[Interventionist endoscopic ultrasonography. A retrospective analysis of 60 procedures]. / Ultrasonografía endoscópica intervencionista. Análisis retrospectivo de 60 procedimientos.

INTRODUCTION AND OBJECTIVE: interventionist endoscopic ultrasonography is increasingly used because of its growing indications. We present here our retrospective and initial experience (60 procedures) with endoscopic ultrasonography (EUS) both for diagnosis (EUS-FNA) and therapy (EUS-guided tumorectomy and mucosectomy). PATIENTS AND METHOD: in a group with 27 cases including 10 submucosal tumors (SMTs), 2 adenopathies, and 15 potential pancreatic tumors (8 pancreatic cancers), a sectorial EUS-FNA at 7.5 MHz was performed for diagnosis prior to therapy (mainly surgical). A pancreatic pseudocyst was drained. In 21 cases with 27 SMTs (10 patients with 13 carcinoids) a tumorectomy was carried out using the standard loop or assisted polypectomy technique with submucosal injection, and in a few cases (two) using elastic band ligation following a radial EUS at 7.5, 12, or 20 MHz. In 6 cases of superficial gastroesophageal cancer or gastric dysplasia an endoscopic mucosal resection (classic EMR) was performed after EUS or MPs at 7.5 and 20 MHz. Fifty-five patients with 60 lesions, 29 femaes and 26 males with a mean age of 60 years (30-88 years) were retrospectively analyzed. RESULTS: diagnostic precision (P), sensitivity (S), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for EUS-FNA was 85, 83, 100, 100, and 43%, respectively, when comparing results with specimen histology. P was higher for adenopathies (100%) and pancreatic tumors (87%) than for SMTs (80%). No complications arose, except for one episode of upper gastrointestinal bleeding (UGIB) (3.7%) that was endoscopically and satisfactorily treated in a gastric SMT. In the group with 21 patients (10 carcinoids with 13 tumors) 27 SMTs were endoscopically treated by tumorectomy with no perforation and only 2 UGIBs (7.4%), one of them self-limited, recorded. Endoscopic resection was complete in 92% of cases. No complications occurred with classic EMR, and all patients are still alive with no evidence of relapse, either local or metastatic. In this group the rate of complete resections was 100%. CONCLUSIONS: EUS-FNA is a safe technique with high diagnostic accuracy. EUS-guided tumorectomy and mucosectomy are also safe and effective techniques in the endoscopic management of these tumors.

Endoscopic staging of low-grade gastric MALT lymphoma.

INTRODUCTION: Endoscopic ultrasonography (EUS) has already proven useful in the assessment of submucosal lesions, and the staging of gastrointestinal cancer, particularly gastric MALT-type lymphoma. The goal of this paper was EUS staging. PATIENTS AND METHOD: 24 patients (10 females, 14 males) with a median age of 56 years and possibly gastric MALT lymphoma (25 cases) were studied using videoendoscopy, biopsies, and echoendoscopy with 7.5- and 20-MHz radial EUS, and also with 12- and 20-MHz miniprobes (MPs). Nineteen patients were definitely evaluated (7 females, 12 males) as having 20 MALT-type lymphomas, as five patients were post-hoc disregarded when an invasive, high-grade gastric lymphoma (3c) or plasmocytoma (2c) was subsequently demonstrated. Of these 19 patients, all had T1 lesions except for two with T2 lesions; one patient had a gastroduodenal T1 lymphoma. Echographic findings with MPs were compared to EUS (gold standard) and histology both before and after eradication. Then, patients were followed up every 1-3-6 months using videoendoscopy and MPs. RESULTS: Echoendoscopy correctly identified T stages in 90% of cases. MPs identified T stages in 88% of cases, and N stages in 33% of cases, with results being slightly inferior to those obtained with conventional EUS (91 vs. 45%); they were consequently used for follow-up. After eradication, all but two patients are in complete remission and have been followed every 1-3-6 months using MPs without echographic abnormalities, except for a patient who relapsed.

EUS-guided mucosectomy for gastrointestinal cancer.

