerns 60 infants and children with short bowel syndrome, most commonly caused by necrotizing enterocolitis in this study. Resection of atretic or gangrenous bowel was performed in 53 patients, tapering enteroplasty and primary anastomosis was performed in 13 patients, and temporary enterostomies were performed in 40 patients. Second-look laparotomy was useful in two of four cases of questionable bowel viability. The ileocecal valve was resected in 33 patients and remained intact in 27. The mean length of remaining bowel was 58.4 cm (range 13 to 150 cm). Seven patients with total aganglionosis and mid to proximal small bowel extension were managed with an initial enterostomy, whereas three had a pull-through procedure with an aganglionic patch enteroplasty. All patients received total parenteral nutrition and early enteral feedings. Home hyperalimentation was attempted when 50 percent of the calorie intake was enteral. Intestinal adaptation required from 3 to 14 months. Frequent setbacks were related to catheter sepsis, rotavirus infection, carbohydrate intolerance, and liver dysfunction. The overall survival rate was 85 percent, with mortality due to liver failure and sepsis associated with total parenteral nutrition.

Adolescent↗

Early postoperative change of plasma levels of amino acids in neonates with perforative peritonitis and its prognostic significance.

As a possible prognostic index, plasma levels of amino acids were serially measured for 1 week in 22 neonates with perforative peritonitis including gastric rupture and necrotizing enterocolitis and 28 neonatal surgical patients without infection as a control, who were subjected to total parenteral nutrition with hypertonic glucose and amino acids formulated for neonates. Plasma levels of branched chain amino acids significantly increased on the first day after operation in peritonitis group, whereas plasma levels of phenylalanine and histidine increased on the third postoperative day and tyrosine increased seventh postoperative day. In the peritonitis group, 5 neonates died within 2 weeks after operation (early death group) because of cardiopulmonary failure and 5 neonates died with hyperbilirubinemia from 1 month to 6 months after operation (late death group). The early death group showed increased levels of total amino acids compared with those in the late death group and survivors. The late death group also showed higher levels of total amino acids than survivors. Plasma levels of tyrosine increased in the early and late death groups compared with survivors. These results indicated that serial measurements of plasma amino acids early after operation showed the existence of liver dysfunction in addition to the derangement of amino acid metabolism in the liver and muscle caused by septic insult, which predicted the prognosis of perforative peritonitis in neonates.

Amino Acids↗

Molecular mechanisms underlying the development of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a disease that is extremely difficult to manage and is markedly increasing in incidence. Malignant transformation generally occurs in the setting of liver dysfunction related to a number of different diseases, including viral hepatitis, alcoholic liver disease, and aflatoxin exposure. Short of surgical or ablative approaches, no standard therapy exists for HCC and the prognosis is poor. Perhaps our best hope is that further elucidation of the specific molecular features underlying the disease will translate into innovative, and potentially disease-specific strategies to manage this difficult cancer. Exposure to aflatoxin is associated with a specific mutation in the tumor-suppressor gene p53. The exact molecular events underlying hepatocarcinogenesis in the setting of viral infection have yet to be elucidated, although there is evidence to suggest that virus-encoded proteins contribute to malignant transformation. Both hepatitis B X antigen and hepatitis C core protein appear to interact with a variety of cellular proteins leading to alterations in signal transduction and transcriptional activity. These events presumably cooperate to facilitate malignant progression by promoting extended hepatocyte survival, evasion of the immune response, and acquisition of mutations through genomic instability.

Animals↗

Hypoprothrombinemia associated with interleukin-2 therapy: correction with vitamin K.

