Living related liver transplantation. Why this option has been discarded in a pediatric liver transplant program in Chile.

Living related living transplantation (LRLT) has opened new possibilities for planning transplantation in better conditions for children with emergency situations and chronic liver diseases. Since we began the LRLT program in 1999, we have performed 57 pediatric liver transplants, 17 (29.8%) using living related donors (LRD). The aim of this study was to analyze the reasons why LRD were discarded as a therapeutic option. All pediatric patients were prospectively included in our Microsoft Excel database that was reviewed for obtaining information about causes why the LRLT could not be done. LRLT was proposed in 28 cases and performed in 17 (60.7%). The reasons for LRD rejection were: parent's fear of surgical complications in four cases; drug abuse in two; a mother without family support; medical reasons in two; and only one, due to anatomical reasons and in one case, cadaveric graft transplantation was performed while completing the father's evaluation. From these eleven cases, the indications for liver transplant were acute liver failure (ALF) in seven, biliary atresia in three, and Alagille syndrome in one. Nine were transplanted with cadaveric organs, but two patients with ALF died awaiting a liver. Efforts should be made to clarify the advantages and the disadvantages of LRD in each case, allowing parents to make a free, well-informed decision.

Combined liver and kidney transplantation in a multicenter transplantation program in Chile.

INTRODUCTION: Combined liver and kidney transplantation (CLKT) is an exceptional therapeutic procedure limited to a few diseases with advanced compromise of these organs. Hyperoxaluria type I and polycystic disease are the most frequent indications. The aim of this article was to report our indications and results of CLKT in a multicenter transplantation program in Chile. MATERIAL AND METHODS: Our Excel database was reviewed to select patients who were treated with CLKT between 1993 and July 2004. RESULTS: Among 242 liver transplantations (LT) and 48 kidney transplantations (KT), 7 were CLKT, representing 2.8% of LT and 14.5% of KT. Four patients were women and 3 were male of average age 46.8 years. One patient was a child. Most frequent indications were chronic renal failure associated with terminal liver disease and polycystic disease. One patient needed liver retransplantation due to hepatic vein thrombosis. One patient had a biliary fistula and another had a urinary fistula, treated conservatively. Acute liver rejection took place in 3 cases, 1 of which required antibodies. Two patients died, 1 due to aspergillosis and the other due to vascular complications in the transplanted liver. Actuarial survival rates were 71.4% at 1 and 5 years. Chronic renal failure is not a contraindication to LT. CONCLUSION: CLKT is an acceptable option for these patients.

Potentiation of ischemia-reperfusion liver injury by hyperthyroidism in the rat.

Parameters related to hepatic oxidative stress, cell injury, and liver histology were determined in control rats and in animals treated with 3,3',5-triiodothyronine (T3), after in vitro perfusion under normoxic or ischemia-reperfusion conditions. Thyroid calorigenesis was found concomitantly with higher rates of hepatic O2 consumption and thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) depletion, enhanced TBARS/GSH ratio as indicator of oxidative stress, and higher sinusoidal lactate dehydrogenase (LDH) efflux compared to control values, assessed under normoxic conditions. Perfused livers from control animals subjected to ischemia-reperfusion exhibited significant increases in the TBARS/GSH ratio and in the sinusoidal LDH efflux over values obtained under normoxic conditions, concomitantly with the appearance of small foci of necrotic cells in centrilobular and midzonal areas of the liver lobule. These parameters were further modified in the liver of hyperthyroid rats subjected to ischemia-reperfusion, with elevations in the TBARS/GSH ratio and in the sinusoidal LDH efflux largely exceeding the sum of effects elicited by hyperthyroidism or ischemia-reflow alone. In this situation, liver injury was more pronounced than in control rats, being characterized by multifocal areas of necrotic cells, irregularly distributed in the hepatic lobule, with lymphoid and macrophagic reaction. It is concluded that the concurrence of the hepatic mechanisms related to the oxidative stress underlying thyroid calorigenesis and ischemia-reoxygenation exacerbates liver injury, which seems to be mediated by potentiation of the prooxidant state of the organ.

Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat.