INTRODUCTION: the only way of improving prognosis and survival in gastrointestinal cancer is early diagnosis, with intramucosal localization as confirmed by endoscopic ultrasonography (EUS) or 20-MHz miniprobes (MPs) (T1) being most appropriate. Endoscopic mucosal resection (EMR) has proven effective in the treatment of this sort of lesions. PATIENTS AND METHOD: in a group (18 cases) with 15 cases of superficial gastrointestinal cancer and 3 cases of severe gastric dysplasia, 9 cases (3 esophageal, 4 gastric, 2 rectal) underwent a classic EMR following EUS or a 7.5- and 20-MHz miniprobe exploration. RESULTS: ultrasonographic studies showed a T1 in all but one esophageal case (Tis), and in both gastric dysplasias, with no changed layer structure being demonstrated in the latter (T0). No complications arose with classic EMR, and all 9 patients are alive and free from local or metastatic recurrence, except for one esophageal case, which recurred distally to the esophageal lesion (metachronous). CONCLUSIONS: echoendoscopically-assisted EMR is a safe, effective technique in the endoscopic management of superficial gastrointestinal (esophageal, gastric, colorectal) cancer. Recurrence most likely depends upon cancer multiplicity.

Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes.

The three monokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) modulate acute phase plasma protein synthesis in adult human hepatocytes. Only IL-6 stimulates the synthesis of the full spectrum of acute phase proteins as seen in inflammatory states in humans, i.e. synthesis and secretion of C-reactive protein, serum amyloid A, fibrinogen, alpha 1-antitrypsin, alpha 1-antichymotrypsin and haptoglobin are increased while albumin, transferrin and fibronectin are decreased. IL-1 beta as well as TNF alpha, although having a moderate effect on the positive acute phase proteins and inhibiting the synthesis of fibrinogen, albumin and transferrin, fail to induce serum amyloid A and C-reactive protein. These data suggest that IL-6 plays the key role in the regulation of acute phase protein synthesis in human hepatocytes.

Intracellular glutathione in human hepatocytes incubated with S-adenosyl-L-methionine and GSH-depleting drugs.

The present study was undertaken to investigate (a) whether S-adenosyl-L-methionine (SAMe) added to culture medium can increase intracellular glutathione (GSH) levels in human hepatocytes and (b) whether SAMe can prevent the GSH depletion found in human hepatocytes incubated with GSH-depleting drugs (paracetamol, opiates, ethanol). Incubation of hepatocytes with increasing concentrations of SAMe resulted in a dose-dependent elevation of intracellular GSH content, which reached its maximum (35% increase) at 30 microM after 20 h. SAMe, as the only sulfur source in the medium, was efficient in repleting GSH-depleted hepatocytes following treatment with diethyl maleate. Incubation of human hepatocytes with SAMe attenuated the GSH depletion of cells incubated with toxic concentrations of paracetamol (2 mM), heroin (0.5 mM) and methadone (0.2 mM). A decrease in GSH due to exposure of hepatocytes to 50 mM ethanol was prevented when SAMe was simultaneously added to ethanol, and human hepatocytes maintained their GSH levels like non ethanol-treated cells. The experimental results of our work give the first direct evidence of the ability of exogenously administered SAMe to increase intracellular GSH levels in human hepatocytes and to prevent the GSH depletion caused by paracetamol, opiates and ethanol.

The effects of buprenorphine on the metabolism of human hepatocytes.

Adult human hepatocytes cultured in chemically defined conditions were used as a biological model to examine the metabolic effects of buprenorphine on the human liver. Cell extension and monolayer formation of human hepatocytes were affected in a dose-dependent manner after 24 hr of exposure to the drug. According to the several endpoints evaluated (cellular protein, intracellular lactate dehydrogenase activity and the MTT test), the half-maximal cytotoxic effect (IC(50)) of buprenorphine was close to 100 mum. Longer exposure of hepatocytes to buprenorphine (72 hr) increased its cytotoxicity, and the IC(50) of the drug was reduced to 50 mum. Lower concentrations of the drug (in the 5-50-mum range) significantly impaired the metabolic functions of the hepatocytes. Incubation of the cells with 40 mum-buprenorphine for 24 hr reduced the glycogen content to 60% of the initial content and 50 mum-buprenorphine inhibited glycogen synthesis in glucagon-depleted human hepatocytes by about 40%. Albumin synthesis was the most sensitive metabolic parameter, and 24-hr exposure of hepatocytes to 10 mum-buprenorphine, a concentration with no apparent cytotoxic effects, reduced albumin synthesis to 50%. Urea synthesis was moderately affected by buprenorphine. Glutathione content was reduced in a dose-dependent manner by the drug, reaching a minimum value (60% of control values) after 6 hr of exposure to 50 mum of the opiate. Analysis of the data on the therapeutic dosage of buprenorphine and other opiates showed that the toxicity risk index of buprenorphine, like that of meperidine, lies somewhere between that of morphine and methadone.