We noted that patients treated with high-dose interleukin (IL)-2 (600,000 IU/kg every 8 h by intravenous bolus) at our institution frequently developed prolongation of their prothrombin time (PT). We therefore performed a prospective study of coagulation function during IL-2 treatment. Since IL-2 treated individuals are known to develop cholestatic liver dysfunction, we hypothesized that the hypoprothrombinemia was due to deficiency of liver-synthesized clotting factors and could be prevented by vitamin K replacement. Alternating patients served as controls or received prophylactic subcutaneous subcutaneous vitamin K. While the nine control patients did not exhibit a significant increase (mean +/- SD) in PT (13.6 +/- 0.6 s pretreatment, 15.0 +/- 2.2 on day 4, and 15.0 +/- 2.5 on day 7, p = 0.77 by repeated measures analysis), three patients developed marked increases in PT (greater than 18 s). Changes in partial thromboplastin time (PTT) over this interval were also not statistically significant. Factor VII levels decreased in all patients from 106 +/- 22 to 59 +/- 16 and 52 +/- 26% on days 4 and 7 (p = 0.0002). Factor VII levels in four patients dropped below the lower limit of normal. Prophylactic treatment of seven patients with vitamin K on days 1-8 of the IL-2 therapy protocol resulted in diminished changes in PT and factor VII compared to control patients (p = 0.02 and 0.003 respectively). No vitamin K-treated patient developed PT or Factor VII levels significantly outside the normal range. Prophylactic vitamin K can prevent hypoprothrombinemia in patients treated with IL-2. This may be of importance in patients with decreased hepatic vitamin K stores, who may be at risk for bleeding complications.

Blood Coagulation↗

Late biliary stenosis after conservative management of traumatic liver rupture: case report.

An extensive liver rupture developed in a 50-year-old woman after she received severe blunt injuries in a criminal assault. Nonsurgical management of the liver injury led to recovery of the patient despite a serious blood loss and multiorgan failure. However, 3 months after the injury a complete left bile duct stenosis with liver dysfunction and two hepatic artery pseudoaneurysms were found. Biliodigestive bypass restored normal liver function.

Aneurysm, False↗

Brain death does not affect hepatic allograft function and survival after orthotopic transplantation in a canine model.

BACKGROUND: Brain death has been shown to decrease graft function and survival in rodent models. The aim of this study was to evaluate how brain death affects graft viability in the donor and liver tolerance to cold preservation as assessed by survival in a canine transplant model. METHODS: Beagle dogs were used for the study. Non-brain dead (BD) donors served as controls. Brain death was induced by sudden inflation of a subdural balloon catheter with continuous monitoring of arterial blood pressure and electroencephalographic activity. Sixteen hours after confirmation of brain death, liver grafts were retrieved. All livers were flushed in situ and preserved for 24 hr in cold University of Wisconsin solution before transplantation. Recipient survival rates, serum hepatic enzyme levels, coagulation, and metabolic parameters of the recipients were analyzed. RESULTS: No significant changes were observed in serum aminotransferases (alanine and aspartate transaminases) and lactate dehydrogenase levels in the BD donor. After preservation, control (n=6) and BD livers (n=5) showed full functional recovery after transplant with 100% survival in both groups at day 7. There was no significant difference in peak serum alanine, aspartate transaminases, and lactate dehydrogenase after transplantation in recipients who received a liver from BD donor compared to control group. BD livers were functionally as capable as control livers in correcting metabolic acidosis during the first 24 hr posttransplantation. Coagulation profiles (index normalized ratio, activated partial thromboplastin time) after reperfusion were similar between groups. CONCLUSION: In contrast to previous reports in rodent models, our study shows that brain death does not cause significant liver dysfunction in the donor before organ removal. Donor brain death and prolonged liver graft preservation do not interact significantly to impair liver function and survival after transplantation.

Adenosine↗

Effects of continuous hepatitis with persistent hepatitis C viremia on outcome after resection of hepatocellular carcinoma.