Parameters related to hepatic oxidative stress, cell injury, phagocytic activity, and liver histology were studied in control rats and in animals subjected to L-3,3',5-triiodothyronine (T3) and/or lindane administration. Hyperthyroidism elicited a calorigenic response and increased rates of hepatic O2 uptake, which were not modified by lindane treatment. T3 diminished serum lindane levels as well as those in the liver and adipose tissue, whereas lindane enhanced serum T3 levels in animals given T3. Compared with control rats, lindane significantly increased the rate of formation of thiobarbituric acid reactants (TBARS) by the liver, with no changes in either the reduced glutathione (GSH) content, the TBARS/GSH ratio as indicator of oxidative stress, or in the fractional rates of lactate dehydrogenase (LDH) and GSH efflux from perfused livers as integrity parameters. Hyperthyroidism induced GSH depletion in the liver, with a significant enhancement in the TBARS formation, the TBARS/GSH ratio, and in the fractional LDH and GSH efflux. These parameters were increased further by joint T3 and lindane administration in a magnitude exceeding the sum of the effects produced by the separate treatments. In addition, hyperthyroidism led to Kupffer cell hyperplasia and significant increases in serum glutamate oxalacetate transaminase (GOT) and in hepatic zymosan-induced chemiluminescence, while liver myeloperoxidase (MPO) activity was found unchanged, compared with controls. Rats treated with lindane presented normal liver histology, with no changes in biochemical parameters related to cell injury. The joint administration of T3 and lindane, however, elicited a marked elevation in serum GOT and glutamate pyruvate transaminase (GPT), concomitantly with extensive liver necrosis and the presence of granulomas containing lymphocytes, Kupffer cells and polymorphonuclear leukocytes (PMN). In this condition, hepatic zymosan-induced light emission and MPO activity were enhanced over control values. It is concluded that hyperthyroidism increases the susceptibility of the liver to the toxic effects of lindane, which seems to be accomplished by potentiation of the hepatic oxidative stress status. The latter effect may be conditioned by an enhanced phagocytic respiratory burst activity due to the observed Kupffer cell hyperplasia and PMN infiltration, in addition to the increased production of reactive oxygen species in parenchymal cells.

Type IV gastric ulcer: a new hypothesis.

In 1965 Johnson proposed his classification for gastric ulcer, which was subsequently adopted by the majority of surgeons. However, for many years we have observed the high frequency of subcardial or juxtacardial ulcers near the esophagogastric junction, which has not been reported elsewhere. In this article we describe the characteristics of this type of gastric ulcer and propose to designate it as a type IV gastric ulcer. This nomenclature is based on its clinical and pathophysiologic features. The anatomically "high" gastric ulcer has an incidence of 27.4%; its main features include a frequent association with the type O blood group; a low basal and stimulated acid output, a high incidence of upper gastrointestinal bleeding, a slower emptying of fluids, and a high percentage of deep penetrating ulcer.

Kupffer cell function in thyroid hormone-induced liver oxidative stress in the rat.

The influence of thyroid hormone (L-3, 3', 5-triiodothyronine, T3) on Kupffer cell function was studied in the isolated perfused rat liver by colloidal carbon infusion. Rates of carbon uptake were determined from the influent minus effluent concentration difference and the flow rate, and the respective carbon-induced respiratory activity was calculated by integration of the area under the O2 curves during carbon infusion. In the concentration range of 0.2 to 2.0 mg of carbon/ml, livers from euthyroid rats exhibited a sigmoidal-type kinetics of carbon uptake, with a Vmax of 4.8 mg/g liver/min and a concentration of 0.82 mg/ml for half-maximal rate; carbon-induced O2 uptake presented a hyperbolic-type kinetics, with a Vmax of 4.57 mumol of O2/g liver and a K(m) of 0.74 mg of carbon/ml, which significantly correlates with the carbon uptake rates. Light-microscopy showed that carbon was taken up exclusively by non-parenchymal cells, predominantly by Kupffer cells. Thyroid calorigenesis was found in parallel with increased rates of hepatic O2 consumption and thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) depletion, and higher sinusoidal lactate dehydrogenase (LDH) efflux compared to control values. In the concentration range of 0.25 to 0.75 mg/ml, carbon infusion did not modify liver LDH efflux in control rats, while it was significantly enhanced in T3-treated animals. In this latter group, higher carbon concentrations (1 and 1.3 mg/ml) led to loss of viability of the liver. At 0.25 to 0.75 mg of carbon/ml, both the rates of carbon uptake and the associated carbon-induced respiratory activities were significantly increased by T3 treatment, effects that were abolished by pretreatment of the rats with gadolinium chloride (GdCl3). In addition, GdCl3 decreased by 50% the changes induced by T3 in hepatic GSH content and TBARS formation. It is concluded that hyperthyroidism enhances Kupffer cell function, correlated with the increased number of liver macrophages observed histologically, which may represent an alternate source of reactive O2 species to that induced in parenchymal cells, thus contributing to the enhanced oxidative stress status developed.