Main pancreatic duct: morphlogy after acute biliary pancreatitis with magnetic resonance cholangiopancreatography after secretin stimulation.

OBJECTIVE: to assess whether a magnetic resonance cholangiopancreatography performed after an acute biliary pancreatitis leads to pancreatic morphological alterations and if secretin stimulation influences the visualization of the pancreatic tree. METHOD: forty patients with acute biliary pancreatitis, 25 female (62,5/) and 15 male (37,5/), 27 mild and 13 severe, were prospectively and consecutively studied. All patients had undergone cholecystectomy. No altered pancreatic functions were observed. Morphology of the pancreas and of the main pancreatic duct were assessed by magnetic resonance cholangiopancreatography five years after the episode of pancreatitis and a comparative study between patients and case controls was carried out. Secretin was given in 16 cases in whom the visualization of the duct was incomplete or absent. Ductal morphology before and after secretin stimulation was compared. RESULTS: significant differences were observed when the diameter and length of the main pancreatic duct were compared in patients and control cases and was completely visualized in 60% of the cases, and could be seen in all patients after secretin stimulation. The comparative statistical analysis of the length and diameter of the pancreatic duct before and after the secretin stimulation showed significant differences. CONCLUSION: acute biliary pancreatitis leads to morphological alterations, regarded as scar lesions which do not become chronic. Secretin stimulation improves the visualization of the main pancreatic duct.

[Acute left ventricular systolic dysfunction after pericardial effusion drainage]. / Disfunção sistólica aguda de ventrículo esquerdo após drenagem de derrame pericárdico.

A patient with a thymoma and initially normal ventricular systolic function developed cardiac tamponade, which was relieved by pericardiocentesis. After four days, the tumor was removed and, one week after the relief of tamponade, she developed severe left ventricular systolic dysfunction, that recovered in three days with venous therapy.

Toxicity of paracetamol in human hepatocytes. Comparison of the protective effects of sulfhydryl compounds acting as glutathione precursors.

The hepatotoxicity of N-acetyl-p-aminophenol (acetaminophen, paracetamol) was investigated in hepatocyte cultures obtained from eight different human liver biopsies. Incubation of hepatocytes with paracetamol resulted in a dose- and time-dependent glutathione depletion. Glutathione decreased linearly for 8 h, reaching a minimum after 12 h of exposure. Cytotoxicity, assessed as loss of cellular protein from plates, was observed only when glutathione decreased below 20% for more than 12 h. However, in one donor, cytotoxicity was observed with even a moderate glutathione decrease. Prestimulation of hepatocytes with 1 mM phenobarbital or 2 microM methylcholanthrene for 48 h did not lead to a significant increase of paracetamol toxicity, although the glutathione levels in 3-methylcholanthrene-treated cells were somewhat lower. Several metabolic precursors were examined in vitro for their ability to increase intracellular glutathione and the results showed the following sequence: N-acetylcysteine greater than thioproline greater than cysteine greater than 2-oxo-4-thiazolidine carboxylic acid greater than methionine. However, only N-acetylcysteine, thioproline, and cysteine substantially increased glutathione levels when 1 mM paracetamol was present in the incubation medium and thus prevented its toxicity. N-acetylcysteine elevated glutathione even after 24 h of preexposure to paracetamol. The fact that cell damage did not correlate with glutathione levels in all human cultures suggests that glutathione depletion may not be the only determinant of paracetamol toxicity in human hepatocytes.

Usefulness of oral video push enteroscopy in Crohn's disease.