The effect of persistent hepatitis C viremia on the outcome after resection of hepatocellular carcinoma (HCC) was investigated in 59 consecutive patients with a single small HCC (< or = 3.0 cm in diameter). The presence of serum hepatitis C virus (HCV) RNA was evaluated using a reverse transcription polymerase chain reaction method as well as a branched DNA probe method. Clinicopathologic findings were compared between patients with and without viremia and the risk factors for poor outcome were evaluated. Hepatitis C virus (HCV) RNA was not detected in the sera from 7 patients (group 1), but was detected in the sera from the other 52 patients (group 2). Alanine aminotransferase (ALT) activity was significantly higher in group 2 than in group 1. The proportion of patients with active hepatitis was significantly higher in group 2. In group 2, new HCC often developed after the operation and four patients died of liver dysfunction. HCV viremia, high ALT activity, high concentration of total bilirubin, and liver cirrhosis were related to recurrence after the operation. Multivariate analysis indicated that HCV viremia and high ALT activity were independent risk factors for recurrence of HCC. Continuous hepatitis with persistent HCV viremia worsened the outcome after the resection of HCC by causing new development of HCC and deterioration of liver function. In patients with HCV-related HCC, but without HCV viremia, satisfactory results can be expected after liver resection.

Aged↗

Hepatic progenitors and strategies for liver cell therapies.

Liver cell therapies, including liver cell transplantation and bioartificial livers, are being developed as alternatives to whole liver transplantation for some patients with severe liver dysfunction. Hepatic progenitors are proposed as ideal cells for use in these liver cell therapies given their ability to expand extensively, differentiate into all mature liver cells, have minimal immunogenicity, be cryopreservable, and reconstitute liver tissue when transplanted. We summarize our ongoing efforts to develop clinical programs of hepatic progenitor cell therapies with a focus on hepatic stem cell biology and strategies that have emerged in analyzing that biology.

Animals↗

Hepatitis: still a concern?

Although some forms of viral hepatitis were identified more than 50 years ago, hepatitis continues to have an impact on the practice of dentistry. Possible transmission in the dental setting, management of the chronically ill, and legal issues related to treatment of infectious patients combine to emphasize that hepatitis is still an important issue for dental health care workers. Currently, 7 viral forms are recognized. Those with predominantly enteral modes of transmission--including HAV, HEV, and HFV--are of minor concern in the dental environment. HBV, the most infectious blood-borne pathogen, has been largely controlled in this country by vaccination and the use of universal precautions. HDV is an incomplete virus that has HBV infection as a prerequisite. HCV is of great concern today for several reasons. A high percentage of HCV infections results in chronic disease. Most cases remain asymptomatic for an extended period of time, and many have no identifiable risk factors. Currently, no vaccination is available for HCV. Patients infected with HCV present a management challenge, because they may ultimately develop serious liver dysfunction. In fact, HCV infection is presently the most common reason for liver transplantation. By understanding the various forms of viral hepatitis and following recommended infection control and vaccination protocols, the dental healthcare worker can treat infected patients in a manner that is safe for both patients and dental health care workers.

Blood-Borne Pathogens↗

A maternally transmitted lethal neonatal progeroid syndrome with prominent genitourinary and gastrointestinal features.

Twin brothers and their maternal uncle with a previously undescribed neonatal progeroid syndrome are presented. In addition to progeroid features, they had pseudo-obstruction of the urinary and gastrointestinal tracts, severe leucocytosis, liver dysfunction, and low complex III and IV in muscle but not in liver. Previously described neonatal progeroid syndromes and syndromes featuring pseudo-obstruction are discussed. The two most likely aetiological mechanisms are an X linked single gene disorder or a mitochondrial disorder. The evidence for these possibilities is presented.

Abnormalities, Multiple↗

Hypoxic suppression of E. coli-induced NF-kappa B and AP-1 transactivation by oxyradical signaling.