Outcomes of orthotopic liver transplantation in Chile.

Our liver transplant program was started in 1993 in a private clinic and a public hospital. Thereafter, a rapid increase in adults and pediatric candidates for this therapeutic option lead to this analysis of results in 165 orthotopic liver transplants (OLT) in 143 patients between November 1993 and December 2002. Seventy-four OLT were performed in 66 adult patients and 91 in the pediatric group. Liver grafts came from cadaveric donors in 145 cases (74 adults and 71 children). The technique of living-related donor was utilized in 20 pediatric cases. Main indications for OLT in the adult group were HCV cirrhosis, primary biliary cirrhosis; biliary atresia and acute liver failure were the indications in pediatric patients. Retransplantation was needed for 23 patients, including 9 adults and 14 children. The most frequent causes of death were sepsis, graft primary nonfunction, and vascular complications. Actuarial survivals at 1 and 5 years were 80.7% and 72.6% for the adult group and 82% and 74.8% for the pediatric group, respectively. Our results are comparable to those published by large, experienced, international centers, with much better financial support.

Epidemiology and results of liver transplantation for acute liver failure in Chile.

Acute liver failure (ALF) is a severe, life-threatening condition associated with a high mortality rate. The objective of this study is to present the experience of a Chilean liver transplant program with orthotopic liver transplantation (OLT) for ALF. All patients with the diagnosis of ALF evaluated in our program between January 1995 and May 2003 were included in the analyses of etiology and outcomes. Candidates for OLT activated on a national waiting list were transplanted with cadaveric or living-related donor (LRD) organs. Twenty-seven patients age 1 to 19 years (median, 7.4 years) were transplanted at a median weight of 30.7 kg including 17 cadaveric and 10 with LRD livers. Most frequent etiologies were hepatitis A in 10 cases (37%) and unknown in 12 (48.1%). One donor experienced superficial phlebitis. Four patients were retransplanted (14.8%). Twenty patients are alive with 1- and 5-year survival rates of 74.1% At a median follow up of 34 months (range = 2 to 120). Seven patients died due to sepsis, multiorganic failure, graft primary nonfunction, intracranial hemorrhage, and intraoperative cardiac arrest. This experience revealed results comparable to international reports, allowing survival of patients destined to die.

Histological analysis of liver parenchyma and choledochal wall, and external diameter and intraluminal pressure of the common bile duct in controls and patients with common bile duct stones with and without acute suppurative cholangitis.

The purpose of this prospective controlled study was to determine the changes in intraluminal pressure and diameter of the common bile duct in a total of 121 bile patients with choledocholithiasis, and the consequences of these alterations for choledochal mucosa and liver histology. In fact, the reflux of bacteria from the obstructed biliary tract into the bloodstream is responsible for producing the clinical syndrome of acute suppurative cholangitis. Group I (26 patients) served as controls, Group II (50) had choledocholithiasis with clear green bile, and Group III (45) were patients with acute suppurative cholangitis with pus in the biliary tract. Ultrasonography revealed gallstones in all the patients. The external diameter of the common bile duct in patients with choledocholithiasis and acute suppurative cholangitis was significantly greater than in those of the other groups. Patients with acute suppurative cholangitis also had a higher intraluminal pressure than those of Groups I or II.

[Chronic hepatitis C and celiac sprue: an infrequent association]. / Hepatitis crónica por virus C y enfermedad celíaca: una asociación infrecuente.

Celiac sprue (CS) has been described in association with hepatitis C virus (HCV) as another immunologic manifestation of this infectious disease. We report 2 patients, a 42-year-old woman and a 59-year-old man, with chronic HCV hepatitis. Upper digestive endoscopy and duodenal biopsy were performed to investigate diverse symptoms. The results of histological analysis and serological study were compatible with CS. The association between both diseases, including immunological aspects and the implications of anti-HCV treatment, is discussed.

[Ductal epithelial lesions and pancreatic adenocarcinoma]. / Lesiones epiteliales ductales y adenocarcinoma pancreatico.

Epithelial alterations in pancreatic ducts may have a premalignant nature. We compared the incidence of different lesions in 49 pancreatic cancer specimens compared to 100 controls. Simple hyperplasia, mucosecretory metaplasia and pyloric metaplasia were evenly distributed among groups. In contrast, papillary hyperplasia, intestinal metaplasia and dysplasia were significantly more frequent in pancreas with carcinoma. Therefore, these lesions may have a precancerous nature.