BACKGROUND AND STUDY AIMS: Oral endoscopic examination of the small bowel is of vital importance when studying various clinical conditions. In this study we evaluate the diagnostic yield of push-type enteroscopy in patients with undiagnosed suspected clinical Crohn's disease using lower and upper endoscopy and double contrast X-ray in order to establish the diagnostic value of this instrument in the jejunum. PATIENTS AND METHODS: Eight patients displaying symptoms of Crohn's disease, five adults with chronic diarrhea and abdominal pain and three children with retarded growth and weight loss associated with diarrhea underwent ambulatory enteroscopy using a Pentax videoenteroscope. RESULTS: The average depth of insertion beyond the ligament of Treitz was 125 cm. Four patients (50%) were found to have macroscopic and/or microscopic lesions of Crohn's disease in the small intestine, which went unrecognized by other standard endoscopic and radiologic methods. Tolerance was good and there were no complications related to the procedure. CONCLUSION: Oral videoenteroscopy with biopsy is a safe and useful procedure for diagnosis of Crohn's disease in selected patients with suggestive symptoms and can be of great diagnostic value after failure of conventional endoscopic X-ray methods.

Hepatotoxicity of the opioids morphine, heroin, meperidine, and methadone to cultured human hepatocytes.

Adult human hepatocytes in chemically defined culture conditions were incubated with morphine, heroin, meperidine, and methadone to investigate their potential hepatotoxicity to human liver. Cytotoxic effects were observed at about 100 times the plasma concentrations required to produce analgesia in human nonaddicts. Concentrations of 1 mM morphine, heroin, and meperidine reduced the glycogen content by 50%, while even 0.2 mM methadone produced a depletion of 70% after 24 h of treatment. Concentrations of 0.8 mM morphine and heroin, 0.4 mM meperidine, and 0.005 mM methadone inhibited the albumin synthesis by about 50% after 24 h of pretreatment. Intracellular glutathione was reduced to 50% of that of controls after 2-3 h of incubation with 2 mM morphine and 1 mM heroin, while 1 mM meperidine and 0.2 mM methadone produced a reduction of about 30% after 6 h incubation. The results show that therapeutic doses of the opioids is unlikely to produce irreversible damage to human hepatocytes, but opiate doses during tolerance or abuse may be a cause of liver dysfunction.

Drug biotransformation by human hepatocytes. In vitro/in vivo metabolism by cells from the same donor.

BACKGROUND/AIMS: Cultured human hepatocytes are considered a close model to human liver. However, the fact that hepatocytes are placed in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism in vitro reflect that of the liver in vivo? This issue was examined by investigating the in vitro and in vivo metabolism of aceclofenac, an analgesic/anti-inflammatory drug. METHODS: Hepatocytes isolated from programmed liver biopsies were incubated with aceclofenac, and the metabolites formed were investigated by HPLC. During the course of clinical recovery, patients were given the drug, and the metabolites, largely present in the urine, were analyzed. In vitro and in vivo data of the same individual were compared. RESULTS: The relative abundance of oxidized metabolites in vitro (i.e. 4'OH-aceclofenac + 4'OH-diclofenac vs. total hydroxylated metabolites; Spearman's p = 0.855), as well the hydrolysis of aceclofenac (4'OH-diclofenac vs. 4'OH-aceclofenac + 4'OH-diclofenac; p = 0.691) correlated well with in vivo data. The conjugation of the drug in vitro (24.6 +/- 7.6%) was lower than that in vivo (44.9 +/- 5.3%). The rate of 4'OH-aceclofenac formation in vitro correlated with the amount of metabolites excreted in urine after 16 h (p = 0.95). CONCLUSIONS: The in vitro/in vivo metabolism of the drug was surprisingly similar in each patient. The variability observed in vitro reflected an existing phenotypic variability among donors.

Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6.

Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin-1 beta, recombinant interleukin-6 and tumor necrosis factor-alpha. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein-mRNA and C-reactive protein-protein synthesis. Also, fibrinogen and alpha-1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level.

Effects of hepatocyte growth factor on the growth and metabolism of human hepatocytes in primary culture.