Transactivation of the DNA-binding proteins nuclear factor-kappa B (NF-kappa B) and activator protein (AP)-1 by de novo oxyradical generation is a stereotypic redox-sensitive process during hypoxic stress of the liver. Systemic trauma is associated with splanchnic hypoxia-reoxygenation (H/R) followed by intraportal gram-negative bacteremia, which collectively have been implicated in posttraumatic liver dysfunction and multiple organ damage. We hypothesized that hypoxic stress of the liver before stimulation by Escherichia coli serotype O55:B5 (EC) amplifies oxyradical-mediated transactivation of NF-kappa B and AP-1 as well as cytokine production compared with noninfectious H/R or gram-negative sepsis without prior hypoxia. Livers from Sprague-Dawley rats underwent perfusion for 180 min with or without 0.5 h of hypoxia (perfusate PO(2), 40 +/- 5 mmHg) followed by reoxygenation and infection with 10(9) EC or 0.9% NaCl infusion. In H/R + EC livers, nuclear translocation of NF-kappa B and AP-1 was unexpectedly reduced in gel shift assays vs. normoxic EC controls, as were perfusate TNF-alpha and IL-1 beta levels. Preceding hypoxic stress paradoxically increased postbacteremic reduced-to-oxidized glutathione ratios plus nuclear localization of I kappa B alpha and phospho-I kappa B alpha, but not JunB/FosB profiles. Notably, xanthine oxidase inhibition increased transactivation as well as cytokine production in H/R + EC livers. Thus brief hypoxic stress of the liver before intraportal gram-negative bacteremia potently suppresses activation of canonical redox-sensitive transcription factors and production of inflammatory cytokines by mechanisms including xanthine oxidase-induced oxyradicals functioning in an anti-inflammatory signaling role. These results suggest a novel multifunctionality of oxyradicals in decoupling hepatic transcriptional activity and cytokine biosynthesis early in the posttraumatic milieu.

Animals↗

Pathology of AIDS-related liver disease.

Hepatomegaly and abnormalities of serum liver tests are common problems in patients with acquired immune deficiency syndrome. Opportunist infections (Mycobacterium avium-intracellulare and cytomegalovirus) and neoplasms (lymphoma, Kaposi's sarcoma) are among the most prevalent hepatic lesions in AIDS. Although Kupffer cells and endothelial cells are potential sites of human immunodeficiency virus 1 (HIV-1) infection, current studies do not indicate that the liver is a major reservoir for this virus. Drug hepatotoxicity, multimicrobial infections of the biliary tree resembling sclerosing cholangitis and a variety of nonspecific hepatic changes should be considered in evaluating AIDS patients or HIV-1-infected patients with evidence of liver dysfunction.

Acquired Immunodeficiency Syndrome↗

Equipment review: the molecular adsorbents recirculating system (MARS).

The molecular adsorbents recirculating system (MARS) is a form of artificial liver support that has the potential to remove substantial quantities of albumin-bound toxins that have been postulated to contribute to the pathogenesis of liver cell damage, haemodynamic instability and multi-organ failure in patients with acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF). These toxins include fatty acids, bile acids, tryptophan, bilirubin, aromatic amino acids and nitric oxide. Data from controlled clinical trials are limited so far. One of two studies performed on small numbers of patients with AoCLF suggest a survival benefit, but no controlled data are available in the ALF setting. Our preliminary experience with MARS therapy, instituted late in the clinical course of five patients with severely impaired liver function, including three with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease, indicates some clinical efficacy. However, the overall survival rate (1 of 5; 20%) remained poor. More data obtained from larger cohorts of patients enrolled in randomised controlled studies will be required in both the AoCLF and ALF settings to identify categories of liver failure patients who might benefit most from MARS treatment, to ascertain the most appropriate timing of intervention and to determine the overall impact on outcome, including cost-effectiveness.

Humans↗

Fatal multiple organ failure following massive hornet stings.

We describe a fatal outcome in a three-year-old child following massive stings by the oriental hornet (Vespa orientalis). The primary clinical features were coma, respiratory failure, coagulopathy, renal failure and liver dysfunction. On postmortem the main organs involved were brain, lungs, kidney and liver.