[Fungal infections in 2 cases of fulminant hepatitis]. / Infección por hongos en dos casos de hepatitis fulminante.

Infectious complications are highly prevalent in patients with fulminating hepatitis. We report 2 female patients, aged 42 and 80 years old, with fulminating hepatitis caused by virus B and virus non-A non B, who died 20 and 25 days after initiation of the disease. Post mortem examinations showed severe C albicans infection of the gastrointestinal tract. A literature review is included.

[Transvenous hepatic biopsy in patients with blood coagulation disorders]. / Biopsia hepatica transvenosa en pacientes con defectos de la coagulacion sanguinea.

Severe clotting defects represent the main contraindication to percutaneous liver biopsy. A transvenous liver puncture technique has been developed for patients suffering from blood coagulation disorders. This approach was attempted in 17 of 148 consecutive patients (12%) in whom a needle liver biopsy was indicated. Hepatic tissue samplings were successfully obtained in 16 subjects. The mean size of the specimens was 7 mm. The clinical diagnosis or therapy were modified in 7 patients when the histopathology report was available. No complications related to the procedure occurred. Our early experience suggests that transvenous liver biopsy is indicated in one/ninth of cases in whom hepatic tissue sample is required for diagnosis. This technique is safe, and it has a high success rate to provide liver tissue samples.

[Retractile mesenteritis. Report of 4 cases]. / Mesenteritis retráctil. Comunicación de cuatro casos.

Retractile mesenteritis is a rare condition in which the inflammation process of the mesentery is the characteristic pathological. The histologic changes are variable proportions of fat necrosis, chronic inflammation and fibrosis. The clinical presentation of this process is diverse, also the natural history is variable, ranging from a benign to fatal disease. We reviewed 4 cases of retractile mesenteritis and evaluated the clinical manifestations. There was no gender predominance. The patients aged range was 63-69 years (average 65) Patients more often presented with abdominal mass (cases n: 1 and n: 4), and chronic diarrhea (cases n: 1 and 3). The etiology is unknown, the treatment is empirical, including corticosteroids, colchicine, immunosuppressive drugs and oral progesterone.

[Morphology of the myenteric plexus of the small intestine in patients with liver cirrhosis]. / Morfologia de los plexos mientericos del intestino delgado en pacientes con cirrosis hepática.

BACKGROUND: Patients with liver cirrhosis develop small bowel dysmotility of unknown etiology. Morphological features in the enteric nervous system and the intestinal smooth muscle may shed light on pathophysiology of the gut motility disturbances in this disease. AIM: To investigate the morphology of the myenteric plexuses and smooth muscle layers of the small intestine in patients with liver cirrhosis. PATIENTS AND METHODS: Full thickness biopsies of duodenum, jejunum and ileum from seven cirrhotic patients and seven controls were stained with several techniques, including silver impregnation. Neuronal counting and light microscopy studies were stained performed. RESULTS: The neuronal count was not significantly different in patients with cirrhosis compared to controls in duodenal samples (1.6 +/- 0.4 cel/mm vs 1.6 +/- 0.2 cel/mm), jejunal tissue (1.2 +/- 0.3 cel/mm vs 1.4 +/- 0.2 cel/mm), and in ileal specimens (0.8 +/- 0.3 cel/mm vs 0.9 +/- 0.2 cel/mm). In both groups, evidence of fibrosis or inflammation in myenteric plexuses and in smooth muscle was not found. Also, intestinal neuronal dysplasia was absent in cirrhotic patients as in controls. CONCLUSION: These results suggest that small bowel dysmotility in patients with liver cirrhosis is not related to structural changes in myenteric plexuses or in intestinal smooth muscle noted by light microscopy.

[Benign polypoid lesions of the gallbladder. Their relation to gallbladder adenocarcinoma]. / Lesiones polipoídeas benignas de la vesicula biliar. Relación con adenocarcinoma vesicular.

Out of 12,153 cholecystectomies performed over a period of 10 years, 114 polypoid lesions were found in 81 removed gallbladders (0.7%). 225 adenocarcinomas of the gallbladder were found in the same population (1.85%). The mean age of patients with polypoid lesions was 46 years, with a male to female ratio of 1:2.7. 94% of lesions measured less than 10 mm and only 9.6% were adenomas. Among these, dysplastic alterations were found in all and one had evidence of early adenocarcinoma. The mean age of patients with adenocarcinoma was 62 years with a male to female ratio of 1:6. Residual adenomas were found in 2 cases and multiple adenomas coexisted in another case. Thus, polypoid lesions of the gallbladder are less frequent than adenocarcinoma. Only adenomas show a potential to evolve to malignant lesions, but their low incidence makes them an unimportant precursor of gallbladder carcinoma.