The effect of recombinant human hepatocyte growth factor (h-rHGF), a potent mitogen for hepatocytes, was investigated in primary cultures of human hepatocytes. Here, we describe a series of experiments to investigate the kinetics of its mitogenic action, as well as its metabolic effects on cultured human hepatocytes. The h-rHGF is a potent signal for initiating DNA synthesis in human hepatocytes, with maximal stimulatory effects at 10 ng/mL (0.1 pmol/L). The kinetics of DNA synthesis showed a lag of about 48 to 72 hours, followed by a maximum at 96 hours. At least 48 hours of continuous exposure to h-rHGF are required to initiate DNA synthesis in quiescent human hepatocytes. Cell cycle analysis by flow cytometry showed that most of quiescent 2c cells have left G0/G1 and entered the cell cycle (S and G2/M phases) by 96 hours of continuous exposure to h-rHGF. When compared with other growth factors, h-rHGF was a much more potent mitogen. The effects of 10 ng/mL (0.1 pmol/L) h-rHGF on DNA synthesis were only achieved by 1.5 pmol/L epidermal growth factor (EGF), 0.1 mumol/L insulin, or 1 mumol/L glucagon. It is noteworthy that the effect of h-rHGF was potentiated by glucagon but not by insulin or EGF. The stimulatory effect of HGF on DNA synthesis was gradually inhibited by h-rHGF transforming growth factor beta (TGF-beta) in the range 1 to 10 ng/ml. The HGF also influenced the expression of other hepatic genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell cycle progression proteins (cyclins), oncogene expression, and signal transduction during the proliferative response of human hepatocytes to hepatocyte growth factor.

Human hepatocytes stimulated with human recombinant hepatocyte growth factor (h-rHGF) (10 ng/mL) displayed a characteristic lag period before entering into the S phase. The duration of this delay was dependent on the timing of h-rHGF addition to cultures. The highest peak of DNA synthesis was observed at 120 hours of culture when hepatocytes were stimulated with h-rHGF at 72 hours of culture. This was accompanied by an early peak of c-jun and c-fos synthesis (3 hours after addition of h-rHGF) followed by c-myc (6 hours) and increased expression of cyclins A, B, D, and E (12 hours after h-rHGF). A significant dose-dependent increase in inositol 1,4,5-P3 was observed within 45 seconds after stimulation with the factor. This was followed by an immediate increase in the cytosolic-free calcium. Cyclic adenosine monophosphate (cAMP) levels did not change after stimulation with the factor. Tyrosine phosphorylation seems to be an early event in the course of the stimulatory effect of h-rHGF on DNA synthesis of hepatocytes; genistein, a tyrosine kinase inhibitor, impaired the stimulatory effect of h-rHGF on DNA synthesis dose dependently. On the other hand, the action of the factor was negatively regulated by protein kinase C activation, as shown by the increased stimulatory effect of h-rHGF on DNA synthesis upon inhibition of protein kinase C by H7.

Culture of human hepatocytes from small surgical liver biopsies. Biochemical characterization and comparison with in vivo.

High yields of human hepatocytes (up to 23 X 10(6) viable cells/g) were obtained from small surgical liver biopsies (1 to 3 g) by a two-step collagenase microperfusion method. Cell viability was about 95%, attachment efficiency of hepatocytes seeded on fibronectin-coated plates was 80% within 1 h after plating, and cells survived for about 2 wk in serum-free Ham's F12 containing 0.2% bovine serum albumin, 10(-8) M insulin, and 10(-8) M dexamethasone. To evaluate the metabolism of human hepatocytes in serum-free conditions, we measured their most characteristic biochemical functions and compared them to those reported for human liver. After 24 h in culture, glycogen content was 1250 +/- 177 nmol glucose/mg cell protein and remained stable for several days. Gluconeogenesis from lactate in hormone-free media was (3.50 +/- 0.17 nmol glucose.mg-1.min-1) similar to that reported for human liver. Insulin at 10(-8) M activated glycolysis (X1.40) and glycogenesis (X1.34), and glucagon at 10(-9) M stimulated gluconeogenesis (X1.35) and glycogenolysis (X2.18). Human hepatocytes synthesized albumin, transferrin, fibrinogen, alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, haptoglobin, alpha 2-macroglobulin, and plasma fibronectin and excreted them to the culture medium. Maximum protein synthesis was stimulated by 10(-9) M dexamethasone. Basal urea synthesis oscillated between 2.5 and 3.5 nmol.mg-1 cell protein.min-1, about 5 times the value estimated for human liver. Cytochrome P-450 decreased in culture but it was still 20% of freshly isolated hepatocytes by Day 5 in culture. In addition, ethoxycumarin-O-deethylase and aryl hydrocarbon hydroxylase could be induced in vitro by treatment with methyl cholanthrene. Glutathione levels were similar to those reported for human liver (35 nmol.mg-1). The results of our work show that adult human hepatocytes obtained from small surgical biopsies and cultured in chemically defined conditions express their most important metabolic functions to an extent that is similar to that reported for adult human liver.