Animals↗

[A case of hepatocellular carcinoma with tumor thrombus in the right atrium successfully treated by arterial administration of lipiodol-SMANCS].

In February, 1996, a 73-year-old male with liver dysfunction was admitted to our hospital for further examination and treatment of liver tumor. The liver tumor was revealed by imaging examination, which was mainly in the S4-S8 of liver with a thrombus growing from the right anterior branch to the right branch of the portal vein, and from the right hepatic vein to the inferior vena cava and right atrium. The serum AFP and PIVKA-II levels were elevated to 3.610 ng/ml and 54 AU/ml, respectively. The patient was diagnosed as having hepatocellular carcinoma, and was treated by arterial administration of anticancer drugs (epirubicin hydrochloride, mitomycin C and carboplatin) and TAE. Though the main tumor (S4-S8 of liver) was reduced by TAE, the portal and atrial tumor thrombus did not respond. One month after TAE (20 May, 1996), the first arterial administration of Lipiodol-SMANCS was given, followed by 4 successive procedures with an interval of about 1.5 months (total dose 15 mg), resulting in remarkable tumor thrombus shrinkage and reduction of AFP levels to 80 ng/ml. This case shows that arterial administration of SMANCS may be one of the effective treatments for hepatocellular carcinoma, even with tumor thrombus of hepatic vein, IVC and right atrium.

Aged↗

[Rapidly progressive irradiated cervical cancer that metastasized to the liver during therapy for idiopathic thrombocytopenic purpura].

A 37-year-old woman was given a diagnosis of cervical cancer in August 1994. Because of severe thrombocytopenia, she was given radiation therapy at 50 Gy with great effectiveness. The thrombocytopenia was diagnosed as idiopathic thrombocytopenic purpura. Because the patient refused to undergo a splenectomy operation, she was treated with prednisolone, gamma-globulin, and danazol with no effect. In January 1995 she began receiving azathioprine and her platelet count gradually increased. In March, she complained of severe left abdominal pain but abdominal computed tomography (CT) scans showed no abnormal findings. Nonetheless, the patient's lumbago persisted and her liver dysfunction was progressive. Abdominal CT scans performed on April 18 disclosed multiple liver tumors. The patient died on April 28. Autopsy revealed that the cervical cancer was the primary origin of the liver tumors. We concluded that extra precautions should be taken when administering immunosuppressive therapy to patients with a history of malignant diseases.

Adult↗

Hepatic resection in patients with cirrhosis and hepatocellular carcinoma.

Hepatic resection can be performed safely in carefully selected patients with cirrhosis. To minimize morbidity and mortality, it is essential to reliably estimate functional hepatic reserve and the extent of tumor before resection is performed. Child's classification is a reliable predictor of long term survival, but a more sensitive measure of hepatic function is needed to predict early morbidity and mortality. Child's classification can also be used to stratify patients and exclude those at high risk from hepatic resection. Promising predictors of operative mortality focus on the mitochondrial function of hepatocytes and include cytochrome a (+a3) contents and the redox tolerance index. Patients with advanced cirrhosis are not candidates for extensive hepatic resection and require careful evaluation before consideration for any hepatic resection. In patients with well-compensated cirrhosis and unifocal tumors, the procedure of choice is an anatomic resection of the tumor. If tumor size and location allows, a segmentectomy offers the best outcome, minimizing postoperative liver dysfunction while offering a long term outcome not dissimilar to a major liver resection. In highly selected patients with incidental tumors, a central tumor and perhaps in patients with multifocal hepatocellular carcinoma, hepatic transplantation may be of benefit. By using the appropriate predictors of hepatic function, refined surgical techniques and optimal postoperative care, a mortality rate of less than 10 per cent is achievable in cirrhotic patients with hepatocellular carcinoma who require resection.

Carcinoma, Hepatocellular↗