[Hepatic angiosarcoma: report of 4 cases]. / Angiosarcoma hepático: comunicación de 4 casos.

Hepatic angiosarcoma is an infrequent vascular liver tumor of high malignancy. Four patients (two males) are presented, in whom a histopathological study was performed. All patients died and in three a necropsy was executed.

[Potential difference of the gastric mucosa in gastroduodenal disease. Relation with endoscopical and histologic findings]. / Diferencia de potencial de la mucosa gástrica en patología gastroduodenal. Relación con los hallazgos endoscópicos e histológicos.

Most studies of gastric transmucosal potential difference concern acute damage. We studied this phenomenon in 168 patients with different pathologic processes: erosive gastritis, duodenal and prepyloric ulcer, atrophic gastritis, gastric ulcer and normal controls. Ag-AgCl electrodes and Agar-KCl bridges were used to record potential differences. Biopsies were taken from gastric antrum and body and potential differences were related to endoscopic and histologic findings. Maximal values of -29.2 + 2 and -22.2 + 1.6 for body and antrum, respectively, were found in normals. Lowest values (-19.4 + 1.4 and -14.3 + 1.5, respectively) were found in gastric ulcer, with intermediate values for the other conditions. Normal histologic findings were associated to potentials of -31 + 2 and -20 + 3.1 whereas lower values were recorded in patients with moderate or severe atrophic changes. Our findings suggest a relation between mucosal atrophy and lower transmucosal potential differences.

[Esophageal potential difference in patients with peptic ulcer and gastritis]. / Diferencia de potencial esofágico en pacientes con úlcera péptica y gastritis.

A potential difference is generated by the active transport of electrolytes through low permeability epithelium such as the gastric and esophageal mucosa. A decrease in this potential has been proposed as an indicator of mucosal damage. We measured potential difference in 151 patients undergoing endoscopy for duodenal ulcer, gastritis or as a control group. Mean for the whole group was -18 + 0.5 mV, range -4 to -37. No differences were found among groups. Due to the ample variation in potential difference both at the gastric and esophageal levels, its determination was of no use in localizing the boundary between gastric and esophageal mucosa.

[Biopsy and endoscopic prospective study of the prevalence of intestinal metaplasia in the gastroesophageal junction in controls and in patients with gastroesophageal reflux]. / Estudio prospectivo endoscópico y biópsico de la prevalencia de metaplasia intestinal en la unión gastro-esofágica en controles y en pacientes con reflujo gastroesofágico.

BACKGROUND: The classic diagnosis of Barret esophagus is based on the finding of three of more cm of distal esophagus covered by specialized columnar epithelium. However, at the present time, it is based on the presence of intestinal metaplasia in the junction of squamous-columnar mucosae. AIM: To assess the prevalence of Barret esophagus using endoscopic and pathological criteria in healthy subjects and in individuals with gastroesophageal reflux. PATIENTS AND METHODS: One hundred thirty nine controls and 372 patients with symptoms of gastroesophageal reflux subjected to an upper gastrointestinal endoscopy were studied. Patients with Barret esophagus were classified as having a "mini Barret" when the pathological presence of intestinal metaplasia was the only finding. A "short Barret esophagus" was diagnosed when less than 3 cm were covered with fingerings of mucosal substitutions and "extensive Barret esophagus" when more than 3 cm of esophageal mucosa were substituted. RESULTS: Two percent of controls, 12.4% of patients with gastroesophageal reflux without esophagitis and 11.7% of such patients with esophagitis had intestinal metaplasia in the gastroesophageal junction. Patients with Barret esophagus were older than the rest of patients. "Short Barret esophagus" is six times more frequent than "extensive Barret esophagus". Esophageal erosions, peptic ulcers and stenosis were more frequent in patients with extensive Barret esophagus. The prevalence of dysplasia was similar in all types of Barret esophagus. CONCLUSIONS: Intestinal metaplasia was very infrequent in control patients. In subjects with gastroesophageal reflux, classic endoscopic diagnosis may miss up to 80% of patients with Barret esophagus. Thus, gastroesophageal junction biopsies must be obtained in all patients with symptoms of gastroesophageal reflux.