Oncostatin M down-regulates basal and induced cytochromes P450 in human hepatocytes.

The effects of oncostatin M on the expression of different cytochrome P450 (CYP) isozymes has been investigated in human hepatocytes. The dose-response and time-course analyses of effects on CYP1A2 and CYP3A4 isozymes revealed that maximal inhibition was reached after 48 hr of exposure of human hepatocytes to 25 units/ml oncostatin M. Reductions in CYP1A2 and CYP3A4 activity produced by oncostatin M correlated with decreases in protein content, de novo protein synthesis and specific mRNA levels, thus suggesting that oncostatin M could down-regulate CYP expression at the transcriptional level. The inhibitory potency of oncostatin M on CYP expression was compared with that of other cytokines belonging to the interleukin-6 receptor family (interleukin-6, interleukin-11 and leukemia inhibitory factor), and interferon-gamma, which is recognized to inhibit human CYP expression, and granulocyte colony-stimulating factor, a cytokine that shares structural homology with the interleukin-6 family but has a different transduction signal. Maximal reductions in CYP1A2 activity were reached after 48 hr of treatment with cytokines. At that time, oncostatin M showed the highest inhibitory effects on CYP1A2 activity (38% of control), followed by interferon (49% of control) and interleukin-6 (60% of control), whereas minor effects were produced by the other cytokines (74-80%). Comparable decreases were observed for CYP2A6, CYP2B6 and CYP3A4 activities. Enzymatic activity and de novo protein synthesis of 3-methylcholanthrene-induced CYP1A2 and dexamethasone-induced CYP3A4 were also reduced to a much greater extent by oncostatin M than by other cytokines. The results show that oncostatin M is the most effective cytokine in down-regulating CYP isozymes in human hepatocytes, and its effects were evident even after removal of the cytokine from the culture medium.

Ultrasonografía endoscópica intervencionista. Análisis retrospectivo de 60 procedimientos / Interventionist endoscopic ultrasonography. A retrospective analysis of 60 procedures

Introducción y objetivo: la ultrasonografía endoscópica intervencionista cada día se realiza con más frecuencia debido a que goza de mayores indicaciones. Presentamos nuestra experiencia retrospectiva e inicial (60 procedimientos) en ultrasonografía endoscópica (USE) intervencionista diagnóstica (USE-PAAF) y terapéutica (tumorectomía y mucosectomía guiada por USE). Pacientes y método: en un grupo de 27 casos, con 10 tumores submucosos (TSM), 2 adenopatías y 15 posibles tumores de páncreas (8 cánceres de páncreas), se practicó USE-PAAF sectorial con 7,5 MHz con fines diagnósticos previa a la actuación terapéutica (fundamentalmente quirúrgica). Un caso de seudoquiste pancreático fue drenado. En 21 casos con 27 TSM (10 enfermos con 13 carcinoides) se practicó tumorectomía mediante la técnica convencional de polipectomía con asa o asistida con inyección submucosa, y en pocos casos (dos) ligando la lesión con bandas elásticas, previa USE radial con 7,5, 12, o 20 MHz. En 6 casos de cáncer superficial gastroesofágico o displasia gástrica se ha practicado resección mucosa endoscópica (RME clásica) previa USE o MS de 7,5 y 20 MHz. Se analizaron retrospectivamente 55 pacientes con 60 lesiones, 29 mujeres y 26 varones, con una edad media de 60 años (30-88 años). Resultados: la precisión diagnóstica (P), sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y valor predictivo negativo (VPN) de la USE-PAAF fue del 85, 83, 100, 100, y 43%, respectivamente, al comparar los resultados con la histología de la pieza. La P fue mayor para las adenopatías (100%) y tumores pancreáticos (87%) que para los TSM (80%). No hubo complicaciones excepto una hemorragia digestiva alta (HDA) (3.7%) que se trató endoscópicamente y satisfactoriamente en un TSM gástrico. En el grupo de 21 enfermos (10 carcinoides con 13 tumores) se trataron endoscópicamente mediante tumorectomía 27 TSM sin que se registrara ninguna perforación, y tan sólo 2 HDA (7,4%) una de ellas autolimitada. La resección endoscópica fue completa en el 92% de los casos. Con la técnica de la RME clásica no hubo complicaciones, y todos los pacientes están vivos y sin evidencia de recidiva local o metastásica. En este grupo el porcentaje de resección completa fue del 100%. Conclusiones: la USE-PAAF es una técnica segura con una buena precisión diagnóstica. La tumorectomía y la mucosectomía asistidas por USE son también técnicas seguras y eficaces en el tratamiento endoscópico de dichos tumores

Introduction and objective: interventionist endoscopic ultrasonography is increasingly used because of its growing indications. We present here our retrospective and initial experience (60 procedures) with endoscopic ultrasonography (EUS) both for diagnosis (EUS-FNA) and therapy (EUS-guided tumorectomy and mucosectomy). Patients and method: in a group with 27 cases including 10 submucosal tumors (SMTs), 2 adenopathies, and 15 potential pancreatic tumors (8 pancreatic cancers), a sectorial EUS-FNA at 7.5 MHz was performed for diagnosis prior to therapy (mainly surgical). A pancreatic pseudocyst was drained. In 21 cases with 27 SMTs (10 patients with 13 carcinoids) a tumorectomy was carried out using the standard loop or assisted polypectomy technique with submucosal injection, and in a few cases (two) using elastic band ligation following a radial EUS at 7.5, 12, or 20 MHz. In 6 cases of superficial gastroesophageal cancer or gastric dysplasia an endoscopic mucosal resection (classic EMR) was performed after EUS or MPs at 7.5 and 20 MHz. Fifty-five patients with 60 lesions, 29 femaes and 26 males with a mean age of 60 years (30- 88 years) were retrospectively analyzed. Results: diagnostic pecision (P), sensitivity (S), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for EUS-FNA was 85, 83, 100, 100, and 43%, respectively, when comparing results with specimen histology. P was higher for adenopathies (100%) and pancreatic tumors (87%) than for SMTs (80%). No complications arose, except for one episode of upper gastrointestinal bleeding (UGIB) (3.7%) that was endoscopically and satisfactorily treated in a gastric SMT. In the group with 21 patients (10 carcinoids with 13 tumors) 27 SMTs were endoscopically treated by tumorectomy with no perforation and only 2 UGIBs (7.4%), one of them self-limited, recorded. Endoscopic resection was complete in 92% of cases. No complications occurred with classic EMR, and all patients are still alive with no evidence of relapse, either local or metastatic. In this group the rate of complete resections was 100%. Conclusions: EUS-FNA is a safe technique with high diagnostic accuracy. EUS-guided tumorectomy and mucosectomy are also safe and effective techniques in the endoscopic management of these tumors

Estadificación por ecoendoscopia en el linfoma gástrico tipo MALT de bajo grado / Endoscopic staging of low-grade gastric malt lymphoma

Introducción: la ultrasonografía endoscópica (USE) ha demostrado ya su utilidad en la evaluación de las lesiones submucosas, en la estadificación del cáncer digestivo en general, y del linfoma gástrico tipo MALT en particular. El objetivo de este trabajo fue la estadificación por USE. Pacientes y método: veinticuatro enfermos (10 mujeres y 14 varones) con edad media de 56 años y con posible linfoma gástrico tipo MALT (25 casos) fueron estudiados con videoendoscopia, biopsias y ecoendoscopia con USE radial de 7,5 y 20 MHz, y con minisondas (MS) de 12 y 20 MHz. Se evaluaron definitivamente 19 pacientes (7 mujeres y 12 varones) con 20 MALT, ya que cinco enfermos se desestimaron por demostrarse a posteriori que presentaban un linfoma gástrico invasivo de alto grado (3c) o un plasmocitoma (2c). De los 19 pacientes todos eran T1 menos dos pacientes que eran T2, y otra presentaba un linfoma T1 gastroduodenal. Los hallazgos ecográficos de las MS fueron comparados con la USE (gold standard) y con la histología antes y después de la erradicación. Después, fueron seguidos cada 1, 3 y 6 meses mediante videoendoscopia y MS. Resultados: la ecoendoscopia identificó el estadio T correcto en el 90% de los casos. Las MS identificaron el estadio T en el 88% de los casos y la N en el 33% de los casos, con resultados discretamente inferiores a los obtenidos con la USE convencional (91 y 45%), por lo que se utilizaron en el seguimiento. Después de la erradicación, todos menos dos están en remisión completa y han sido seguidos cada 1, 3 y 6 meses con las MS sin observar anomalías ecográficas, excepto una paciente que hizo una recidiva

Introduction: endoscopic ultrasonography (EUS) has already proven useful in the assessment of submucosal lesions, and the staging of gastrointestinal cancer, particularly gastric MALT-type lymphoma. The goal of this paper was EUS staging. Patients and method: 24 patients (10 females, 14 males) with a median age of 56 years and possibly gastric MALT lymphoma (25 cases) were studied using videoendoscopy, biopsies, and echoendoscopy with 7.5- and 20-MHz radial EUS, and also with 12- and 20-MHz miniprobes (MPs). Nineteen patients were definitely evaluated (7 females, 12 males) as having 20 MALT-type lymphomas, as five patients were post-hoc disregarded when an invasive, high-grade gastric lymphoma (3c) or plasmocytoma (2c) was subsequently demonstrated. Of these 19 patients, all had T1 lesions except for two with T2 lesions; one patient had a gastroduodenal T1 lymphoma. Echographic findings with MPs were compared to EUS (gold standard) and histology both before and after eradication. Then, patients were followed up every 1-3-6 months using videoendoscopy and MPs. Results: echoendoscopy correctly identified T stages in 90% of cases. MPs identified T stages in 88% of cases, and N stages in 33% of cases, with results being slightly inferior to those obtained with conventional EUS (91 vs. 45%); they were consequently used for follow-up. After eradication, all but two patients are in complete remission and have been followed every 1-3-6 months using MPs without echographic abnormalities, except for a patient who relapsed

Mucosectomía guiada por USE en el cáncer digestivo / EUS-guided mucosectomy for gastrointestinal cancer

Introducción: la única forma de mejorar el pronóstico y la supervivenciadel cáncer digestivo es su diagnóstico precoz, siendosu estadio ideal la localización intramucosa, confirmada por ultrasonografíaendoscópica (USE) o minisondas (MS) de 20 MHz (T1).La resección mucosa endoscópica (RME) se ha demostrado eficazen el tratamiento de este tipo de lesiones.Pacientes y método: en un grupo (18 casos) de 15 casos decáncer superficial digestivo y 3 displasias severas gástricas, se hanpracticado en 9 casos (3 de esófago, 4 de estómago, y 2 de recto)RME clásica, previa USE o MS de 7,5 y 20 MHz.Resultados: los estudios ultrasonográficos demostraron entodos los casos que se trataba de un T1 menos en un caso, esofágico(Tis), y en los dos casos de displasias gástricas, en los cualesno se pudo demostrar alteración de la estructura de capas (T0).Con la técnica de RME clásica no hubo complicaciones, y los9 están vivos, sin recidiva local o metastásica, excepto un caso,esofágico, que recidivó distalmente a la lesión esofágica (metacrónico).Conclusiones: la RME asistida por ecoendoscopia es una técnicasegura y eficaz en el tratamiento endoscópico del cáncer superficialdigestivo (esofágico, gástrico y colorrectal). La recidivaprobablemente está en función de la multiplicidad del cáncer

Introduction: the only way of improving prognosis and survivalin gastrointestinal cancer is early diagnosis, with intramucosallocalization as confirmed by endoscopic ultrasonography (EUS)or 20-MHz miniprobes (MPs) (T1) being most appropriate. Endoscopicmucosal resection (EMR) has proven effective in the treatmentof this sort of lesions.Patients and method: in a group (18 cases) with 15 cases ofsuperficial gastrointestinal cancer and 3 cases of severe gastricdysplasia, 9 cases (3 esophageal, 4 gastric, 2 rectal) underwent aclassic EMR following EUS or a 7.5- and 20-MHz miniprobe exploration.Results: ultrasonographic studies showed a T1 in all but oneesophageal case (Tis), and in both gastric dysplasias, with nochanged layer structure being demonstrated in the latter (T0).No complications arose with classic EMR, and all 9 patientsare alive and free from local or metastatic recurrence, except forone esophageal case, which recurred distally to the esophageal lesion(metachronous).Conclusions: echoendoscopically-assisted EMR is a safe, effectivetechnique in the endoscopic management of superficialgastrointestinal (esophageal, gastric, colorectal) cancer. Recurrencemost likely depends upon cancer multiplicity